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Article ; Online: Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies.

Stergiou, Ioanna E / Tsironis, Christos / Papadakos, Stavros P / Tsitsilonis, Ourania E / Dimopoulos, Meletios Athanasios / Theocharis, Stamatios

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the ... ...

Abstract	Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome's implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.
MeSH term(s)	Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Inflammation/metabolism ; Lymphoma/etiology ; Lymphoma/therapy ; Tumor Microenvironment
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2024-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042369
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Article ; Online: Glomerulonephritis and inflammatory bowel disease: A tale of gut-kidney axis dysfunction.

Doumas, Stavros A / Tsironis, Christos / Bolaji, Abdul-Adl / Garantziotis, Panagiotis / Frangou, Eleni

Autoimmunity reviews

2023 Volume 22, Issue 6, Page(s) 103327

Abstract: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to ... ...

Abstract	The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality. Herein, we review the GN landscape in IBD and define the clinical and pathogenic associations reported to date in the literature. Underlying pathogenic mechanisms suggest either the initiation of antigen-specific immune responses in the inflamed gut that cross react with non-intestinal sites, such as the glomerulus, or that extraintestinal manifestations are gut-independent events that occur due to an interaction between common genetic and environmental risk factors. We present data associating GN with IBD either as a bona fide extraintestinal manifestation or reporting it as an extraneous co-existing entity, involving various histological subtypes, such as focal segmental glomerulosclerosis, proliferative GN, minimal change disease, crescentic GN, but most emphatically IgA nephropathy. Supporting the pathogenic interplay between gut inflammation and intrinsic glomerular processes, enteric targeting the intestinal mucosa with budesonide reduced IgA nephropathy-mediated proteinuria. Elucidating the mechanisms at play would provide insight not only into IBD pathogenesis but also into the gut's role in the development of extraintestinal diseases, such as glomerular diseases.
MeSH term(s)	Humans ; Glomerulonephritis, IGA ; Glomerulonephritis/complications ; Kidney Glomerulus ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/pathology ; Inflammation/pathology
Language	English
Publishing date	2023-03-28
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2023.103327
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Article ; Online: Risk Factors for Chronic Abdominal Pain After RYGB: Are Patients Adequately Selected Beforehand?

Ortega, Patricia M / Scholtz, Samantha / O'Donnell, Karen / Hakky, Sherif / Purkayastha, Sanjay / Tsironis, Christos / Moorthy, Krishna / Aggarwal, Ravi / Ahmed, Ahmed R

Obesity surgery

2024 Volume 34, Issue 5, Page(s) 1748–1755

Abstract: Purpose: Chronic abdominal pain after RYGB is a known issue. Identifying the potential patient-related and modifiable risk factors might contribute to diminish the risk for this undesirable outcome.: Methods: A single-center retrospective cohort ... ...

Abstract	Purpose: Chronic abdominal pain after RYGB is a known issue. Identifying the potential patient-related and modifiable risk factors might contribute to diminish the risk for this undesirable outcome. Methods: A single-center retrospective cohort study with prospective data collection was conducted with inclusion of all patients who underwent RYGB surgery between 2015 and 2021. Data from the NBSR and medical records were used. Patients with chronic abdominal pain were defined when pain lasting or recurring for more than 3 to 6 months. Results: Six hundred sixty-four patients who underwent RYGB surgery were included with a median follow-up of 60.5 months. Forty-nine patients (7.3%) presented with chronic abdominal pain. Postoperative complications (OR 13.376, p = 0.020) and diagnosis of depression (OR 1.971, p = 0.037) were associated with developing abdominal pain. On the other hand, ex-smokers (OR 0.222, p = 0.040) and older age (0.959, p = 0.004) presented as protective factors. Conclusion: Postoperative complications and diagnosis of depression are risk factors for chronic pain after RYGB. The role of the bariatric MDT remains crucial to select these patients adequately beforehand.
MeSH term(s)	Humans ; Obesity, Morbid/surgery ; Gastric Bypass/adverse effects ; Retrospective Studies ; Abdominal Pain/epidemiology ; Abdominal Pain/etiology ; Risk Factors ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-024-07193-6
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Article ; Online: Increased glycemic variability in pregnant women with Roux-en-Y gastric bypass compared with sleeve gastrectomy.

Alexiadou, Kleopatra / Ansari, Saleem / Jones, Bryony / Yu, Christina / Dornhorst, Anne / Oliver, Nick / Tsironis, Christos / Purkayastha, Sanjay / Ahmed, Ahmed / Agha-Jaffar, Rochan / Khoo, Bernard / Tan, Tricia M-M

BMJ open diabetes research & care

2024 Volume 12, Issue 1

Abstract: Introduction: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of ...

Abstract	Introduction: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes. Research design and methods: Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care. Results: Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9-7.8 mmol/L (70-140 mg/dL), compared with SG. Conclusions: Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.
MeSH term(s)	Infant, Newborn ; Humans ; Female ; Pregnancy ; Gastric Bypass/adverse effects ; Pregnant Women ; Blood Glucose Self-Monitoring ; Blood Glucose ; Pregnancy Outcome/epidemiology ; Gastrectomy/adverse effects
Chemical Substances	Blood Glucose
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2732918-5
ISSN	2052-4897 ; 2052-4897
ISSN (online)	2052-4897
ISSN	2052-4897
DOI	10.1136/bmjdrc-2023-003642
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Article: Cholecystectomy for Complicated Gallbladder and Common Biliary Duct Stones: Current Surgical Management.

Argiriov, Yanna / Dani, Melanie / Tsironis, Christos / Koizia, Louis J

Frontiers in surgery

2020 Volume 7, Page(s) 42

Abstract: Gallstone disease accounts for the vast majority of acute surgical admissions in the UK, with a major treatment being cholecystectomy. Practice varies significantly as to whether surgery is performed during the acute symptomatic phase, or after a period ... ...

Abstract	Gallstone disease accounts for the vast majority of acute surgical admissions in the UK, with a major treatment being cholecystectomy. Practice varies significantly as to whether surgery is performed during the acute symptomatic phase, or after a period of recovery. Differences in practice relate to operative factors, patient factors, surgeon factors and hospital and trust wide policies. In this review we summarize recent evidence on management of gallstone disease, particularly with respect to whether cholecystectomy should occur during index presentation or following recovery. We highlight morbidity and mortality studies, cost, and patient reported outcomes. We speculate on barriers to change in service delivery. Finally, we propose potential solutions to optimize care.
Language	English
Publishing date	2020-07-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2020.00042
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Article ; Online: Patient perspectives on surgeon-specific outcome reports in bariatric surgery.

Lam, Kyle / Nazarian, Scarlet / Gadi, Nishita / Hakky, Sherif / Moorthy, Krishna / Tsironis, Christos / Ahmed, Ahmed / Kinross, James M / Purkayastha, Sanjay

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

2022 Volume 18, Issue 6, Page(s) 704–713

Abstract: Background: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown.: ... ...

Abstract	Background: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown. Objectives: The aims of this study were to determine patient awareness, views and priorities for outcome reporting in bariatric surgery, and to provide recommendations for future surgeon-specific outcome reporting through the United Kingdom National Bariatric Surgery Registry. Setting: Bariatric surgical unit in a UK university teaching hospital. Methods: We adapted a previously validated questionnaire and surveyed the views of 150 patients in a single bariatric surgical unit. We collected data concerning awareness, views, and future priorities for outcome reporting. Results: A full 73% of participants were unaware they could access SSOR. Of the participants that were unaware, 75% stated that they would have accessed SSOR had they been aware they could. Of the participants that had previously accessed SSOR, 86% stated they understood the data, although 61% indicated it did not influence their choice of surgeon. The majority of participants favored public release of outcome reports at the surgeon-level (75%) and hospital-level (83%). The 3 main priorities indicated by participants for future outcome reporting were complication rates (91%), patient reported outcome measures (90%), and reoperation rate (89%), all at the surgeon level. Conclusion: Patient awareness of outcome reporting is poor. Efforts must be made to increase awareness of SSOR. Patients should be incorporated as key stakeholders in determining future outcome reporting in bariatric surgery.
MeSH term(s)	Bariatric Surgery ; Humans ; Patient Reported Outcome Measures ; Surgeons ; Surveys and Questionnaires ; United Kingdom/epidemiology
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2274243-8
ISSN	1878-7533 ; 1550-7289
ISSN (online)	1878-7533
ISSN	1550-7289
DOI	10.1016/j.soard.2022.02.020
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Article ; Online: Levodopa-induced dyskinesia in Parkinson's disease: still no proof? A meta-analysis.

Giannakis, Alexandros / Chondrogiorgi, Maria / Tsironis, Christos / Tatsioni, Athina / Konitsiotis, Spiridon

Journal of neural transmission (Vienna, Austria : 1996)

2018 Volume 125, Issue 9, Page(s) 1341–1349

Abstract: We investigated whether there is a linear relationship between levodopa (LD) dose and treatment duration, and the development of levodopa-induced dyskinesia (LID) among patients with early untreated Parkinson's disease (PD). We performed a meta-analysis ... ...

Abstract	We investigated whether there is a linear relationship between levodopa (LD) dose and treatment duration, and the development of levodopa-induced dyskinesia (LID) among patients with early untreated Parkinson's disease (PD). We performed a meta-analysis of randomized-controlled trials (RCTs) comparing LD monotherapy to any other antiparkinsonian treatment in early PD patients. Meta-regressions were conducted including as covariates the effects of LD dose, treatment duration, and age. We further proceeded in subgroup analyses based on the type of medications in the non-LD monotherapy (control) group and on whether patients in the control group received additional levodopa or not. Thirteen eligible RCTs were included, which revealed a significantly higher risk for dyskinesia in patients initially treated with LD monotherapy compared to any other treatment (OR = 2.82). None of the subsequent meta-regressions revealed any significant relationship with dose, treatment duration or age. Patients treated on LD monotherapy or MAOΙ plus LD were at a greater risk to develop LID than patients who received DA only or DA plus supplemental LD. The increased heterogeneity compromised the robustness of the results. The alleged correlation between LID and LD dose and treatment duration cannot be verified based on the data available so far. Well-designed, large-scale, long-term, RCTs on drug-naïve PD patients could allow the better comprehension of the pattern of the association between LID and LD treatment parameters.
MeSH term(s)	Antiparkinson Agents/administration & dosage ; Antiparkinson Agents/adverse effects ; Antiparkinson Agents/therapeutic use ; Causality ; Dose-Response Relationship, Drug ; Dyskinesia, Drug-Induced/etiology ; Humans ; Levodopa/administration & dosage ; Levodopa/adverse effects ; Levodopa/therapeutic use ; Parkinson Disease/drug therapy ; Parkinson Disease/physiopathology ; Randomized Controlled Trials as Topic ; Regression Analysis
Chemical Substances	Antiparkinson Agents ; Levodopa (46627O600J)
Language	English
Publishing date	2018-01-19
Publishing country	Austria
Document type	Journal Article ; Meta-Analysis
ZDB-ID	184163-4
ISSN	1435-1463 ; 0300-9564
ISSN (online)	1435-1463
ISSN	0300-9564
DOI	10.1007/s00702-018-1841-0
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Article ; Online: Bariatric Surgical Services Within a Pandemic Can Continue Safely: the Initial Experience of a UK Centre of Excellence.

Moussa, Osama / Ortega, Patricia / Mansour, Sami / Flod, Sara / Cousins, Jonathan / Hameed, Saira / Tan, Trisha / Miras, Alex / Chahal, Harvinder / Hakky, Sherif / Moorthy, Krishna / Tsironis, Christos / Ahmed, Ahmed / Purkayastha, Sanjay

Obesity surgery

2021 Volume 31, Issue 12, Page(s) 5483–5485

MeSH term(s)	Bariatric Surgery ; Bariatrics ; Humans ; Obesity, Morbid/surgery ; Pandemics ; United Kingdom
Language	English
Publishing date	2021-08-03
Publishing country	United States
Document type	Letter
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-021-05593-6
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Article: Investigation of the antidyskinetic site of action of metabotropic and ionotropic glutamate receptor antagonists. Intracerebral infusions in 6-hydroxydopamine-lesioned rats with levodopa-induced dyskinesia

Maranis, Sotirios / Stamatis, Dimitrios / Tsironis, Christos / Konitsiotis, Spiridon

European journal of pharmacology. 2012 May 15, v. 683, no. 1-3

2012

Abstract: Long-term levodopa replacement therapy in Parkinson's disease is confounded by abnormal involuntary movements, known as levodopa induced dyskinesia (LID). Dysfunctional glutamatergic neurotransmission has been implicated in the pathogenesis of LID making ...

Abstract	Long-term levodopa replacement therapy in Parkinson's disease is confounded by abnormal involuntary movements, known as levodopa induced dyskinesia (LID). Dysfunctional glutamatergic neurotransmission has been implicated in the pathogenesis of LID making metabotropic and ionotropic glutamate receptors attractive novel therapeutic targets. The objective of the present study was to investigate the antidyskinetic site of action of different glutamate receptor antagonists in the brain. For that purpose, metabotropic glutamate subtype 5 (3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride, MTEP), NMDA NR2B selective ((aR,bS)-a-(4-Hydroxyphenyl)-b-methyl-4-(phenylmethyl)-1-piperidinepropanol maleate, Ro 25-6981) and AMPA (2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt, NBQX) receptor antagonists or saline were administered by intracerebral infusion in the caudate–putamen (CPu), the substantia nigra zona reticulata (SNr) or the subthalamic nucleus (STN) of 6-hydroxydopamine-lesioned rats exhibiting LID. Dyskinesia was assessed with the modified version of the rat Abnormal Involuntary Movements scale (AIMS). Ro 25-6981 and to a lesser extent NBQX improved dyskinesia (82% and 19% reduction in AIM score respectively) after infusion in the caudate–putamen. None of the three drugs managed to noticeably reduce AIM score after infusion in the SNr. MTEP was the only drug that produced a reduction in AIM score (48%) when infused in STN. In conclusion, while the striatum proved important in the antidyskinetic action of NMDA and AMPA receptor antagonists, the results of this study highlight also the importance of the metabotropic glutamate receptors that reside in the STN as therapeutic targets in the treatment of LID.
Keywords	L-dopa ; Parkinson disease ; antagonists ; brain ; drugs ; dyskinesia ; glutamic acid ; maleates ; pathogenesis ; pyridines ; rats ; receptors ; therapeutics
Language	English
Dates of publication	2012-0515
Size	p. 71-77.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2012.02.036
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Article ; Online: Investigation of the antidyskinetic site of action of metabotropic and ionotropic glutamate receptor antagonists. Intracerebral infusions in 6-hydroxydopamine-lesioned rats with levodopa-induced dyskinesia.

Maranis, Sotirios / Stamatis, Dimitrios / Tsironis, Christos / Konitsiotis, Spiridon

European journal of pharmacology

2012 Volume 683, Issue 1-3, Page(s) 71–77

Abstract	Long-term levodopa replacement therapy in Parkinson's disease is confounded by abnormal involuntary movements, known as levodopa induced dyskinesia (LID). Dysfunctional glutamatergic neurotransmission has been implicated in the pathogenesis of LID making metabotropic and ionotropic glutamate receptors attractive novel therapeutic targets. The objective of the present study was to investigate the antidyskinetic site of action of different glutamate receptor antagonists in the brain. For that purpose, metabotropic glutamate subtype 5 (3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride, MTEP), NMDA NR2B selective ((aR,bS)-a-(4-Hydroxyphenyl)-b-methyl-4-(phenylmethyl)-1-piperidinepropanol maleate, Ro 25-6981) and AMPA (2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt, NBQX) receptor antagonists or saline were administered by intracerebral infusion in the caudate-putamen (CPu), the substantia nigra zona reticulata (SNr) or the subthalamic nucleus (STN) of 6-hydroxydopamine-lesioned rats exhibiting LID. Dyskinesia was assessed with the modified version of the rat Abnormal Involuntary Movements scale (AIMS). Ro 25-6981 and to a lesser extent NBQX improved dyskinesia (82% and 19% reduction in AIM score respectively) after infusion in the caudate-putamen. None of the three drugs managed to noticeably reduce AIM score after infusion in the SNr. MTEP was the only drug that produced a reduction in AIM score (48%) when infused in STN. In conclusion, while the striatum proved important in the antidyskinetic action of NMDA and AMPA receptor antagonists, the results of this study highlight also the importance of the metabotropic glutamate receptors that reside in the STN as therapeutic targets in the treatment of LID.
MeSH term(s)	Animals ; Anti-Dyskinesia Agents/administration & dosage ; Anti-Dyskinesia Agents/therapeutic use ; Disease Models, Animal ; Dyskinesia, Drug-Induced/drug therapy ; Dyskinesia, Drug-Induced/etiology ; Dyskinesia, Drug-Induced/physiopathology ; Excitatory Amino Acid Antagonists/administration & dosage ; Excitatory Amino Acid Antagonists/therapeutic use ; Infusions, Intraventricular ; Levodopa/adverse effects ; Male ; Oxidopamine ; Phenols/administration & dosage ; Phenols/therapeutic use ; Piperidines/administration & dosage ; Piperidines/therapeutic use ; Putamen/drug effects ; Quinoxalines/administration & dosage ; Quinoxalines/therapeutic use ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, AMPA/antagonists & inhibitors ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Substantia Nigra/drug effects ; Subthalamic Nucleus/drug effects ; Thiazoles/administration & dosage ; Thiazoles/therapeutic use
Chemical Substances	3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine ; Anti-Dyskinesia Agents ; Excitatory Amino Acid Antagonists ; NR2B NMDA receptor ; Phenols ; Piperidines ; Quinoxalines ; Receptor, Metabotropic Glutamate 5 ; Receptors, AMPA ; Receptors, Metabotropic Glutamate ; Receptors, N-Methyl-D-Aspartate ; Ro 25-6981 ; Thiazoles ; 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (118876-58-7) ; Levodopa (46627O600J) ; Oxidopamine (8HW4YBZ748)
Language	English
Publishing date	2012-05-15
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2012.02.036
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