Hasil untuk "Diseases of the digestive system. Gastroenterology"

C. Marras, J. Beck, J. Bower et al.

Estimates of the prevalence of Parkinson’s disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson’s disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537–614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood. A large study that combines data from five different projects in four different regions across North America provides an updated estimate of the prevalence of Parkinson’s disease (PD). Connie Marras at Toronto Western Hospital in Canada and colleagues found that PD prevalence among individuals over 45 years of age is higher among men than women and that it increases with age in both sexes. They estimate that the overall prevalence of PD is 572 per 100,000 and that in the US in 2010 there were 680,000 individuals with PD. As life expectancy increases this number is projected to increase to over one million by 2030. These figures, which the authors note should be considered minimum prevalence estimates, warn of the impact that PD will have on North America’s healthcare systems in the near future.

Robert S. Sandler, James E. Everhart, Mark Donowitz et al.

Eliane Münte, Phillipp Hartmann

With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence has proposed the microbiota-derived metabolites short-chain fatty acids (SCFAs) as a potential factor in the pathophysiology of MASLD and related metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM). By influencing key pathways involved in energy homeostasis, insulin sensitivity, and inflammation, SCFAs play an important role in gut microbiota composition, intestinal barrier function, immune modulation, and direct metabolic signaling. Furthermore, recent animal and human studies on therapeutic strategies targeting SCFAs demonstrate their potential for treating these metabolic disorders.

Lin Y. Hung, Nuno D. Alves, Andrew Del Colle et al.

A. Sisó-Almirall, P. Brito-Zerón, Laura Conangla Ferrín et al.

Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors’ clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.

Ruiyun Sun, Xiaoqian Zhang, Junyan Qiao et al.

ABSTRACT Aims We aimed to analyze the characteristics of clinical features and hepatic injury characteristics of IM in different age groups. Methods A retrospective study was conducted on IM patients hospitalized in Beijing Youan Hospital, Capital Medical University from July 2015 to July 2025. General data, clinical features, and laboratory information were collected. Results Two hundred patients were enrolled, among them 49.5% were children, and 50.5% were adults. The results indicated that adults had longer fever duration (9 vs. 7 days) and hospitalization days (8 vs. 7 days), a higher proportion of splenomegaly (76.24% vs. 46.46%) and hepatic injury (99.01% vs. 67.68%) (all p < 0.05). Significant differences were observed between the two groups in the level of ALT (368 vs. 90 U/L) and AST (227 vs. 68 U/L) (all p < 0.05). No significant difference was observed between groups regarding gender, maximum temperature, sore throat, decreased appetite, tonsils covered with white membrane, hepatomegaly, hilar lymphadenopathy, leukocytes count, lymphocytes count, CRP, procalcitonin, albumin, EBV‐DNA, short lymph node diameter, CD4+ T cells, and CD8+ T cells (all p > 0.05). Conclusions Both adults and children typically present with the classic triad of IM. However, adults are more prone to prolonged fever, more prominent lymphadenopathy, and an increased incidence of splenomegaly. Hepatic injury is a common complication of IM, occurring with higher incidence and greater severity in adults compared to children; adults more frequently present with concurrent cholestasis and have a predisposition to developing severe liver injury.

Sebastián Eustaquio Martín Pérez, Hakim Al Lal Abdel Lah, Nelson Hernández García et al.

Nociplastic pain, commonly observed in conditions such as Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome, arises from altered central pain processing and involves complex mechanisms, including interactions between the gut–brain axis and immune dysregulation. Conventional therapies often fail to address this type of pain effectively, leading to interest in alternative approaches such as fecal microbiota transplantation. This technique has been proposed to restore gut microbial balance and modulate systemic inflammation, neuroinflammation, and neurotransmitter signaling. This systematic review, conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42024611939), evaluated 13 studies with n = 409 participants, including clinical trials, case reports, and retrospective analyses. A quality assessment was performed using appraisal tools such as Cochrane RoB 2, ROBINS-I, NOS, and CARE. The results suggest that fecal microbiota transplantation may reduce pain intensity and improve fatigue and quality of life, particularly in patients with Fibromyalgia and irritable bowel syndrome. However, outcomes for Chronic Fatigue Syndrome and psoriatic arthritis were inconsistent and limited by methodological flaws, small sample sizes, and variability in protocols and donor selection. Although adverse events were minimal, the current evidence is insufficient to support widespread clinical use. High-quality, standardized studies are needed to confirm the efficacy of fecal microbiota transplantation. Until then, its application should remain experimental and interpreted with caution.

Ester Ciociola, Tanmoy Dutta, Kavitha Sasidharan et al.

Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. The disease has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms that promote this protection. Methods We downregulated MARC1 in primary human hepatocytes (PHHs) using short interfering RNA (siRNA). We measured neutral lipid content by Oil-Red O staining and fatty acid oxidation by radiolabeled tracers. We also performed RNA-sequencing and proteomic analysis using LC-MS. Additionally, we analyzed data from 239,075 participants from the UK Biobank. Results Downregulation of MARC1 reduced neutral lipid content in PHHs homozygous for the wild type (p.A165, risk), but not for the mutant (p.T165, protective), allele. We found that this reduction was mediated by increased fatty acid utilization via β-oxidation. Consistent with these results, we found that the levels of 3-hydroxybutyrate, a by-product of β-oxidation, were higher in carriers of the rs2642438 minor allele among samples from the UK biobank, indicating higher β-oxidation in these individuals. Moreover, downregulation of the MARC1 p.A165 variant resulted in a more favorable phenotype by reducing ferroptosis and reactive oxygen species levels. Conclusions MARC1 downregulation in carriers of the risk allele results in lower hepatocyte neutral lipids content due to higher β-oxidation, while upregulating beneficial pathways involved in cell survival.

Rachel Geow, Gina Arena, Chiang Siah et al.

Background: An orodispersible form of budesonide has recently been approved for the targeted treatment of eosinophilic oesophagitis in the United Kingdom, Europe, Australia, Canada and the United States, following favourable results from a randomised controlled trial. This is the first dedicated real-world study exploring the safety and efficacy of budesonide orodispersible tablets for induction therapy in the treatment of eosinophilic oesophagitis while providing insights into its management. Objectives: The primary objective was histologic remission, defined as less than 5 eosinophils per high-powered field. The secondary objectives included histologic response (>50% reduction in peak eosinophil count), clinical remission (complete resolution of symptoms documented on clinic letters), clinical response (improvements in symptoms as reported on clinical letters), endoscopic remission (Endoscopic Reference Score (EREFS) score = 0), and endoscopic response (improvement in EREFS score). The EREFS scores were calculated based on the severity and presence of rings, longitudinal furrows, strictures, oedema and exudates on endoscopic images. Adverse events and safety profiles were also recorded. Design: A multicentre cohort study examining the effectiveness of 1 mg, twice daily, budesonide orodispersible tablet induction therapy for the treatment of eosinophilic oesophagitis. Methods: Ethics approval was obtained through the Western Australia Health: Governance, Evidence, Knowledge, Outcomes system for assessment of Audit and Quality Activities. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results: A total of 43 patients (29 males, 14 females; median age 39) were recruited. Forty-one patients were included in the analysis. After induction therapy, 30 patients (73%) achieved histologic remission, and 35 patients (85%) demonstrated histologic response. Thirty-nine patients (95%) achieved clinical response, and 28 patients (68%) achieved clinical remission. An endoscopic response was seen in 37 patients (90%), and 16 patients (39%) achieved endoscopic remission. No significant adverse events were identified. Conclusion: Budesonide orodispersible tablet is an effective induction therapy for eosinophilic oesophagitis, as evidenced by its high histologic remission rate and favourable safety profile.

Madhusmita Rout, D. Sanghera, ON BEHALF OF THE INVESTIGATORS OF THE AIDHS CONSORTIU

Background: Despite the success of genome-wide association studies (GWAS), the genetic mechanisms that predispose people to type 2 diabetes (T2D) remain poorly understood. Metabolomics has rapidly progressed from a single-gene/single-metabolite association to a genome-wide/metabolome-wide approach. However, limited data are available on non-white populations. Here, we have performed global lipidomic profiling and a targeted genetic association study to understand the genetic influences of T2D-associated variants on circulating lipid metabolites using a T2D cohort of Punjabi Sikhs from India. Methods: Untargeted lipidomic analysis was performed on blood samples of 3000 individuals (1723 T2D cases and 1277 controls) using liquid chromatography and high-resolution mass spectrophotometry (LC-MS). The association of T2D with 7463 (1743 known and 5720 unknown) metabolites was identified using multivariate mixed regression modeling. We further analyzed the association of 366 and 391 T2D-associated metabolites in serum and plasma, respectively, by conducting a GWAS using up to 14,959,825 million imputed SNPs as part of discovery and replication cohorts. Results: Our study identified 11 significant associations (p ranging from 6.8×10−10 to 4.8x10-20), including nine robust signals in the genes (TRPV4, RIPOR2, LDHC, MYRF, FADS1, and DNAH11) involved in transient receptor potential (TRP) channel, and calcium signaling pathways with the metabolites connected with energy metabolism, fatty acid transport, inflammation, and glucose metabolism. Conclusions: In our first metabolome-GWAS in Asian Indians, we have identified novel molecular signatures and pathways associated with T2D. If validated, these results can potentially contribute to developing new therapeutic strategies to improve the prediction and treatment of T2D. M. Rout: None. D.K. Sanghera: None. National Institutes of Health (R01DK082766, R01DK118427); National Institute of Diabetes and Digestive and Kidney Diseases grants from the Presbyterian Health Foundation of Oklahoma

Nhu Tung Tran, Quoc Thanh Truong, Khuyen Thi Nguyen et al.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of Langerhans cells, a type of dendritic cell essential for immune response. While LCH predominantly affects children, its manifestation in adults, especially within the gastrointestinal (GI) tract, is exceedingly rare. We present a unique case of a 56-year-old female with rare GI manifestations of LCH. The patient initially noticed pimple-like lesions around her anal orifice, which evolved into prominent protruding lesions over 3 months. Subsequent colonoscopy revealed multiple ulcers in the colorectal area, particularly concentrated in the sigmoid colon. Histopathological examination of biopsy samples, combined with immunohistochemical staining, confirmed the diagnosis of LCH. This case underscores the importance of a comprehensive diagnostic approach, especially when patients are present with atypical symptoms. The current literature suggests that such GI manifestations of LCH in adults are infrequent, making this case a valuable contribution to the understanding of LCH’s clinical spectrum. Plain language summary A rare case of a digestive system disorder in an adult featuring unusual bumps and ulcers Langerhans cell histiocytosis (LCH) is an uncommon disease where certain immune cells, called Langerhans cells, grow more than they should. This disease is mostly seen in children, but it’s very rare in adults, especially affecting the digestive tract. We discuss the case of a 56-year-old woman who had unusual symptoms, including bump-like lesions around the opening of her anus that turned into larger, protruding bumps over three months. She also had multiple ulcers, mainly in the lower part of her large intestine. A detailed examination of tissue samples from her digestive tract confirmed that she had LCH. This case highlights the need for thorough medical evaluations when adults have unusual symptoms in their digestive system. The findings from this case add to the limited information we have about how LCH can appear in adults, particularly in the digestive system.

K. Kostev, S. Kluge, Jens Bohlken

Background: Studies reported a higher in-hospital mortality in patients living with dementia (PlwD) with limited evidence across age groups, clinical departments and admission diagnoses. Study aim was to compare the in-hospital mortality rate of PlwD with non-demented controls across groups, clinical departments and admission diagnoses. Methods: This case-control study included patients aged ≥ 60 years hospitalized in one of 36 German hospitals between January 2019 and July 2023. PlwD were matched to non-demented controls. The associations between dementia and in-hospital mortality across groups were assessed using univariable logistic regression analyses. Results: 29,203patients with and 29,203 without dementia were included (mean age: 84 years, 60% female). PlwD had a significantly higher in-hospital mortality rate than non-dementia controls. The excess mortality rate was highest in the youngest age group (60–70 years), decreased with age, and became non-significant in the oldest age group (≥ 90 years). Significant differences were found for digestive system, cardiovascular and cerebrovascular disorders, endocrine, nutritional and metabolic diseases, and pneumonia, as well as for internal medicine and gastroenterology departments. Conclusion: The excess mortality rate was highest in younger age groups, where the general mortality and complication rate is relatively low in the general population. Appropriate approaches are needed.

S. Parasa, H. Patel, Kevin F. Kennedy

Nicola Reggidori, L. Bucci, V. Santi et al.

Background & Aims Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006–2020) in Italy. Methods Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006–2010; 2011–2015; 2016–2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and Implications Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients’ eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.

Daniel A. Kuppers, Jonathan Linton, Sergio Ortiz Espinosa et al.

Human CD34 + hematopoietic stem and progenitor cells (HSPCs) are a standard source of cells for clinical HSC transplantations as well as experimental xenotransplantation to generate “humanized mice”. To further extend the range of applications of these humanized mice, we developed a protocol to efficiently edit the genomes of human CD34 + HSPCs before transplantation. In the past, manipulating HSPCs has been complicated by the fact that they are inherently difficult to transduce with lentivectors, and rapidly lose their stemness and engraftment potential during in vitro culture. However, with optimized nucleofection of sgRNA:Cas9 ribonucleoprotein complexes, we are now able to edit a candidate gene in CD34 + HSPCs with almost 100% efficiency, and transplant these modified cells in immunodeficient mice with high engraftment levels and multilineage hematopoietic differentiation. The result is a humanized mouse from which we knocked out a gene of interest from their human immune system.

T. Torres, P. Filipe, F. Menezes Brandão et al.

INTRODUCTION Psoriasis is a common, chronic, and inflammatory skin disorder with a high personal, social and economic burden and important implications for healthcare systems. The aim of this study was to provide an epidemiological characterization of individuals with psoriasis in Portugal. MATERIAL AND METHODS A large observational, cross-sectional, nationwide, population-based survey study developed by the Portuguese Psoriasis Group of the Portuguese Society of Dermatology and Venereology (GPP-SPDV). A structured questionnaire was designed and applied by experienced interviewers to a random, representative sample of Portuguese individuals with psoriasis and/or psoriatic arthritis. Patients were considered to have psoriasis if they replied positively to one of the following questions: "Does any physician have ever diagnosed you with psoriasis?" or "Do you have a skin disorder characterized by scaling, reddish skin lesions located in the elbows/knees/scalp?". RESULTS A total of 6381 individuals were interviewed, of which 283 met the criteria for psoriasis, corresponding to a prevalence rate of 4.4% (95% CI 3.95 - 4.98). Out of the participants that met psoriasis criteria, 24% had suggestive signs/symptoms but did not have a clinical diagnosis established and were not being monitored by a physician. Although more than 70% of participants had active disease (scaling, erythema, or pruritus) and one third had joint symptoms, only 12% were on systemic treatment. Fifty percent of participants with psoriasis (n = 139) had relevant comorbidities (most frequently depression/anxiety and cardiometabolic diseases). Sixteen percent of participants with psoriasis (n = 46) reported that psoriasis interfered with their daily activities (median impact of 5 in a 0 - 10 scale) and 12% mentioned the disease had an impact in their sexual life (median impact of 5 in a 0 - 10 scale). CONCLUSION The results of this study suggest that the prevalence rate of psoriasis is likely to be high in Portugal, and several gaps exist at different levels of healthcare delivery to these patients, from diagnosis to treatment. This study provides important data for the future planning of interventions targeting the improvement of psoriasis care in Portugal.

D. Yelin, I. Margalit, M. Nehme et al.

Background: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients. Methods: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients’ characteristics, features of acute disease and effect on daily life were sought. Results: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5–9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status. Conclusion: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions.

Santhi Swaroop Vege

Muhammad B. Hammami, Nathalie H. Urrunaga

Swapnil Patel, Suman Ankathi, Purvi Haria et al.

Purpose The current study was conducted to examine the role of consolidation chemotherapy after neoadjuvant radiation therapy (NART) in decreasing the involvement of the mesorectal fascia (MRF) in high-risk locally advanced rectal cancers (LARCs). Methods In total, 46 patients who received consolidation chemotherapy after NART due to persistent MRF involvement were identified from a database. A team of 2 radiologists, blinded to the clinical data, studied sequential magnetic resonance imaging (MRI) scans to assess the tumor response and then predict a surgical plan. This prediction was then correlated with the actual procedure conducted as well as histopathological details to assess the impact of consolidation chemotherapy. Results The comparison of MRI-based parameters of sequential images showed significant downstaging of T2 signal intensity, tumor height, MRF involvement, diffusion restriction, and N category between sequential MRIs (P<0.05). However, clinically relevant downstaging (standardized mean difference, >0.3) was observed for only T2 signal intensity and diffusion restriction on diffusion-weighted imaging. No clinically relevant changes occurred in the remaining parameters; thus, no change was noted in the extent of surgery predicted by MRI. Weak agreement (Cohen κ coefficient, 0.375) and correlation (Spearman rank coefficient, 0.231) were found between MRI-predicted surgery and the actual procedure performed. The comparison of MRI-based and pathological tumor response grading also showed a poor correlation. Conclusion Evidence is lacking regarding the use of consolidation chemotherapy in reducing MRF involvement in LARCs. The benefit of additional chemotherapy after NART in decreasing the extent of planned surgery by reducing margin involvement requires prospective research.