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Article ; Online: The Colorectal Cancer Screening Program in Romania - ROCCAS - is Ready for the Implementation at National Level.

Gheorghe, Cristian / Bunduc, Stefania

Journal of gastrointestinal and liver diseases : JGLD

2023 Volume 32, Issue 4, Page(s) 427–430

MeSH term(s)	Humans ; Romania/epidemiology ; Early Detection of Cancer ; Mass Screening ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology
Language	English
Publishing date	2023-12-21
Publishing country	Romania
Document type	Editorial
ZDB-ID	2427021-0
ISSN	1842-1121 ; 1841-8724
ISSN (online)	1842-1121
ISSN	1841-8724
DOI	10.15403/jgld-5329
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Article ; Online: GAVE: a gastroenterologist challenge.

Vadan, Roxana / Bunduc, Stefania / Gheorghe, Liana / Gheorghe, Cristian

Journal of gastrointestinal and liver diseases : JGLD

2021 Volume 30, Issue 1, Page(s) 168–169

MeSH term(s)	Gastroenterologists ; Gastroenterology ; Humans ; Hypertension, Portal ; Patient Readmission ; Renal Insufficiency, Chronic
Language	English
Publishing date	2021-03-13
Publishing country	Romania
Document type	Letter ; Comment
ZDB-ID	2427021-0
ISSN	1842-1121 ; 1841-8724
ISSN (online)	1842-1121
ISSN	1841-8724
DOI	10.15403/jgld-2921
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Article ; Online: No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis.

Horváth, István László / Bunduc, Stefania / Hankó, Balázs / Kleiner, Dénes / Demcsák, Alexandra / Szabó, Bence / Hegyi, Péter / Csupor, Dezső

Scientific reports

2023 Volume 13, Issue 1, Page(s) 2791

Abstract: Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and ... ...

Abstract	Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and meta-analysis we evaluated the association between the use of PPIs in the management of AP and various clinical outcomes. We conducted the systematic research in six databases without restrictions on January 24th, 2022. We investigated adult patient with AP, who were treated with PPI compared to conventional therapy. The pooled odds ratios, mean differences, and corresponding 95% confidence intervals were calculated with random effect model. We included six RCTs and three cohort studies, consisting of 28,834 patients. We found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI treatment. PPI use was associated with a higher risk of GI bleeding, however this finding could be due to the patients' comorbid conditions. We found no significant difference in the rates of 7-day mortality, length of hospital stay, and acute respiratory distress syndrome between the groups. The available data on this topic are limited; therefore, further well designed RCTs are needed to evaluate the potential benefits and adverse effects of PPIs in AP.
MeSH term(s)	Adult ; Humans ; Proton Pump Inhibitors/adverse effects ; Acute Disease ; Pancreatitis/drug therapy ; Peptic Ulcer/drug therapy ; Gastrointestinal Hemorrhage/drug therapy
Chemical Substances	Proton Pump Inhibitors
Language	English
Publishing date	2023-02-16
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-29939-5
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Article ; Online: Nabiximols is Efficient as Add-On Treatment for Patients with Multiple Sclerosis Spasticity Refractory to Standard Treatment: A Systematic Review and Meta-Analysis of Randomised Clinical Trials.

Kleiner, Dénes / Horváth, István László / Bunduc, Stefania / Gergő, Dorottya / Lugosi, Katalin / Fehérvári, Péter / Hegyi, Péter / Csupor, Dezső

Current neuropharmacology

2023 Volume 21, Issue 12, Page(s) 2505–2515

Abstract: Background: Spasticity affects 54% of multiple sclerosis (MS) patients at disease onset, but this rate gradually increases with disease progression. Spasticity does not fully respond to standard treatment in one-third of the patients.: Objective: Our ...

Abstract	Background: Spasticity affects 54% of multiple sclerosis (MS) patients at disease onset, but this rate gradually increases with disease progression. Spasticity does not fully respond to standard treatment in one-third of the patients. Objective: Our systematic review and meta-analysis assessed whether add-on nabiximols, can improve MS-associated refractory spasticity. Methods: The systematic literature search was performed in Web of Science, MEDLINE, Scopus, CENTRAL, and Embase, on 15/10/2021, without restrictions. We included in the review blinded, randomized, placebo-controlled trials evaluating the efficacy of nabiximols in adult MS patients with refractory spasticity, by comparison with placebo. The primary outcome was responder rate by spasticity numerical rating scale (NRS). Secondary outcomes were spasticity-related parameters. We used random effect models to calculate odds ratios (OR) or mean differences and the corresponding 95% CI. Bias-factors were assessed with Cochrane risk of bias tool (RoB2). (PROSPERO ID: CRD42021282177). Results: We identified 9 eligible articles, of which 7 (1128 patients) were included in the meta-analysis. The spasticity numerical rating scale (NRS) was significantly higher in the nabiximols group than in the placebo group (OR 2.41 (95% CI 1.39; 4.18)). Secondary outcomes were in accordance with our primary results. At least some concerns were detected in the risk of bias analysis. Conclusion: Our results indicate that nabiximols is efficient in MS associated spasticity, refractory to standard treatment and it may be considered as add-on symptomatic therapy. Nevertheless, further studies are needed to establish the optimal treatment protocol - dose, duration, moment of initiation, disease type.
MeSH term(s)	Adult ; Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/drug therapy ; Treatment Outcome ; Dronabinol/therapeutic use ; Cannabidiol/therapeutic use ; Muscle Spasticity/drug therapy ; Muscle Spasticity/chemically induced ; Muscle Spasticity/complications ; Randomized Controlled Trials as Topic
Chemical Substances	nabiximols (K4H93P747O) ; Dronabinol (7J8897W37S) ; Cannabidiol (19GBJ60SN5)
Language	English
Publishing date	2023-07-28
Publishing country	United Arab Emirates
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2192352-8
ISSN	1875-6190 ; 1570-159X
ISSN (online)	1875-6190
ISSN	1570-159X
DOI	10.2174/1570159X21666230727094431
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Article: Risk factors for diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis.

Zahariev, Olga Julia / Bunduc, Stefania / Kovács, Adrienn / Demeter, Dóra / Havelda, Luca / Budai, Bettina Csilla / Veres, Dániel Sándor / Hosszúfalusi, Nóra / Erőss, Bálint Mihály / Teutsch, Brigitta / Juhász, Márk Félix / Hegyi, Péter

Frontiers in medicine

2024 Volume 10, Page(s) 1257222

Abstract: Introduction: Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as ... ...

Abstract	Introduction: Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as high as 59% over time. However, information on risk factors is limited. We aimed to identify risk factors for developing PD or DM following AP. Methods: We systematically searched three databases up to 4 September 2023 extracting direct, within-study comparisons of risk factors on the rate of new-onset PD and DM in AP patients. When PD and DM event rates could not be separated, we reported results for this composite outcome as PD/DM. Meta-analysis was performed using the random-effects model to calculate pooled odds ratios (OR) with 95% confidence intervals (CI). Results: Of the 61 studies identified, 50 were included in the meta-analysis, covering 76,797 participants. The studies reported on 79 risk factors, and meta-analysis was feasible for 34 risk factor and outcome pairs. The odds of developing PD/DM was significantly higher after severe and moderately severe AP (OR: 4.32; CI: 1.76-10.60) than mild AP. Hypertriglyceridemic AP etiology (OR: 3.27; CI: 0.17-63.91) and pancreatic necrosis (OR: 5.53; CI: 1.59-19.21) were associated with a higher risk of developing PD/DM. Alcoholic AP etiology (OR: 1.82; CI: 1.09-3.04), organ failure (OR: 3.19; CI: 0.55-18.64), recurrent AP (OR: 1.89; CI: 0.95-3.77), obesity (OR: 1.85; CI: 1.43-2.38), chronic kidney disease (OR: 2.10; CI: 1.85-2.38), liver cirrhosis (OR: 2.48; CI: 0.18-34.25), and dyslipidemia (OR: 1.82; CI: 0.68-4.84) were associated with a higher risk of developing DM. Discussion: Severe and moderately severe AP, alcoholic and hypertriglyceridemic etiologies, pancreatic necrosis, organ failure, recurrent acute pancreatitis and comorbidities of obesity, chronic kidney disease liver disease, and dyslipidemia are associated with a higher risk of developing PD or DM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021281983.
Language	English
Publishing date	2024-01-09
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1257222
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Article ; Online: Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

Gulyás, Eszter / Horváth, István László / Engh, Marie Anne / Bunduc, Stefania / Dembrovszky, Fanni / Fehérvári, Péter / Bánvölgyi, András / Csupor, Dezső / Hegyi, Péter / Karvaly, Gellért Balázs

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7793

Abstract: An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making ... ...

Abstract	An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.
MeSH term(s)	Adult ; Humans ; beta-Lactams ; Critical Illness/therapy ; Drug Monitoring/methods ; Randomized Controlled Trials as Topic ; Anti-Bacterial Agents
Chemical Substances	beta-Lactams ; Anti-Bacterial Agents
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-58200-w
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Article ; Online: Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study.

Varzaru, Bianca / Iacob, Razvan Andrei / Bunduc, Stefania / Manea, Ioana / Sorop, Andrei / Spiridon, Andreea / Chelaru, Raluca / Croitoru, Adina / Topala, Mihaela / Becheanu, Gabriel / Dumbrava, Mona / Dima, Simona / Popescu, Irinel / Gheorghe, Cristian

International journal of molecular sciences

2024 Volume 25, Issue 5

Abstract: Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with ... ...

Abstract	Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank
MeSH term(s)	Humans ; Neutrophils/pathology ; Prognosis ; Prospective Studies ; Lymphocyte Count ; Lymphocytes/pathology ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Cell-Free Nucleic Acids ; Retrospective Studies
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2024-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25052854
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Article: Low molecular weight heparin decreases mortality and major complication rates in moderately severe and severe acute pancreatitis-a systematic review and meta-analysis.

Patoni, Cristina / Bunduc, Stefania / Frim, Levente / Veres, Dániel Sándor / Dembrovszky, Fanni / Éliás, Anna Júlia / Pálinkás, Dániel / Hegyi, Péter / Erőss, Bálint Mihály / Hegyi, Péter Jenő

Frontiers in medicine

2023 Volume 10, Page(s) 1241301

Abstract: Background: Routine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice.: Objectives: We aimed to analyze the efficacy and safety of adding ... ...

Abstract	Background: Routine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice. Objectives: We aimed to analyze the efficacy and safety of adding anticoagulants therapy to AP management. Methods: The systematic search was performed in three databases on the 14th of October 2022 without restrictions. Randomized controlled trials (RCTs) and observational studies that reported the differences in the outcomes of AP for patients receiving anticoagulants (intervention group) in addition to the standard of care (SOC), compared to patients managed by SOC alone (control group), were eligible. A random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding 95%-confidence intervals (CI). We performed subgroup analysis for study design and disease severity, among other criteria. Results: Of the 8,223 screened records, we included eight in the meta-analysis. Except one, all studies reported on low-molecular-weight heparin (LMWH). Both RCTs and observational studies reported results in favor of the LMWH group. Subgroup RCTs' analysis revealed significantly decreased odds of mortality [OR 0.24; 95%CI 0.17-0.34] and multiple organ failure [OR 0.32; 95%CI 0.17-0.62] in the intervention group. Moreover, the need for endoscopic or surgical interventions [OR 0.41; 95%CI 0.28-0.61] were significantly reduced by LMWH. The subgroup analyzes for moderate and severe cases, respectively, yielded similar results. Due to limited data, we could no perform subgroup analysis for mild cases. Conclusion: LMWH therapy reduces major complication rates in moderate and severe AP. Across all identified RCTs, LMWH were initiated early after AP diagnosis and improved its prognosis.
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1241301
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Article ; Online: Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis.

Éliás, Anna Júlia / Barna, Viktória / Patoni, Cristina / Demeter, Dóra / Veres, Dániel Sándor / Bunduc, Stefania / Erőss, Bálint / Hegyi, Péter / Földvári-Nagy, László / Lenti, Katalin

BMC medicine

2023 Volume 21, Issue 1, Page(s) 262

Abstract: Background: Probiotics are often used to prevent antibiotic-induced low-diversity dysbiosis, however their effect is not yet sufficiently summarized in this regard. We aimed to investigate the effects of concurrent probiotic supplementation on gut ... ...

Abstract	Background: Probiotics are often used to prevent antibiotic-induced low-diversity dysbiosis, however their effect is not yet sufficiently summarized in this regard. We aimed to investigate the effects of concurrent probiotic supplementation on gut microbiome composition during antibiotic therapy. Methods: We performed a systematic review and meta-analysis of randomized controlled trials reporting the differences in gut microbiome diversity between patients on antibiotic therapy with and without concomitant probiotic supplementation. The systematic search was performed in three databases (MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)) without filters on 15 October 2021. A random-effects model was used to estimate pooled mean differences (MD) with 95% confidence intervals (CI). This review was registered on PROSPERO (CRD42021282983). Results: Of 11,769 identified articles, 15 were eligible in the systematic review and 5 in the meta-analyses. Quantitative data synthesis for Shannon (MD = 0.23, 95% CI: [(-)0.06-0.51]), Chao1 (MD = 11.59 [(-)18.42-41.60]) and observed OTUs (operational taxonomic unit) (MD = 17.15 [(-)9.43-43.73]) diversity indices revealed no significant difference between probiotic supplemented and control groups. Lacking data prevented meta-analyzing other diversity indices; however, most of the included studies reported no difference in the other reported α- and ß-diversity indices between the groups. Changes in the taxonomic composition varied across the eligible studies but tended to be similar in both groups. However, they showed a potential tendency to restore baseline levels in both groups after 3-8 weeks. This is the first meta-analysis and the most comprehensive review of the topic to date using high quality methods. The limited number of studies and low sample sizes are the main limitations of our study. Moreover, there was high variability across the studies regarding the indication of antibiotic therapy and the type, dose, and duration of antimicrobials and probiotics. Conclusions: Our results showed that probiotic supplementation during antibiotic therapy was not found to be influential on gut microbiome diversity indices. Defining appropriate microbiome diversity indices, their standard ranges, and their clinical relevance would be crucial.
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Probiotics/adverse effects ; Dietary Supplements ; Anti-Bacterial Agents/adverse effects ; Dysbiosis
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-02961-0
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Article ; Online: Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing: A cohort analysis.

Bunduc, Stefania / Varzaru, Bianca / Iacob, Razvan Andrei / Sorop, Andrei / Manea, Ioana / Spiridon, Andreea / Chelaru, Raluca / Croitoru, Adina Emilia / Becheanu, Gabriel / Dumbrava, Mona / Dima, Simona / Popescu, Irinel / Gheorghe, Cristian

World journal of gastroenterology

2023 Volume 29, Issue 18, Page(s) 2864–2874

Abstract: Background: Genetic tests are increasingly performed for the management of unresectable pancreatic cancer. For genotyping aimed samples current guidelines recommend using core specimens, although based on moderate quality evidence. However, in clinical ... ...

Abstract	Background: Genetic tests are increasingly performed for the management of unresectable pancreatic cancer. For genotyping aimed samples current guidelines recommend using core specimens, although based on moderate quality evidence. However, in clinical practice among the endoscopic ultrasound (EUS) guided tissue acquisition methods, fine needle aspiration (FNA) is the most widely performed. Aim: To assess the adequacy for next generation sequencing (NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma (PDAC) samples. Methods: Between November 2018 and December 2021, 105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center. Either 22 gauge (G) or 19G FNA needles were used. One pass was dedicated to DNA extraction. DNA concentration and purity (A260/280, A260/230) were assessed by spectrophotometry. We assessed the differences in DNA parameters according to needle size and tumor characteristics (size, location) and the adequacy of the extracted DNA for NGS (defined as A260/280 ≥ 1.7, and DNA yield: ≥ 10 ng for amplicon based NGS, ≥ 50 ng for whole exome sequencing [WES], ≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and Results: Our cohort included 49% male patients, aged 67.02 ± 8.38 years. The 22G needle was used in 71% of the cases. The DNA parameters across our samples varied as follows: DNA yield: 1289 ng (inter quartile range: 534.75-3101), A260/280 = 1.85 (1.79-1.86), A260/230 = 2.2 (1.72-2.36). DNA yield was > 10 ng in all samples and > 100 ng in 93% of them (one sample < 50 ng). There were no significant differences in the concentration and A260/280 between samples by needle size. Needle size was the only independent predictor of A260/230 which was higher in the 22G samples ( Conclusion: EUS-FNA PDAC samples yield DNA adequate for subsequent NGS. DNA amount was similar between 22G and 19G FNA needles. DNA purity parameters may vary indirectly with needle size.
MeSH term(s)	Humans ; Male ; Female ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/genetics ; Pancreas/pathology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Adenocarcinoma/diagnostic imaging ; Adenocarcinoma/genetics ; Cohort Studies ; High-Throughput Nucleotide Sequencing ; Pancreatic Neoplasms
Language	English
Publishing date	2023-06-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v29.i18.2864
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