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Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres

World Journal of Gastroenterology 2019年第39期25卷 5991-6005页

作者： Melissa Frizziero Xin Wang Bipasha Chakrabarty alexa childs Tu V Luong Thomas Walter Mohid S Khan Meleri Morgan Adam Christian Mona Elshafie Tahir Shah Annamaria Minicozzi Wasat Mansoor Tim Meyer Angela Lamarca Richard A Hubner Juan W Valle Mairéad G McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Analytics and Development The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Pathology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Medical Oncology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom UCL Cancer Institute University College LondonLondon WC1E 6AGUnited Kingdom Department of Histopathology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom Department of Gastroenterology and Medical Oncology Edouard Herriot HospitalHospices Civils de LyonLyon 69003France Department of Gastroenterology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Cellular Pathology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Hepatology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Surgical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Division of Cancer Sciences University of ManchesterManchester M13 9PLUnited Kingdom

BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic *** is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be *** To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of *** Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European *** data were retrospectively collected from medical *** samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of *** responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours ***-Meier analysis was applied to estimate survival *** between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and Cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 ***:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases *** distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine ***-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of *** was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal *** localised cases,median recurre

关键词： Mixed neuroendocrine non-neuroendocrine neoplasm 2017 World Health Organisation classification Mixed adeno-neuroendocrine carcinoma Gastro-enteropancreatic tract Digestive system Neuroendocrine neoplasms Survival outcomes

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya alexa Olivarez George D.Bittner Dale R.Sengelaub Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality

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World Journal of Transplantation 2024年第2期14卷 62-75页

作者： Faisal Inayat Pratik Patel Hassam Ali Arslan Afzal Hamza Tahir Ahtshamullah Chaudhry Rizwan Ishtiaq Attiq Ur Rehman Kishan Darji Muhammad Sohaib Afzal Gul Nawaz alexa Giammarino Sanjaya K Satapathy Department of Internal Medicine Allama Iqbal Medical CollegeLahorePunjab 54550Pakistan Division of Gastroenterology Mather Hospital and Zucker School of Medicine at Hofstra UniversityPort JeffersonNY 11777United States Division of Gastroenterology and Hepatology East Carolina University Brody School of MedicineGreenvilleNC 27834United States Department of Internal Medicine Jefferson Einstein HospitalPhiladelphiaPA 19141United States Department of Internal Medicine St.Dominic's HospitalJacksonMS 39216United States Department of Internal Medicine Saint Francis Hospital and Medical CenterHartfordCT 06105United States Division of Hepatology Geisinger Wyoming Valley Medical CenterWilkes-BarrePA 18711United States Department of Internal Medicine Campbell University and Cape Fear Valley Medical CenterFayettevilleNC 28301United States Department of Internal Medicine North Shore University Hospital and Zucker School of Medicine at Hofstra UniversityManhassetNY 11030United States Division of Hepatology North Shore University Hospital and Zucker School of Medicine at Hofstra UniversityManhassetNY 11030United States

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern *** with comorbid conditions are at risk of adverse outcomes following *** organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 *** could lead to higher rates of inpatient complications and mortality in this patient ***,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent *** To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United *** We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample *** with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding *** primary outcomes included trends in LT hospitalizations before and during the COVID-19 *** outcomes included comparative trends in inpatient mortality and transplant rejection in LT *** A total of 15720 hospitalized LT recipients were *** 0.8% of patients had a secondary diagnosis of COVID-19 *** both cohorts,the median admission age was 57 *** linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December *** to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December *** hospitalizations during the COVID-19 pandemic had a higher associ

关键词： Liver transplant recipients Solid organ transplantation COVID-19 Hospitalization Transplant rejection Mortality

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第09期 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of Texas Program in Neuroscience Indiana University Department of Molecular Biosciences University of Texas

Successful polyethylene glycol fusion(PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1) rapidly restore electrophysiological continuity;(2) prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3) promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch) or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3) above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than N

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Signaling events during initiation of arbuscular mycorrhizal symbiosis

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Journal of Integrative Plant Biology 2014年第3期56卷 250-261页

作者： alexa M.Schmitz Maria J.Harrison Boyce Thompson Institute for Plant Research Plant Pathology and Plant-Microbe Biology Cornell University

Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal （AM） fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression.

关键词： Arbuscular mycorrhizal fungi chitin chitooligosaccharide cutin LysM MAMP-triggered immunity Myc-LCO Nod factor strigolactones symbiosis

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Serrated lesions:A challenging enemy

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World Journal of Gastroenterology 2021年第34期27卷 5625-5629页

作者： alexa Trovato Alla Turshudzhyan Micheal Tadros Albany Medical College AlbanyNY 12208United States Department of Medicine University of ConnecticutSchool of MedicineFarmingdaleCT 06032United States Department of Gastroenterology Albany Medical CenterAlbanyNY 12208United States

The serrated pathway accounts for 30%-35%of colorectal cancer(CRC).Unlike hyperplastic polyps,both sessile serrated lesions(SSLs)and traditional serrated adenomas are premalignant lesions,yet SSLs are considered to be the principal serrated precursor of *** lesions represent a challenge in detection,classification,and removal–contributing to post-colonoscopy ***,it is of the utmost importance to characterize these lesions properly to ensure complete removal.A retrospective cohort study developed a diagnostic scoring system for SSLs to facilitate their detection endoscopically and subsequent *** the study,it can be ascertained that both indistinct border and mucus cap are essential in both recognizing and diagnosing serrated *** proximal colon poses technical challenges for some endoscopists,which is why high-quality colonoscopy plays such an important *** indistinct border of some SSLs poses another challenge due to difficult complete ***,it is imperative that gastroenterologists use the key features of mucus cap,indistinct borders,and size of at least five millimeters along with a high-quality colonoscopy and a good bowel preparation to improve the SSL detection rate.

关键词： Sessile serrated lesions Colonoscopy Polyps Colorectal cancer screening Hyperplastic polyps Traditional serrated adenomas

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Data-driven Modelling for the Prediction of the Postoperative Electrode Position in Deep Brain Stimulation

Data-driven Modelling for the Prediction of the Postoperativ...

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作者： alexa Singer 上海交通大学

学位级别：硕士

Deep brain stimulation（DBS）is a neurosurgical procedure for treating neurodegenerative diseases and neurological disorders such as Parkinson’s disease（PD）and *** electrode placement accuracy is crucial to exploit the potential of the surgical treatment and avoid stimulation-induced ***,current surgical planning systems based on pre-operative MR and CT images of the brain cannot take into account intra-operative brainshift,resulting in suboptimal electrode placement undermining clinical *** this dissertation,a support vector regression（SVR）model was constructed based on 92 patient-specific data of PD patients,aiming to introduce a brain-shift aware pre-operative trajectory planning method to be incorporated on top of the current static pre-operative *** model was tested on 22 unseen *** target nuclei were manually delineated based on pre-operative MR and CT *** coordinates of the two nuclei were collected and compared to the post-surgical electrode position from CT images to quantify brain-shift caused *** of a total of 45 features showed that the pre-operative target coordinates are the parameters mainly related to the displacement of the electrode and thus driving the model prediction for both *** mean absolute error（MAE）of the prediction of the post-operative coordinates was 0.69 mm during validation and 0.76 mm on unseen *** study demonstrates the potential of using SVR modelling to improve current DBS surgical planning procedure and pre-operative risk-assessment.

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Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： alexa R Weingarden Samuel J S Rubin John Gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States Stanford University School of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI *** also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

关键词： Immune checkpoint inhibitors Cytotoxic T-lymphocyte antigen 4 Programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

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Practical considerations for colorectal cancer screening in older adults

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World Journal of Gastrointestinal Oncology 2022年第6期14卷 1086-1102页

作者： Dana Gornick Anusri Kadakuntla alexa Trovato Rebecca Stetzer Micheal Tadros Albany Medical College Albany Medical CollegeAlbanyNY 12208United States Division of Geriatrics Albany Medical CenterAlbanyNY 12208United States Division of Gastroenterology Albany Medical CenterAlbanyNY 12208United States

Recent guidelines recommend that colorectal cancer(CRC)screening after age 75 be considered on an individualized basis,and discourage screening for people over 85 due to competing causes of *** the heterogeneity in the health of older individuals,and lack of data within current guidelines for personalized CRC screening approaches,there remains a need for a clearer framework to inform clinical decision-making.A revision of the current approach to CRC screening in older adults is even more compelling given the improvements in CRC treatment,post-treatment survival,and increasing life expectancy in the *** this review,we aim to examine the personalization of CRC screening cessation based on specific factors influencing life and health expectancy such as comorbidity,frailty,and cognitive *** will also review screening modalities and endoscopic technique for minimizing risk,the risks of screening unique to older adults,and CRC treatment outcomes in older patients,in order to provide important information to aid CRC screening decisions for this age *** review article offers a unique approach to this topic from both the gastroenterologist and geriatrician perspective by reviewing the use of specific clinical assessment tools,and addressing technical aspects of screening colonoscopy and periprocedural management to mitigate screening-related complications.

关键词： Colorectal cancer Colonoscopy Cancer screening Early detection of cancer Aged Elderly

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