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  1. Article ; Online: 15-Year Experience with Multimodality Therapy Including Esophagectomy for Elderly Patients with Locoregional Esophageal Cancer.

    Sawyer, W Peter / Luo, Xinyi / Welch, Andrew M / Bolton, Nathan M / Brown, Russell / Bolton, John S

    Journal of the American College of Surgeons

    2021  Volume 232, Issue 4, Page(s) 580–588

    Abstract: Background: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk ... ...

    Abstract Background: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population.
    Study design: Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger."
    Results: One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS).
    Conclusions: Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients.
    MeSH term(s) Age Factors ; Aged ; Aged, 80 and over ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/etiology ; Chemoradiotherapy, Adjuvant/methods ; Chemoradiotherapy, Adjuvant/statistics & numerical data ; Comorbidity ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/mortality ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/therapy ; Esophagectomy/adverse effects ; Esophagectomy/statistics & numerical data ; Esophagogastric Junction/pathology ; Esophagogastric Junction/surgery ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoadjuvant Therapy/statistics & numerical data ; Neoplasm Staging ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Risk Assessment/statistics & numerical data ; Risk Factors ; Survival Analysis ; Treatment Outcome
    Language English
    Publishing date 2021-02-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1181115-8
    ISSN 1879-1190 ; 1072-7515
    ISSN (online) 1879-1190
    ISSN 1072-7515
    DOI 10.1016/j.jamcollsurg.2020.11.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Effect of Glucagon-Like Peptide 1 Receptor Blockade on Glucagon-Induced Stimulation of Insulin Secretion.

    Farahani, Rahele A / Egan, Aoife M / Welch, Andrew A / Laurenti, Marcello C / Cobelli, Claudio / Dalla Man, Chiara / Vella, Adrian

    Diabetes

    2022  Volume 72, Issue 4, Page(s) 449–454

    Abstract: Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on β-cells. However, its net contribution to physiologic insulin secretion in humans is ... ...

    Abstract Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on β-cells. However, its net contribution to physiologic insulin secretion in humans is unknown. To address this question, we studied individuals without diabetes in two separate experiments. Each subject was studied on two occasions in random order. In the first experiment, during a hyperglycemic clamp, glucagon was infused at 0.4 ng/kg/min, increasing by 0.2 ng/kg/min every hour for 5 h. On one day, exendin-9,39 (300 pmol/kg/min) was infused to block GLP-1R, while on the other, saline was infused. The insulin secretion rate (ISR) was calculated by nonparametric deconvolution from plasma concentrations of C-peptide. Endogenous glucose production and glucose disappearance were measured using the tracer-dilution technique. Glucagon concentrations, by design, did not differ between study days. Integrated ISR was lower during exendin-9,39 infusion (213 ± 26 vs. 191 ± 22 nmol/5 h, saline vs. exendin-9,39, respectively; P = 0.02). In the separate experiment, exendin-9,39 infusion, compared with saline infusion, also decreased the β-cell secretory response to a 1-mg glucagon bolus. These data show that, in humans without diabetes, glucagon partially stimulates the β-cell through GLP-1R.
    MeSH term(s) Humans ; Glucagon/metabolism ; Insulin Secretion ; Insulin/metabolism ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide 1 ; Blood Glucose ; Peptide Fragments/pharmacology ; Glucose/pharmacology
    Chemical Substances Glucagon (9007-92-5) ; Insulin ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide 1 (89750-14-1) ; Blood Glucose ; Peptide Fragments ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db22-0709
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.

    Schembri Wismayer, Daniel / Laurenti, Marcello C / Song, Yilin / Egan, Aoife M / Welch, Andrew A / Bailey, Kent R / Cobelli, Claudio / Dalla Man, Chiara / Jensen, Michael D / Vella, Adrian

    American journal of physiology. Endocrinology and metabolism

    2023  Volume 325, Issue 2, Page(s) E119–E131

    Abstract: Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose ...

    Abstract Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose,
    MeSH term(s) Humans ; Glucose/metabolism ; Fatty Acids, Nonesterified ; Blood Glucose/metabolism ; Diabetes Mellitus ; Glucose Intolerance/metabolism ; Insulin/metabolism ; Insulin Resistance/physiology
    Chemical Substances Glucose (IY9XDZ35W2) ; Fatty Acids, Nonesterified ; Blood Glucose ; Insulin
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603841-4
    ISSN 1522-1555 ; 0193-1849
    ISSN (online) 1522-1555
    ISSN 0193-1849
    DOI 10.1152/ajpendo.00043.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans.

    Welch, Andrew A / Farahani, Rahele A / Egan, Aoife M / Laurenti, Marcello C / Zeini, Maya / Vella, Max / Bailey, Kent R / Cobelli, Claudio / Dalla Man, Chiara / Matveyenko, Aleksey / Vella, Adrian

    The Journal of clinical investigation

    2023  Volume 133, Issue 22

    Abstract: BACKGROUNDProglucagon can be processed to glucagon-like peptide1 (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this ...

    Abstract BACKGROUNDProglucagon can be processed to glucagon-like peptide1 (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this is affected by type 2 diabetes.METHODSWe therefore studied individuals with and without type 2 diabetes on two occasions in random order. On one occasion, exendin 9-39, a competitive antagonist of the GLP-1 Receptor (GLP1R), was infused, while on the other, saline was infused. The tracer dilution technique ([3-3H] glucose) was used to measure glucose turnover during fasting and during a hyperglycemic clamp.RESULTSExendin 9-39 increased fasting glucose concentrations; fasting islet hormone concentrations were unchanged, but inappropriate for the higher fasting glucose observed. In people with type 2 diabetes, fasting glucagon concentrations were markedly elevated and persisted despite hyperglycemia. This impaired suppression of endogenous glucose production by hyperglycemia.CONCLUSIONThese data show that GLP1R blockade impairs islet function, implying that intra-islet GLP1R activation alters islet responses to glucose and does so to a greater degree in people with type 2 diabetes.TRIAL REGISTRATIONThis study was registered at ClinicalTrials.gov NCT04466618.FUNDINGThe study was primarily funded by NIH NIDDK DK126206. AV is supported by DK78646, DK116231 and DK126206. CDM was supported by MIUR (Italian Minister for Education) under the initiative "Departments of Excellence" (Law 232/2016).
    MeSH term(s) Humans ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Glucagon/metabolism ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-1 Receptor ; Glucose/metabolism ; Hyperglycemia/metabolism ; Insulin/metabolism
    Chemical Substances Blood Glucose ; Glucagon (9007-92-5) ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon-Like Peptide-1 Receptor ; Glucose (IY9XDZ35W2) ; Insulin ; GLP1R protein, human
    Language English
    Publishing date 2023-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI173495
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Characterization of viability, scarring and hibernation of the myocardium supplied by epicardial coronary arteries with low flow grades.

    Al-Mohammad, Abdallah / Norton, Murdoch Y / Welch, Andrew E / Walton, Stephen

    Nuclear medicine communications

    2017  Volume 38, Issue 8, Page(s) 657–665

    Abstract: Objective: The aim of this study was to analyse the relationship between reduced coronary artery flow and myocardial viability, scarring and hibernation.: Patients and methods: Coronary flow grades and collateral vessels were scored using the ... ...

    Abstract Objective: The aim of this study was to analyse the relationship between reduced coronary artery flow and myocardial viability, scarring and hibernation.
    Patients and methods: Coronary flow grades and collateral vessels were scored using the thrombolysis in myocardial infarction trial (TIMI) and the Rentrop and Cohen scoring systems, respectively. N-ammonia and fluorine-18-fluorodeoxyglucose (F-FDG) are the perfusion and metabolic markers on PET, respectively. The left ventricle was divided into three coronary territories. The area with the highest N-ammonia uptake was considered the reference region. Myocardial regions with F-FDG uptake of at least 50% of the reference region were considered viable and those with F-FDG uptake less than 50% of the reference region were considered scarred. Hibernation was considered present if the viable myocardium had significant wall motion abnormality.
    Results: There were 80 (71 males) patients with 240 myocardial territories. TIMI 2-3 arteries supplied 151 regions (group A), and 89 regions were supplied by TIMI 0-1 arteries (group B). Viable myocardium was present in 140 (93%) regions of group A and in 76 (85%) regions of group B (P=0.068). Scarring was present in 40 (26%) regions in group A and in 49 (55%) regions in group B (P<0.0001). Wall motion data were available in 215 regions: 133 regions in group A and 82 regions in group B. Hibernating myocardium was predicted in 36 (28%) regions in group A and in 34 (41%) regions in group B (P<0.05).
    Conclusion: Myocardial regions supplied by arteries with TIMI 0-1 are characterized by significantly increased incidence of hibernation and scarring. Video abstract: http://links.lww.com/NMC/A115.
    Language English
    Publishing date 2017-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 758141-5
    ISSN 1473-5628 ; 0143-3636
    ISSN (online) 1473-5628
    ISSN 0143-3636
    DOI 10.1097/MNM.0000000000000683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book: The royal navy in the cod wars

    Welch, Andrew

    Britain and Iceland in conflict 1958 - 61, 1972 - 73, 1975 - 76

    2006  

    Author's details by Andrew Welch
    Language English
    Size XII, 324 S., Ill., Kt., 25 cm
    Publisher Maritime Books
    Publishing place Liskeard
    Document type Book
    Note Includes bibliographical references
    ISBN 1904459234 ; 9781904459231
    Database Former special subject collection: coastal and deep sea fishing

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  7. Article ; Online: Laparoscopic ultrasound for the diagnosis of choledocholithiasis: quick, safe, and effective.

    Shaaban, Hossam / Welch, Andrew / Rao, Sudhindra

    Surgical laparoscopy, endoscopy & percutaneous techniques

    2014  Volume 24, Issue 3, Page(s) 274–276

    Abstract: Visualization of the common bile duct during laparoscopic cholecystectomy is frequently required to confirm or exclude choledocholithiasis. Although on-table cholangiogram (OTC) is the traditional imaging technique, laparoscopic ultrasound (LUS) is ... ...

    Abstract Visualization of the common bile duct during laparoscopic cholecystectomy is frequently required to confirm or exclude choledocholithiasis. Although on-table cholangiogram (OTC) is the traditional imaging technique, laparoscopic ultrasound (LUS) is increasingly deployed for this purpose. We are reporting a 31-month experience with an LUS, starting from the initial set up of the equipment. We retrospectively studied 70 patients who underwent LUS during their laparoscopic cholecystectomy operation over a period of 31 months. Data about preoperative investigation, intraoperative findings, and postoperative outcome were retrospectively collected and analyzed. LUS was found to be quick, safe, and effective in the intraoperative diagnosis of the common bile duct stones. It does not add significantly to the operative time and is inherently safer than intraoperative cholangiogram owing to the fact that it does not involve ionizing radiation. It is also more convenient, as there is no need to wear protective lead to avoid the side effects of ionizing radiation.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Choledocholithiasis/diagnostic imaging ; Diagnosis, Differential ; Endosonography/methods ; Female ; Follow-Up Studies ; Humans ; Laparoscopy/methods ; Male ; Middle Aged ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Young Adult
    Language English
    Publishing date 2014-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1475108-2
    ISSN 1534-4908 ; 1530-4515 ; 1051-7200
    ISSN (online) 1534-4908
    ISSN 1530-4515 ; 1051-7200
    DOI 10.1097/SLE.0b013e31828fa907
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Gated metabolic myocardial imaging, a surrogate for dual perfusion-metabolism imaging by positron emission tomography.

    AlMohammad, Abdallah / Norton, Murdoch Y / Welch, Andrew E / Sharp, Peter F / Walton, Stephen

    Open heart

    2017  Volume 4, Issue 2, Page(s) e000581

    Abstract: Objective: Perfusion-metabolism mismatch pattern on positron emission tomography (PET) predicts hibernating myocardium. We assess the ECG-gated metabolic PET as a surrogate for the perfusion-metabolism mismatch pattern on PET imaging.: Methods: 13: ...

    Abstract Objective: Perfusion-metabolism mismatch pattern on positron emission tomography (PET) predicts hibernating myocardium. We assess the ECG-gated metabolic PET as a surrogate for the perfusion-metabolism mismatch pattern on PET imaging.
    Methods: 13
    Results: We studied 55 patients (48 males), mean age 62 years. All were in sinus rhythm, and had impaired left ventricular contraction. Perfusion-metabolism mismatch pattern was found in 26 patients. Metabolism-mechanical mismatch pattern was found in 25 patients. The results were concordant in 52 patients (95%). As a surrogate for perfusion-metabolism mismatch pattern, demonstration of metabolism-mechanical mismatch pattern is highly sensitive (92%) and specific (97%). In this cohort, the positive and negative predictive accuracy of the new method are 96% and 93%, respectively.
    Conclusion: Metabolism-mechanical mismatch pattern could predict perfusion-metabolism mismatch pattern in patients with myocardial viability criteria on PET. Prospective validation against the gold standard of improved myocardial contraction after revascularisation is needed.
    Language English
    Publishing date 2017-07-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2747269-3
    ISSN 2053-3624 ; 2044-6055
    ISSN 2053-3624 ; 2044-6055
    DOI 10.1136/openhrt-2016-000581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Modeling Mixed Vascular and Alzheimer's Dementia Using Focal Subcortical Ischemic Stroke in Human ApoE4-TR:5XFAD Transgenic Mice.

    Hayden, Eric Y / Huang, Julia M / Charreton, Malena / Nunez, Stefanie M / Putman, Jennifer N / Teter, Bruce / Lee, Jason T / Welch, Andrew / Frautschy, Sally / Cole, Gregory / Teng, Edmond / Hinman, Jason D

    Translational stroke research

    2020  Volume 11, Issue 5, Page(s) 1064–1076

    Abstract: Subcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer's disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We ... ...

    Abstract Subcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer's disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We designed a novel mouse model of subcortical white matter ischemic stroke and AD that can inform our understanding of the cellular and molecular mechanisms of mixed vascular and AD dementia. Subcortical white matter ischemic stroke underlying forelimb motor cortex was induced by local stereotactic injection of an irreversible eNOS inhibitor. Subcortical white matter ischemic stroke or sham procedures were performed on human ApoE4-targeted-replacement (TR):5XFAD mice at 8 weeks of age. Behavioral tests were done at 7, 10, 15, and 20 weeks. A subset of animals underwent
    MeSH term(s) Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Apolipoprotein E4/genetics ; Brain/metabolism ; Brain/physiopathology ; Brain Ischemia/genetics ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Disease Models, Animal ; Humans ; Ischemic Stroke/genetics ; Ischemic Stroke/metabolism ; Ischemic Stroke/pathology ; Mice, Transgenic
    Chemical Substances Amyloid beta-Peptides ; Apolipoprotein E4
    Language English
    Publishing date 2020-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541897-X
    ISSN 1868-601X ; 1868-4483
    ISSN (online) 1868-601X
    ISSN 1868-4483
    DOI 10.1007/s12975-020-00786-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: First experience of COVID-19 screening of health-care workers in England.

    Hunter, Ewan / Price, David A / Murphy, Elizabeth / van der Loeff, Ina Schim / Baker, Kenneth F / Lendrem, Dennis / Lendrem, Clare / Schmid, Matthias L / Pareja-Cebrian, Lucia / Welch, Andrew / Payne, Brendan A I / Duncan, Christopher J A

    Lancet (London, England)

    2020  Volume 395, Issue 10234, Page(s) e77–e78

    MeSH term(s) Betacoronavirus/genetics ; Betacoronavirus/isolation & purification ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; England ; Health Personnel ; Mass Screening ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Quarantine ; Real-Time Polymerase Chain Reaction ; Return to Work ; SARS-CoV-2 ; State Medicine ; Time Factors
    Keywords covid19
    Language English
    Publishing date 2020-04-22
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(20)30970-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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