bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing quantile-varying covariate effects under the accelerated failure time model
Authors: Reeder Harrison T , Lee Kyu Ha , Haneuse Sebastien
Published: January 2023

An important task in survival analysis is choosing a structure for the relationship between covariates of interest and the time-to-event outcome. For example, the accelerated failure time (AFT) model structures each covariate effect as a constant multiplicative shift in the outcome distribution across all survival quantiles. Though parsimonious, this structure cannot detect or capture effects that differ across quantiles of the distribution, a limitation that is analogous to only permitting proportional hazards in the Cox model. To address this, we propose a general framework for quantile-varying multiplicative effects under the AFT model. Specifically, we embed flexible regression structures within the AFT model and derive a novel formula for interpretable effects on the quantile scale. A regression standardization scheme based on the g-formula is proposed to enable the estimation of both covariate-conditional and marginal effects for an exposure of interest. We implement a user-friendly Bayesian approach for the estimation and quantification of uncertainty while accounting for left truncation and complex censoring. We emphasize the intuitive interpretation of this model through numerical and graphical tools and illustrate its performance through simulation and application to a study of Alzheimer’s disease and dementia.
Flexible evaluation of surrogacy in platform studies
Authors: Sachs Michael C , Gabriel Erin E , Crippa Alessio , Daniels Michael J
Published: January 2023

Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on the type of trial setting. There have been many proposed methods for trial-level surrogate evaluation, but none, to our knowledge, for the specific setting of platform studies. As platform studies are becoming more popular, methods for surrogate evaluation using them are needed. These studies also offer a rich data resource for surrogate evaluation that would not normally be possible. However, they also offer a set of statistical issues including heterogeneity of the study population, treatments, implementation, and even potentially the quality of the surrogate. We propose the use of a hierarchical Bayesian semiparametric model for the evaluation of potential surrogates using nonparametric priors for the distribution of true effects based on Dirichlet process mixtures. The motivation for this approach is to flexibly model relationships between the treatment effect on the surrogate and the treatment effect on the outcome and also to identify potential clusters with differential surrogate value in a data-driven manner so that treatment effects on the surrogate can be used to reliably predict treatment effects on the clinical outcome. In simulations, we find that our proposed method is superior to a simple, but fairly standard, hierarchical Bayesian method. We demonstrate how our method can be used in a simulated illustrative example (based on the ProBio trial), in which we are able to identify clusters where the surrogate is, and is not useful. We plan to apply our method to the ProBio trial, once it is completed.
FROM RENDERING TO REALITY WITH 3D TECHNOLOGY – A NEW INTRODUCER FOR GASTRIC BYPASS CIRCULAR ANASTOMOSIS
Authors: Díaz del Gobbo R , Pardo López S , Díaz del Gobbo G , Guariglia C A , Farré Font R , Güell Farré M , Ayala Márquez B , Collera Ormazábal P
Published: January 2023

Introduction

A key step during laparoscopic gastric bypass circular anastomosis is the introduction of the stapler through the abdominal wall. The adipose panniculus and the 25mm circular flat surface of the endo-stapler involve a technical challenge.

Methods

To show the creative process and development of an innovative device designed directly by the surgeon, inspired by the technique of laparoscopic trocar placement for the introduction of the circular endo-stapler into the abdominal cavity. From a render, a digital image created with a 3D model, a realistic appearance is given to the initial idea. Using 3D printers, a first prototype is obtained, later adapted to achieve a safer shape and a more suitable size. Thus, a second prototype was born, meeting the safety and design standards to be used in the operating room. Its design and printing were conducted by a company, complying with patents, and guaranteeing the safety of the material used.

Results

We present three cases, standardizing the use of the device in the introduction of the endo-stapler and demonstrating its easier passage through the abdominal wall, serving as a guide, giving fluidity and less trauma to the procedure. After performing the anastomosis, we highlight its easy removal using a suture fixed on its peak, which allows it to be safely removed.

Conclusions

The surgeon is the one who best knows the instruments they need and how to optimize them. 3D technology makes it possible to give life to the innovative ideas of surgeons, for surgeons.
CORRELATION BETWEEN RADIOLOGICAL (PCIR) AND SURGICAL (PCIS) PERITONEAL CARCINOMATOSIS INDEX (PCI)
Authors: Ramos Montes C , Cernuda García A , Moreno Gijón M , Amoza Pais S , Mesa Álvarez A , Suárez A A , Sanz Álvarez L , Turienzo Santos E O
Published: January 2023

Introduction

The Peritoneal Carcinomatosis Index (PCI) is used for the selection of candidates for cytoreductive surgery (CRS)+HIPEC and as a prognostic for resectability.

The accuracy of MDCT (Multidetector Computed Tomography) is evaluated by analyzing the degree of correlation between preoperative PCIr and surgical PCIs.

Methods

We conducted an observational, longitudinal, single-center and retrospective study between May 2014 and 2018 on patients operated upon for peritoneal carcinomatosis. Preoperative TCDM were interpreted by an expert radiologist and PCIs were calculated intraoperatively.

Comparison was performed using the Concordance Correlation Coefficient (CCC). The Bland-Altman method was used to represent the difference between observations, with a 95% confidence interval (CI). The sensitivity and specificity of PCIr <20 as a predictor of resectability was also assessed.

Results

Mean PCIs of the 50 patients undergoing CRS+HIPEC was 11.8 (9.5), and mean PCIr was 11.0 (10.1). The CCC between both was 0.94 (95% CI 0.91–0.97). Sensitivity of PCIr was 0.82 (95%CI 0.68–0.92), being resectable 37/40 patients with PCIr <20. Specificity of PCIr fell to 0.40 (95%CI 0.05–0.85), by failing to achieve complete cytoreduction in 2/10 patients with PCIr ≥20. Positive predictive value was 0.92 (95%CI 0.80–0.98), and negative predictive value was 0.20 (95%CI 0.03–0.56).

Conclusions

MDCT interpreted by an expert radiologist is an indispensable tool for the selection of patients who are candidates for CRS+HIPEC. A PCIr ≥20 is not synonymous with unresectability.
RETROSPECTIVE STUDY OF THE LAPAROSCOPIC APPROACH TO SMALL BOWEL OBSTRUCTION
Authors: Carrasco Aguilera B , López-Negrete Cueto E , Martínez Izquierdo G , Rodicio Miravalles J L , Moreno Gijón M , Díaz Vico T , Sanz Álvarez L , Granero Trancón J E
Published: January 2023

Introduction

Exploratory laparotomy has classically been the treatment for adhesive small bowel obstruction (ASBO). Laparoscopic approaches have proven to be a beneficial technique in selected patients. Despite being minimally invasive and associated with low morbidity it is still not a widespread technique.

Methods

Descriptive, retrospective study from January 2011 to April 2022, of 43 patients with ASBO operated by laparoscopy in a tertiary hospital. Demographic, surgical and evolutionary variables were analysed.

Descriptive statistics using non-parametric tests. Univariate logistic regression.

Results

The median age was 67 years (44–77.5), 65% women and 63.3% had previous surgery. In CT (93%) mean loop dilatation was 37.2±6mm and reported as single adhesive band in 62.7%.

Time to surgery <24h in 51.1% and mean operative time 85±48 minutes. 74.1% had AAST classification (The American Association for the Surgery of Trauma) ≤II, conversion rate 27.9% and 3 patients suffered iatrogenesis.

After surgery 43% had oral tolerance <48h with a median postoperative stay of 6 days.

Median follow-up of 48.7 months with 6.9% reoperation, 4.6% readmission, Clavien-Dindo <1 in 70% and no deaths.

There was a relation (p<.05) between conversion-AAST grading ≤II (OR 0.33) and between conversion-surgical time (OR 1.02).

Conclusions

Laparoscopy is a safe approach in patients with OIB in our setting. Our series reflects effective results, in a prolonged mean follow-up, with a low readmission rate and a conversion to open surgery similar to previous series, with only an association between the degree of obstruction and the operative time with the obstruction.
DESIGN AND STUDY OF DIFFERENT PVDF STRUCTURES
Authors: Durán Rey D , Brito Pereira R , Ribeiro C , Sánchez Margallo J A , Cisóstomo V , Lanceros Méndez S , Sánchez Margallo F M
Published: January 2023

Introduction

Tissue engineering (TE) is a promising technology that can develop structures very similar to native tissues to improve or replace their biological functions. Polyvinylidene fluoride (PVDF) is a new thermoplastic polymer widely used in biomedical applications. Each structure of PVDF has different mechanical and biological characteristics depending on its morphology and the methodology employed.

Methods

Doctor blade, salt leaching, and electrospinning methodologies were used to design different PVDF structures, including films, porous membranes, and electrospun membranes, respectively. Furthermore, electrospun PVDF membranes were developed according to the direction of the strands, obtaining membranes that were oriented as well as with random orientation. All these morphologies were subjected to mechanical, cytotoxicity and degradation studies.

Results

All PVDF morphologies underwent a minimum modification of 16% with respect to their original size. The porous membranes were the most fragile structures, and the electrospun membranes were the most resistant. According to ISO standard 10993–5, a material is considered to be biocompatible when the values are higher than 70%, and all PVDF morphologies had cell viability values above the 70% threshold. Finally, results showed that there was no degradability, regardless of the method or structure designed.

Conclusions

PVDF is a material with good mechanical characteristics, given that structures designed with electrospinning can withstand more stress. In addition, this material is non-degradable and biocompatible, broadening the range of biomedical and TE applications.
DESIGN AND STUDY OF DIFFERENT SILK FIBROIN STRUCTURES
Authors: Durán Rey D , Brito Pereira R , Ribeiro C , Sánchez Margallo J A , Cisóstomo V , Lanceros Méndez S , Sánchez Margallo F M
Published: January 2023

Introduction

Tissue engineering (TE) has the capacity to design structures very similar to native tissues in order to restore, maintain or improve their biological functions. Silk fibroin (SF) is a natural protein that has been used in a wide variety of TE applications. Each SF structure has different mechanical and biological characteristics depending on the morphology and methodology employed.

Methods

Bombyx mori silkworm cocoons were extracted and processed to obtain SF. Subsequently, films, porous membranes, and electrospun membranes were designed using doctor blade, salt leaching, and electrospinning methodologies, respectively. Furthermore, electrospun SF membranes were developed according to the direction of the strands, obtaining membranes that were oriented as well as with random orientation. All these morphologies were subjected to mechanical, cytotoxicity and degradation studies.

Results

The most fragile SF structures were the films and the porous membranes, which underwent a maximum modification of approximately 5% with respect to their original size. However, electrospun membranes underwent a change in size of more than 20%. All SF morphologies had biocompatibility values close to 100%. Finally, there was a degradability between 3–5% at 4 weeks in all structures.

Conclusions

SF has very good mechanical characteristics when designed by electrospinning techniques. Although SF is biocompatible, there is a degradation of the material, which may affect the mechanical properties of the designed structure.
SUBJECTIVE USABILITY VALIDATION OF A LEARNING MANAGEMENT SYSTEM FOR ONLINE TRAINING OF MINIMALLY INVASIVE SURGERY: COMPARISON BETWEEN EXPERTS AND STUDENTS
Authors: Sánchez-Peralta L F , Ortega-Morán J F , Gómez E J , Guzmán-García C , Ferencz A , Tiu C , Pagador J B , Sánchez-Margallo F M
Published: January 2023

Introduction

Remote learning has been increasingly required after the COVID-19 pandemic. In this regard, an integrative Learning Management System (LMS) that connects external assets for technical and nontechnical skills training in minimally invasive surgery has been implemented. Before its wider use as a training tool, a comparison of usability perception between experts and students has been performed.

Methods

The system usability scale (SUS) was used. Users rated the 10-item questionnaire on a 5-point Likert-scale (5-Strongly agree, 1-Strongly disagree), with odd questions referring to positive aspects and even questions to negative ones. Two profiles were considered: experts in surgical training and students and residents. They were requested to use the LMS and complete any of the implemented courses. Comparison between groups was done with a Mann-Whitney U-test.

Results

Seven experts and 110 students participated in the study. Overall, SUS score by experts reached a mean value of 67.14 points [Q1 = 68.05, Q3= 76.81; interquartile range (IQR) = 9.67], while the mean SUS score given by students was 73.09 [Q1 = 65.00, Q3= 84.38; IQR = 19.38]. When comparing both groups, significant differences were not found (p-value=0.639).

Conclusions

Since SUS scores are usually considered to be valid when the average is greater than 68, experts were slightly below, while students surpassed this threshold. Nevertheless, since there were no significant differences, it might be assumed that usability of the LMS is acceptable and it will not hinder the training process, although further studies to prove its pedagogical value are required.
MECHANICAL PRINCIPLES OF THE OPERATION OF LINEAR SURGICAL STAPLING
Authors: Cernuda Cabal C , Valdes Vega P , López-Negrete E , Fernández Rodríguez M R , Cortizo Rodríguez J L , Sierra Velasco J M , Rodríguez García J I
Published: January 2023

Introduction

The widespread use of mechanical suture devices in visceral surgery and the continuous improvement of them requires a deeper knowledge of their mechanisms. In this work, these mechanisms are accessed through reverse engineering techniques, to improve knowledge of them, which must be shared by both engineers for their design and surgeons for their use and innovation.

Methods

A search was carried out in the databases of the Spanish Patent and Trademark Office (OEPM), and practical work was developed in the laboratories of the Polytechnic School of Engineering, using specific instruments for an adequate “dissection” of linear mechanical endosuture devices, both manual and motorized or intelligent. Three-dimensional models of singular mechanisms and a descriptive analysis of the mechanisms used were carried out.

Results

The mechanisms used in linear staplers have been characterized and documentary materials and 3D formats have been developed for better understanding by surgeons.

Conclusions

The knowledge of the mechanisms involved in linear mechanical endosutures allows surgeons and engineers to face unforeseen events during interventions, propose innovations to both techniques and equipment, and changes that could lead to improvements in the life cycle (reuse, waste treatment) and associated costs.
A BUNDLE INCLUDING ORAL ANTIBIOTICS AND MECHANICAL BOWEL PREPARATION REDUCES SURGICAL SITE INFECTIONS IN ELECTIVE COLORECTAL SURGERY. PRAGMATIC COHORT STUDY
Authors: Badia J M , Arroyo García N , Vázquez A , Pera M , Parés D , Fraccalvieri D , Limón E , Pujol M
Published: January 2023

Introduction

The efficacy of perioperative bundled interventions implemented at a multicenter level has been poorly studied.

Methods

A colorectal 6-element prevention bundle (antibiotic prophylaxis, oral antibiotic prophylaxis (OAP), mechanical bowel preparation (MBP), laparoscopy, normothermia, and wound retractor), introduced in 61 hospitals, was analysed. Surgical site infection (SSI) rates were compared before (G1, 2011–2016), and after (G2, 2016–2020) the bundle implementation.

Results

37849 procedures were included. 5462 overall SSI (14.43%), and 2838 (7.5%) organ-space SSI (O/S-SSI) were detected. SSI decreased from 18.38% to 10.62% with the application of the bundle (OR 0,503). Similarly, O/S-SSI diminished from 9.15% (G1) to 5.72% (G2), OR 0.602. Compared to the previous year, SSI decreased by 23% after the first year of bundle implementation. 29.26% of SSIs were diagnosed post-discharge. 54.5% required readmission. The reduction was similar between high, medium and low volume hospitals. Overall SSI was 16.71%, when no measure was applied, and 6.23% when all 6 were implemented. Lack of application of the bundle increased the probability of SSI (OR 3.020) and O/S-SSI (OR 1.556). In a univariate analysis, all measures except normothermia were associated with a decrease in overall SSI, while only laparoscopy and OAP were for O/S-SSI. Multivariate analysis confirmed that laparoscopy, OAP, and wound protectors decrease overall SSI, but only OAP and laparoscopy had an effect on O/S-SSI.

Conclusions

A preventive bundle decreased overall and O/S SSI rates in elective colon and rectal surgery. The OR for SSI was 1.5 to 3 times higher before than after the bundle implementation.
INTRACHOLECYSTIC PAPILLARY NEOPLASM: A NEW ENTITY
Authors: del Val Ruiz P , Carrasco Aguilera B , Celis Pinto J C , Ramos Montes C , Cembellín Prieto A , Granero Castro P , González-Pinto Arrillaga I M , Granero Trancón J E
Published: January 2023

Introduction

Gallbladder neoplasms are a rare pathology with an incidence of 1–2 cases per 100,000 inhabitants. In the group of gallbladder neoplasms, adenocarcinoma of the gallbladder is the most common (95% of the total).

Intracholecystic papillary neoplasm (ICPN) is a new entity considered to be a premalignant lesion of the gallbladder. In the few published series, it is found in 0.5–4% of cholecystectomies and up to 6% of intracholecystic adenocarcinomas are located on an ICPN.

We present the case of a patient with an ICPN with a brief review of its epidemiology and characteristics.

Clinical case

A 65-year-old woman with a history of supraglottic squamous cell carcinoma, squamous cell carcinoma of the lung and metastasis in the tail of the pancreas of squamous cell carcinoma who, after 2 years of stable disease with Pembrolizumab and radiotherapy, presented with an atypical thickening of the gallbladder on ultrasound of the abdomen.

It was decided to perform a programmed cholecystectomy, with discharge 24 hours after the intervention.

Subsequent anatomopathological analysis revealed a 0.8 cm nodular thickening with histological findings of non-infiltrating ICPN in the context of chronic inflammatory changes of the gallbladder.

Discussion

ICPN usually presents as an incidental finding, although 50% of cases present with right hypochondrium pain and fever.

It is a poorly described premalignant lesion that requires further studies in order to define its tumorogenesis, clinicopathologic characteristics and actual prevalence.
NLR AND PLR: NEW PREDICTORS OF COMPLICATED DIVERTICULITIS AND THE NEED FOR INTERVENTION
Authors: del Val Ruiz P , Carrasco Aguilera B , Menéndez Corteguera A B , García Alonso L , Valentín Gamazo I , Fernández Hevia M , García Flórez L J , García Trancón J E
Published: January 2023

Introduction

The most commonly used analytical parameters to predict severity (CRP, PCT, leukocyte count, % neutrophils…) are well known, whereas biomarkers such as the neutrophil-lymphocyte index (NLR) and the platelet-lymphocyte index (PLR) are less known and have utility during the diagnosis of acute diverticulitis (AD).

Methods

Retrospective study of 176 patients diagnosed with AD during 2019. The association between multiple acute phase reactants (PLRs) and the presence of complication of AD was studied.

Results

The mean age was 62.8 years, being more frequent in women (59.7%). According to the Hinchey classification 46 (26.1%) AD were complicated; Hinchey Ib: 32 (18.2%), Hinchey II: 10 (5.7%), Hinchey III: 3 (1.7%) and Hinchey IV: 1 (0.6%). Of all of them, 14 patients required surgery.

A statistically significant increase in all RFA was observed in complicated AD and in cases of invasive treatment.

It was shown that CRP has greater discriminative power to detect complicated AD with ROC curves (AUC: 76.6% (95% CI: 0.676–0.856)). However, regarding the need for invasive treatment, the NLR (AUC 77.8%; 95% CI: 0.648–0.908) was found to be more accurate.

For the classification of uncomplicated vs. complicated AD, the cut-off points were CRP (9.05), NLR (6.23) and PLR (141.93), with CRP being the most accurate.

Conclusions

The NLR and PLR are easy and inexpensive indices to obtain to diagnose AD and their accuracy is comparable to that of other RFA commonly used in diagnosis.
PREVENTION OF SEROMA IN BREAST SURGERY
Authors: Martínez Izquierdo G , Calvo Rodríguez D , García Alonso L , Ramos Montes C , Ibero Casadiego P , Menéndez Corteguera A , Alonso Martínez B , Llaneza Folgueras A
Published: January 2023

Introduction

Axillary lymphadenectomy is an essential procedure in the treatment of axillary breast metastases, with seroma formation being its most frequent complication. In the literature there are controversial studies on the best method of prevention of axillary seroma.

Methods

A retrospective observational study was carried out in 77 patients who underwent axillary lymphadenectomy in 2021.

Epidemiological, intraoperative and follow-up-related data and complications were taken into account, with the aim of analyzing the relationship between the application of hemostatic materials, such as Hempatch®, in the axillary site after lymphadenectomy and the presentation of axillary seroma.

For the statistical analysis, the IBM SPSS Statistics version 20 program was used.

Results

Hemopatch® was applied to the axillary site in 55.8% of cases. 35.1% of the patients presented axillary seroma and in 32.5% no complication was observed. The application of Hemopatch® showed a significant relationship with the mean volume of drainage in the first 3 postoperative days (p=0.000), as well as with the total volume in these first 3 days after surgery (p=0.000) and with the early withdrawal of the drainage (p=0.000). No relationship, however, could be demonstrated between the use of Hemopatch® in the axillary site and the prevention of axillary seroma (p=0.728).

Conclusions

The application of Hemopatch® in the axillary site does not imply a decrease in the rate of seroma or in the total volume drained, but a reduction in the volume drained has been observed during the first 3 postoperative days, which facilitates its early removal.
FUNCTIONAL MAPPING OF NOVEL HISTONE POST-TRANSLATIONAL ALTERATIONS IN COLON CANCER
Authors: Díaz Vico T , Fernández Martínez D , Tejedor Vaquero J R , Fernández Hevia M , García Santos G , Fernández Fraga M , García Flórez L J
Published: January 2023

Introduction

Epigenetic alterations are related to the process of tumorigenesis and resistance to oncological therapies. Although more than 60 types of histone post-translational modifications (HPTMs) have been described, the alterations that manifest simultaneously in tumor tissue have not been systematically studied in colorectal cancer (CRC). This project aims to develop a new screening methodology to delineate epigenetic alterations present in CRC and to obtain a set of biomarkers related to malignancy and tumor response.

Methods

Using state-of-the-art tandem mass spectrometry (MS-MS) techniques, a direct injection protocol will be performed to simultaneously identify the presence of >200 HPTMs-related peptides in a cohort of primary tumors and paired healthy CRC tissue. Patterning of spectra and statistical analyses will be performed with the automated processing algorithm EpiProfile 2.0.

Results

A histone extraction protocol optimized for human tumor samples was developed. Likewise, we managed to make MS/MS sample processing more flexible by implementing a multiplatform workflow (Thermo / Sciex), which will increase the screening and data analysis capacity. Through this process we managed to detect >200 peptides related to HPTMs in control samples, and we observed significant differences in certain HPTMs with pharmacological treatments in primary cultures.

Conclusions

These results will allow the identification of epigenetic biomarkers related to grade, stage and recurrence in the context of CRC.
IDENTIFICATION OF EPIGENETIC VULNERABILITIES IN THE ADENOMA-CARCINOMA SEQUENCE
Authors: Díaz Vico T , Fernández Martínez D , Tejedor Vaquero J R , Fernández Hevia M , García Santos G , Fernández Fraga M , García Flórez L J
Published: January 2023

Introduction

Numerous studies have documented the functional effect of different driver mutations on the development and progression of colorectal cancer (CRC). However, the molecular-level impact of each of these mutations on the epigenome/transcriptome, as well as the phenotype-related longitudinal effects of these mutations have not been characterized in detail. This work proposes an experimental design based on the integration of different -omic layers in order to identify molecular vulnerabilities with therapeutic potential in the adenoma-carcinoma sequence.

Methods

The proposed experimental model contemplates the introduction of sequential mutations in the APC/KRAS/TP53 and SMAD4 genes with CRISPR/Cas9 technology in human colon organoids obtained from healthy mucosa. To determine the molecular alterations at each step of the sequence, a paired RNA expression and DNA methylation analysis will be performed at the whole genome level with the respective massive next-generation sequencing technologies / EPIC arrays. Finally, to identify possible functional associations between the epigenome/transcriptome, an integration analysis of these -omics will be performed with novel computational algorithms, also including the integration of these data with information available from international consortia.

Results

The project is currently in the initial stages of development. The model and the most updated results available to date will be discussed in detail during the congress.

Conclusions

These results will allow the identification of molecular vulnerabilities with therapeutic potential in the context of CRC.
ROLE OF MULTI-PARAMETRIC MAGNETIC RESONANCE (MPMR) PREDICTING THE NEED FOR PROSTATE RE-BIOPSY IN PATIENTS WITH ATYPICAL SMALL ACINAR PROLIFERATION (ASAP): A MONOCENTRIC STUDY
Authors: Abad López P , González Padilla D A , Gómez Rivas J , Ibáñez Vázquez L , Arévalo Ruales R , Infante Hernández S , Galante Romo M I , Moreno Sierra J
Published: January 2023

Introduction

The European Urology guidelines recommended until 2020 to re-biopsy patients with ASAP in prostate tissue, given the high possibility of detecting cancer in a biopsy (approximately 30%), however the second rate of clinically significant prostate cancer is relatively low (reported between 5 and 20% of these biopsies).

The role of mpMRI prior to re-biopsy in these patients is currently unknown. To date there are only two publications that have included patients with ASAP and re-biopsy with previous mpMRI.

Methods

Descriptive and retrospective study. Data were collected from 66 patients between March 2015 and May 2021, who were diagnosed with ASAP in a first prostate biopsy (either with MRI before or after it) and a second biopsy (re-biopsy) performed by image fusion. MRI- transrectal ultrasound (cognitive or software) with transrectal or transperineal sample collection.

Results

In 27 of 66 patients (40.9%) the biopsy was positive: in 2 cases ASAP appeared in the re-biopsy, followed by ISUP1 (clinically not significant) in 14 patients (21.21%). Only in 11 patients (16.7%) did the biopsy yield a clinically significant prostate cancer result (ISUP2 or higher).

Among the 29 patients who had positive MRI (PIRADS 3 or higher), 18 cases (62%) had positive biopsies: 10 patients (34.4%) had ISUP1 while 8 (27.5%) patients had ISUP2 or higher.

Conclusions

Performing mpMRI before or after the biopsy in patients with ASAP can help avoid unnecessary biopsies.
PILOT STUDY FOR THE CREATION OF A STROKE MODEL IN RABBITS USING ENDOVASCULAR TECHNIQUES
Authors: Lucas-Cava V , Bote J , Moreno-Lobato B , Picado-Román N , Sun F , Sánchez-Margallo F M
Published: January 2023

Introduction

Due to the clinical implications of stroke in patients, the “2IQBIONEURO” project promoted by the Interreg VA Spain-Portugal programme (POCTEP) aims to study the treatment of neurological diseases associated with ageing. The aim was to evaluate the feasibility of the technique of selective cerebral artery (CA) embolisation for the creation of a stroke model in rabbits.

Methods

In 3 rabbits, through a 4Fr introducer in the femoral artery, a 4Fr Cobra catheter and 0.035″ guide was placed in the aortic arch to perform angiography of the brachiocephalic trunk. Under road-mapping, the right common carotid artery was catheterised, and its bifurcation into its external and internal branches was visualised with angiography in an oblique position (90°). With a 1.5Fr microcatheter and 0.008″ microguidewire inserted coaxially, the internal carotid artery was catheterised to perform superselective angiography of the cerebral vasculature. The microcatheter was positioned in the CA for embolisation by injection of PVA (100–200 µm) until stasis was reached as an end point or when reflux occurred. MRI monitoring was performed before and after embolisation (2, 5 and 24 hours). After 24 hours, neurological evaluation and macroscopic postmortem study with tetrazolium were performed.

Results

Successful occlusion of the CA was achieved in all animals whose lesion was observed on MRI.

Conclusions

The development of a stroke model in rabbits by selective embolisation of the CA is feasible, and can be used for the preclinical study of stroke.
PRELIMINARY RESULTS ON FUNCTIONALIZATION OF POLYPROPYLENE SURGICAL MESHES
Authors: Patrocinio D , Pagador J B , Galván V , Duarte M , Sánchez Francisco
Published: January 2023

Introduction

Due to inflammatory response in patients, many efforts have been devoted to developing advanced (biological or bioactive) surgical meshes. Some of them look for new synthetic materials and others work to improve their biocompatibility through different methods (coating, soaking, plasma). However, it is critical to avoid pore obstruction or lose mechanical properties while its amphiphilic behaviour is increased.

Methods

A deposition method was used to functionalize surgical meshes with a polypropylene derivative block copolymer that improved its amphiphilic behaviour. Therefore, this copolymer was dispersed on several solvents with different polarities and chemical natures. Then, meshes were immersed and a chemical adsorption-based coating was performed. Additionally, a qualitative study was carried out by optical and fluorescence microscopy on two size samples: small (1 cm2 squares) and large (standard T bone shapes).

Results

First, pore obstruction was perfectly avoided in small samples but was partially present in large samples. Second, the deposition was thicker with polar solvent in both sizes. And finally, fluorescence analysis showed a homogeneous and smooth coating with the most polar solvent.

Conclusions

After exposure to UV light, small samples show a better coating while large one's present irregular adherences on their surface. Moreover, the aprotic polar solvent provides a thickness layer and a smooth mesh surface.
MICROVESICLE SURFACE PROTEIN DETECTION AS A POTENTIAL BIOMARKER IN COLORECTAL CANCER
Authors: García-Santos G , Serrano Pertierra E , Pino Peco G , Fernández Hevia M , Duque Alcorta J M , Sánchez Domínguez L , Blanco López M C , García Flórez L J
Published: January 2023

Introduction

Colorectal cancer (CRC) is the third leading cause of death from cancer in the world; early detection is a key factor for patient´s prognosis. Microvesicles (MVs) are subcellular structures delimited by lipid bilayer intimately involved in physio-pathological processes such as cancer. Our objective is the characterization and detection of surface proteins in plasma derived MVs, as well as their usefulness as a tool in the detection of CRC.

Methods

Circulating MVs in peripheral blood of healthy individuals, with adenomas, high grade adenoma or carcinoma were isolated and characterized. MVs CD9, CD147 and EpCaM MVs surface proteins quantification was performed using an innovative lateral flow immunoassay (LFIA) developed in our laboratory.

Results

The characterization of the plasma MVs confirmed our previous observations, presenting a lower concentration of MVs in the groups of high-grade adenoma and mainly CRC. However, the carcinoma group presents a higher amount of protein per MV suggesting a greater MV´s complexity in this group. The analysis of surface antigens by LFIA show an unexpectedly significant reduction of these proteins in the carcinoma group.

Conclusions

The detection of antigens on the surface of MVs by LFIA may be able to discriminate patients with CRC and could emerge as an alternative test that complements CRC screening programs.
USAGE OF ANTERIOR SUBCUTANEOUS INTERNAL FIXATOR FOR TREATMENT OF PELVIC FRACTURES (INFIX): OUR EXPERIENCE
Authors: Adeba García M , García Granja S , García Portal G , Alonso Viana L , Fernández Álvarez M , Laguna Becero M E , Hernández Elena J , Pérez Núñez M
Published: January 2023

Introduction

Anterior subcutaneous internal fixator(INFIX) was proposed to treat anterior pelvic ring injury. INFIX was initially designed as an alternative to the external fixator, but recently its indications have been expanded, using it as a definitive treatment, and multiple complications have been reported.

Methods

Retrospective study of 11 polytrauma patients with pelvic fractures treated with anterior subcutaneous internal fixator after a high energy trauma between January (2018)-September (2021)

Results

11 polytrauma patients. The average age was 50,5 years old. The mechanism of injury was precipitation, 5 run over and 2 vehicle accidents. According to Tile classification: type B:6 and type C:5, according to Young classification: lateral compression:3, anteroposterior compression:6 and vertical shear:2.

The average time of implantation of INFIX was 4,3 days (0–17). In 10 cases a sacroiliac screw was associated at the same time of surgery and in one patient spinopelvic fixation.

The patients sitting was allowed 24 hours after surgery and partial weight-bearing 6 weeks later. The average time until removal was 5 months and the average follow up was 10 months.

Complications rate was 63,63%(n=7):3 Lateral femoral cutaneous nerve(LFCN) paresthesia:two of them temporary and another persistant one, 1 supracetabular screw osteolysis. 2 implant infections, 1 of them treated with implant removal and reosteosynthesis with symphysis plates. 1 common iliac vein thrombosis resolved with antithrombotic treatment.

Conclusions

Anterior subcutaneous internal fixator provides initial stability in pelvic fractures with a fast and simple technique. However, some complications have been reported. The main complication is LFCN paresthesia, especially during implantation and removal of the fixator.
USEFULNESS OF THE AGE-ADJUSTED CHARLSON COMORBIDITY INDEX AS A PREDICTOR OF MORBIDITY AND MORTALITY IN PATIENTS OVER 80 YEARS OF AGE WITH COLORECTAL CANCER
Authors: García González L A , Fernández Arias S , Del Val P , Corteguera A , de Santiago I , García Flórez L J , Granero Trancón J E
Published: January 2023

Introduction

The age adjusted Charlson Comorbidity Index (aCCI) is the most widely used prognostic tool in patients with comorbidity. Our aim is to evaluate its relationship with postoperative morbidity and mortality.

Methods

Retrospective observational analysis of 145 patients >80 years with CRC operated upon between 2018–2020 in a tertiary center with 2-year follow-up. Pre- and postoperative variables such as aCCI, tumor stage and location, Clavien-Dindo and 2-year survival were selected. Survival analysis was performed according to Kaplan-Meier and ROC curves to predict postoperative mortality/complications. To determine association, a Cox univariate regression model was used.

Results

The mean age was 86 years, the right colon was the most frequent tumor location and laparoscopy was the predominant approach. Only 12.4% presented major complications (Clavien-Dindo >=3). There was no statistically significant association between aCCI and surgical complications HR 1.118 (p 0.095), and there was a relationship with the development of medical complications OR 1.28 (p 0.020) with a sensitivity of 71% and a cut-off point of aCCI 7.5 AUC 0. 637. Overall survival at 2 years was 79% (26 deaths). We did not find a statistically significant association between aCCI and mortality (p 0.286), a weak predictor AUC 0.582.

Conclusions

Elevated aCCI is not related to a higher risk of postoperative morbidity and mortality and has little predictive capacity for surgical complications; however, aCCI >7 is associated with a higher probability of medical complications.

Prospective studies are needed to include multivariable analyses associated with aCCI.
Brain sciences and the R words
Authors: Muniz Terrera Graciela
Published: January 2023

Our Associate Editor, Graciela Muniz Terrera, discusses the importance of reproducibility in neuroscience and our special collection of papers on the topic.
Economic stimulus measures in the pandemic: the role of fiscal decentralisation
Authors: Elgin Ceyhun , Yalaman Abdullah , Yasar Sezer
Published: January 2023

Is fiscal federalism associated with economic policy responses and stimulus measures adopted by national and sub-national governments to mitigate the adverse economic effects of the COVID-19 pandemic? In this paper, we provide empirical evidence that it indeed is. Our results indicate that even after controlling for various relevant factors, countries with fiscally federal (decentralised) governments have adopted larger fiscal and macro-financial policy packages (as a percent of GDP). However, there are no significant differences in monetary-policy responses between centralised and decentralised governments. We also show that these results are robust to using different federalism measures, including different sets of control variables and different econometric specifications that include an instrumental variable estimation.
Specialist Herbivore Performance on Introduced Plants During Native Host Decline
Authors: Horne Grace M , Manderino Rea , Jaffe Samuel P
Published: January 2023

Ash (Fraxinus spp.) is in rapid decline across the northeastern USA due to the invasive emerald ash borer (Agrilus planipennis Fairmaire). Three recently co-occurring confamilial species may serve as alternative larval host plants for ash-reliant Lepidoptera. These prospective hosts are nonnative shrubs often planted in managed suburban landscapes and are sometimes invasive or naturalized in North America. Given the imminent decline of ash trees, we considered potential downstream effects on insect herbivores historically specialized on ash foliage. We measured the performance of three ash-specialist hawkmoths (Lepidoptera: Sphingidae) on native white ash (Fraxinus americana L.) and alternative host plants: common lilac (Syringa vulgaris L.), weeping forsythia [Forsythia suspensa (Thunb.) Vahl], and European privet (Ligustrum vulgare L.). We found the nonnative host plants provided varied support for larval survival to pupation, with biomass and growth rate affected differently by both plant and insect identity. Nearly all caterpillars reared on one alternative host, European privet, exhibited distinct malformations of the wing buds at pupation. Given caterpillar presence on privet in the field, privet may constitute an ecological trap (i.e., when female moths select a sub-optimal host, offspring survival and fitness are reduced). This work demonstrates how performance testing can reveal species-specific effects of host plant loss on mono- or oligophagous insects. For some ash specialists, alternative nonnative host plants may be suboptimal, but some cultivated host plants may be able to support certain specialist insects during native host decline. We suggest that landscaping decisions can be tailored to support threatened insect species.
The Originality of Outsiders: Innovation in the Investment Treaty System
Authors: Roberts Anthea , St John Taylor
Published: January 2023

In recent years, several proposals by states to reform or displace investor-state dispute settlement (ISDS) have gained prominence. While many factors shape which reform proposals states support, here we focus on one important, but often overlooked, factor: the ‘insider’ or ‘outsider’ status of the government officials who formulate states’ proposals. Based on five years of para-ethnographic observation and interviews with officials involved in ISDS reform, and informed by the interdisciplinary innovation literature, we explore how individuals who have not spent their careers within the field of investment arbitration (and are perceived as ‘outsiders’ by those within that field) have developed more disruptive reform proposals while arbitral insiders have typically proposed sustaining reforms. We illuminate these dynamics in the ISDS reform debates with case studies of four actors: the USA, the European Union, Bahrain and Brazil.
Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods
Authors: Toprak Betül , Brandt Stephanie , Brederecke Jan , Gianfagna Francesco , Vishram-Nielsen Julie K K , Ojeda Francisco M , Costanzo Simona , Börschel Christin S , Söderberg Stefan , Katsoularis Ioannis , Camen Stephan , Vartiainen Erkki , Donati Maria Benedetta , Kontto Jukka , Bobak Martin , Mathiesen Ellisiv B , Linneberg Allan , Koenig Wolfgang , Løchen Maja-Lisa , Di Castelnuovo Augusto , Blankenberg Stefan , de Gaetano Giovanni , Kuulasmaa Kari , Salomaa Veikko , Iacoviello Licia , Niiranen Teemu , Zeller Tanja , Schnabel Renate B
Published: January 2023

Aims

To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables.

Methods and results

In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82–2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13–1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10–1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02–1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index.

Conclusion

Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.
Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm
Authors: Wei Hui-Qiang , Liao Zili , Liang Yuanhong , Fang Xianhong , Liao Hongtao , Deng Hai , Wei Wei , Huang Yingjie , Liu Yang , Liu Fangzhou , Lin Weidong , Liang Jackson J , Xue Yumei , Wu Shulin , Zhan Xianzhang
Published: January 2023

Aims

The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm.

Methods and results

This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT.

Conclusion

Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.