A Primary Health Care Program and COVID-19. Impact in Hospital Admissions and Mortality.

BACKGROUND: Most patients with mild or moderate COVID infection did not require hospital admission, but depending on their personal history, they needed medical supervision. In monitoring these patients in primary care, the design of specific surveillance programs was of great help. Between February 2021 and March 2022, EDCO program was designed in Tenerife, Spain, to telemonitor patients with COVID infection who had at least one vulnerability factor to reduce hospital admissions and mortality. OBJECTIVE: The aim of this study is to describe the clinical course of patients included in the EDCO program and to analyze which factors were associated with a higher probability of hospital admission and mortality. DESIGN: Retrospective cohort study. PATIENTS: We included 3848 patients with a COVID-19 infection age over 60 years old or age over 18 years and at least one vulnerability factor previously reported in medical history. MAIN MEASURES: Primary outcome was to assess risk of admission or mortality. KEY RESULTS: 278 (7.2%) patients required hospital admission. Relative risks (RR) of hospital admission were oxygen saturation ≤ 92% (RR: 90.91 (58.82-142.86)), respiratory rate ≥ 22 breaths per minute (RR: 20.41 (1.19-34.48), obesity (RR: 1.53 (1.12-2.10), chronic kidney disease (RR:2.31 (1.23-4.35), ≥ 60 years of age (RR: 1.44 (1.04-1.99). Mortality rate was 0.7% (27 patients). Relative risks of mortality were respiratory rate ≥ 22 breaths per minute (RR: 24.85 (11.15-55.38), patients with three or more vulnerability factors (RR: 4.10 (1.62-10.38), oxygen saturation ≤ 92% (RR: 4.69 (1.70-15.15), chronic respiratory disease (RR: 3.32 (1.43-7.69) and active malignancy (RR: 4.00 (1.42-11.23). CONCLUSIONS: Vulnerable patients followed by a primary care programme had admission rates of 7.2% and mortality rates of 0.7%. Supervision of vulnerable patients by a Primary Care team was effective in the follow-up of these patients with complete resolution of symptoms in 91.7% of the cases.

Non-Islet Cell Tumor Hypoglycemia Secondary to a 20 cm Intra-Abdominal Leiomyoma in a Male Patient: A Case Report and Literature Review.

Non-islet cell tumor hypoglycemia (NICTH) is a rare clinical entity associated with large mesenchymal tumors. Its pathogenesis is most commonly mediated by tumor overproduction of "big" insulin-like growth factor-2. Here, we present a 54-year-old male who presented with noninsulin-mediated hypoglycemia and a 20 cm intra-abdominal leiomyoma. His hypoglycemic episodes resolved after the resection of his tumor. To our knowledge, this is the only documented case in the English literature of NICTH associated with leiomyoma in a male patient. NICTH due to a benign leiomyoma should be in the differential diagnosis for any patient with hypoglycemia and an abdominal mass.

Biodegradable Biocomposite of Starch Films Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Reinforced by Microfibrillated Cellulose.

Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.

A complex receptor locus confers responsiveness to necrosis and ethylene-inducing like peptides in Brassica napus.

Brassica crops are susceptible to diseases which can be mitigated by breeding for resistance. MAMPs (microbe-associated molecular patterns) are conserved molecules of pathogens that elicit host defences known as pattern-triggered immunity (PTI). Necrosis and Ethylene-inducing peptide 1-like proteins (NLPs) are MAMPs found in a wide range of phytopathogens. We studied the response to BcNEP2, a representative NLP from Botrytis cinerea, and showed that it contributes to disease resistance in Brassica napus. To map regions conferring NLP response, we used the production of reactive oxygen species (ROS) induced during PTI across a population of diverse B. napus accessions for associative transcriptomics (AT), and bulk segregant analysis (BSA) on DNA pools created from a cross of NLP-responsive and non-responsive lines. In silico mapping with AT identified two peaks for NLP responsiveness on chromosomes A04 and C05 whereas the BSA identified one peak on A04. BSA delimited the region for NLP-responsiveness to 3 Mbp, containing ~245 genes on the Darmor-bzh reference genome and four co-segregating KASP markers were identified. The same pipeline with the ZS11 genome confirmed the highest-associated region on chromosome A04. Comparative BLAST analysis revealed unannotated clusters of receptor-like protein (RLP) homologues on ZS11 chromosome A04. However, no specific RLP homologue conferring NLP response could be identified. Our results also suggest that BR-SIGNALLING KINASE1 may be involved with modulating the NLP response. Overall, we demonstrate that responsiveness to NLP contributes to disease resistance in B. napus and define the associated genomic location. These results can have practical application in crop improvement.

In vivo single-cell high-dimensional mass cytometry analysis to track the interactions between Klebsiella pneumoniae and myeloid cells.

In vivo single-cell approaches have transformed our understanding of the immune populations in tissues. Mass cytometry (CyTOF), that combines the resolution of mass spectrometry with the ability to conduct multiplexed measurements of cell molecules at the single cell resolution, has enabled to resolve the diversity of immune cell subsets, and their heterogeneous functionality. Here we assess the feasibility of taking CyTOF one step further to immuno profile cells while tracking their interactions with bacteria, a method we term Bac-CyTOF. We focus on the pathogen Klebsiella pneumoniae interrogating the pneumonia mouse model. Using Bac-CyTOF, we unveil the atlas of immune cells of mice infected with a K. pneumoniae hypervirulent strain. The atlas is characterized by a decrease in the populations of alveolar and monocyte-derived macrophages. Conversely, neutrophils, and inflammatory monocytes are characterized by an increase in the subpopulations expressing markers of less active cells such as the immune checkpoint PD-L1. These are the cells infected. We show that the type VI secretion system (T6SS) contributes to shape the lung immune landscape. The T6SS governs the interaction with monocytes/macrophages by shifting Klebsiella from alveolar macrophages to interstitial macrophages and limiting the infection of inflammatory monocytes. The lack of T6SS results in an increase of cells expressing markers of active cells, and a decrease in the subpopulations expressing PD-L1. By probing Klebsiella, and Acinetobacter baumannii strains with limited ability to survive in vivo, we uncover that a heightened recruitment of neutrophils, and relative high levels of alveolar macrophages and eosinophils and the recruitment of a characteristic subpopulation of neutrophils are features of mice clearing infections. We leverage Bac-CyTOF-generated knowledge platform to investigate the role of the DNA sensor STING in Klebsiella infections. sting-/- infected mice present features consistent with clearing the infection including the reduced levels of PD-L1. STING absence facilitates Klebsiella clearance.

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

Urinary concentration of Cathepsin D as a relievable marker of preeclampsia.

BACKGROUND: The early and accurate diagnosis of preeclampsia is crucial to avoid serious complications for both the mother and baby. However, the current diagnostic methods are limited, and there is a need for new diagnostic biomarkers. Previous studies have shown that cathepsin D (CTD) participates in the pathophysiology of preeclampsia and is present in urine samples, making it a potential biomarker for the disease. This study aimed to compare urinary and serum levels of CTD in preeclamptic and normotensive women and analyze its potential role as a diagnostic biomarker in preeclampsia. METHODS: The study included thirty-nine patients with preeclampsia and twelve normotensive pregnant women as controls. Biomarkers were determined using Multiplex Assay kit, and serum prolactin (Prl) and urinary TNF-α levels were also evaluated. Statistical analysis was conducted using the Mann-Whitney U test. RESULTS: We found that urinary and serum CTD levels were significantly higher in the preeclampsia group than in the normotensive group, suggesting that CTD could be a diagnostic biomarker for preeclampsia. No significant differences were found in the levels of serum prolactin or urinary TNF-α between the two groups. CONCLUSIONS: The study provides evidence that non-invasive biological samples such as urine can be used to improve new therapeutic strategies for the early management of preeclampsia.

A Preliminary Investigation into Search and Matching for Tumor Discrimination in World Health Organization Breast Taxonomy Using Deep Networks.

Breast cancer is one of the most common cancers affecting women worldwide. It includes a group of malignant neoplasms with a variety of biological, clinical, and histopathologic characteristics. There are more than 35 different histologic forms of breast lesions that can be classified and diagnosed histologically according to cell morphology, growth, and architecture patterns. Recently, deep learning, in the field of artificial intelligence, has drawn a lot of attention for the computerized representation of medical images. Searchable digital atlases can provide pathologists with patch-matching tools, allowing them to search among evidently diagnosed and treated archival cases, a technology that may be regarded as computational second opinion. In this study, we indexed and analyzed the World Health Organization breast taxonomy (Classification of Tumors fifth ed.) spanning 35 tumor types. We visualized all tumor types using deep features extracted from a state-of-the-art deep-learning model, pretrained on millions of diagnostic histopathology images from the Cancer Genome Atlas repository. Furthermore, we tested the concept of a digital "atlas" as a reference for search and matching with rare test cases. The patch similarity search within the World Health Organization breast taxonomy data reached >88% accuracy when validating through "majority vote" and >91% accuracy when validating using top n tumor types. These results show for the first time that complex relationships among common and rare breast lesions can be investigated using an indexed digital archive.

Hyperactive delirium during emergency department stay: analysis of risk factors and association with short-term outcomes.

To investigate factors related to the development of hyperactive delirium in patients during emergency department (ED) stay and the association with short-term outcomes. A secondary analysis of the EDEN (Emergency Department and Elderly Needs) multipurpose multicenter cohort was performed. Patients older than 65 years arriving to the ED in a calm state and who developed confusion and/or psychomotor agitation requiring intravenous/intramuscular treatment during their stay in ED were assigned to delirium group. Patients with psychiatric and epileptic disorders and intracranial hemorrhage were excluded. Thirty-four variables were compared in both groups and outcomes were adjusted for age, sex, Charlson Comorbidity Index, Barthel Index and polypharmacy. Hyperactive delirium that needed treatment were developed in 301 out of 18,730 patients (1.6%). Delirium was directly associated with previous episodes of delirium (OR: 2.44, 95% CI 1.24-4.82), transfer to the ED observation unit (1.62, 1.23-2.15), chronic treatment with opiates (1.51, 1.09-2.09) and length of ED stay longer than 12 h (1.41, 1.02-1.97) and was indirectly associated with chronic kidney disease (0.60, 0.37-0.97). The 30-day all-cause mortality was 4.0% in delirium group and 2.9% in non-delirium group (OR: 1.52, 95% CI 0.83-2.78), need for hospitalization 25.6% and 25% (1.09, 0.83-1.43), in-hospital mortality 16.4% and 7.3% (2.32, 1.24-4.35), prolonged hospitalization 54.5% and 48.6% (1.27, 0.80-2.00), respectively, and 90-day post-discharge combined adverse event 36.4% and 35.8%, respectively (1.06, 0.82-2.00). Patients with previous episodes of delirium, treatment with opioids and longer stay in ED more frequently develop delirium during ED stay and preventive measures should be taken to minimize the incidence. Delirium is associated with in-hospital mortality during the index event.

Performance of externally validated machine learning models based on histopathology images for the diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer: A systematic review.

Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations/diagnoses as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2-2.6) and 1.8 (95% CI, 1.3-2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11-3.29) for recurrence, and between 0.09 (95% CI, 0.01-0.70) and 0.65 (95% CI, 0.43-0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results. Increasing the availability of validation datasets and implementing standardized methods and reporting protocols may facilitate future analyses.

Composite Biomarker Image for Advanced Visualization in Histopathology.

Immunohistochemistry (IHC) biomarkers are essential tools for reliable cancer diagnosis and subtyping. It requires cross-staining comparison among Whole Slide Images (WSIs) of IHCs and hematoxylin and eosin (H&E) slides. Currently, pathologists examine the visually co-localized areas across IHC and H&E glass slides for a final diagnosis, which is a tedious and challenging task. Moreover, visually inspecting different IHC slides back and forth to analyze local co-expressions is inherently subjective and prone to error, even when carried out by experienced pathologists. Relying on digital pathology, we propose "Composite Biomarker Image" (CBI) in this work. CBI is a single image that can be composed using different filtered IHC biomarker images for better visualization. We present a CBI image produced in two steps by the proposed solution for better visualization and hence more efficient clinical workflow. In the first step, IHC biomarker images are aligned with the H&E images using one coordinate system and orientation. In the second step, the positive or negative IHC regions from each biomarker image (based on the pathologists' recommendation) are filtered and combined into one image using a fuzzy inference system. For evaluation, the resulting CBI images, from the proposed system, were evaluated qualitatively by the expert pathologists. The CBI concept helps the pathologists to identify the suspected target tissues more easily, which could be further assessed by examining the actual WSIs at the same suspected regions.

Immunohistochemistry Biomarkers-Guided Image Search for Histopathology.

Medical practitioners use a number of diagnostic tests to make a reliable diagnosis. Traditionally, Haematoxylin and Eosin (H&E) stained glass slides have been used for cancer diagnosis and tumor detection. However, recently a variety of immunohistochemistry (IHC) stained slides can be requested by pathologists to examine and confirm diagnoses for determining the subtype of a tumor when this is difficult using H&E slides only. Deep learning (DL) has received a lot of interest recently for image search engines to extract features from tissue regions, which may or may not be the target region for diagnosis. This approach generally fails to capture high-level patterns corresponding to the malignant or abnormal content of histopathology images. In this work, we are proposing a targeted image search approach, inspired by the pathologists' workflow, which may use information from multiple IHC biomarker images when available. These IHC images could be aligned, filtered, and merged together to generate a composite biomarker image (CBI) that could eventually be used to generate an attention map to guide the search engine for localized search. In our experiments, we observed that an IHC-guided image search engine can retrieve relevant data more accurately than a conventional (i.e., H&E-only) search engine without IHC guidance. Moreover, such engines are also able to accurately conclude the subtypes through majority votes.

Designing Cell Delivery Peptides and SARS-CoV-2-Targeting Small Interfering RNAs: A Comprehensive Bioinformatics Study with Generative Adversarial Network-Based Peptide Design and In Vitro Assays.

Nucleic acid technologies with designed intracellular delivery systems are some of the most promising therapies of the future. Small interfering (si)RNAs inhibit gene expression and protein synthesis and may complement current vaccines with faster design and production. Although successful delivery remains an issue, delivery peptides may help to fill this gap. Here, we address this issue by applying bioinformatic approaches to design new putative cell delivery peptides and siRNAs for COVID-19 variants and other related viral diseases. Of the 29,880 RNA sequences analyzed, 62 were identified in silico as able to target the virus mRNA sequence, and from the 9,984 peptide sequences analyzed, 10 were selected as delivery peptides. From the latter, we further performed in vitro studies of the two best-ranked peptides and compared them with the broadly used TAT delivery peptide. One of them, seq5, displayed better internalization results with about double intensity signal compared to TAT after a 1 h incubation time in GFP-HeLa cells. This peptide has, thus, the features of a delivery peptide and could be used for cargo intracellular delivery.

Overview of Benchtop Models for Comparison of Surgical Treatments for Benign Prostatic Hyperplasia.

PURPOSE OF REVIEW: Benign prostatic hyperplasia (BPH) is a disease of the lower urinary tract which often requires surgical treatment. Recently, there has been a deluge of new treatment options, rarely validated or compared to current treatments on a benchtop model. The purpose of this review is to examine the literature and report which benchtop models are currently being used, which therapies have been tested on them, and what outcomes are being studied on each model. RECENT FINDINGS: There are various benchtop models to choose from, each with their unique benefits and drawbacks. Perfused porcine kidney models are used to assess bleeding on the benchtop, ex-vivo human prostate helps to see specific interactions of devices with the prostatic tissue, and all other models have evaluated tissue ablation rates and depth of coagulation. There are currently no synthetic or non-animal tissues being used for this purpose, and surgical techniques such as enucleation, water-jet ablation, prostate stents, and water vapor thermal therapy have no representation in these benchtop tests. Benchtop testing serves an important role in the evaluation and comparison of surgical treatments for BPH. This testing allows these therapies to be objectively compared to one another, helping novel medical devices in their path to market and urologists make treatment decisions. Future directions may include further validation of the animal models currently being used and development of synthetic models which mimic the prostate on the benchtop.

Grade of Primary Cutaneous Leiomyosarcoma Dictates Risk for Metastatic Spread and Disease-Specific Mortality.

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.

Oclusión intestinal en paciente renal crónico secundario a bezoar de telas Reporte de un caso clínico / Intestinal Occlusion in a Chronic Renal Patient Secondary to Textile Bezoar. Clinical Case Report

Resumen Los "bezoar" son conglomerados de materiales no comestibles ingeridos voluntaria o involuntariamente, no digeridos e incapaces de transitar por el tracto intestinal. Principalmente afectan a jóvenes mujeres o adolescentes que presentan el fenómeno llamado "pica", y a pesar de que se ha registrado una alta prevalencia de este fenómeno en pacientes con enfermedad renal crónica (ERC), ha sido poco estudiado. Caso clínico: Paciente del sexo masculino de 35 años de edad que cursa con ERC KDIGO-5 en tratamiento con diálisis peritoneal; se obtiene el hallazgo de "bezoar plástico" transoperatorio (laparotomia por oclusión intestinal) a 10 cm de la válvula ileocecal. El paciente fallece por complicaciones de la patología de origen. Se plantea la necesidad de realizar la búsqueda de comportamientos en pacientes con ERC, que indiquen al cirujano la sospecha, dado que los pacientes generalmente ocultan u omiten referir sobre la ingesta de material extraño.

Abstract The "bezoar" are conglomerates of inedible materials ingested voluntarily or involuntarily, which are not digested and are unable to pass through the intestinal tract. They mainly affect young women or adolescents who present the phenomenon called "pica", despite the fact that a high prevalence of this phenomenon of "pica" has been registered in patients with chronic kidney disease, it has been little studied. Clinical case: A 35-year-old male with CKD KDIGO-5 undergoing peritoneal dialysis treatment, which was found to have a transoperative "plastic bezoar" (laparotomy for intestinal occlusion) 10 cm from the ileocecal valve. The patient died due to complications of his pathology. Discussion: the clinical case raises the need to search for behaviors such as pica in patients with CKD, as well as to develop the suspicion to the surgeon, since patients generally hide or ignore reporting foreign material phagia.

Hourglass, a rapid analysis framework for heterogeneous bioimaging data, identifies sex disparity in IL-6/STAT3-associated immune phenotypes in pancreatic cancer.

Integration and mining of bioimaging data remains a challenge and lags behind the rapidly expanding digital pathology field. We introduce Hourglass, an open-access analytical framework that streamlines biology-driven visualization, interrogation, and statistical assessment of multiparametric datasets. Cognizant of tissue and clinical heterogeneity, Hourglass systematically organizes observations across spatial and global levels and within patient subgroups. Applied to an extensive bioimaging dataset, Hourglass promptly consolidated a breadth of known interleukin-6 (IL-6) functions via its downstream effector STAT3 and uncovered a so-far unknown sexual dimorphism in the IL-6/STAT3-linked intratumoral T-cell response in human pancreatic cancer. As an R package and cross-platform application, Hourglass facilitates knowledge extraction from multi-layered bioimaging datasets for users with or without computational proficiency and provides unique and widely accessible analytical means to harness insights hidden within heterogeneous tissues at the sample and patient level. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy.

Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene MKL1 displayed ethnic stratification, with the variant being significantly more prevalent in the African cohort and resulting in reduced transcript levels as measured by qPCR. Functional validation of MKL1 by shRNA-mediated knockdown of MKL1 resulted in a more resistant phenotype. Gene expression analysis identified the developmentally associated TGFB1I1 as the most significant gene associated with sensitivity. qPCR among a panel of sensitive and resistant LCLs revealed immunoglobulin class-switching as well as differences in the expression of B cell activation markers. Flow cytometry showed heterogeneity within some cell lines relative to surface Ig isotype with a shift to more IgG+ cells among the resistant lines. Pretreatment with prednisolone could partly reverse the resistant phenotype. Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.

Role of Bladder Functional Testing Prior to Surgeries for Benign Prostatic Obstruction.

PURPOSE OF REVIEW: There is no consensus on preoperative functional testing prior to surgeries for benign prostatic obstruction causing lower urinary tract symptoms (LUTS). RECENT FINDINGS: Surgical management offers definite benefits, but the results are not always satisfactory. The urodynamic study (UDS) is the gold standard for assessing bladder outlet obstruction (BOO) which is the best predictor of surgical success. Yet, it is not recommended by our urologic societies as standard testing prior to surgery. In this narrative review of the literature, we report recent findings and controversies regarding the benefits and downside of UDS, and the use of other less-invasive approaches to achieve this goal. The lack of strong evidence for or against performing UDS was surprising. Prospective UDS data may not predict surgical outcomes if there is no consensus on criteria that directs surgical intervention. However, confirming the presence of BOO and characterizing the bladder function to identify detrusor over- and underactivity may help counselling and setting patient's post-operative expectations. Urocuff, a non-invasive testing offers promising results to address this problem with a less-invasive assessment of BOO. We emphasize better pre-operative characterization of patients to confirm BOO and better define subgroups to improve surgical decision-making.

Simpatectomía torácica para hiperhidrosis focal: una revisión de alcance / Thoracic sympathectomy for focal hyperhidrosis: a Scoping Review

La hiperhidrosis focal primaria (HH) es un trastorno que consiste en sudoración que excede lo requerido para la termorregulación y afecta a 3 de cada 100 personas en la población general. Es considerada una enfermedad con alto impacto en la calidad de vida. La fisiopatología involucra el eje hipotálamo- sistema nervioso autónomo. A lo largo de la historia se han descrito múltiples terapias médicas y quirúrgicas con resultados variables. En la literatura se evidencia un vacío en el conocimiento acerca de la simpatectomía torácica (ST) y su utilidad en el contexto de HH. En miras a mejorar la calidad de vida de estos pacientes, realizamos una revisión cuidadosa de la literatura disponible actualmente, encontrando que la ST es un procedimiento seguro y efectivo, con altas tasas de éxito y satisfacción en estos pacientes.

Primary focal hyperhidrosis (HH) is a disorder consisting of sweating in excess of that required for thermoregulation and affects 3 out of 100 people in the general population. It is considered a disease with a high impact on quality of life. Pathophysiology involves the hypothalamic-autonomic nervous system axis. Throughout history, multiple medical and surgical therapies have been described with variable results. The literature shows a gap in knowledge about thoracic sympathectomy and its usefulness in the context of HH. To improve the quality of life of these patients, we carried out a careful review of the currently available literature, finding that ST is a safe and effective procedure, with high rates of success and satisfaction in these patients.