Immune pathway through endometriosis to ovarian cancer.

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. AIM: To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. METHODS: We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. RESULTS: The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. CONCLUSION: In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis.

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative. AIM: To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication. METHODS: We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. RESULTS: The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study. CONCLUSION: Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.

Helicobacter pylori infection: How does age influence the inflammatory pattern?

The inflammatory pattern during Helicobacter pylori (H. pylori) infection is changeable and complex. During childhood, it is possible to observe a predominantly regulatory response, evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-ß1 and IL-10, in addition to high expression of the transcription factor FOXP3. On the other hand, there is a predominance of cytokines associated with the Th1 and Th17 responses among H. pylori-positive adults. In the last few years, the participation of the Th17 response in the gastric inflammation against H. pylori infection has been highlighted due to the high levels of TGF-ß1 and IL-17 found in this infectious scenario, and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection. Moreover, this cytokine profile might play a pivotal role in the effectiveness of anti-H. pylori vaccines. It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H. pylori, and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.

Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral: Current knowledge.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 93 million cases and 2 million deaths in the world. SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community. However, a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations, such as diarrhea, nausea, vomiting, and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019. Furthermore, current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination. Moreover, studies have shown a high risk of contamination through hospital surfaces and personal fomites. Indeed, viable SARS-CoV-2 specimens can be obtained from aerosols, which raises the possibility of transmission through aerosolized viral particles from feces. Therefore, the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should be considered. In addition, a possible viral spread to sources of drinking water, sewage, and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern, especially in the least developed countries. Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces, studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and, then, to reinforce preventive measures against this infection, leading to a more satisfactory control of the incidence of the infection.