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High stage and recurrent ovarian clear cell carcinoma (OCC) are associated with poor prognosis and resistance to chemotherapy. A distinguishing histological feature of OCC is abundant cytoplasmic stores of glucose, in the form of glycogen, that can be mobilized for cellular metabolism. Here, we report the effect on preclinical models of OCC of disrupting glycogen utilization using the glucose analogue 2-deoxy-D-glucose (2DG). At concentrations significantly lower than previously reported for other cancers, 2DG markedly improves the efficacy in vitro of carboplatin chemotherapy against chemo-sensitive TOV21G and chemo-resistant OVTOKO OCC cell lines, and this is accompanied by the depletion of glycogen. Of note, 2DG doses-of more than 10-fold lower than previously reported for other cancers-significantly improve the efficacy of carboplatin against cell line and patient-derived xenograft models in mice that mimic the chemo-responsiveness of OCC. These findings are encouraging, in that 2DG doses, which are substantially lower than previously reported to cause adverse events in cancer patients, can safely and significantly improve the efficacy of carboplatin against OCC. Our results thus justify clinical trials to evaluate whether low dose 2DG improves the efficacy of carboplatin in OCC patients.

Background : CUB domain-containing protein 1 (CDCP1) is a cell surface receptor regulating key signalling pathways in malignant cells. CDCP1 has been proposed as a molecular target to abrogate oncogenic signalling pathways and specifically deliver anti-cancer agents to tumors. However, the development of CDCP1-targeting agents has been questioned by its frequent proteolytic processing which was thought to result in shedding of the CDCP1 extracellular domain limiting its targetability. In this study, we investigated the relevance of targeting CDCP1 in the context of pancreatic ductal adenocarcinoma (PDAC) and assess the impact of CDCP1 proteolysis on the effectiveness of CDCP1 targeting agents. Methods : The involvement of CDCP1 in PDAC progression was assessed by association analysis in several PDAC cohorts and the proteolytic processing of CDCP1 was evaluated in PDAC cell lines and patient-derived cells. The consequences of CDCP1 proteolysis on its targetability in PDAC cells was assessed using immunoprecipitation, immunostaining and biochemical assays. The involvement of CDCP1 in PDAC progression was examined by loss-of-function in vitro and in vivo experiments employing PDAC cells expressing intact or cleaved CDCP1. Finally, we generated antibody-based imaging and therapeutic agents targeting CDCP1 to demonstrate the feasibility of targeting this receptor for detection and treatment of PDAC tumors. Results : High CDCP1 expression in PDAC is significantly associated with poorer patient survival. In PDAC cells proteolysis of CDCP1 does not always result in the shedding of CDCP1-extracellular domain which can interact with membrane-bound CDCP1 allowing signal transduction between the different CDCP1-fragments. Targeting CDCP1 impairs PDAC cell functions and PDAC tumor growth independently of CDCP1 cleavage status. A CDCP1-targeting antibody is highly effective at delivering imaging radionuclides and cytotoxins to PDAC cells allowing specific detection of tumors by PET/CT imaging and superior anti-tumor effects compared to gemcitabine in in vivo models. Conclusion : Independent of its cleavage status, CDCP1 exerts oncogenic functions in PDAC and has significant potential to be targeted for improved radiological staging and treatment of this cancer. Its elevated expression by most PDAC tumors and lack of expression by normal pancreas and other major organs, suggest that targeting CDCP1 could benefit a significant proportion of PDAC patients. These data support the further development of CDCP1-targeting agents as personalizable tools for effective imaging and treatment of PDAC., Competing Interests: Competing Interests: Thomas Kryza, Tashbib Khan, Simon Puttick, Tahleesa Cuda, Elena I Deryugina, James P. Quigley, Yaowu He and John D. Hooper are inventors on a patent that includes monoclonal antibody 10D7 used in this study. No potential conflicts of interest were disclosed by the other authors., (© The author(s).)

CUB-domain containing protein 1 (CDCP1) is a cancer associated cell surface protein that amplifies pro-tumorigenic signalling by other receptors including EGFR and HER2. Its potential as a cancer target is supported by studies showing that anti-CDCP1 antibodies inhibit cell migration and survival in vitro , and tumor growth and metastasis in vivo . Here we characterize two anti-CDCP1 antibodies, focusing on immuno-conjugates of one of these as a tool to detect and inhibit ovarian cancer. Methods : A panel of ovarian cancer cell lines was examined for cell surface expression of CDCP1 and loss of expression induced by anti-CDCP1 antibodies 10D7 and 41-2 using flow cytometry and Western blot analysis. Surface plasmon resonance analysis and examination of truncation mutants was used to analyse the binding properties of the antibodies for CDCP1. Live-cell spinning-disk confocal microscopy of GFP-tagged CDCP1 was used to track internalization and intracellular trafficking of CDCP1/antibody complexes. In vivo , zirconium 89-labelled 10D7 was detected by positron-emission tomography imaging, of an ovarian cancer patient-derived xenograft grown intraperitoneally in mice. The efficacy of cytotoxin-conjugated 10D7 was examined against ovarian cancer cells in vitro and in vivo . Results : Our data indicate that each antibody binds with high affinity to the extracellular domain of CDCP1 causing rapid internalization of the receptor/antibody complex and degradation of CDCP1 via processes mediated by the kinase Src. Highlighting the potential clinical utility of CDCP1, positron-emission tomography imaging, using zirconium 89-labelled 10D7, was able to detect subcutaneous and intraperitoneal xenograft ovarian cancers in mice, including small (diameter <3 mm) tumor deposits of an ovarian cancer patient-derived xenograft grown intraperitoneally in mice. Furthermore, cytotoxin-conjugated 10D7 was effective at inhibiting growth of CDCP1-expressing ovarian cancer cells in vitro and in vivo . Conclusions : These data demonstrate that CDCP1 internalizing antibodies have potential for killing and detection of CDCP1 expressing ovarian cancer cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Acquired Megacolon (AMC) is a condition involving persistent dilatation and lengthening of the colon in the absence of organic disease. Diagnosis depends on subjective radiological, endoscopic or surgical findings in the context of a suggestive clinical presentation. This review sets out to investigate diagnostic criteria of AMC., Methods: The literature was searched using the databases - PubMed, Medline via OvidSP, ClinicalKey, Informit and the Cochrane Library. Primary studies, published in English, with more than three patients were critically appraised based on study design, methodology and sample size. Exclusion criteria were studies with the following features: post-operative; megarectum-predominant; paediatric; organic megacolon; non-human; and failure to exclude organic causes., Results: A review of 23 articles found constipation, abdominal pain, distension and gas distress were predominant symptoms. All ages and both sexes were affected, however, symptoms varied with age. Changes in anorectal manometry, histology and colonic transit are consistently reported. Studies involved varying patient numbers, demographics and data acquisition methods., Conclusions: Outcome data investigating the diagnosis of AMC must be interpreted in light of the limitations of the low-level evidence studies published to date. Proposed diagnostic criteria include: (1) the exclusion of organic disease; (2) a radiological sigmoid diameter of ~ 10 cm; (3) and constipation, distension, abdominal pain and/or gas distress. A proportion of patients with AMC may be currently misdiagnosed as having functional gastrointestinal disorders. Our conclusions are inevitably tentative, but will hopefully stimulate further research on this enigmatic condition.

Background: Diverticulosis and redundant colon are colonic conditions for which underlying pathophysiology, management and prevention are poorly understood. Historical papers suggest an inverse relationship between these two conditions. However, no further attempt has been made to validate this relationship. This study set out to assess the correlation between diverticulosis and colonic redundancy., Methods: Redundant colon, diverticulosis and patient demographics were recorded during colonoscopy. Multivariate binary logistic regression was performed with redundant colon as the dependent variable and age, gender and diverticulosis as independent variables. Nagelkerke R 2 and a receiver operator curve were calculated to assess goodness of fit and internally validate the multivariate model., Results: Redundant colon and diverticulosis were diagnosed in 31 and 113 patients, respectively. The probability of redundant colon was increased by female gender odds ratio (OR) 8.4 (95% CI 2.7-26, p = 0.00020) and increasing age OR 1.7 (95% CI 1.1-2.6, p = 0.017). Paradoxically, diverticulosis strongly reduced the probability of redundant colon with OR of 0.12 (95% CI 0.42-0.32, p = 0.000039). The Nagelkerke R 2 for the multivariate model was 0.29 and the area under the curve at ROC analysis was 0.81 (95% CI 0.73-0.90 p-value 3.1 × 10 -8 )., Conclusions: This study found an inverse correlation between redundant colon and diverticulosis, supporting the historical suggestion that the two conditions rarely occur concurrently. The underlying principle for this relationship remains to be found. However, it may contribute to the understanding of the aetiology and pathophysiology of these colonic conditions.

Introduction: Perianal pseudolymphoma is a rare lymphoproliferative disorder that can mimic cutaneous lymphoma. The condition can present acutely with concerns of perianal sepsis. The purpose of this case review is to review the current literature on perianal pseudolymphoma and emphasise to the surgical community its presentation, suggested aetiology and management., Case Presentation: In this case report, we detail the case of a 28-year-old female who presented with perianal pseudolymphoma. Malignant lymphoproliferative diseases required exclusion. Conservative management of this rare condition was successful., Discussion: We highlight the differential diagnoses, investigations and treatment options for a rare condition. A review of the literature on the limited published data on perianal pseudolymphoma is briefly discussed., Conclusion: The aim of this case report is to highlight the existence of such a rare condition that can imitate an acute surgical presentation and its successful conservative management., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Anastomotic leak is the anathema of colorectal surgery. Early diagnosis is an essential segue to early intervention. A temporary defunctioning ileostomy does not prevent an anastomotic leak and presents inherent complications of its own. Drain fluid biomarkers have been studied in colorectal surgery but not in ileal pouch surgery., Objective: This study aimed to assess drain fluid amylase as a biomarker of anastomotic leak after ileal pouch surgery and without a diverting ileostomy., Design: This was a multicenter prospective observational cohort study., Settings: The study was conducted at 4 tertiary hospitals in Queensland, Australia., Patients: This study included elective patients undergoing restorative proctectomy and ileal pouch surgery., Interventions: Measurement of rectal tube amylase and drain fluid amylase., Main Outcome Measures: The primary measure was observation of increased drain fluid amylase on the day of anastomotic leak., Results: Fifty-three patients were studied. On the day of anastomotic leak, 4 patients in the anastomotic leak group who experienced an early anastomotic leak recorded a median drain fluid amylase of 21,897 U/L compared with a median drain fluid amylase of 25 U/L for those in the no anastomotic leak group ( p < 0.0001)., Limitations: This study relies on the anastomotic leak occurring while the pelvic drain is in situ., Conclusions: The measurement of drain fluid amylase is a sensitive biomarker of early clinical anastomotic leak in patients undergoing restorative proctectomy with an ileal pouch and when a diverting ileostomy is not incorporated. This simple, inexpensive, and noninvasive test should be considered in all patients with ileal pouches as an adjunct to the clinical diagnosis and differentiation of anastomotic leak from other postoperative complications. See Video Abstract at http://links.lww.com/DCR/B958 .Estudio multicéntrico de la amilasa del líquido de drenaje como biomarcador para la detección de fugas anastomóticas después de una cirugía de reservorio ileal sin ileostomía de derivación., Antecedentes: La fuga anastomótica es el anatema de la cirugía colorrectal. El diagnóstico precoz es una transición esencial a la intervención temprana. Una ileostomía desfuncionalizante temporal no evita una fuga anastomótica y presenta sus propias complicaciones inherentes. Los biomarcadores del líquido de drenaje se han estudiado en la cirugía colorrectal, pero no en la cirugía del reservorio ileal., Objetivo: El objetivo fue evaluar la amilasa del líquido de drenaje como biomarcador de fuga anastomótica después de cirugía de reservorio ileal y sin ileostomía de derivación., Diseo: Este fue un estudio de cohorte observacional prospectivo multicéntrico., Ajustes: El estudio se realizó en 4 hospitales terciarios en Queensland, Australia., Pacientes: Se incluyeron pacientes electivos sometidos a proctectomía restauradora y cirugía de reservorio ileal., Intervenciones: Medición de la amilasa del tubo rectal y amilasa del líquido de drenaje., Principales Medidas De Resultado: La medida principal fue la observación del aumento de la amilasa en el líquido de drenaje el día de la fuga anastomótica., Resultados: Cincuenta y tres pacientes fueron estudiados. Los 4 pacientes que experimentaron una fuga anastomótica temprana registraron una mediana de amilasa en el líquido de drenaje de 21 897 U/L el día de la fuga anastomótica en comparación con una mediana de amilasa en el líquido de drenaje de 25 U/L para aquellos en el grupo sin fuga anastomótica (p < 0,0001)., Limitaciones: Este estudio se basa en que la anastomosis ocurre mientras el drenaje pélvico está in situ., Conclusiones: La medición de amilasa en el líquido de drenaje es un biomarcador sensible de fuga anastomótica clínica temprana en pacientes sometidos a proctectomía restauradora con reservorio ileal y cuando no se incorpora ileostomía derivativa. Esta prueba simple, económica y no invasiva se debe considerar en todos los pacientes con reservorio ileal como complemento del diagnóstico clínico y la diferenciación de la fuga anastomótica de otras complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B958 . (Traducción-Dr Yolanda Colorado )., (Copyright © The ASCRS 2022.)

Sulfonamides are promising classical carbonic anhydrase (CA; EC 4.2.1.1) inhibitors, being used for several medical purposes such as diuretics, anticonvulsants, topically acting antiglaucoma agents, for antiobesity and anticancer therapies. Herein, a series of chalcone-based benzenesulfonamides (3a‒m) was synthesized and assessed for its inhibitory activity against a panel of four human carbonic anhydrases (hCA isoforms I, II, IX, and XII). Most compounds displayed single- to double-digit nanomolar inhibition constants (K i s), with some derivatives being more potent and/or selective than the standard drug acetazolamide (AAZ). Among the synthesized compounds, 3g compound demonstrated the highest inhibitory activity against the hCA II isoform (K i  = 2.5 nM) with 30-, 9-, and 11-fold selectivity for hCA II over the I, IX, and XII isoforms, respectively. Structure-activity relationships for different substitution patterns were analyzed. Additionally, a molecular docking study showed that compound 3g bound to hCA II by coordinating with the zinc ion through the deprotonated benzenesulfonamide moiety, in addition to a hydrogen bond formed between an oxygen of the sulfonamide moiety and Thr199. Moreover, the chalcone core participated in van der Waals interactions with some active site residues, such as Ile91, Val121, and Leu198. Consequently, this report introduces a successful approach toward identifying compound 3g as a highly potent and selective chalcone-based benzenesulfonamide inhibitor of hCA II worthy of further investigation., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Background: Anastomotic leak (AL) is the anathema of colorectal surgery. Early diagnosis is an essential segue to early intervention. A temporary diverting ileostomy (TDI) does not prevent an AL and presents inherent complications of its own. Numerous drain fluid biomarkers (BM) have been studied in colorectal surgery and extravasated intraluminal substances (EILS) such as amylase have shown promise. The aim of this study was to assess drain fluid amylase (DFA) as a BM of AL after minimally invasive rectal resection without a TDI., Methods: A single centre prospective cohort study performed from 2018 to 2021. The primary outcome was DFA measured daily whilst the drain was in situ. Rectal tube amylase was also measured for the first two post-operative days to quantitate the intra-luminal levels of the enzyme. DFA was compared between patients who experienced AL and those who did not., Results: Of the 62 patients studied, six (9.7%) experienced AL. There was a statistically significant difference in DFA between patients who experienced AL (Median:1373.5 U/L; IQR: 306-7953) and patients who did not experience an AL (Median: 27.0 U/L; IQR: 16-38); p < 0.0001., Conclusions: The measurement of drain fluid amylase is a highly sensitive BM of early clinical anastomotic leak in patients undergoing a rectal resection with an extraperitoneal anastomosis and when a TDI is not incorporated. This simple, inexpensive and non-invasive test should be considered in all patients as an adjunct to the clinical diagnosis and differentiation of AL from other postoperative complications., (© 2022 Royal Australasian College of Surgeons.)

Purpose: To describe and update stercoral colitis clinical risk factors, relative frequency, location, and CT imaging features correlated with surgical and pathological results. Methods: CT reports over a 5-year period (05/2017–05/2022) at a single medical center were searched. Main inclusion criteria were luminal distention with formed stool, wall thickening, and surrounding inflammation. Positive cases were graded as mild (early or developing stercoral colitis) versus moderate-to-severe based on CT findings. Medical records were reviewed for risk factors and outcome data in moderate-to-severe cases. P-values were tabulated for comparison. Results: 545 total cases (71 (60, 82) years, 278 males) were identified on CT, including 452 mild (82.9%) and 93 moderate-to-severe cases (17%, 67 (55, 79) years, 48 females). Twenty cases showed evidence of perforation (3.7% total cohort, 22% moderate-to-severe cohort). Diagnosis as an incidental finding was frequent (46.0% of mild cases). Most cases involved the rectum (97.6% of mild cohort and 69% of moderate-to-severe cohort). The sigmoid was involved in 31% of moderate-to-severe cases, but 95% of the perforated subcohort (19/20, 13/20 without rectal involvement). Among the moderate-to-severe cohort, perforation was associated with slightly increased wall thickness (6.4 vs. 5.7 mm, p = 0.03), opioid use (50 vs. 23%, p = 0.04), and disease-specific mortality (11 vs. 0%, p =0.04). Perforation was less associated with major neurocognitive disorders (20 vs. 60%, p = 0.003), institutionalized status (5 vs. 38%, p = 0.005), and a prescribed bowel regimen (30 vs. 63%, p = 0.01). Conclusion: Stercoral colitis may be under-reported. Perforation tends to favor sigmoid involvement and a less traditional patient cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: This review summarizes recent advances in the nuclear medicine theranostic approach. It covers the repurposing of historical radiotracers for new indications and highlights new radiotracers in solid malignancies. Additionally, the potential of combining theranostics with immunotherapy is explored, underscoring the promise of personalized and targeted therapies. The progress in theranostics signifies an exciting era in nuclear medicine with potential benefits for diverse cancer types. The theranostic approach in oncology holds significant importance in personalized medicine and stands as an exciting field of molecular medicine. Significant achievements have been made in this field in recent decades, particularly in treating neuroendocrine tumors using 177-Lu-radiolabeled somatostatin analogs and, more recently, in addressing prostate cancer through prostate-specific-membrane-antigen targeted radionuclide therapy. The promising clinical results obtained in these indications paved the way for the further development of this approach. With the continuous discovery of new molecular players in tumorigenesis, the development of novel radiopharmaceuticals, and the potential combination of theranostics agents with immunotherapy, nuclear medicine is poised for significant advancements. The strategy of theranostics in oncology can be categorized into (1) repurposing nuclear medicine agents for other indications, (2) improving existing radiopharmaceuticals, and (3) developing new theranostics agents for tumor-specific antigens. In this review, we provide an overview of theranostic development and shed light on its potential integration into combined treatment strategies. [ABSTRACT FROM AUTHOR]

Aim: Anastomotic leak (AL) is the most important complication of intestinal surgery with an anastomosis. Whilst a number of studies have defined risk factors for AL, frustratingly, low-risk patients still develop AL. Studies have looked at drain fluid analysis for detection of AL, but these findings have failed to translate into routine clinical practice. This umbrella systematic review aims to provide an overview of the promising candidate biomarkers (BMs) that show potential to translate into clinical practice., Methods: A systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane, KSR Evidence and the Epistemonikos databases on the 14 April 2021. Only systematic reviews of cohort or controlled studies measuring drain fluid biomarkers in humans were included. The methodological quality of the reviews was assessed using the AMSTAR 2 instrument. Clinical trial registries were searched for trials actively investigating drain fluid BMs. Candidate BMs were classified, and threshold values investigated., Results: Nine systematic reviews, published between 2007 and 2020, met the inclusion criteria, and contained a total of 36 cohort studies. A total of 38 different BMs were studied. The most promising category of drain fluid BM was the extravasated intra-luminal substances (EILS) and five registered trials of these BMs were found. Two of nine reviews were of moderate quality., Conclusions: The majority of BMs show inconsistent threshold values and are in the experimental stage. A number are not readily available for adoption into routine clinical practice. Most do not state a cut-off value to be considered as diagnostic., (© 2021 Association of Coloproctology of Great Britain and Ireland.)

Ovarian cancer is the most lethal gynecological malignancy and is often associated with both DNA repair deficiency and extensive metabolic reprogramming. While still emerging, the interplay between these pathways can affect ovarian cancer phenotypes, including therapeutic resistance to the DNA damaging agents that are standard-of-care for this tumor type. In this review, we will discuss what is currently known about cellular metabolic rewiring in ovarian cancer that may impact DNA damage and repair in addition to highlighting how specific DNA repair proteins also promote metabolic changes. We will also discuss relevant data from other cancers that could be used to inform ovarian cancer therapeutic strategies. Changes in the choice of DNA repair mechanism adopted by ovarian cancer are a major factor in promoting therapeutic resistance. Therefore, the impact of metabolic reprogramming on DNA repair mechanisms in ovarian cancer has major clinical implications for targeted combination therapies for the treatment of this devastating disease., (© 2024 The Author(s). BioEssays published by Wiley Periodicals LLC.)

Background: In this prospective cohort study, we evaluated features of "adult‐onset megacolon with focal hypoganglionosis." Methods: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. Key results: The median age of the patients with adult‐onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0–74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72–86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7–16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190–338) in the proximal and 95 cells/cm (IQR, 45–213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, −5.4 points (surgery) vs. ‐0.3 points (medical treatment); p < 0.001]. Conclusions and inferences: Adult‐onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients. [ABSTRACT FROM AUTHOR]

Aim: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer., Method: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021., Results: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I 2  = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I 2  = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant., Conclusion: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Current understanding of Multiple Sclerosis (MS) pathophysiology implicates perturbations in adaptive cellular immune responses, predominantly T cells, in Relapsing-Remitting forms (RRMS). Nevertheless, from a clinical perspective MS is a heterogeneous disease reflecting the heterogeneity of involved biological systems. This complexity requires advanced analysis tools at the single-cell level to discover biomarkers for better patient-group stratification. We designed a novel 44-parameter mass cytometry panel to interrogate predominantly the role of effector and regulatory subpopulations of peripheral blood myeloid subsets along with B and T-cells (excluding granulocytes) in MS, assessing three different patient cohorts: RRMS, PPMS (Primary Progressive) and Tumefactive MS patients (TMS) (n=10, 8, 14 respectively). We further subgrouped our cohort into inactive or active disease stages to capture the early underlying events in disease pathophysiology. Peripheral blood analysis showed that TMS cases belonged to the spectrum of RRMS, whereas PPMS cases displayed different features. In particular, TMS patients during a relapse stage were characterized by a specific subset of CD11c+CD14+ CD33+, CD192+, CD172+-myeloid cells with an alternative phenotype of monocyte-derived macrophages (high arginase-1, CD38, HLA-DR-low and endogenous TNF-a production). Moreover, TMS patients in relapse displayed a selective CD4 T-cell lymphopenia of cells with a Th2-like polarised phenotype. PPMS patients did not display substantial differences from healthy controls, apart from a trend toward higher expansion of NK cell subsets. Importantly, we found that myeloid cell populations are reshaped under effective disease-modifying therapy predominantly with glatiramer acetate and to a lesser extent with antiCD20, suggesting that the identified cell signature represents a specific therapeutic target in TMS. The expanded myeloid signature in TMS patients was also confirmed by flow cytometry. Serum neurofilament light-chain levels confirmed the correlation of this myeloid cell signature with indices of axonal injury. More indepth analysis of myeloid subsets revealed an increase of a subset of highly cytolytic and terminally differentiated NK cells in PPMS patients with leptomeningeal enhancement (active-PPMS), compared to those without (inactive-PPMS). We have identified previously uncharacterized subsets of circulating myeloid cells and shown them to correlate with distinct disease forms of MS as well as with specific disease states (relapse/remission). [ABSTRACT FROM AUTHOR]

Early adequate treatment of patients with acute pancreatitis leads to a decrease in mortality and reduces the financial burden on medical institutions and the patient, which encourages the continued search for optimal markers for assessing severity and predicting the course of the disease. The aim of this work is to study the modern aspects of the pathogenesis of acute pancreatitis and the role of various biomarkers in the diagnosis of the severity of the course of the disease and the prediction of its complications. The study of the features of the pathogenesis of acute pancreatitis continues, which naturally contributes to the emergence of new diagnostic markers of this disease. It has been proven that most of the etiological factors that cause acute pancreatitis (alcohol, hypoxia, hypercalcemia, hyperlipidemia, certain pharmacological drugs) also contribute to abnormally high oscillations of the Ca2+ level. Therefore, it can be assumed that in acute pancreatitis, Ca2+ is a common trigger for various etiological factors, which trigger the pathological process. In turn, the enzymatic cascade is the starting point for the development of local and systemic inflammatory reactions, manifested by local and systemic effects. Based on the study of the features of the course of severe forms of acute pancreatitis, we established the role of vitamin D deficiency in the development of the disease. In addition, the study of the activity of tissue plasminogen activator and/or the level of thrombin-antithrombin III complex can be interesting as markers of the development of thrombohemorrhagic complications. An increase in the number of positive results of a serological examination for Helicobacter pylori (immunoglobulin M) in patients with a severe course of acute pancreatitis after 7 days from the moment of hospitalization gives reason to consider this indicator as one of the predictors of the development of purulent complications of the disease. Preliminary studies using the proposed diagnostic markers give encouraging results regarding the prognosis for the disease and the life of this extremely complex category of patients. [ABSTRACT FROM AUTHOR]

In electrocatalysis we seldom think about the competing direct reduction reactions that may happen alongside catalytically mediated reduction‐ with direct redox chemistry often happening slower but in competition with, catalysis. One class of compounds of interest from this perspective are iron sulfides. In addition to being structurally similar to many metalloproteins, iron sulfides are also among nature's strongest chemical reductants and reported to act as catalysts for key chemical reactions including proton, nitrite, and nitrate reduction. It is important that iron sulfides can act as catalysts because they are also strong enough reductants to mediate some of the same reactions directly. This is paradoxical because in order to be a catalyst for reduction, an iron sulfide cannot also be oxidised. To investigate this phenomenon further, we assembled a test set of iron sulfides spanning both amorphous iron sulfide (FeSam) as well as the crystalline iron sulfides greigite, pyrite, and troilite. These were used to explore the relationship between direct reduction and catalysis of a reduction reaction with a secondary electron source, NO2− was chosen as a test substrate. The trends in direct reduction followed the least stable material (FeSam) to the most stable material (FeS2). Of the phases studied, troilite (FeS) showed the largest difference between direct and catalytic reduction, however amorphous iron sulfide showed the greatest selectivity for NH3/NH4+ production as both a direct reductant and a catalyst. [ABSTRACT FROM AUTHOR]

There are special considerations when treating anastomotic leak after restorative proctocolectomy and ileal pouch–anal anastomosis. The epidemiology, risk factors, anatomic considerations, diagnosis and management, as well as the short- and long-term consequences to the patient are unique to this patent population. Additionally, there are specific concerns such as "tip of the J" leaks, transanal management of anastomotic leak/presacral sinus, functional outcomes after leak, and considerations of redo pouch procedures. [ABSTRACT FROM AUTHOR]

After discussion with the patient and family, the patient progressed to laparotomy with high anterior resection of the rectosigmoid colon. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed severe faecal loading throughout the entire colon with a markedly dilated rectosigmoid colon measuring 19 cm transversely without a significantly distended caecum, consistent with an acquired megacolon. A 73-year-old male was referred to a regional referral hospital by his general practitioner with abdominal pain and severe constipation on a background of lifelong chronic constipation (CC) and fragile X syndrome (FXS). [Extracted from the article]

Objective: To explore the effect of the cluster nursing mode combined with blood pressure regulation on the surgical tolerance of patients with esophageal cancer and hypertension. Methods: The clinical data of 86 patients with esophageal cancer and hypertension treated in our hospital (February 2016-February 2017) were retrospectively analyzed. The patients were randomly split into research group and reference group, with 43 cases in each group. The reference group received routine nursing, while the research group received cluster nursing combined with blood pressure regulation. The SBP, DBP and heart rates at D1 (at admission), D2 (2 h before surgery) and D3 (2 h after surgery) were compared between the two groups. In addition, the surgical tolerance, ESCA scores at 1 month after discharge, personality and behavior characteristics before and after intervention, and incidence of postoperative complications were also compared between the two groups. Results: With no obvious difference in SBP, DBP and heart rates at D1 between the two groups (P > 0.05), the SBP, DBP and heart rates at D2 and D3 in the research group were obviously lower compared with the reference group (P < 0.001). With no obvious difference in the number of patients with surgical tolerance of Grades I, II and III after intervention between two groups (P > 0.05), the number of patients with surgical tolerance of Grade IV in the research group was significantly higher than that in the reference group (P < 0.05). The scores of self-concept, self-care skills, self-care responsibility and health knowledge in the research group at 1 month after discharge were obviously higher compared with the reference group (P < 0.001). The scores of EPQ-L (lie), EPQ-P (psychoticism) and EPQ-N (neurosism) after intervention in both groups were obviously lower compared with those before intervention (P < 0.001), and the scores of EPQ-L, EPQ-P and EPQ-N after intervention in the research group were significantly lower than those in the reference group (P < 0.001). The total incidence of postoperative complications in the research group was significantly lower compared with the reference group (P < 0.05). Conclusion: Cluster nursing combined with blood pressure regulation can significantly improve the surgical tolerance of patients with esophageal cancer and hypertension and enhance the self-care ability after surgery, with obvious therapeutic effect, which is worthy of promotion and application. [ABSTRACT FROM AUTHOR]

Hydrilla verticillata is an aquatic weed that grows densely throughout the water column and is costly to manage. The hydrilla tip mining midge, Cricotopus lebetis, a potential augmentative biological control agent of hydrilla, feeds on the apical meristem preventing growth. The goal of this study was to quantify the influence of a predator (mosquitofish, Gambusia sp.) and a competitor (hydrilla leafcutter moth, Parapoynx diminutalis) and their interactions, on the ability of the midge to survive and feed on hydrilla. The first experiment involved six treatments established in 37.8 L tanks with combinations of the organisms, including larval C. lebetis. Survival to adult midge eclosion was significantly reduced in the presence of the predator but was unaffected by the competitor's presence alone. Apical meristem damage was reduced when both the competitor and predator were present. The second experiment included four treatments with C. lebetis egg masses or larvae and the presence or absence of mosquitofish. Adding C. lebetis as eggs rather than as larvae increased midge survival in the absence of the predator. Midge survival was lower when larvae were added, but the predator had no additional effect. To facilitate successful establishment of the midge and control of hydrilla, high numbers of larvae should be released to overcome predation. [ABSTRACT FROM AUTHOR]

Background: Dual-energy CT is able to distinguish between materials based on differences in X-ray absorption at different X-ray beam energies. The strong k-edge photoelectric effect of materials with a high atomic number makes this modality ideal for identifying iodine-containing compounds. We aim to evaluate dual-energy CT for the detection of Gastrografin (GG) (diatrizoate, Bayer PLC, Reading, UK) enteric contrast medium and validate the conditions for the measurement in ex vivo samples.Methods: Dual-energy CT acquisitions were performed to detect Gastrografin in serial dilutions of water, saline and body fluids. We also evaluated the stability of Gastrografin solutions over time at room temperature. Stool specimens were examined to validate the proposed study protocol for clinical applications.Results: Concentrations as low as 0.2% of Gastrografin were reproducibly detected in vitro and ex vivo samples by DECT, with linear readings ranging from 0.2% to 25% Gastrografin. Gastrografin was shown to be stable in ex vivo biological samples, and there was no difference in detection over time. Gastrografin was detected in stool specimens when administered orally. The detection curves followed the expected saturation effect at high concentrations of iodine.Conclusions: Dual-energy CT offers a convenient, quick, reliable and reproducible method for detecting and quantifying the presence of Gastrografin in ex vivo clinical specimens. Biological solutions containing Gastrografin are stable over time. A minimum dilution level of 25% is suggested to avoid beam saturation and inaccurate results. [ABSTRACT FROM AUTHOR]

Chronic constipation (CC) is one of the most common gastrointestinal disorders worldwide. Its pathogenesis, however, remains largely unclear. The purpose of the present work was to gain an insight into the role of contractility and microbiota in the etiology of CC. To this end, we studied spontaneous and evoked contractile activity of descending colon segments from patients that have undergone surgery for refractory forms of CC. The juxta-mucosal microbiota of these colon samples were characterized with culture-based and 16S rRNA sequencing techniques. In patients with CC the spontaneous colonic motility remained unchanged compared to the control group without dysfunction of intestinal motility. Moreover, contractions induced by potassium chloride and carbachol were increased in both circular and longitudinal colonic muscle strips, thus indicating preservation of contractile apparatus and increased sensitivity to cholinergic nerve stimulation in the constipated intestine. In the test group, the gut microbiota composition was assessed as being typically human, with four dominant bacterial phyla, namely Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, as well as usual representation of the most prevalent gut bacterial genera. Yet, significant inter-individual differences were revealed. The phylogenetic diversity of gut microbiota was not affected by age, sex, or colonic anatomy (dolichocolon, megacolon). The abundance of butyrate-producing genera Roseburia, Coprococcus, and Faecalibacterium was low, whereas conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased in the gut microbiomes of the constipated patients. As evidenced by our study, specific microbial biomarkers for constipation state are absent. The results point to a probable role played by the overall gut microbiota at the functional level. To our knowledge, this is the first comprehensive characterization of CC pathogenesis, finding lack of disruption of motor activity of colonic smooth muscle cells and insufficiency of particular members of gut microbiota usually implicated in CC. [ABSTRACT FROM AUTHOR]

Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age‐dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ‐specific vascular endothelial cells (VECs). Long‐living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA‐seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin‐like‐4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established. [ABSTRACT FROM AUTHOR]

Is to design personalised, super-selective therapies and to identify more precise means of monitoring response to treatment in routine The now well-established tracks M2M - Molecule to Man (basic and translational science) and Do.MoRe (radionuclide therapy and dosimetry) promise to promote high-quality research through interaction between basic and translational clinical Scientists and to present the latest achievements and developments in the fields of clinical molecular imaging and nuclear medicine therapy. Radiobiology and Dosimetry for Radioembolisation Therapy Problems Related to Dosimetry for Therapy Based on. [Extracted from the article]

Objective: Chronic megacolon is rarely encountered in clinical practice beyond infancy or early childhood. Most cases are sporadic, and some are familial megacolon and present during adolescence or adulthood. There is a need for diagnostic criteria and identifying genetic variants reported in non-Hirschsprung's megacolon.Methods: PubMed search was conducted using specific key words.Results: This article reviews the clinical manifestations, current diagnostic criteria, and intraluminal measurements of colonic compliance to confirm the diagnosis when the radiological imaging is not conclusive. Normal ranges of colonic compliance at 20, 30, and 44 mmHg distension are provided. The diverse genetic associations with chronic acquired megacolon beyond childhood are reviewed, including the potential association of SEMA3F gene in a family with megacolon.Conclusions: Measuring colonic compliance could be standardized and simplified by measuring volume at 20, 30, and 44 mmHg distension to identify megacolon when radiology is inconclusive. Diverse genetic associations with chronic acquired megacolon beyond childhood have been identified. [ABSTRACT FROM AUTHOR]

In recent papers, Eric Schwitzgebel ( Philosophical Studies, 172, 1697-1721, 2015, Philosophia, 44, 877-883, 2016) argues that if physicalism is true, then the United States is probably conscious. My primary aim here is to demonstrate that the source of Schwitzgebel's conditional argument is the 'Problem of Other Minds,' which is a general problem; wherefore, Schwitzgebel's conclusion should be revised and applied not only to physicalism, but to most contemporary theories of the mind. I analyze the difference between Schwitzgebel's argument and other arguments against functionalism, arguing that the difference between them is rooted in referring to the causal role of the whole system, rather than referring to the casual role of the system's parts. This key difference between functionalism and behaviorism explains why the source of Schwitzgebel's argument stems from the problem of other minds. I conclude that however counterintuitive from a metaphysical point of view, the United States may have its own stream of consciousness, but it has nothing to do with physicalism in particular. [ABSTRACT FROM AUTHOR]

Various properties of MnS thin films deposited on glass substrate by a simple and novel nebulized spray technique are described in this work. The thickness of MnS thin film increases linearly with increase in molar ratio and substrate temperature. From the X-ray diffraction study, the impact of molar ratio and substrate temperature is well pronounced in the formation of well crystalline MnS thin films. The SEM images showed more grains formation and well defined compact nature composed of single type densely packed grains. The AFM images exhibited that all the films show homogenous surface with pinhole free in nature. The decrease in average transmittance of films with increasing substrate temperature and molar ratio are due to the influence of grain growth induced by the enhancement in crystalline behavior of the films. It is observed that the energy band gaps of MnS thin films are decreased with increasing substrate temperature and molar ratio. The intensity of emission peaks increased with increasing solution concentration and substrate temperature owing to the change in surface area to volume ratio of MnS micro/nano-structures with molar ratio. All the Raman peaks showed the vibrations of Mn-S bonds. The magnetic study confirmed the ferromagnetic behavior of MnS films at 5 K, whereas the film exhibits paramagnetic behavior at 300 K. [ABSTRACT FROM AUTHOR]

The article presents the list of the authors including the Ackermann U.; Akamatsu G.; and the Akhurst T.

Background: Anastomotic leak (AL) is a serious complication in digestive surgery. Early diagnosis might allow clinicians to anticipate appropriate management. The aim of this study was to assess the predictive value of amylase concentration in drain fluid for the early diagnosis of digestive tract AL. Materials and Methods: Hundred and fourteen consecutive patients "at risk" of AL, in whom a flexible drainage was placed by surgeon's choice after digestive anastomosis were included. Patients with eso-gastric, bilio-digestive, and pancreatic anastomoses were excluded. Drain amylase measurement (DAM) was routinely performed on postoperative day (POD) 1, 3, 5–7. DAM values were compared between patients with postoperative AL versus patients without AL. A receiver-operating curve (ROC) with calculation of the areas under the ROC curves area under curves was performed and a cutoff value of DAM was calculated. Results: AL occurred in 25 patients (AL group) and 89 patients did not present AL (C group). The mean DAM was significantly higher in AL group versus C Group on POD 1, 3, and 5. A cutoff value of 307 IU/L predicted the occurrence of AL with a sensitivity and specificity of 91% and 100%, respectively. Positive and negative predictive values were 100% and 97.5%, respectively. Patients with AL had an elevated DAM prior to the appearance of any clinical signs of AL. Conclusion: High level DAM could accurately predict AL for proximal and distal digestive tract anastomoses. This simple, noninvasive, and low-cost method can accurately predict early AL and help physicians to perform appropriate imaging and treatment. [ABSTRACT FROM AUTHOR]

If you're a materialist, you probably think that rabbits are conscious. And you ought to think that. After all, rabbits are a lot like us, biologically and neurophysiologically. If you're a materialist, you probably also think that conscious experience would be present in a wide range of naturally-evolved alien beings behaviorally very similar to us even if they are physiologically very different. And you ought to think that. After all, to deny it seems insupportable Earthly chauvinism. But a materialist who accepts consciousness in weirdly formed aliens ought also to accept consciousness in spatially distributed group entities. If she then also accepts rabbit consciousness, she ought to accept the possibility of consciousness even in rather dumb group entities. Finally, the United States would seem to be a rather dumb group entity of the relevant sort. If we set aside our morphological prejudices against spatially distributed group entities, we can see that the United States has all the types of properties that materialists tend to regard as characteristic of conscious beings. [ABSTRACT FROM AUTHOR]