The efficacy of culture-guided versus empirical therapy with high-dose proton pump inhibitor as third-line treatment of Helicobacter pylori infection: A real-world clinical experience.

BACKGROUND AND AIM: Most consensuses recommend culture-guided therapy as third-line Helicobacter pylori treatment. This study aimed to investigate the efficacies of culture-guided therapy and empirical therapy with high-dose proton pump inhibitor (PPI) in the H. pylori third-line treatment. METHODS: Between August 2012 and October 2021, H. pylori-infected patients with at least two failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose rabeprazole and/or bismuth. They were categorized into three groups: patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy, patients who had positive results of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy, and patients who had a negative result of culture were treated by an empirical therapy with high-dose rabeprazole plus amoxicillin, tetracycline and levofloxacin. A post-treatment assessment was conducted at week 8. RESULTS: We recruited 126 patients. The eradication rates of culture-guided non-bismuth quadruple therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 84.0%, 87.0%, and 66.7% (95% confidence interval: 73.8-94.2%, 77.3-96.7%, and 49.8-83.6%), respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (85.4% vs 66.7%; 95% confidence interval, 0.4% to 37.0%, P = 0.022). CONCLUSIONS: Culture-guided therapy with high-dose PPI achieves a higher eradication rate than empirical therapy with high-dose PPI in the third-line treatment of H. pylori infection. The eradication rate of rescue therapy with bismuth plus two susceptible antibiotics is not inferior to that with three susceptible antibiotics.

Establishing the blood reference interval of pancreatic elastase-1: A prospective study.

BACKGROUND AND AIM: Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS: In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS: The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2  = 0.998) or frozen (R2  = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2  = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (ß = 0.106, P = 0.033), lipase (ß = 0.154, P = 0.007), and CA19-9 (ß = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION: The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Tailored susceptibility-guided therapy via gastric juice PCR for the first-line H. pylori eradication, a randomized controlled trial.

BACKGROUND/PURPOSE: Clarithromycin-based standard triple therapy is still commonly adopted by 81.4% of physicians in real-world practice but yields low eradication rates. Therefore, we conducted this study to compare the efficacy of gastric juice-guided therapy for first-line eradication with the standard triple therapy, in order to provide an alternative to real-world practice. METHODS: A total of 182 treatment-naïve Hp-infected patients were included and randomly allocated to either susceptibility-guided therapy (SGT) with gastric juice PCR or Clarithromycin-based standard triple therapy (STT) for 7 days. RESULTS: The intention-to-treat eradication rates were 89% (81/91) in SGT and 75.8% in STT (p < 0.031). The per-protocol eradication rates were 91.0% (81/89) in SGT and 79.3% (69/87) in STT (p < 0.034). Among the subgroups of different antibiotic resistance, patients with SGT demonstrated superior eradication rates (91.7% vs 45.5%, p < 0.027) in the subgroup of both clarithromycin resistance and levofloxacin resistance. CONCLUSION: This prospective randomized controlled trial demonstrated the reliable efficacy of susceptibility-guided therapy via gastric juice PCR for the first-line Hp eradication. In Asia-Pacific area, where standard triple therapy is still adopted by the majority of the physicians, it is a recommended alternative to overcome the increasing antibiotic resistance.

The impact of urine microbiota in patients with lower urinary tract symptoms.

INTRODUCTION: Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at - 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson's correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. RESULTS: We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman's correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05). CONCLUSION: Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.

Nutritional and dietary strategy in the clinical care of inflammatory bowel disease.

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Coronary Artery Spasm as Related to Anxiety and Depression: A Nationwide Population-Based Study.

OBJECTIVE: Anxiety and depression are risk factors for obstructive coronary artery disease (CAD), but their effects on coronary artery spasm (CAS) remain unestablished. METHODS: Patient records in this population-based study were retrospectively collected from the Taiwan National Health Insurance Research Database. Using propensity score matching, we used 1:1:1 ratio stratification into a control group of 10,325 individuals without CAS or CAD, a CAS group comprising 10,473 patients, and a CAD group comprising 10,473 patients during 2000-2012. RESULTS: The prevalence of CAS and CAD was 0.067% and 8.7%, respectively, in the general population. The prevalence of anxiety and depression diagnoses was significantly higher in patients with new-onset CAS than in those with new-onset CAD and controls without CAS/CAD, even after propensity score matching. Compared with CAD, anxiety and depression diagnoses conferred a higher risk of developing CAS (odds ratio [OR] = 2.29, 95% confidence interval [CI], 2.14-2.45, p < .001, and OR = 1.34, 95% CI, 1.08-1.66, p = .007, respectively). The association was even stronger when comparing CAS with the control group without CAD or CAS (OR = 5.20, 95% CI, 4.72-5.74, p < .001, and OR = 1.98, 95% CI, 1.50-2.62, p < .001, respectively). The increased risk of new-onset CAS as related to previous anxiety and depression diagnoses was comparable between males and females. CONCLUSIONS: Compared with CAD or the general population, anxiety and depression diagnoses confer a higher risk of developing CAS. No sex differences are found for the association of anxiety and depression with CAS.

Fecal microbiota transplantation: Review and update.

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.

Effects of Analyzer Detection Method, Ethnicity, and Reference Individuals on Reference Interval of Immature Platelet Fraction.

BACKGROUND: Immature platelet fraction (IPF) is a new biomarker for thrombopoiesis and inflammation. However, the reference interval (RI) is wildly discrepant among published reports. This study aimed to establish the RI of IPF for a population in Taiwan and evaluate the effects the detection method of the analyzer, ethnicity, and reference individuals have on the RI of IPF. METHODS: The RI of absolute IPF (A-IPF) and IPF% were established with healthy subjects from the outpatient services of the Health Management Department of Taichung Veterans General Hospital between January 1, 2015 and March 1, 2016. These values were used along with published reports for meta-analysis. RESULTS: A-IPF (109/L) and IPF% of Taiwanese were 6.9 - 7.6 and 3.1 - 3.4, respectively. Significant differences were found when performing paired comparisons of the RI of A-IPF and IPF% published in reports. For A-IPF, there was only one paired comparison with a significant difference (Z > 1.96) across 6 reports. Thus, the contribution of the factors examined on the RI of IPF cannot be determined. For IPF%, there were 8 paired comparisons with significant differences across 10 reports. The discrepancy rates of RI for IPF% were 41.2%, 50.0%, and 25.0% with the difference of reference individuals, the analyzer method, and ethnicity, respectively. CONCLUSIONS: The RIs of Taiwanese for A-IPF and IPF% were established. Furthermore, the analyzer detection method and the reference individuals contribute to the discrepancy of the RI for IPF% and should be considered cautiously when the value of IPF is interpreted.

Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease.

The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.

Confirmed False Positive Proteinuria in Patients with Systemic Lupus Erythematosus Taking Hydroxychloroquine: a Spot Sample Measurement.

BACKGROUND: A false-positive screening result is associated with harmful treatment or follow-up costs. This study aimed to estimate the rate of false positive proteinuria with the dipstick in patients with systemic lupus erythematosus (SLE) taking hydroxychloroquine. METHODS: A total of 334 patients with a positive dipstick and confirmed by total urine protein with quantification assay were enrolled. The experimental group included those with SLE taking hydroxychloroquine, and the rest was the control group. The difference of the rate of false positive in the dipstick was analyzed using the chi-square test and odds ratio (OR) between groups. Qualitative tracking of potential interference in the dipstick was performed. RESULTS: The results revealed that the rate of false positive with a dipstick for the experimental and control groups were 29.5% and 5.0% (p = 0.000), respectively. The OR with 95% confidence interval (CI) of the rate of false positive for the experimental group with respect to the control group was 5.95 (95% CI: 2.80 - 12.65). Qualitative tracking showed that the dipstick was influenced to become false-positive when hydroxychloroquine concentration was ≥ 30 mg/dL. CONCLUSIONS: Hydroxychloroquines like plaquenil or geniquin may lead to a high rate of false positive with the dipstick method. A quantification assay is recommended for proteinuria measurement in patients with SLE taking hydroxychloroquines.

A Point-of-Care Prothrombin Time Test on a Microfluidic Disk Analyzer Using Alternate Spinning.

In this study, we conducted a fully integrated point-of-care prothrombin time test on a microfluidic disk analyzer. The microfluidic functions integrated on the disk were capable of separating whole blood, decanting plasma, and mixing it with reagents in sequence under alternate spinning. The assay protocol was completed by alternate spinning without using microvalves or surface modification. Clinical sample tests on prothrombin time measurement were conducted by both the microfluidic disk analyzer and the reference instrument used in medical centers. The test results showed a good correlation and agreement between the two instruments.

Evaluating the performance of urine conductivity as screening for early stage chronic kidney disease.

BACKGROUND: This study aimed to determine if urine conductivity (Cond) is better for screening early stage chronic kidney disease (CKD) instead of the currently routinely used parameters of urine creatinine (UCr), urine osmolality (Osmo), urine specific gravity (SpGr), and urine protein (UP). METHODS: One hundred and forty participants (86 male, 54 female) with eGFR > 60 were grouped as either early stage CKD (kidney damage longer than 3 months with either structural or functional abnormalities [n = 72]) or the control group (without CKD and without kidney damage or functional abnormalities [n = 681]). Sensitivty (Sn) and specificity (Sp) of UP and the ROC curves were calculated. The area under the curve (AUC) with 95% confidence interval (CI) was used to compare Cond, UCr, Osmo, and SpGr. Pearson's correlation was used to analyze the correlation between Cond and UCr, Osmo, and SpGr in the early stage CKD group. RESULTS: The Sn and Sp of UP were 22.2% and 92.6%, respectively. By ROC analysis, Cond had the largest AUC (0.752, 95% CI: 0.672-0.832), with 52.9% Sn and 86.1% Sp. Pearson's correlation showed that the coefficient (p < 0.01) of Cond to UCr, Osmo, and SpG were 0.696, 0.907, and 0.820, respectively. CONCLUSIONS: Cond has better screening ability than UP for early stage CKD and may be a potential surrogate parameter for Osmo, SpGr and UCr.

Bloodstream Coinfections and Antimicrobial Resistance in Hospitalized COVID-19 Patients: A Single-center Retrospective Study.

BACKGROUND/AIM: Bloodstream infections in patients with COVID-19 are linked to higher mortality rates, whilst data on epidemiology and resistance patterns remains scarce to guide management and prevent antibiotic resistance. This research focuses on the prevalence, clinical features, causative microorganisms, and antimicrobial susceptibility of bacterial and fungal secondary bloodstream co-infections in hospitalized patients with COVID-19. PATIENTS AND METHODS: In this retrospective study analysis of 230 patients with COVID-19 from Central Taiwan (June 2021 to June 2022), pathogens were identified via MALDI-TOF MS and Vitek 2 system with Clinical & Laboratory Standards Institute (CLSI) standards. RESULTS: In the cohort, 17.8% experienced bloodstream infections, resulting in a total of 45 isolates from the 41 bloodstream infection patients: predominantly gram-positive bacteria (Staphylococcus and Enterococcus) at 69%, gram-negative at 29% (Escherichia coli and Klebsiella pneumoniae), and fungi at 2%. Infected patients showed significantly elevated levels of white blood count (WBC), C-reactive protein (CRP) and procalcitonin (PCT). Of note, resistance to common antibiotics, such as fluoroquinolones, cephalosporins, and oxacillin was significant, especially in K. pneumoniae, Acinetobacter species, and S. aureus infections. CONCLUSION: Our study highlights the influence of bacterial infections in hospitalized patients with COVID-19. The bacterial infections were discovered to impact the clinical trajectory of COVID-19, potentially exacerbating or mitigating its symptoms, severity and fatality. These insights are pivotal to addressing clinical challenges in COVID-19 management and underscoring the need for tailored medical interventions. Understanding these co-infections is thus essential for optimizing patient care and improving overall outcomes in the post COVID-19 pandemic era.

Determining cut-off values and predictors for the Snaith-Hamilton Pleasure Scale: comparison between clinical and school settings.

BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

End-of-life care costs and place of death across health and social care sectors.

OBJECTIVES: This study explores the relationship between end-of-life care costs and place of death across different health and social care sectors. METHODS: We used a linked local government and health data of East London residents (n=4661) aged 50 or over, deceased between 2016 and 2020. Individuals who died in hospital were matched to those who died elsewhere according to a wide range of demographic, socioeconomic and health factors. We reported mean healthcare costs and 95% CIs by care sectors over the 12-month period before death. Subgroup analyses were conducted to investigate if the role of place of death differs according to long-term conditions and age. RESULTS: We found that mean difference in total cost between hospital and non-hospital decedents was £4565 (95% CI £3132 to £6046). Hospital decedents were associated with higher hospital cost (£5196, £4499 to £5905), higher mental healthcare cost (£283, £78 to £892) and lower social care cost (-£838, -£1,209 to -£472), compared with individuals who died elsewhere. Subgroup analysis shows that the association between place of death and healthcare costs differs by age and long-term conditions, including cancer, mental health and cardiovascular diseases. CONCLUSION: This study suggests that trajectories of end-of-life healthcare costs vary by place of death in a differential way across health and social care sectors. High hospital burden for cancer patients may be alleviated by strengthening healthcare provision in less cost-intensive settings, such as community and social care.

Screening Cases of Suspected Early Stage Chronic Kidney Disease from Clinical Laboratory Data: The Comparison between Urine Conductivity and Urine Protein.

(1) Background: Chronic kidney disease (CKD) affects more than 800 million global population. Early detection followed by clinical management is among the best approaches for the affected individuals. However, a sensitive screening tool is not yet available. (2) Methods: We retrospectively reviewed 600 patients aged >20 years with a full range of estimated glomerular filtration rate (eGFR) for clinical assessment of kidney function between 1 January 2020, to 30 April 2021, at the Taichung Veterans General Hospital, Taichung, Taiwan. With stratified sampling based on the level of eGFR, participants were evenly grouped into training and validation sets for predictive modeling. Concurrent records of laboratory data from urine samples were used as inputs to the model. (3) Results: The predictive model proposed two formulae based on urine conductivity for detecting suspected early-stage CKD. One formula, P_male45, was for used male subjects aged ≥45 years, and it had a prediction accuracy of 76.3% and a sensitivity of 97.3%. The other formula, P_female55, was used for female subjects aged ≥55 years. It had a prediction accuracy of 81.9% and a sensitivity of 98.4%. Urine conductivity, however, had low associations with urine glucose and urine protein levels. (4) Conclusion: The two predictive models were low-cost and provided rapid detection. Compared to urine protein, these models had a better screening performance for suspected early-stage CKD. It may also be applied for monitoring CKD in patients with progressing diabetes mellitus.

Electroencephalographic Microstates are Correlated with Global Functioning in Schizophrenia But Not in Bipolar Disorder.

Objectives. Microstate studies of electroencephalograms (EEGs) on schizophrenia (SCZ) and bipolar disorder (BD) demonstrated categorical differences. The relationship between microstate indices and clinical symptoms in each group, however, remained unclear. Our objective was to examine associations between EEG microstates and the core features of SCZ and BD. Methods. This study examined the resting EEG data of 40 patients with SCZ, 19 patients with BD (12 BD type I and 7 BD type II), and 16 healthy controls. EEG topographic maps were divided into four canonical microstate classes: A, B, C, and D. The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale, Hamilton Depression Rating Scale (HAMD), and Global Assessment of Functioning (GAF) were used to measure clinical symptoms and global functioning. Results. There was a significant inverse correlation between the proportion of time spent in microstate class A and GAF in patients with SCZ but not BD. Furthermore, the occurrence of microstate class A was positively correlated with the Positive Scale scores of the PANSS. Nevertheless, there were no group differences between the microstate classes. Conclusions. The results of this study indicate a negative correlation between microstate class A and global functioning in SCZ but not in BD. The association may be mediated by positive symptoms of SZ. Neural mechanisms underlying this relationship require further investigation.

Reciprocal Regulation of Cancer-Associated Fibroblasts and Tumor Microenvironment in Gastrointestinal Cancer: Implications for Cancer Dormancy.

Gastrointestinal (GI) cancers remain a major cause of cancer-related deaths worldwide. Despite the progress made in current treatments, patients with GI cancers still have high recurrence rates after initial treatment. Cancer dormancy, which involves the entry and escape of cancer cells from dormancy, is linked to treatment resistance, metastasis, and disease relapse. Recently, the role of the tumor microenvironment (TME) in disease progression and treatment has received increasing attention. The crosstalk between cancer-associated fibroblasts (CAF)-secreted cytokines/chemokines and other TME components, for example, extracellular matrix remodeling and immunomodulatory functions, play crucial roles in tumorigenesis. While there is limited direct evidence of a relationship between CAFs and cancer cell dormancy, this review explores the potential of CAF-secreted cytokines/chemokines to either promote cancer cell dormancy or awaken dormant cancer cells under different conditions, and the therapeutic strategies that may be applicable. By understanding the interactions between cytokines/chemokines released by CAFs and the TME, and their impact on the entry/escape of cancer dormancy, researchers may develop new strategies to reduce the risk of therapeutic relapse in patients with GI cancers.