Gastric calcinosis ulcer in a renal transplanted patient.

A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of long-lasting epigastric pain and nausea. An esophagogastroduodenoscopy was performed, visualising a nodular lesion of 1 cm diameter with a depressed and ulcerated base. Microscopically the lesion was in relation with a metastatic calcinosis ulcer. Pantoprazole was initiated and serum phosphocalcic levels adjusted, achieving symptom remission. In the follow-up esophagogastroduodenoscopy, the lesion was healing with a fibrinous base and the histopathological report diagnosed superficial gastritis.

Ustekinumab for corticodependent immune-mediated colitis by pembrolizumab, an alternative for patients with concomitant liver injury.

Pembrolizumab, a programmed cell death receptor (PD-1) inhibitor, have improved the prognosis in several types of cancer. Despite the important clinical benefits, checkpoint inhibition have been associated with inflammatory and immune-related side effects (irAE).

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia-PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.

Tumor recurrence after liver transplantation for diffuse biliary papillomatosis in the absence of invasive carcinoma.

Intraductal papillary neoplasm of the bile duct (IPNB) or biliary papillomatosis (BP) is a premalignant entity with high risk of malignant transformation. When the disease extends widely from the intrahepatic to the extrahepatic biliary tree, liver transplantation (LT) is the only option available. We present the case of a 43-year-old male who was admitted in our hospital with an acute cholangitis. He was diagnosed of diffuse biliary and pancreatic papillomatosis. Firstly, we performed a cephalic pancreaticoduodenectomy, then we completed a total pancreatectomy, and finally, after confirming the absence of foci of carcinoma infiltration or lymph nodes involvement, a LT was performed. Foci of carcinoma infiltration or lymph nodes involvement in the liver were not found. After a two-year follow-up the patient developed liver recurrence and the biopsy showed a biliary adenocarcinoma. In 2010, Vibert et al. published a series of three cases concluding that in the absence of invasive carcinoma and positive lymph nodes, LT can be performed with success. The present case is the first to describe recurrence of the disease after LT in the absence of invasive carcinoma and positive lymph nodes in the literature. When the disease affects widely the entire biliary duct, small micro-invasive foci may not be detected. Nevertheless, although we know that it is a recurrent entity, the pathogenesis is unknown, and we do not know if it is possible that papillomatosis recurs over the new liver.

Switching from endoscopic submucosal dissection to salvage piecemeal knife-assisted snare resection to remove a lesion: A preoperative risk score from the beginning.

BACKGROUND AND AIMS: endoscopic submucosal dissection (ESD) in the Western setting remains a challenge. Therefore, other simplified techniques such as knife-assisted snare resection (KAR) have been reported to overcome this issue. METHODS: patients who underwent an ESD for the treatment of gastrointestinal neoplasms were included in a retrospective cross-sectional observational study. Factors associated with the end of ESD as a salvage p-KAR were identified and a logistic regression model was developed. RESULTS: a total of 136 lesions in 133 patients were analyzed. Operator experience of under 50 cases and the combination of lesion size > 30 mm and colorectal location were independent predictive factors for switching to a salvage p-KAR according to the multivariate logistic regression analysis. We developed a risk scoring system based on these four variables (experience, size, location and the combination of size and location) with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The diagnostic accuracy of the score for a cut-off point ≥ 5 had a sensitivity of 0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80). CONCLUSION: a simple predictive score system that includes four preoperative factors accurately predicts ESD to finish as a p-KAR. A careful selection of cases considering these variables could be useful to achieve better outcomes in the Western setting.

Selecting embryos with the highest implantation potential using data mining and decision tree based on classical embryo morphology and morphokinetics.

PURPOSE: The objective of this work was to determine which embryonic morphokinetic parameters up to D3 of in vitro development have predictive value for implantation for the selection of embryos for transfer in clinical practice based upon information generated from embryo transfers with known implantation data (KID). METHODS: A total of 800 KID embryos (100% implantation rate (IR) per transfer and 0% IR per transfer) cultured in an incubator with Time-Lapse system were retrospectively analysed. Of them, 140 embryos implanted, whereas 660 did not. RESULTS: The analysis of morphokinetic parameters, together with the embryo morphology assessment on D3, enabled us to develop a hierarchical model that places the classical morphological score, the t4 and t8 morphokinetic values, as the variables with the best prognosis of implantation. CONCLUSION: In our decision tree, the classical morphological score is the most predictive parameter. Among embryos with better morphological scores, morphokinetics permits deselection of embryos with the lowest implantation potential.

Hernia Correction After Liver Transplantation Using Nonvascularized Fascia.

Background: Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation. Methods: We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period. Results: Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5-66 y), whereas the mean recipient age was 58 y (31-66 y). The median patient height and weight were 163 cm (117-185 cm) and 76 kg (17-104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5-116 mo). The sizes of the aponeurotic defects varied from 6 × 6 to 25 × 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up. Conclusions: With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.

Value of a simple method to assess chronic rejection in renal allograft on electron microscopy.

Electron microscopy is a powerful tool for the assessment of complex lesions in nontumor renal pathology, however it is a time-consuming procedure. We evaluated a simple method to assess morphological signs of chronic rejection in renal allograft that seems to have prognostic significance.

Membranous glomerulopathy in renal allograft: an ultrastructural study of 17 cases.

BACKGROUND: Membranous glomerulopathy is a common complication of renal allograft. However, its incidence and prognosis are not well defined, because an undetermined number of them pass undiagnosed under the generic epigraph of chronic allograft nephropathy. MATERIALS AND METHODS: To assess the diagnostic refinement supplied by electron microscopy to conventional light and immunofluorescence procedures the authors reviewed 17 cases of electron microscopy-confirmed membranous glomerulonephritis in kidney allograft. In addition, they searched for other features of graft injury, particularly lesions associated with alloimmune reaction, in order to evaluate the contribution of each lesion to the long-term outcome of the allograft. RESULTS: In 4 of the 17 cases of their series the diagnosis of membranous glomerulopathy was made by electron microscopy. In addition, in 5 samples, lesions of chronic alloimmune rejection were present (in 4 cases the diagnosis was based on electron microscopy findings). At the end point of the study, 3 of the 5 patients with chronic alloimmune injury were in dialysis, 1 had died with functioning allograft, and the fifth suffered severe renal failure but was not in dialysis. On the other hand, 3 of the 12 patients without evidence of alloimmune injury had returned to the dialysis program. CONCLUSIONS: Electron microscopy is a useful tool in the assessment of renal allograft pathology and can provide additional morphological features of prognostic relevance.

Submucosal Necrotic Nodule of the Colon: An Enigmatic Entity Potentially Related to Anisakis Infection.

CONTEXT.­: Discrete submucosal necrotic nodules may rarely manifest as colon polyps. OBJECTIVE.­: To characterize the clinical and pathologic features of this lesion, which has been under-studied in the literature. DESIGN.­: We conducted an international search to compile a series. For each potential case, photomicrographs were centrally reviewed to confirm the diagnosis. We gathered clinical and pathologic information on each confirmed case. RESULTS.­: The final cohort included 25 patients, with 23 having 1 lesion and 2 having several (31 lesions total). Mean patient age was 62 years; 13 patients (52%) were male. Symptoms were nonspecific, although 4 patients (16%) had blood in stool; 14 patients were asymptomatic. Patient history and medications appeared noncontributory. Most cases were located in the right colon (n = 18; 58%). Mean lesion size was 0.4 cm (range, 0.1-1.7 cm). Histology typically showed a centrally necrotic nodule with peripheral fibrosis, chronic inflammation, and sometimes palisading granulomatous inflammation. Percent necrosis ranged from 5% to 95% (average, 70%), and percent fibrosis ranged from 3% to 70% (average, 25%). In 3 cases, degenerated parasitic structures consistent with Anisakis could be seen on hematoxylin-eosin and trichrome special stain. No patient experienced disease recurrence. CONCLUSIONS.­: Submucosal necrotic nodules can present as colon polyps. Most cases are unifocal, and patients do well on follow-up. At least some examples appear to be caused by Anisakis, implicating patient diet. Patients are often asymptomatic, and many cases show no histologic evidence of the causative agent.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer.

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability to predict response to treatment of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. Based on their results, a series of recommendations are made to optimize the determination of these biomarkers and thus help standardize the diagnosis and treatment of these tumours.

MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.

[Diseases associated with bloodstream infections caused by the new species included in the old Streptococcus bovis group]. / Cuadros clínicos asociados a bacteriemia causada por las nuevas especies incluidas en el antiguo grupo Streptococcus bovis.

OBJECTIVE: We sought to identify possible diseases associated with bloodstream infections caused by new species of S. bovis group isolated in blood cultures and by studying patient records METHODS: Forty-four consecutive blood culture isolates initially designated S. bovis were further characterised using phenotypic methods Patient records were examined. RESULTS: We identified 15 Streptococcus gallolyticus subsp. gallolyticus, 24 Streptococcus gallolyticus subsp. pasteurianus, and 5 Streptococcus infantarius isolates in 44 BSI episodes. CONCLUSIONS: The association between S. bovis bacteraemia and endocarditis and/or colon carcinoma is highly dependent on the causative species. Streptococcus gallolyticus subsp. gallolyticus is a surrogate for endocarditis and/or bowel disease, whereas Streptococcus gallolyticus subsp. pasteurianus is a surrogate for hepato-biliary disease.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer.

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion, to predict response to treatment.In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. As a result, this article proposes a series of recommendations to optimize the determination of these biomarkers to help standardize the diagnosis and treatment of these tumours.

Predicting youth at high risk of aging out of foster care using machine learning methods.

BACKGROUND: Youth who exit the nation's foster care system without permanency are at high risk of experiencing difficulties during the transition to adulthood. OBJECTIVE: To present an illustrative test of whether an algorithmic decision aid could be used to identify youth at risk of existing foster care without permanency. METHODS: For youth placed in foster care between ages 12 and 14, we assessed the risk of exiting care without permanency by age 18 based on their child welfare service involvement history. To develop predictive risk models, 28 years (1991-2018) of child welfare service records from California were used. Performances were evaluated using F1, AUC, and precision and recall scores at k %. Algorithmic racial bias and fairness was also examined. RESULTS: The gradient boosting decision tree and random forest showed the best performance (F1 score = .54-.55, precision score = .62, recall score = .49). Among the top 30 % of youth the model identified as high risk, half of all youth who exited care without permanency were accurately identified four to six years prior to their exit, with a 39 % error rate. Although racial disparities between Black and White youth were observed in imbalanced error rates, calibration and predictive parity were satisfied. CONCLUSIONS: Our study illustrates the manner in which potential applications of predictive analytics, including those designed to achieve universal goals of permanency through more targeted allocations of resources, can be tested. It also assesses the model using metrics of fairness.

Cystic liver neoplams: A single centre experience and literature review. / Neoplasias quísticas hepáticas: experiencia en un único centro y revisión de la literatura.

INTRODUCTION: The hepatic cystic tumour is a very rare neoplasm, representing about 5% of all cystic liver neoplasms. The preoperative diagnosis is difficult and can lead to confusion. The aim of this study is to analyze a number of cases operated at our centre with an histologic diagnosis of liver cystic neoplasms and also to describe the sintomathology, diagnosis and management as per the recent classification. METHODS: A retrospective analysis was performed including all the cystic liver neoplasms operated between January 2000 and December 2019. The study was performed based on the pre-existing pathology archives. The 2010 previous cases were reclassified following the new 2010 OMS classification. RESULTS: The study sample was of 10 patients, identifying 6 of them as mucinous cystic liver neoplasms, and the other 4 as intraductal papillary biliary neoplasms. The majority of the patients were women (8/10) and the median age was 47 years. Regarding the treatment, 3 hepatectomy and 7 enucleations were performed. Frozen section intraoperatively was not required in any case. In one case, variable cellular atypia with areas of adenocarcinoma was observed, and the patient received neoadyuvant chemotherapy with taxol and carboplatin. In all cases the resection margins were negative. CONCLUSION: Cystic liver neoplasms are infrequent tumours with a difficult differential diagnosis. Therefore, with a high radiological suspicious, the treatment should be a complete resection to avoid recurrences and malignancies.

Perspectives on automated composition of workflows in the life sciences.

Scientific data analyses often combine several computational tools in automated pipelines, or workflows. Thousands of such workflows have been used in the life sciences, though their composition has remained a cumbersome manual process due to a lack of standards for annotation, assembly, and implementation. Recent technological advances have returned the long-standing vision of automated workflow composition into focus. This article summarizes a recent Lorentz Center workshop dedicated to automated composition of workflows in the life sciences. We survey previous initiatives to automate the composition process, and discuss the current state of the art and future perspectives. We start by drawing the "big picture" of the scientific workflow development life cycle, before surveying and discussing current methods, technologies and practices for semantic domain modelling, automation in workflow development, and workflow assessment. Finally, we derive a roadmap of individual and community-based actions to work toward the vision of automated workflow development in the forthcoming years. A central outcome of the workshop is a general description of the workflow life cycle in six stages: 1) scientific question or hypothesis, 2) conceptual workflow, 3) abstract workflow, 4) concrete workflow, 5) production workflow, and 6) scientific results. The transitions between stages are facilitated by diverse tools and methods, usually incorporating domain knowledge in some form. Formal semantic domain modelling is hard and often a bottleneck for the application of semantic technologies. However, life science communities have made considerable progress here in recent years and are continuously improving, renewing interest in the application of semantic technologies for workflow exploration, composition and instantiation. Combined with systematic benchmarking with reference data and large-scale deployment of production-stage workflows, such technologies enable a more systematic process of workflow development than we know today. We believe that this can lead to more robust, reusable, and sustainable workflows in the future.

Primary retroperitoneal liposarcoma: clinical and histological analysis of ten cases.

Retroperitoneal liposarcoma constitutes an uncommon and locally aggressive malignancy. We performed a retrospective analysis of 10 patients (6 males; mean age: 63.2+/-11 years) with histologically proven retroperitoneal liposarcoma seen at our institution between 1999 and 2007. Presence of a palpable abdominal mass was the main symptom at diagnosis. All patients underwent complete surgical resection. Negative microscopic margin was achieved in four cases. Histological analysis revealed the following subtypes: well-differentiated (6 cases), dedifferentiated (two cases), pleomorphic, and myxoid/round cell (one case each). Concomitant resection of adjacent organs was needed in five cases. Half of the patients developed tumor recurrence, mainly limited to the retroperitoneum or abdominal cavity. The mean recurrence-free survival was 43.3 months (95%CI: 25.7-60.8), with 3- and 5-year overall survival rates of 79% and 61%, respectively. Patients undergoing complete resection with clear margins showed a near-significant trend toward increased recurrence-free survival (62.9 vs. 29.3 months; P=0.06).

Parameterized Specification, Configuration and Execution of Data-Intensive Scientific Workflows.

Data analysis processes in scientific applications can be expressed as coarse-grain workflows of complex data processing operations with data flow dependencies between them. Performance optimization of these workflows can be viewed as a search for a set of optimal values in a multidimensional parameter space consisting of input performance parameters to the applications that are known to affect their execution times. While some performance parameters such as grouping of workflow components and their mapping to machines do not affect the accuracy of the analysis, others may dictate trading the output quality of individual components (and of the whole workflow) for performance. This paper describes an integrated framework which is capable of supporting performance optimizations along multiple such parameters. Using two real-world applications in the spatial, multidimensional data analysis domain, we present an experimental evaluation of the proposed framework.