Search Results (140)

Neuronal ceroid lipofuscinoses (NCLs) are paediatric neurodegenerative disorders that primarily affect the central nervous system (CNS). The high prevalence of gastrointestinal (GI) symptoms has prompted researchers and clinicians to move beyond an exclusively “brain-centric” perspective. At the molecular level, mutations in CLN genes lead to lysosomal dysfunction and impaired autophagy, resulting in intracellular accumulation of storage material that disrupts both central and enteric neuronal homeostasis. To systematically examine current clinical and preclinical knowledge on gut involvement in NCLs, with a focus on recent findings related to the enteric nervous system and gut microbiota. We conducted a systematic review following the PRISMA guidelines using PubMed as the sole database. Both clinical (human) and preclinical (animal) studies were included. A total of 18 studies met the inclusion criteria, focusing on gastrointestinal dysfunction, nervous system involvement, and gut microbiota. We found that the nature of GI symptoms was multifactorial in NCLs, involving not only the CNS but also the autonomic and enteric nervous systems, which were affected early by lysosomal deposits and enteric neuron degeneration. Of note, preclinical studies showed that gene therapy could improve not only CNS manifestations but also GI ones, which may have beneficial implications for patient care. While the role of the ENS seems to be clearer, that of gut microbiota needs to be further clarified. Current evidence from preclinical models highlighted alterations in the composition of the microbiota and suggested a possible influence on the progression and modulation of neurological symptoms. However, these results need to be confirmed by further studies demonstrating the causality of this relationship. GI involvement is a key feature of NCLs, with early impact on the enteric nervous system and possible links to gut microbiota. Although preclinical findings—particularly on gene therapy—are encouraging due to their dual impact on both CNS and GI manifestations, the causal role of the gut microbiota remains to be fully elucidated. In this context, the development of sensitive and specific outcome measures to assess GI symptoms in clinical trials is crucial for evaluating the efficacy of future therapeutic interventions. Full article

H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori. Full article

Celiac disease (CD) is a chronic and immune-mediated disorder triggered by the ingestion of gluten in some genetically predisposed individuals. CD can be associated with extra-gastrointestinal manifestations and diseases affecting several organs. In this review, the aim is to analyze and discuss the pancreatic alterations and/or comorbidities that could arise in the context of pediatric CD. Exocrine pancreatic insufficiency (EPI) can be observed in a variable fraction (up to 30%) of children diagnosed with CD at the diagnosis; indeed, it usually resolves after the implementation of a gluten-free diet (GFD). The main pathophysiological mechanisms of EPI could be represented by the impaired pattern of gastrointestinal hormones in CD patients. Conversely, pancreatitis seems to be a very rare comorbidity in CD children, since very few cases have been described in children. Therefore, there is no evidence that pancreatitis (including autoimmune forms) represents a relevant comorbidity in pediatric CD. Type 1 diabetes mellitus (T1DM) is a well-known and frequent comorbidity in CD children. The main determinant of this epidemiological association is the common HLA-related predisposing background, even if other (non-HLA-related) genetic and environmental factors (viruses, gut microbiome, and others) are likely to be also implicated in the development of both these autoimmune diseases. T1DM children with concomitant CD may experience specific challenges in the adherence to GFD, which has no negative impact on the glycemic and, in general, metabolic control of diabetes, if it is properly implemented and followed up. Full article

Malignant gastrointestinal neuroectodermal tumor (MGNET) and clear cell sarcoma (CCS) of soft tissue represent related, extremely rare, malignant mesenchymal neoplasms. Both entities are genetically characterized by the same molecular alterations, EWSR1::CREB1 fusions. Malignant gastrointestinal neuroectodermal tumor has significant morphological overlap with CCS, although it tends to lack overt features of melanocytic differentiation. Recently, rare MGNET cases were reported in extragastrointestinal sites. The diagnosis represents a major challenge and significantly impacts therapeutic planning. In this study, we reported the clinicopathologic features of a molecularly confirmed MGNET of the neck and provided a review of the pertinent literature. Full article

Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According to the International League of Associations for Rheumatology criteria, JSpAs include several specific forms: enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Despite established classifications, the terms and definitions surrounding these conditions can often lead to confusion among healthcare professionals. This ambiguity underscores the need for a standardized approach to nosological classification. The clinical presentation of JSpAs can be multifaceted, encompassing both articular and extra-articular manifestations. Articular symptoms may include enthesitis and varying forms of arthritis, while extra-articular involvement can range from uveitis to gastrointestinal, cardiovascular, pulmonary, neurological, and renal complications. These diverse manifestations highlight the systemic nature of the disease and the importance of a holistic approach to diagnosis and treatment. While laboratory tests for SpAs are often non-specific, imaging modalities such as musculoskeletal ultrasound and magnetic resonance imaging play a crucial role in the early detection of inflammatory lesions. These imaging techniques can provide valuable insights into disease progression and aid in the formulation of appropriate treatment plans. Current treatment guidelines advocate for a “stepwise” approach to therapy, beginning with nonsteroidal anti-inflammatory drugs and progressing to glucocorticoids, disease-modifying antirheumatic drugs, and biological agents, particularly anti-tumor necrosis factor alpha agents. The primary objective of treatment is to achieve clinical remission or, at a minimum, to attain low disease activity. Regular monitoring of disease activity is imperative; however, the lack of validated assessment tools for the pediatric population remains a significant challenge. JSpAs pose unique challenges in terms of diagnosis and management due to their diverse manifestations and the complexities of their classification. Ongoing research and clinical efforts are essential to refine our understanding of these conditions, improve treatment outcomes, and enhance quality of life for affected children and their families. Effective management hinges on early detection, individualized treatment plans, and continuous monitoring, ensuring that patients receive the most appropriate care tailored to their specific needs. Full article

Background/Objectives: Extra-gastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors arising outside the gastrointestinal tract, making up <5% of all GISTs. Rectovaginal EGISTs are particularly uncommon, with limited available data. This study systematically reviews the clinicopathological features, management, and outcomes of rectovaginal EGISTs. Methods: A systematic review of the English-language literature was conducted for studies on rectovaginal EGISTs (search date: 15 January 2025). Results: Thirty-one studies, including 40 female patients (mean age: 55.2 ± 15.4 years), met the inclusion criteria. Presenting symptoms included vaginal bleeding (24.3%), palpable mass (13.5%), constipation (10.8%), and abdominal pain (8.1%); however, the majority of patients (45.9%) were asymptomatic. Surgical excision was undertaken in 95% of patients, more often via local resection (61.1%). A high-grade mitotic index (>5/50 HPF) was noted in 63.2%. CD117, DOG-1, and vimentin was expressed in all cases, while CD34 was positive in 97.1%. Adjuvant therapy with tyrosine kinase inhibitors (TKIs) was administered in 57.5%, and neoadjuvant therapy was rare (8.6%). Recurrence occurred in 39.4% over a median follow-up of 40 ± 61.5 months, with a median disease-free survival (DFS) of 48 months. One death occurred 13 months postoperatively. Conclusions: Rectovaginal EGISTs are exceedingly rare and often asymptomatic, complicating preoperative diagnosis. Surgical resection remains the cornerstone of treatment, complemented by stage-specific neoadjuvant or adjuvant TKI therapy. The challenging location predisposes to recurrence, underscoring the need for further studies to optimize management and improve outcomes. Full article

The Blastocystis sp. is a common enteric parasite found in humans and various animals. Blastocystis spp. infections may be asymptomatic or symptomatic, with gastrointestinal and extra-intestinal symptoms, such as diarrhea, nausea, abdominal pain, bloating, vomiting, or anorexia. The disease leading to symptoms is usually observed in participants with immune deficiency. We report the case of weight loss and diarrhea in a Blastocystis sp. infection in a 64-year-old renal transplant recipient. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, frequently present with extra-intestinal manifestations. Virtually all patients with IBD could be at risk for developing inflammatory arthropathies within the spectrum of spondyloarthritis (SpA). In this context, prompt recognition of musculoskeletal “red flags” (lower back pain, dactylitis, enthesitis, swelling of peripheral joints, musculoskeletal chest pain, family history of SpA, psoriasis, and anterior uveitis) is crucial for early referral and multidisciplinary management by gastroenterologists and rheumatologists. Recent advances have refined diagnostic tools including questionnaires, alongside imaging modalities and laboratory markers, enhancing the detection of SpA in IBD patients. Effective treatment strategies targeting both gastrointestinal and musculoskeletal symptoms may significantly reduce long-term morbidity in these patients. In this narrative review, we aimed to underscore the importance of integrating clinical, diagnostic, and therapeutic approaches for optimal patient management and outcome over time. Full article

Radiolabelled fibroblast activation protein inhibitor (FAPI) tracers have the potential to overcome the limitations of 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and improve the diagnosis and staging of hepato-pancreato-biliary (HPB) cancers. This study aims to compare the diagnostic performance of radiolabelled FAPI versus [¹⁸F]FDG PET imaging in HPB cancers. A systematic search of PubMed, Embase, Web of Science and Cochrane Library was performed to identify eligible studies on the diagnostic performance of FAPI PET for primary HPB tumours (hepatocellular carcinoma (HCC), pancreatic cancer (PC) and biliary tract cancer (BTC)) and for liver metastases of gastrointestinal origin. The diagnostic performance was defined as a combination of detection rate and semi-quantitative tracer uptake. A random-effects model was used to calculate the risk differences. In total, 28 studies were included. Histopathology was the reference standard for the primary tumour in 26 studies (93%). The detection rate of radiolabelled FAPI in comparison to [¹⁸F]FDG was significantly higher in HCC (0.33, 95% CI: 0.20–0.47 and 0.34, 95% CI: 0.23–0.45) and BTC (0.27, 95% CI: 0.11–0.43 and 0.28, 95% CI: 0.08–0.48), in the patient- and lesion-based analyses, respectively. In PC, no differences were observed. Radiolabelled FAPI outperformed [¹⁸F]FDG in the lesion-based detection of lymph node, liver and extra-hepatic metastases. In all HPB cancers, the mean SUVmax was significantly higher with radiolabelled FAPI compared to [¹⁸F]FDG. Molecular imaging with FAPI PET seems to have several benefits over [¹⁸F]FDG PET in HPB cancer diagnostics, with an overall higher tracer uptake, and higher detection rates in HCC and BTC. Full article

Background: Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described. However, the research is moving fast, and new data regarding pathogenic pathways, patients’ classification, potential candidate biomarkers, and dietary interventions are emerging. Methods: This literature review aims to address the state of the art and summarize the latest updates in this field from 2019 to date. Results and Conclusions: Clinical studies regarding NCGWS in the last five years are reported to shed light on this complex condition and to guide specialists towards a more in-depth, prompt, and objective diagnosis. Full article

Background/Objectives: Functional dyspepsia is associated with abdominal pain and nausea, which leads to reduced quality of life, loss of productivity, and economic loss for patients. Itopride hydrochloride (itopride) stimulates the gastrointestinal smooth muscles, thereby promoting gastric emptying. It has been shown to significantly improve symptoms in patients with functional dyspepsia without severe side effects. Itopride has been available in Vietnam for many years; however, the cost-effectiveness of the drug has not been established. The aim of this study is to estimate the cost-effectiveness of itopride for the treatment of functional dyspepsia in Vietnam. Methods: A 3-stage Markov model with the following health states—controlled functional dyspepsia, uncontrolled functional dyspepsia, and dead—was developed. Functional dyspepsia was used to assess itopride over 10 years using 8-week cycles. A broader Vietnamese societal perspective was assumed for the analysis. Input was retrieved from the literature and through local clinical input from physicians in Vietnam. Output was reported as an incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY). A GDP/capita threshold (very cost-effective: 1 × GDP = Vietnamese Dong (VND) 64.1 M, cost-effective: 3 × GDP = VND 192.2 M) was used as recommended by the WHO in Vietnam. One-way and probabilistic sensitivity analyses were performed. Results: Itopride use resulted in an additional 0.28 QALYs at an extra cost of VND 11.2 M. This resulted in an ICER of VND 39.7 M per QALY, which is lower than the threshold of VND 192.2 M. One-way sensitivity analyses showed that the ICER was sensitive to varying the efficacy VND 31.8 M to VND 88.3 M), cost of itopride (ICER: VND 43.1 M to VND 56.5 M), and the health utility values (ICER: VND 45.2 M to VND 55.3 M). More than 80% of the simulations in the probabilistic sensitivity analysis were cost-effective at the 1 × GDP (VND 64.1 M) threshold, and 91.3% were cost-effective at the 3 × GDP (VND 192.2 M) threshold. Conclusion: This study shows that itopride hydrochloride is a very cost-effective treatment for functional dyspepsia in Vietnam, with the ICER (VND 39.7 M/QALY) being even lower than the 1 × GDP (VND 64.1 M) threshold. Full article

In mammals, the pineal hormone melatonin is the most powerful pacemaker of the master circadian clock and is responsible for reproduction in seasonal breeders. It is also well known that melatonin and its metabolites play antioxidant roles in many tissues, including reproductive cells. Melatonin synthesis and secretion from the pineal gland occurs during scotophase (the dark phase during a day–night cycle), while its inhibition is observed during photophase (period of light during a day–night cycle). Short-day breeders, such as goats, are stimulated to breed in a manner dependent on high endogenous levels of melatonin. This hormone can be synthesized in various extra-pineal tissues, such as retina, gastrointestinal tract, ovaries, and testis, with its main function being as a local antioxidant, given that melatonin and its metabolites are potent scavengers of reactive oxygen and nitrogen species. Moreover, it has been reported that some functions of melatonin can be exerted through plasma membrane and intracellular receptors expressed in the male reproductive system, including germ cells, immature and mature spermatozoa. It has been shown that melatonin may enhance gamete cryosurvival mainly by its addition into the media and/or in exogenous melatonin treatments in several species. In the present review, the physiological effects of endogenous melatonin in mammals are described, with a deeper focus on caprine reproduction. Additionally, results from recent investigations on the roles of exogenous melatonin aimed at improving the reproductive efficiency of goat bucks are discussed. There are contradictory findings and a limited amount of research available in the field of goat sperm cryopreservation associated with the use of melatonin. Understanding and improving goat reproduction and production is essential for many marginalized human populations around the world who directly depend on goats to maintain and improve their lifestyle. Full article

Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging, with a high rate of diagnostic error. We present a case of a peripancreatic mass identified by radiology as a gastrointestinal stromal tumor. Endoscopic ultrasound-guided fine-needle aspiration (FNA) of the mass showed a moderately cellular tumor composed of small-to-medium-sized neoplastic cells with round-to-oval nuclei arranged singly and in loose clusters. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin) and negative for CD117. A diagnosis of neoplasm with a neuroendocrine tumor (NET) was made based on FNA cytology. The subsequent surgical resection of the tumor revealed peripancreatic paraganglioma with immunohistochemistry positive for synaptophysin, chromogranin, and S100. The latter delineated the sustentacular cells. Although paraganglioma is a well-recognized tumor, a detailed comparison of peripancreatic paraganglioma versus pancreatic/gastrointestinal NET is still lacking. Full article

Background: Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal (GI) disorder characterized by abdominal pain, altered bowel habits, and bloating, affecting approximately 10.1% of the global population. While current treatments emphasize dietary modifications and symptom management, emerging evidence suggests that physical activity (PA) may help alleviate IBS symptoms. This study evaluated the effects of a structured walking program, “StepFit-18K”, on IBS symptom relief. Methods: A total of 106 participants (68 females and 38 males) completed the 12-week intervention, which consisted of 18,000 additional steps per week (6000 extra steps on three days per week) tracked via fitness devices. The program emphasized step count, ease of adoption, and social support through walking groups. Results: As assessed by validated questionnaires, significant reductions in GI symptoms were observed. The IBS Symptom Severity Score (IBS-SSS) decreased from 118.30 ± 98.73 to 74.46 ± 74.93, with a delta score of −43.84%, highlighting bloating as the most improved symptom. No clinically significant changes were observed in anthropometric or biochemical markers. Conclusions: StepFit-18K is a simple, accessible, and effective form of physical activity that has demonstrated therapeutic benefits for IBS symptoms. This offers an additional application beyond its well-established role in preventing cardiovascular diseases. Full article

Background/Objectives: This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. Methods: In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005–2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: <30 g/day, 30–50 g/day, and >50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Results: Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30–50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63–0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65–0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21–0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31–0.81). Conclusions: The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO’s potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet’s overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms. Full article