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1.
Diagnostics (Basel) ; 14(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39272697

RESUMO

The integration of artificial intelligence (AI) in medical diagnostics represents a significant advancement in managing upper gastrointestinal (GI) cancer, which is a major cause of global cancer mortality. Specifically for gastric cancer (GC), chronic inflammation causes changes in the mucosa such as atrophy, intestinal metaplasia (IM), dysplasia, and ultimately cancer. Early detection through endoscopic regular surveillance is essential for better outcomes. Foundation models (FMs), which are machine or deep learning models trained on diverse data and applicable to broad use cases, offer a promising solution to enhance the accuracy of endoscopy and its subsequent pathology image analysis. This review explores the recent advancements, applications, and challenges associated with FMs in endoscopy and pathology imaging. We started by elucidating the core principles and architectures underlying these models, including their training methodologies and the pivotal role of large-scale data in developing their predictive capabilities. Moreover, this work discusses emerging trends and future research directions, emphasizing the integration of multimodal data, the development of more robust and equitable models, and the potential for real-time diagnostic support. This review aims to provide a roadmap for researchers and practitioners in navigating the complexities of incorporating FMs into clinical practice for the prevention/management of GC cases, thereby improving patient outcomes.

2.
Gut ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39237127

RESUMO

The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe.There are several ways to decrease gastric cancer burden, but the screen and treat strategy for Helicobacter pylori (H. pylori) seems to be the most appropriate for Europe. It has to be noted that increased use of antibiotics would be associated with this strategy.Only organised population-based cancer screening is recommended in the European Union, therefore gastric cancer screening also is expected to fulfil the criteria of an organised screening programme. In this respect, several aspects of screening organisation need to be considered before full implementation of gastric cancer prevention in Europe; the age range of the target group, test types, H. pylori eradication regimens and surveillance strategies are among them. Currently, ongoing projects (GISTAR, EUROHELICAN, TOGAS and EUCanScreen) are expected to provide the missing evidence. Feedback from the decision-makers and the potential target groups, including vulnerable populations, will be important to planning the programme.This paper provides an overview of the recent decisions of the European authorities, the progress towards gastric cancer implementation in Europe and expected challenges. Finally, a potential algorithm for gastric cancer screening in Europe is proposed.

3.
Helicobacter ; 29(4): e13111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39001621

RESUMO

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento
4.
United European Gastroenterol J ; 12(6): 691-704, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685613

RESUMO

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.


Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Adesão à Medicação , Inibidores da Bomba de Prótons , Sistema de Registros , Humanos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Masculino , Adesão à Medicação/estatística & dados numéricos , Feminino , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Europa (Continente) , Adulto , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Resultado do Tratamento , Claritromicina/uso terapêutico , Idoso , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Bismuto/uso terapêutico , Bismuto/administração & dosagem , Bismuto/efeitos adversos
5.
Dig Dis ; 42(3): 240-256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38493766

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY: Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES: There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.


Assuntos
Consenso , Infecções por Helicobacter , Helicobacter pylori , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/terapia , Humanos , África/epidemiologia , Prevalência
6.
J Breath Res ; 18(2)2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38467063

RESUMO

Volatilomics is a powerful tool capable of providing novel biomarkers for the diagnosis of gastric cancer. The main objective of this study was to characterize the volatilomic signatures of gastric juice in order to identify potential alterations induced by gastric cancer. Gas chromatography with mass spectrometric detection, coupled with headspace solid phase microextraction as the pre-concentration technique, was used to identify volatile organic compounds (VOCs) released by gastric juice samples collected from 78 gastric cancer patients and two cohorts of controls (80 and 96 subjects) from four different locations (Latvia, Ukraine, Brazil, and Colombia). 1440 distinct compounds were identified in samples obtained from patients and 1422 in samples provided by controls. However, only 6% of the VOCs exhibited an incidence higher than 20%. Amongst the volatiles emitted, 18 showed differences in their headspace concentrations above gastric juice of cancer patients and controls. Ten of these (1-propanol, 2,3-butanedione, 2-pentanone, benzeneacetaldehyde, 3-methylbutanal, butylated hydroxytoluene, 2-pentyl-furan, 2-ethylhexanal, 2-methylpropanal and phenol) appeared at significantly higher levels in the headspace of the gastric juice samples obtained from patients; whereas, eight species showed lower abundance in patients than found in controls. Given that the difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes or pathways, the former set can be considered potential biomarkers for gastric cancer, which may assist in developing non-invasive breath tests for the diagnosis of this disease. Further studies are required to elucidate further the mechanisms that underlie the changes in the volatilomic profile as a result of gastric cancer.


Assuntos
Neoplasias Gástricas , Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Testes Respiratórios/métodos , Biomarcadores/análise , Compostos Orgânicos Voláteis/análise , Microextração em Fase Sólida/métodos , Suco Gástrico/metabolismo
7.
Helicobacter ; 29(2): e13064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38459689

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection is the most extensively studied risk factor for gastric cancer. As with any bacteria, H. pylori will release distinctive odors that result from an emission of volatile metabolic byproducts in unique combinations and proportions. Effectively capturing and identifying these volatiles can pave the way for the development of innovative and non-invasive diagnostic methods for determining infection. Here we characterize the H. pylori volatilomic signature, pinpoint potential biomarkers of its presence, and evaluate the variability of volatilomic signatures between different H. pylori isolates. MATERIALS AND METHODS: Using needle trap extraction, volatiles in the headspace above H. pylori cultures were collected and, following thermal desorption at 290°C in a splitless mode, were analyzed using gas chromatography-mass spectrometry. The resulting volatilomic signatures of H. pylori cultures were compared to those obtained from an analysis of the volatiles in the headspace above the cultivating medium only. RESULTS: Amongst the volatiles detected, 21 showed consistent differences between the bacteria cultures and the cultivation medium, with 11 compounds being elevated and 10 showing decreased levels in the culture's headspace. The 11 elevated volatiles are four ketones (2-pentanone, 5-methyl-3-heptanone, 2-heptanone, and 2-nonanone), three alcohols (2-methyl-1-propanol, 3-methyl-1-butanol, and 1 butanol), one aromatic (styrene), one aldehyde (2-ethyl-hexanal), one hydrocarbon (n-octane), and one sulfur compound (dimethyl disulfide). The 10 volatiles with lower levels in the headspace of the cultures are four aldehydes (2-methylpropanal, benzaldehyde, 3-methylbutanal, and butanal), two heterocyclic compounds (2-ethylfuran and 2-pentylfuran), one ketone (2-butanone), one aromatic (benzene), one alcohol (2-butanol) and bromodichloromethane. Of the volatile species showing increased levels, the highest emissions are found to be for 3-methyl-1-butanol, 1-butanol and dimethyl disulfide. Qualitative variations in their emissions from the different isolates was observed. CONCLUSIONS: The volatiles emitted by H. pylori provide a characteristic volatilome signature that has the potential of being developed as a tool for monitoring infections caused by this pathogen. Furthermore, using the volatilome signature, we are able to differentiate different isolates of H. pylori. However, the volatiles also represent potential confounders for the recognition of gastric cancer volatile markers.


Assuntos
Dissulfetos , Infecções por Helicobacter , Helicobacter pylori , Pentanóis , Neoplasias Gástricas , Humanos , Álcoois
8.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338911

RESUMO

The human body emits a multitude of volatile organic compounds (VOCs) via tissues and various bodily fluids or exhaled breath. These compounds collectively create a distinctive chemical profile, which can potentially be employed to identify changes in human metabolism associated with colorectal cancer (CRC) and, consequently, facilitate the diagnosis of this disease. The main goal of this study was to investigate and characterize the VOCs' chemical patterns associated with the breath of CRC patients and controls and identify potential expiratory markers of this disease. For this purpose, gas chromatography-mass spectrometry was applied. Collectively, 1656 distinct compounds were identified in the breath samples provided by 152 subjects. Twenty-two statistically significant VOCs (p-xylene; hexanal; 2-methyl-1,3-dioxolane; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; hexadecane; nonane; ethylbenzene; cyclohexanone; diethyl phthalate; 6-methyl-5-hepten-2-one; tetrahydro-2H-pyran-2-one; 2-butanone; benzaldehyde; dodecanal; benzothiazole; tetradecane; 1-dodecanol; 1-benzene; 3-methylcyclopentyl acetate; 1-nonene; toluene) were observed at higher concentrations in the exhaled breath of the CRC group. The elevated levels of these VOCs in CRC patients' breath suggest the potential for these compounds to serve as biomarkers for CRC.


Assuntos
Neoplasias Colorretais , Compostos Orgânicos Voláteis , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Testes Respiratórios/métodos , Compostos Orgânicos Voláteis/metabolismo , Biomarcadores/análise , Neoplasias Colorretais/diagnóstico
9.
Eur J Cancer Prev ; 33(1): 29-36, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38167662

RESUMO

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.


Assuntos
Adenocarcinoma , Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Gastrite Atrófica/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Células Parietais Gástricas/patologia , Gastrinas , Gastrite/diagnóstico , Gastrite/patologia , Mucosa Gástrica/patologia , Biomarcadores , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Infecções por Helicobacter/patologia
10.
Eur J Cancer Prev ; 33(3): 217-222, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37942999

RESUMO

BACKGROUND: Standard triple therapy is commonly prescribed Helicobacter pylori eradication regimen in Europe. However, the world is witnessing declines in eradication success. It is crucial to find better treatment options. AIMS: To evaluate efficacy, compliance and side effects of H. pylori eradication treatment by adding Saccharomyces boulardii . METHODS: We conducted a randomized clinical trial within the GISTAR cohort, consisting of healthy individuals aged 40-64 years. Participants were administered clarithromycin-containing triple therapy (clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg) twice daily. Randomization was applied based on two factors: 1)addition of Saccharomyces boulardii CNCM I-745 500 mg BID or not; 2)treatment duration of 10 or 14 days. Treatment completion and adverse events were assessed via telephone interview 21-28 days after medication delivery. The efficacy was evaluated using a 13C-urea breath test (UBT) six months after treatment. RESULTS: Altogether 404 participants were enrolled; data on adverse events were available from 391. Overall, 286 participants received follow-up UBT. Intention-to-treat analysis revealed higher eradication rates for 10-day probiotic treatment (70.8% vs. 54.6%, P  = 0.022), but not for 14-day. Probiotic subgroups combined showed non-significantly higher efficacy in per-protocol analysis (90.6% vs. 85.0%, P  = 0.183). S. boulardii reduced the frequency of adverse events ( P  = 0.033) in 14-day regimen, particularly treatment-associated diarrhea ( P  = 0.032). However, after the adjustment to control Type I error, results lost their significance. CONCLUSION: Addition of S. boulardii to 14-day clarithromycin-containing triple regimen non-significantly lowers the likelihood of diarrhea and does not increase the eradication rate.


Assuntos
Infecções por Helicobacter , Saccharomyces boulardii , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Claritromicina/efeitos adversos , Claritromicina/uso terapêutico , Diarreia , Suplementos Nutricionais , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Resultado do Tratamento , Adulto , Pessoa de Meia-Idade
11.
Am J Gastroenterol ; 119(4): 646-654, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983769

RESUMO

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Metronidazol/uso terapêutico , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto/uso terapêutico , Amoxicilina/uso terapêutico , Tinidazol , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos
12.
Diagnostics (Basel) ; 13(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958251

RESUMO

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related deaths worldwide. While CRC screening is already part of organized programs in many countries, there remains a need for improved screening tools. In recent years, a potential approach for cancer diagnosis has emerged via the analysis of volatile organic compounds (VOCs) using sensor technologies. The main goal of this study was to demonstrate and evaluate the diagnostic potential of a table-top breath analyzer for detecting CRC. Breath sampling was conducted and CRC vs. non-cancer groups (105 patients with CRC, 186 non-cancer subjects) were included in analysis. The obtained data were analyzed using supervised machine learning methods (i.e., Random Forest, C4.5, Artificial Neural Network, and Naïve Bayes). Superior accuracy was achieved using Random Forest and Evolutionary Search for Features (79.3%, sensitivity 53.3%, specificity 93.0%, AUC ROC 0.734), and Artificial Neural Networks and Greedy Search for Features (78.2%, sensitivity 43.3%, specificity 96.5%, AUC ROC 0.735). Our results confirm the potential of the developed breath analyzer as a promising tool for identifying and categorizing CRC within a point-of-care clinical context. The combination of MOX sensors provided promising results in distinguishing healthy vs. diseased breath samples. Its capacity for rapid, non-invasive, and targeted CRC detection suggests encouraging prospects for future clinical screening applications.

14.
Int J Mol Sci ; 24(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37895026

RESUMO

Despite rapid improvements in the accessibility of whole-genome sequencing (WGS), understanding the extent of human genetic variation is limited by the scarce availability of genome sequences from underrepresented populations. Developing the population-scale reference database of Latvian genetic variation may fill the gap in European genomes and improve human genomics research. In this study, we analysed a high-coverage WGS dataset comprising 502 individuals selected from the Genome Database of the Latvian Population. An assessment of variant type, location in the genome, function, medical relevance, and novelty was performed, and a population-specific imputation reference panel (IRP) was developed. We identified more than 18.2 million variants in total, of which 3.3% so far are not represented in gnomAD and dbSNP databases. Moreover, we observed a notable though distinct clustering of the Latvian cohort within the European subpopulations. Finally, our findings demonstrate the improved performance of imputation of variants using the Latvian population-specific reference panel in the Latvian population compared to established IRPs. In summary, our study provides the first WGS data for a regional reference genome that will serve as a resource for the development of precision medicine and complement the global genome dataset, improving the understanding of human genetic variation.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Letônia , Sequenciamento Completo do Genoma , Genoma Humano , Variação Genética , Genótipo
15.
Sci Rep ; 13(1): 17235, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821503

RESUMO

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Hipersensibilidade , Humanos , Idoso , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/efeitos adversos , Penicilinas/uso terapêutico , Resultado do Tratamento , Hipersensibilidade/tratamento farmacológico
16.
Antibiotics (Basel) ; 12(9)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37760723

RESUMO

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

17.
PLoS One ; 18(8): e0289879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561723

RESUMO

The spread of extended-spectrum beta-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians due to the limited therapeutic options for infections that are caused by these organisms. Here, we developed a panel of ESBL coding genes, evaluated the abundance and prevalence of ESBL encoding genes in patients undergoing H. pylori eradication therapy, and summarized the effects of eradication therapy on functional profiles of the gut microbiome. To assess the repertoire of known beta lactamase (BL) genes, they were divided into clusters according to their evolutionary relation. Primers were designed for amplification of cluster marker regions, and the efficiency of this amplification panel was assessed in 120 fecal samples acquired from 60 patients undergoing H. pylori eradication therapy. In addition, fecal samples from an additional 30 patients were used to validate the detection efficiency of the developed ESBL panel. The presence for majority of targeted clusters was confirmed by NGS of amplification products. Metagenomic sequencing revealed that the abundance of ESBL genes within the pool of microorganisms was very low. The global relative abundances of the ESBL-coding gene clusters did not differ significantly among treatment states. However, at the level of each cluster, classical ESBL producers such as Klebsiella sp. for blaOXY (p = 0.0076), Acinetobacter sp. for blaADC (p = 0.02297) and others, differed significantly with a tendency to decrease compared to the pre- and post-eradication states. Only 13 clusters were common across all three datasets, suggesting a patient-specific distribution profile of ESBL-coding genes. The number of AMR genes detected in the post-eradication state was higher than that in the pre-eradication state, which could be attributed, at least in part, to the therapy. This study demonstrated that the ESBL screening panel was effective in targeting ESBL-coding gene clusters from bacterial DNA and that minor differences exist in the abundance and prevalence of ESBL-coding gene levels before and after eradication therapy.


Assuntos
Helicobacter pylori , Infecções por Klebsiella , Humanos , Helicobacter pylori/genética , Prevalência , Klebsiella , Infecções por Klebsiella/microbiologia , Pacientes , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
18.
Molecules ; 28(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37630241

RESUMO

The human body releases numerous volatile organic compounds (VOCs) through tissues and various body fluids, including breath. These compounds form a specific chemical profile that may be used to detect the colorectal cancer CRC-related changes in human metabolism and thereby diagnose this type of cancer. The main goal of this study was to investigate the volatile signatures formed by VOCs released from the CRC tissue. For this purpose, headspace solid-phase microextraction gas chromatography-mass spectrometry was applied. In total, 163 compounds were detected. Both cancerous and non-cancerous tissues emitted 138 common VOCs. Ten volatiles (2-butanone; dodecane; benzaldehyde; pyridine; octane; 2-pentanone; toluene; p-xylene; n-pentane; 2-methyl-2-propanol) occurred in at least 90% of both types of samples; 1-propanol in cancer tissue (86% in normal one), acetone in normal tissue (82% in cancer one). Four compounds (1-propanol, pyridine, isoprene, methyl thiolacetate) were found to have increased emissions from cancer tissue, whereas eleven showed reduced release from this type of tissue (2-butanone; 2-pentanone; 2-methyl-2-propanol; ethyl acetate; 3-methyl-1-butanol; d-limonene; tetradecane; dodecanal; tridecane; 2-ethyl-1-hexanol; cyclohexanone). The outcomes of this study provide evidence that the VOCs signature of the CRC tissue is altered by the CRC. The volatile constituents of this distinct signature can be emitted through exhalation and serve as potential biomarkers for identifying the presence of CRC. Reliable identification of the VOCs associated with CRC is essential to guide and tune the development of advanced sensor technologies that can effectively and sensitively detect and quantify these markers.


Assuntos
1-Propanol , Neoplasias Colorretais , Humanos , 2-Propanol , Neoplasias Colorretais/diagnóstico
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