Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Short- and long-term outcomes after distal pancreatectomy with radiologic infiltration of splenic vessels for pancreatic ductal adenocarcinoma.

BACKGROUND: The effect of radiologic splenic vessels involvement (RSVI) on the survival of patients with pancreatic adenocarcinoma (PAC) located in the body and tail of the pancreas is controversial, and its influence on postoperative morbidity after distal pancreatectomy (DP) is unknown. This study aimed to determine the influence of RSVI on postoperative complications, overall survival (OS), and disease-free survival (DFS) in patients undergoing DP for PAC. METHODS: A multicenter retrospective study of DP was conducted at 7 hepatopancreatobiliary units between January 2008 and December 2018. Patients were classified according to the presence of RSVI. A Clavien-Dindo grade of >II was considered to represent a major complication. RESULTS: A total of 95 patients were included in the analysis. Moreover, 47 patients had vascular infiltration: 4 had arterial involvement, 10 had venous involvement, and 33 had both arterial and venous involvements. The rates of major complications were 20.8% in patients without RSVI, 40.0% in those with venous RSVI, 25.0% in those with arterial RSVI, and 30.3% in those with both arterial and venous RSVIs (P = .024). The DFS rates at 3 years were 56% in the group without RSVI, 50% in the group with arterial RSVI, and 16% in the group with both arterial and venous RSVIs (P = .003). The OS rates at 3 years were 66% in the group without RSVI, 50% in the group with arterial RSVI, and 29% in the group with both arterial and venous RSVIs (P < .0001). CONCLUSION: RSVI increased the major complication rates after DP and reduced the OS and DFS. Therefore, it may be a useful prognostic marker in patients with PAC scheduled to undergo DP and may help to select patients likely to benefit from neoadjuvant treatment.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BACKGROUND: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. METHODS: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. RESULTS: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91). CONCLUSIONS: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

Parents' perspectives on dental team as advisors to promote HPV vaccination among Spanish adolescents.

PURPOSE: Human papillomavirus (HPV) is a prevalent sexually transmitted infection responsible for many anogenital and oropharyngeal cancers. Dental care providers have the potential to influence vaccine uptake, yet little is known about how patients perceive their role in HPV education and prevention. METHODS: Parents of adolescents aged 9 to 17 years (n = 375) were recruited from Valdeorras District Hospital (Galicia, Spain) to investigate parents' attitudes concerning the involvement of dental care providers in discussions related to HPV. A survey was distributed to the participants, and 343 (91.5%) were included in the analysis. RESULTS: In general, nearly half of the parents reported feeling comfortable regarding discussing HPV with their dentist. Participants described more comfort with dentists than with dental hygienists. Parents' comfort levels were influenced by various social determinants of health, including education level, marital status, geographic origin, and child vaccination status (p > 0.05). CONCLUSION: Parents reported varying comfort levels when discussing HPV and its vaccine with dental professionals, displaying a preference for dentists. Dental settings have the potential to promote vaccination, but the existence of ongoing barriers needs to be addressed.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Textbook outcome in distal pancreatectomy: A multicenter study.

BACKGROUND: Textbook outcome is an interesting quality metrics tool. Information on textbook outcomes in distal pancreatectomy is very scarce. In this study we determined textbook outcome in a distal pancreatectomy multicenter database and propose a specific definition of textbook outcome-distal pancreatectomy that includes pancreatic fistula. METHODS: Retrospective multicenter observational study of distal pancreatectomy performed at 8 hepatopancreatobiliary surgery units from January 1, 2008, to December 31, 2018. The inclusion criteria were any scheduled distal pancreatectomy performed for any diagnosis and age > 18 years. Specific textbook outcome-distal pancreatectomy was defined as hospital stay P < 75, no Clavien-Dindo complications (≥ III), no hospital mortality, and no readmission recorded at 90 days, and the absence of pancreatic fistula (B/C). RESULTS: Of the 450 patients included, 262 (58.2%) obtained textbook outcomes. Prolonged stay was the parameter most frequently associated with failure to achieve textbook outcomes. The textbook outcome group presented the following results. Preoperative: lower American Society of Anesthesiologists score < III, a lower percentage of smokers, and less frequent tumor invasion of neighboring organs or vascular invasion; operative: major laparoscopic approach, and less resection of neighboring organs and less operative transfusion; postoperative: lower percentage of delayed gastric emptying and pancreatic fistula B/C, and diagnosis other an adenocarcinoma. In the multivariate study, the American Society of Anesthesiologists score > II, resection of neighboring organs, B/C pancreatic fistula, and delayed gastric emptying were associated with failure to achieve textbook outcomes. CONCLUSION: The textbook outcome rate in our 450 pancreaticoduodenectomies was 58.2%. In the multivariate analysis, the causes of failure to achieve textbook outcomes were American Society of Anesthesiologists score > II, resection of neighboring organs, pancreatic fistula B/C, and delayed gastric emptying. We believe that pancreatic fistula should be added to the specific definition of textbook outcome-distal pancreatectomy because it is the most frequent complication of this procedure.

Analytical Validation of the PreciseDx Digital Prognostic Breast Cancer Test in Early-Stage Breast Cancer.

BACKGROUND: PreciseDx Breast (PDxBr) is a digital test that predicts early-stage breast cancer recurrence within 6-years of diagnosis. MATERIALS AND METHODS: Using hematoxylin and eosin-stained whole slide images of invasive breast cancer (IBC) and artificial intelligence-enabled morphology feature array, microanatomic features are generated. Morphometric attributes in combination with patient's age, tumor size, stage, and lymph node status predict disease free survival using a proprietary algorithm. Here, analytical validation of the automated annotation process and extracted histologic digital features of the PDxBr test, including impact of methodologic variability on the composite risk score is presented. Studies of precision, repeatability, reproducibility and interference were performed on morphology feature array-derived features. The final risk score was assessed over 20-days with 2-operators, 2-runs/day, and 2-replicates across 8-patients, allowing for calculation of within-run repeatability, between-run and within-laboratory reproducibility. RESULTS: Analytical validation of features derived from whole slide images demonstrated a high degree of precision for tumor segmentation (0.98, 0.98), lymphocyte detection (0.91, 0.93), and mitotic figures (0.85, 0.84). Correlation of variation of the assay risk score for both reproducibility and repeatability were less than 2%, and interference from variation in hematoxylin and eosin staining or tumor thickness was not observed demonstrating assay robustness across standard histopathology preparations. CONCLUSION: In summary, the analytical validation of the digital IBC risk assessment test demonstrated a strong performance across all features in the model and complimented the clinical validation of the assay previously shown to accurately predict recurrence within 6-years in early-stage invasive breast cancer patients.

Evaluation of the validated intraoperative bleeding scale in liver surgery: study protocol for a multicenter prospective study.

Background: Surgical hemostasis has become one of the key principles in the advancement of surgery. Hemostatic agents are commonly administered in many surgical specialties, although the lack of consensus on the definition of intraoperative bleeding or of a standardized system for its classification means that often the most suitable agent is not selected. The recommendations of international organizations highlight the need for a bleeding severity scale, validated in clinical studies, that would allow the selection of the best hemostatic agent in each case. The primary objective of this study is to evaluate the VIBe scale (Validated Intraoperative Bleeding Scale) in humans. Secondary objectives are to evaluate the scale's usefulness in liver surgery; to determine the relationship between the extent of bleeding and the hemostatic agent used; and to assess the relationship between the grade of bleeding and postoperative complications. Methods: Prospective multicenter observational study including 259 liver resections that meet the inclusion criteria: patients scheduled for liver surgery at one of 10 medium-high volume Spanish HPB centers using an open or minimally invasive approach (robotic/laparoscopic/hybrid), regardless of diagnosis, ASA score <4, age ≥18, and who provide signed informed consent during the study period (September 2023 until the required sample size has been recruited). The participating researchers will be responsible for collecting the data and for reporting them to the study coordinators. Discussion: This study will allow us to evaluate the VIBe scale for intraoperative bleeding in humans, with a view to its subsequent incorporation in daily clinical practice. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05369988?term = serradilla&draw = 2&rank = 3, [NCT0536998].

Methods for dynamic and whole volume imaging of the zebrafish heart.

Tissue development and regeneration are dynamic processes involving complex cell migration and cell-cell interactions. We have developed a protocol for complementary time-lapse and three-dimensional (3D) imaging of tissue for developmental and regeneration studies which we apply here to the zebrafish cardiac vasculature. 3D imaging of fixed specimens is used to first define the subject at high resolution then live imaging captures how it changes dynamically. Hearts from adult and juvenile zebrafish are extracted and cleaned in preparation for the different imaging modalities. For whole-mount 3D confocal imaging, single or multiple hearts with native fluorescence or immuno-labeling are prepared for stabilization or clearing, and then imaged. For live imaging, hearts are placed in a prefabricated fluidic device and set on a temperature-controlled microscope for culture and imaging over several days. This protocol allows complete visualization of morphogenic processes in a 3D context and provides the ability to follow cell behaviors to complement in vivo and fixed tissue studies. This culture and imaging protocol can be applied to different cell and tissue types. Here, we have used it to observe zebrafish coronary vasculature and the migration of coronary endothelial cells during heart regeneration.

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience / Influencia del origen e histopatología tumoral tras la resección de metástasis hepáticas de origen no colorrectal no neuroendocrino. Experiencia unicéntrica

Introduction: It remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. Method: A retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. Results: A total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. Conclusion: Based on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection. (AU)

Introducción: No está totalmente aclarado si la resección hepática está justificada en pacientes con metástasis hepáticas no colorrectales no neuroendocrinas (MHNCNN). Hemos realizado un estudio en un solo centro para analizar la supervivencia global (SG), la supervivencia libre de enfermedad (SLE) y posibles factores pronósticos en pacientes con diferentes tipos de MHNCNN. Método: Se realizó un análisis retrospectivo de todos los pacientes que se sometieron a resección hepática de MHNCNN desde enero de 2006 hasta julio de 2019. Resultados: Se analizaron un total de 62 pacientes. El 82,3% presentó metástasis metacrónicas y el 74,2% fueron unilobares. El sitio original del tumor primario (STP) más frecuente fue mama (24,2%), tracto urinario (19,4%), melanoma (12,9%) y páncreas (9,7%). Las histopatologías tumorales primarias más frecuentes fueron el carcinoma de mama (24,2%), el adenocarcinoma no mamario (21%), el melanoma (12,9%) y el sarcoma (12,9%). El procedimiento quirúrgico realizado con mayor frecuencia fue la hepatectomía menor (72,6%). La resección R0 se logró en el 79,5% de los casos. La tasa de complicaciones mayores fue del 9,7% con una tasa de mortalidad a los 90 días del 1,6%. La tasa de SG / SLE a 1, 3 y 5 años fue de 65% / 28%, 45% / 36% y 46% / 28%, respectivamente. Identificamos la respuesta a la terapia neoadyuvante y el STP como posibles factores pronósticos de SG (p = 0,06) y SLE (p = 0,06) respectivamente. Conclusión: Según los resultados de nuestra serie, la resección de MHNCNN produce resultados beneficiosos en términos de SG y SLE. El STP y la respuesta a la terapia neoadyuvante podrían ser los principales factores pronósticos tras la resección. (AU)

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience.

INTRODUCTION: It remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. METHOD: A retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. RESULTS: A total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications' rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. CONCLUSION: Based on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.

Textbook outcome in the surgical treatment of liver hydatid cyst.

BACKGROUND: Textbook outcome is a composite measure used in surgery to define the ideal postoperative period and to assess the quality of care. The aim of this study was to analyze the incidence of textbook outcome and the factors independently associated with its achievement following surgical treatment of liver hydatid cysts. METHODS: Retrospective cohort study of patients operated on for liver hydatid cysts between January 2006 and December 2021. Textbook outcome was achieved when all the following criteria were fulfilled: no mortality within 90 days, no major complications within 90 days, no hospital readmission within 90 days, and no prolonged hospital stay. Univariable and multivariable analyses were performed to identify factors associated with textbook outcome. RESULTS: During the study period, 296 patients underwent surgery. Textbook outcome was recorded in 65.9% (195/296). Female gender (odds ratio 2.02; P = .010), noncomplicated cyst (odds ratio 3.97, P < .001), and radical surgery (odds ratio 2.26, P = .003) were the variables associated with a higher probability of achieving textbook outcome. CONCLUSION: Textbook outcome may be a useful measure to assess the variations in surgical management between different centers, and to improve quality of care after liver hydatid cysts resection.

Memory-driven eye movements prospectively predict dementia in people at risk of Alzheimer's disease.

Introduction: Oculomotor behaviors linked to cognitive performance revealed neurocognitive features of Alzheimer's disease (AD) that can enhance the accuracy of its assessment and diagnosis. Methods: A sample of 107 participants (i.e., 65 mild cognitive impairment [MCI] and 42 controls) were recruited and followed up for 40 months. At baseline, they underwent assessment with the ViewMind digital biomarker, which draws cognitive-related patterns of eye movement while people perform the visual short-term memory binding task. Results: Baseline data predicted that 36 patients with MCI would progress to the AD clinical syndrome (ADS Progressing). The remaining 29 MCI patients were predicted to remain as MCI or progress to other forms of dementia. After 40 months of follow-up, 94% of ADS Progressing patients had received a diagnosis of dementia, whereas none of the non-ADS Progressing had. Discussion: The analysis of eye movement behavior combined with cognitive markers for AD can effectively predict progression to ADS among patients with MCI.

Development and validation of an AI-enabled digital breast cancer assay to predict early-stage breast cancer recurrence within 6 years.

BACKGROUND: Breast cancer (BC) grading plays a critical role in patient management despite the considerable inter- and intra-observer variability, highlighting the need for decision support tools to improve reproducibility and prognostic accuracy for use in clinical practice. The objective was to evaluate the ability of a digital artificial intelligence (AI) assay (PDxBr) to enrich BC grading and improve risk categorization for predicting recurrence. METHODS: In our population-based longitudinal clinical development and validation study, we enrolled 2075 patients from Mount Sinai Hospital with infiltrating ductal carcinoma of the breast. With 3:1 balanced training and validation cohorts, patients were retrospectively followed for a median of 6 years. The main outcome was to validate an automated BC phenotyping system combined with clinical features to produce a binomial risk score predicting BC recurrence at diagnosis. RESULTS: The PDxBr training model (n = 1559 patients) had a C-index of 0.78 (95% CI, 0.76-0.81) versus clinical 0.71 (95% CI, 0.67-0.74) and image feature models 0.72 (95% CI, 0.70-0.74). A risk score of 58 (scale 0-100) stratified patients as low or high risk, hazard ratio (HR) 5.5 (95% CI 4.19-7.2, p < 0.001), with a sensitivity 0.71, specificity 0.77, NPV 0.95, and PPV 0.32 for predicting BC recurrence within 6 years. In the validation cohort (n = 516), the C-index was 0.75 (95% CI, 0.72-0.79) versus clinical 0.71 (95% CI 0.66-0.75) versus image feature models 0.67 (95% CI, 0.63-071). The validation cohort had an HR of 4.4 (95% CI 2.7-7.1, p < 0.001), sensitivity of 0.60, specificity 0.77, NPV 0.94, and PPV 0.24 for predicting BC recurrence within 6 years. PDxBr also improved Oncotype Recurrence Score (RS) performance: RS 31 cutoff, C-index of 0.36 (95% CI 0.26-0.45), sensitivity 37%, specificity 48%, HR 0.48, p = 0.04 versus Oncotype RS plus AI-grade C-index 0.72 (95% CI 0.67-0.79), sensitivity 78%, specificity 49%, HR 4.6, p < 0.001 versus Oncotype RS plus PDxBr, C-index 0.76 (95% CI 0.70-0.82), sensitivity 67%, specificity 80%, HR 6.1, p < 0.001. CONCLUSIONS: PDxBr is a digital BC test combining automated AI-BC prognostic grade with clinical-pathologic features to predict the risk of early-stage BC recurrence. With future validation studies, we anticipate the PDxBr model will enrich current gene expression assays and enhance treatment decision-making.

Artificial intelligence-derived neurofibrillary tangle burden is associated with antemortem cognitive impairment.

Tauopathies are a category of neurodegenerative diseases characterized by the presence of abnormal tau protein-containing neurofibrillary tangles (NFTs). NFTs are universally observed in aging, occurring with or without the concomitant accumulation of amyloid-beta peptide (Aß) in plaques that typifies Alzheimer disease (AD), the most common tauopathy. Primary age-related tauopathy (PART) is an Aß-independent process that affects the medial temporal lobe in both cognitively normal and impaired subjects. Determinants of symptomology in subjects with PART are poorly understood and require clinicopathologic correlation; however, classical approaches to staging tau pathology have limited quantitative reproducibility. As such, there is a critical need for unbiased methods to quantitatively analyze tau pathology on the histological level. Artificial intelligence (AI)-based convolutional neural networks (CNNs) generate highly accurate and precise computer vision assessments of digitized pathology slides, yielding novel histology metrics at scale. Here, we performed a retrospective autopsy study of a large cohort (n = 706) of human post-mortem brain tissues from normal and cognitively impaired elderly individuals with mild or no Aß plaques (average age of death of 83.1 yr, range 55-110). We utilized a CNN trained to segment NFTs on hippocampus sections immunohistochemically stained with antisera recognizing abnormal hyperphosphorylated tau (p-tau), which yielded metrics of regional NFT counts, NFT positive pixel density, as well as a novel graph-theory based metric measuring the spatial distribution of NFTs. We found that several AI-derived NFT metrics significantly predicted the presence of cognitive impairment in both the hippocampus proper and entorhinal cortex (p < 0.0001). When controlling for age, AI-derived NFT counts still significantly predicted the presence of cognitive impairment (p = 0.04 in the entorhinal cortex; p = 0.04 overall). In contrast, Braak stage did not predict cognitive impairment in either age-adjusted or unadjusted models. These findings support the hypothesis that NFT burden correlates with cognitive impairment in PART. Furthermore, our analysis strongly suggests that AI-derived metrics of tau pathology provide a powerful tool that can deepen our understanding of the role of neurofibrillary degeneration in cognitive impairment.

Resection of isolated pancreatic metastases from pulmonary neoplasia: a systematic review.

Several types of cancers have been reported to metastasize to the pancreas. Lung cancer with isolated pancreatic metastasis is extremely rare. In selected patients, surgery is advocated. The aim of our study is to carry out a systematic review of the articles published on the surgical treatment of these patients. Our goal was to realize a systematic review in accordance with PRISMA guidelines. We conducted a literature search using MEDLINE (PubMed), EMBASE and SCOPUS databases to identify all studies published from 1967 to 2020 reporting patients with pancreatic resection for metastatic lung cancer to the pancreas. The data of the articles finally selected were represented in tables. The median age of included patients was calculated as well as the median survival. The proportion of patients was calculated according to sex, type of surgery performed and location of the lesion. 3150 articles were included at the beginning. After the screening process, 20 articles were selected for the systematic review. These articles reported data on 23 patients. Presentation was mainly metachronous, with a disease-free interval of 10 (0-54) months. Of these patients, 43.5% were symptomatic at diagnosis and 34.8% had extrapancreatic metastases. Mean overall survival was 17.65 (± 14.56) months. Based in this review, there is limited evidence on the treatment due to the small number of published articles, most of them being case report. Surgical resection of pancreatic metastases from lung cancer could be a safe procedure and it could improve survival rates in selected patients.

Description of the Method for Evaluating Digital Endpoints in Alzheimer Disease Study: Protocol for an Exploratory, Cross-sectional Study.

BACKGROUND: More sensitive and less burdensome efficacy end points are urgently needed to improve the effectiveness of clinical drug development for Alzheimer disease (AD). Although conventional end points lack sensitivity, digital technologies hold promise for amplifying the detection of treatment signals and capturing cognitive anomalies at earlier disease stages. Using digital technologies and combining several test modalities allow for the collection of richer information about cognitive and functional status, which is not ascertainable via conventional paper-and-pencil tests. OBJECTIVE: This study aimed to assess the psychometric properties, operational feasibility, and patient acceptance of 10 promising technologies that are to be used as efficacy end points to measure cognition in future clinical drug trials. METHODS: The Method for Evaluating Digital Endpoints in Alzheimer Disease study is an exploratory, cross-sectional, noninterventional study that will evaluate 10 digital technologies' ability to accurately classify participants into 4 cohorts according to the severity of cognitive impairment and dementia. Moreover, this study will assess the psychometric properties of each of the tested digital technologies, including the acceptable range to assess ceiling and floor effects, concurrent validity to correlate digital outcome measures to traditional paper-and-pencil tests in AD, reliability to compare test and retest, and responsiveness to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged between 60 and 80 years), of whom 13 (26%) were amyloid-negative, cognitively healthy participants (controls); 12 (24%) were amyloid-positive, cognitively healthy participants (presymptomatic); 13 (26%) had mild cognitive impairment (predementia); and 12 (24%) had mild AD (mild dementia). This study involved 4 in-clinic visits. During the initial visit, all participants completed all conventional paper-and-pencil assessments. During the following 3 visits, the participants underwent a series of novel digital assessments. RESULTS: Participant recruitment and data collection began in June 2020 and continued until June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data were successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports the baseline demographics and characteristics of the population studied as well as the study's progress during the pandemic. CONCLUSIONS: This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. The learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD, aiming to enhance clinical end point strategies with digital technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35442.

Adenosquamous cancer of the pancreas: A multicenter retrospective study / Cancer adenoescamoso de pancreas. Estudio retrospectivo multicéntrico

Introduction: Adenosquamous cancer of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Methods: Multicenter retrospective observational study carried out at three Spanish hospitals. The study period was: January 2010–August 2020. A descriptive analysis of the data was performed, as well as an analysis of global and disease-free survival using the Kaplan–Meier statistic. Results: Of a total of 668 pancreatic cancers treated surgically, twelve were ASCP (1.8%). Patient mean age was 69.2±7.4 years. Male/female ratio was 1:1. The main symptom was jaundice (seven patients). Correct preoperative diagnosis was obtained in only two patients. Nine pancreatoduodenectomies and three distal pancreatosplenectomies were performed. 25% had major complications. Mean tumor size was 48.6±19.4mm. Nine patients received adjuvant chemotherapy. Median survival time was 5.9 months, and median disease-free survival was 4.6 months. 90% of patients presented recurrence. Ten of the twelve patients in the study (83.3%) died, with disease progression being the cause in eight. Of the two surviving patients, one is disease-free and the other has liver metastases. Conclusion: ASCP is a very rare pancreatic tumor with aggressive behavior. It is rarely diagnosed preoperatively. The best treatment, if feasible, is surgery followed by the standard chemotherapy regimens for pancreatic adenocarcinoma.(AU)

Introducción: El cáncer adenoescamoso de páncreas (CPAS) es un subtipo de cáncer de páncreas agresivo e infrecuente que combina un componente glandular y escamoso, y presenta baja supervivencia. Métodos: Estudio observacional retrospectivo multicéntrico realizado en tres hospitales españoles. El período de estudio fue: enero 2010 - agosto 2020. Se realizó un análisis descriptivo de los datos, así como un análisis de supervivencia global y libre de enfermedad mediante Kaplan-Meier. Resultados: De un total de 668 cánceres de páncreas tratados quirúrgicamente, doce fueron CPAS (1,8%). La edad media de los pacientes fue de 69,2±7,4 años. La proporción hombre /mujer fue de 1: 1. El síntoma principal fue la ictericia (siete pacientes). Se obtuvo un diagnóstico preoperatorio correcto en solo dos pacientes. Se realizaron nueve duodenopancretectomías cefálicas y tres pancreatoesplenectomías distales. El 25% tuvo complicaciones mayores. El tamaño medio del tumor fue de 48,6±19,4mm. Nueve pacientes recibieron quimioterapia adyuvante. La mediana de supervivencia fue de 5,9 meses y la mediana de supervivencia libre de enfermedad fue de 4,6 meses. El 90% de los pacientes presentó recidiva. Diez de los doce pacientes del estudio (83,3%) fallecieron, y la progresión de la enfermedad fue la causa en ocho. De los dos pacientes que sobrevivieron, uno está libre de enfermedad y el otro tiene metástasis hepáticas. Conclusión:El CPAS es un tumor pancreático muy raro y de comportamiento agresivo. Rara vez se diagnostica antes de la operación. El mejor tratamiento, si es posible, es la cirugía seguida de los regímenes de quimioterapia estándar para el adenocarcinoma de páncreas.(AU)