UC Groups Research Articles

A comparative effectiveness study of usual care, simple Chuna manual therapy, and complex Chuna manual therapy for the treatment of pelvic biomechanical lesions in patients with non-acute low back pain: a protocol for multicenter, randomized controlled trial

BackgroundChuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care.MethodsThis is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments.DiscussionThis will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis.Trial registrationClinical Research Information Service (CRIS), KCT0009210. Registered on February 28, 2024.

National 30-Day Readmission Trends in IBD 2014-2020-Are We Aiming for Improvement?

Background: Inflammatory bowel disease (IBD) prevalence in Eastern Europe is increasing. The 30-day readmission rate is a crucial quality metric in healthcare, reflecting the effectiveness of initial treatment and the continuity of care post-discharge; however, such parameters are rarely analyzed. The aim of this study was to explore the trends in 30-day readmissions among patients with inflammatory bowel disease in Latvia between 2014 and 2020. Methods: This is a retrospective trends study in IBD-ulcerative colitis and Crohn's disease (UC and CD)-patients in Latvia between 2014 and 2020, involving all IBD patients identified in the National Health service database in the International Classification of Diseases-10 (ICD) classification (K50.X and K51.X) and having at least one prescription for IBD diagnoses. We assessed all IBD-related hospitalizations (discharge ICD codes K50X and K51X), as well as hospitalizations potentially related to IBD comorbidities. We analyzed hospitalization trends and obtained the 30 day all-cause readmission rate, disease specific readmission rate and readmission proportion for specific calendar years. Trends in readmissions and the mean length of stay (LOS) for CD and UC were calculated. Results: Despite a decrease in admission rates observed in 2020, the total number of readmissions for CD and UC has increased. Female patients prevailed through the study period and were significantly older than male patients in both the CD and UC groups, p < 0.05. We noted that there was no trend for 30 day all-cause readmission rate for CD (p > 0.05); however, there was a statistically significant trend for 30 day all-cause readmission for UC patients (p-trend = 0.018) in the period from 2014 to 2019. There was a statistically significant trend for CD-specific readmission rate (p < 0.05); however, no statistically significant trend was observed for UC-specific readmission (p > 0.05). An exploratory analysis did not reveal any statistically significant differences between treated and not-treated IBD patients (p > 0.05). The increasing trend is statistically significant over the period 2014-2018 (p < 0.05); however, the trend interrupts in 2020, which can be associated with the COVID-19 global pandemic and the related changes in admission flows where the gastroenterology capacity was reallocated to accommodate increasing numbers of COVID-19 patients. More studies are needed to evaluate the long-term impact of COVID-19 pandemic and 30-day readmissions. No significant dynamics were observed in the mean total hospitalization costs over the 2014-2020 period.

Genomic comparison of urothelial mucinous adenocarcinoma and colorectal mucinous adenocarcinoma biomarkers and therapeutic implications.

650 Background: Urothelial mucinous adenocarcinoma (UC-MUC-AC), arising from the urothelium, is a rare condition (&lt;2%), typically presenting at an advanced stage with an unfavorable prognosis. The lack of a standard treatment protocol adds complexity, requiring the extension of treatments from UC or organ-specific MUC-AC such as colorectal. Notably, UC-AC bears a histopathological resemblance to intestinal tumors, constituting the predominant subtype. Alternatively, treatment decisions based on gene expression similarities in lieu of histological similarities are an evolving concept in rare cancers. This is an unexplored area in UC-MUC-AC treatment, prompting our hypothesis that an all-encompassing genomic profile could reveal analogous biomarkers shared with CRC-MUC-AC. Methods: Three techniques: DNA sequencing, RNA sequencing (WTS), and immunohistochemistry (IHC) sequencing (protein) with varying measures for gene expression were analyzed at Caris Life Sciences in Phoenix, AZ. Histopathology was used to categorize five cancer site groups: (1) UC arising in the bladder, ureter, urethra, or renal pelvis with any transitional cell carcinoma (TCC)-non-MUC-nonAC [N156 samples], (2) UC nonTCC-nonMUC-AC [N83], (3) UC-MUC-AC [N16], (4) CRC-MUC-AC [N3100] and (5) CRC nonMUC-AC [N38205]. Our primary aim was to determine which group was closest to Group 3, our control. Our secondary aim was to determine if Group 2 was genetically closer to Group 1 or 5. Only genes with positive expression were included in the cluster analysis. ANOVA analysis was conducted to further explore the relationships between the groups. A log transformation was performed to achieve normality. To further investigate pairwise comparisons, a post hoc Dunnett test was employed. Results: In our first analysis, Group 3 UC-MUC-AC gene expression ratio was predominately associated with UC Groups 1 &amp; 2 (24 of 33), and farther to CRC Groups 4 &amp; 5 (9/33) (all p-values &gt;0.05). In the second analysis, the ANOVA overall model comparing gene expression between the histological groups 1, 2 &amp; 5 was statistically significant (p=0.0018). The Dunnett test revealed a farther difference between Group 2, UC nonTCC-nonMUC adenocarcinoma, and 5, CRC non-MUC-AC (p-value =0.001), but closest between Group 2 and 1, UC-TCC-nonMUC-nonAC (p =0.100). Conclusions: Our findings indicate that next-generation sequencing technology has the potential to aid in treatment decisions based on the site of origin, such as UC-AC, rather than relying on traditional histopathological descriptive approaches for extrapolating evidence from treatment protocols used for other cancer origins like CRC. Future research on artificial intelligence could aid physicians with more informed treatment decisions by providing additional insight into how closely tumors match cancer types' genomic and transcriptomic signatures.

MORTALITY IN INFLAMMATORY BOWEL DISEASE: A LONGITUDINAL POPULATION-BASED STUDY IN THE UNITED STATES

Abstract INTRODUCTION Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract. Data are limited regarding how longevity in IBD compares to the general population. The aim of this study was to compare the mean age of death and causes of mortality between patients with IBD and the general population in a nationally representative cohort. METHODS A retrospective study using 2010-2019 data from the National Readmissions Database (NRD) was performed. We identified hospitalized patients with CD and UC using International Classification of Diseases (ICD) codes. We compared the mean age of death and most common causes of mortality in CD, UC, and non-IBD patients. RESULTS The mean age of in-hospital death was significantly lower in the CD group (64.60 years) compared to the UC and non-IBD groups (67.43 and 67.07 years, respectively, p&amp;lt;0.01). Among all age groups, the highest death rates were among those ages 71 through 80 years of age (p&amp;lt;0.01). The UC group had significantly higher rates of death associated with cardiovascular causes, including myocardial infarction, congestive heart failure and cardiovascular disease, and infectious causes, including Clostridioides difficile infection and sepsis. Death rates did not significantly differ among the groups for those with diagnoses of leukemia and lymphoma (p=0.20 and p=0.19, respectively). UC patients had the highest in-hospital rate of death per year from 2010-2019, followed by the CD and non-IBD groups. Common diagnoses associated with death across all ages in the CD, UC, and non-IBD groups included fluid/electrolyte imbalance, respiratory failure, anoxic brain injury, sepsis, and renal failure. CONCLUSION While those with UC had higher in-hospital death dates, those with CD were more likely to die younger compared to the general population. UC patients were more likely to die if diagnosed with cardiovascular disorders or infections. Investigation of factors that drive premature mortality in CD patients and higher rates of mortality in UC patients is crucial to guide practice improvements and for management of co-morbid conditions. Table 1 Patient demographics and hospital characteristics. Figure 1 Death rates comparing non-IBD, CD and UC groups with specific inpatient diagnoses. * p &amp;lt; 0.05.

Photobiomodulation Therapy Plus Usual Care Is Better than Usual Care Alone for Plantar Fasciitis: A Randomized Controlled Trial.

Plantar fasciitis (PF) results in pain-related disability and excessive healthcare costs. Photobiomodulation therapy (PBMT) has shown promise for decreasing both pain and disability related to PF. The purpose was to assess the clinical impact of PBMT on pain and function in people with PF. Prospective, randomized controlled clinical trial. A convenience sample of adults with PF were randomly assigned to one of three groups: (1) usual care, (2) usual care plus nine doses of PBMT with 25W output power over three weeks, or (3) usual care plus nine doses of PBMT with 10W output power over three weeks. Both 10W and 25W PBMT participants received the same total dose (10J/cm2) by utilizing a simple area equation. Pain (with Defense and Veterans Pain Rating Scale) and function (by Foot and Ankle Ability Measure) were measured at baseline, weeks 3, and 6 for all groups, and at 13 and 26 weeks for PBMT groups. PBMT groups experienced a reduction in pain over the first three weeks (from an average of 4.5 to 2.8) after which their pain levels remained mostly constant, while the UC group experienced a smaller reduction in pain (from an average of 4 to 3.8). The effects on pain were not different between PBMT groups. PBMT in both treatment groups also improved function more than the UC group, again with the improvement occurring within the first three weeks. Pain and function improved during the three weeks of PBMT plus UC and remained stable over the following three weeks. Improvements sustained through six months in the PBMT plus UC groups. Level II- RCT or Prospective Comparative Study.

Early Rhythm Control Strategy in Early Atrial Fibrillation Patients.

Atrial fibrillation (AF) pharmaceutical treatment strategy on when to start rhythm control has been debated for decades. In early studies, these 2 strategies exhibited equivalent efficacy; however, more recent studies based on CHA2DS2-VASc score indicated that early rhythm control (ERC) is more beneficial than UC. We hypothesized that ERC might benefit persons with AF in other cardiovascular outcomes, regardless of the CHA2DS2-VASc score. To elucidate this, we conducted the present study.A retrospective cohort study was conducted using the Yinzhou Regional Health Care Database. We included all patients diagnosed with AF within 1 year and excluded those without age/sex information, without ERC/UC treatment prescription, or with ongoing cancer. The primary outcome was major cardiovascular events (MACE). We used inverse probability of treatment weighting (IPTW) for covariate weighting.A total of 7,161 patients diagnosed with early-stage AF were included in this study. Of them, 2,248 and 4,913 were included in the ERC and UC groups, respectively. During the mean follow-up period of 3.2 years (27,945 person-year), and after IPTW, ERC showed significantly lower risk for MACE (HR: 0.75 [0.61, 0.96], P = 0.02) and heart failure (HF; HR: 0.71 [0.54, 0.95], P = 0.01). No significant results were obtained for stroke, cardiovascular death, or all-cause mortality.ERC is more beneficial to early-stage Persons with AF than UC for MACEs, particularly HF.

The effects of chiropractic adjustment on inattention, hyperactivity, and impulsivity in children with attention deficit hyperactivity disorder: a pilot RCT.

Attention deficit hyperactivity disorder (ADHD) is a neurobiological disorder characterized by inattention, hyperactivity, and impulsivity. We hypothesized that chiropractic adjustments could improve these symptoms by enhancing prefrontal cortex function. This pilot study aimed to explore the feasibility and efficacy of 4 weeks of chiropractic adjustment on inattention, hyperactivity, and impulsivity in children with ADHD. 67 children with ADHD were randomly allocated to receive either chiropractic adjustments plus usual care (Chiro+UC) or sham chiropractic plus usual care (Sham+UC). The Vanderbilt ADHD Diagnostic Teacher Rating Scale (VADTRS), Swanson, Nolan and Pelham Teacher and Parents Rating Scale (SNAP-IV), and ADHD Rating Scale-IV were used to assess outcomes at baseline, 4 weeks, and 8 weeks. Feasibility measures such as recruitment, retention, blinding, safety, and adherence were recorded. Linear mixed regression models were used for data analysis. 56 participants (mean age ± SD: 10.70 ± 3.93 years) were included in the analysis. Both the Chiro+UC and Sham+UC groups showed significant improvements in total and subscale ADHD scores at 4 weeks and 8 weeks. However, there were no significant differences between the two groups. This pilot study demonstrated that it was feasible to examine the effects of chiropractic adjustment when added to usual care on ADHD outcomes in children. While both groups showed improvements, the lack of significant between-group differences requires caution in interpretation due to the small sample size. Further research with larger samples and longer follow-up periods is needed to conclusively evaluate the effects of chiropractic adjustments on ADHD in children.

Evaluation of an early-stage prototype polyurethane femoral head implant for hip arthroplasty

IntroductionThi study evalautes a new bone-preserving femoral head cover that mimics the articular cartilage of the femoral head. MethodsA specially developed polyurethane (PU) was evaluated in biocompatibility (cytotoxicity test) and mechanical response to tensile loading. In the cytotoxicity test, steam sterilized (SS) and ethylene oxide sterilized (EtO) PU samples were incubated separately in a cell culture medium. The seeded cell line MG-63 was then added to these sample-incubated cell culture mediums. One negative control group and one positive control group were also evaluated. The cells in each group were cultured for seven days before being quantified using the alamarBlue assay. In the mechanical test, the femoral head cover implants were separated into three groups of three samples. Each group represented a different implant insertion idea: direct insertion (uc sample) and another two insertion modes (is and ss samples) representing implants with enclosure mechanisms. The test consisted of distance-controlled cyclic tensile loadings followed by a failure test. ResultsThe cytotoxicity test results show no significant difference in fluorescence intensity between the negative control, the three SS groups, and one EtO group (P > 0.05). However, the other two EtO groups exhibit significantly lower fluorescence intensity compared with the negative control (P < 0.05). In the mechanical test, the is samples have the highest cyclic loading force at 559.50 ± 51.41 N, while the uc samples exhibit the highest force in the failure test at 632.16 ± 50.55 N. There are no significant differences (P > 0.05) among the uc, is, and ss groups in terms of stiffness. ConclusionThe cytotoxicity test and the mechanical experiment provide initial assessments of the proposed PU femoral head cover implant. The evaluation outcomes of this study could serve as a foundation for developing more functional design and testing methods, utilizing numerical simulations, and developing animal/clinical trials in the future.

Molecular analyses of ADAMTS-1, -4, -5, and IL-17 a cytokine relationship in patients with ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease that develops due to the impaired immune response in genetically susceptible individuals, and its etiopathogenesis is not fully elucidated. IL-17 A is a cytokine that is produced by a type of immune cell called Th17 cells and is involved in the immune response and inflammation. On the other hand, ADAMTS-1, -4, and − 5 are enzymes that are involved in the breakdown of extracellular matrix proteins, including proteoglycans, which are important components of the intestinal wall. This study aimed to evaluate the relationship between interleukin 17 (IL-17 A) cytokine, which plays a role in the pathogenesis of ulcerative colitis, and the inflammation-controlled a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1, -4, and − 5 protein members.MethodsBowel tissue samples and blood serum from 51 patients with UC and 51 healthy controls were included in this study. mRNA expression levels of the ADAMTS-1, -4, -5, and IL-17 A were analyzed by RT-qPCR, and immunohistochemical analyses were performed to evaluate ADAMTS-1, -4, -5, and IL-17 A proteins in tissue samples. In addition, ELISA analysis determined serum levels of the ADAMTS-1, -4, -5, and IL-17 A.ResultsRT-qPCR results reveal that the expression of ADAMTS-1, -4, -5, and IL-17 A genes in the UC tissue samples were significantly high according to the control tissue samples. Also, ADAMTS-1, -4, -5, and IL-17 A proteins revealed enhanced expression pattern UC groups according to the control. Also, ADAMTS-1, -4, -5, and IL-17 A protein showed cytoplasmic localization patterns in both control and UC groups. The serum levels of ADAMTS-1,-5, and IL-17 A were significantly higher in UC samples than in the control group.ConclusionsWe observed a positive correlation between the ADAMTS-1, -5 and IL17A cytokine expression in UC samples. These results provide a new understanding of controlling crucial ADAMTS family protein members by IL-17 A cytokines with UC.

Serum long noncoding RNA H19/micro RNA-675-5p axis as a probable diagnostic biomarker in inflammatory bowel disease

BackgroundA significant body of research strengthens the starring role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the diagnostic utility of lncRNA H19 and miRNA-675-5p in IBD.MethodsThis study included 97 participants, thirty-five ulcerative colitis patients, thirty-two Crohn’s disease patients, and thirty IBD-free controls. History, staging, laboratory investigations, and colonoscopy were performed. Also, quantitative real-time PCR (qPCR) for revealing of lncRNA H19 and miRNA-675-5p was done.ResultsThe estimated serum levels for H19 and miRNA-675-5p in the UC and CD groups in comparison to the control group showed a high statistical difference (P = 0.0001 for each parameter). Based upon the severity of UC patients, both biomarkers showed significantly higher values between remission and moderate cases, with p-values 0.022 and 0.02, respectively. Meanwhile, in CD patients, both biomarkers revealed no statistical significance between remission and any active stage of the disease. Additionally, ROC analysis revealed that H19 could discriminate between UC and control subjects with 94.3% sensitivity and 90.0% specificity, and with 87.5% sensitivity, and 88.5% specificity in the CD group. Furthermore, miR-675-5p was able to discriminate between UC and control subjects with 85.7% sensitivity and 97.3% specificity and with 88.4% sensitivity, 95.2% specificity in the CD group. Logistic regression found a significant predictive utility of using miR-675-5p and H19 in IBD.ConclusionH19 and miRNA-675-5p can be used as diagnostic biomarkers in IBD, with superiority in UC patients with moderate activity.

Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis. By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs). Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients. We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.

Expression of IL-21 and IL-33 in Intestinal Mucosa of Inflammatory Bowel Disease: An Immunohistochemical Study.

Interleukins are considered to be potential therapeutic targets that can alter the prognosis and disease progression of IBD. IL-21 has proven to be involved in effector Th1, Th2 and Th17 responses. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of the colonic Tregs in animal models of colitis and patients with IBD. In this retrospective study, we have studied the expression of these interleukins, using immunohistochemistry, in 121 patients with moderate to severe IBD before and after treatment with biologics. The results were statistically processed using SPSSTM. Increased IL-21 expression was found in the UC and CD groups versus the controls. The IL-33 expression was found to be increased in the post-treatment UC and CD groups, suggesting a protective role of this interleukin against bowel inflammation. The IL-33 expression post-treatment was reversely correlated with the activity index score in CD patients, suggesting a better response to treatment in patients with higher IL-33 mucosa levels. This is the first immunohistochemical study of the expression of those interleukins in bowel mucosa before and after treatment with biologics. These data support a possibly promising future use of these interleukins as biomarkers of severe disease and response to treatment and as potential therapeutic targets for novel monoclonal antibodies.

Oligoelements in serum and intestinal tissue of pediatric IBD patients

IntroductionInflammatory bowel disease (IBD) develops through complex interplay of genetic, microbial, immune, and environmental factors. Trace elements alterations are commonly present in IBD and may have influence on IBD development. Heavy metal pollution is one of the major environmental issues nowadays and IBD incidence is rising in countries where industry starts to develop. Metals are implicated in processes that are connected to IBD pathogenesis. AimThe aim of this study was to investigate toxic and trace element levels in pediatric population of IBD patients both in serum and intestinal mucosa. Materials and methodsThis prospective study enrolled children newly diagnosed with IBD in University children’s hospital in Belgrade. Concentrations of thirteen elements: Al, As, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Se and Zn in serum and intestinal mucosa of 17 newly diagnosed children with IBD (10 Crohn’s disease (CD) and 7ulcerative colitis (UC)) and 10 controls were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Intestinal mucosa samples were taken from terminal ileum and six different colon segments (cecum, ascending colon, colon transversum, descending and sigmoid colon and rectum). ResultsThe results demonstrated significant alterations in serum and intestinal mucosa concentrations of investigated elements. Serum iron was significantly decreased in IBD and CD group, compared to controls while serum Cu significantly differed between three investigated groups with highest concentration observed in CD children. Serum manganese was the highest in the UC subgroup. Terminal ileums of IBD patients contained significantly lower amount of Cu, Mg, Mn and Zn with Mn being significantly decreased also in CD patients compared to control. IBD patients’ caecum contained significantly less Mg and Cu while colon transversum tissue samples from IBD and Crohn’s patients contained significantly more chromium than controls. Moreover, sigmoid colon of IBD patients were poorer in Mg than controls (p < 0.05). Colon Al, As and Cd were significantly reduced in IBD, and UC children compared to control. Correlations of investigated elements in CD and UC groups were different from controls. Biochemical and clinical parameters showed correlation with element concentrations in intestines. ConclusionSera of CD, UC and control children significantly differ in Fe, Cu and Mn levels. Serum manganese was the highest in the UC subgroup creating the most prominent and only significant difference between UC and CD subgroups. Terminal ileum of IBD patients contained significantly lower amount of majority of investigated essential trace elements and toxic elements were significantly reduced in colon of IBD and UC patients. Investigation of macro- and microelement alterations in children and adults has potential to further elucidate IBD pathogenesis.

Clinical significance of squamous differentiation in upper tract urothelial carcinoma treated with radical nephroureterectomy.

451 Background: Upper tract urothelial carcinoma (UTUC) involving the renal pelvis/ureter is histologically similar to bladder cancer in morphological diversity. Although squamous differentiation (SD) is the most common variant in UTUC, the clinical significance of SD in UC has yet to be comprehensively elucidated given the rarity of the disease compared to bladder cancer. To assess the impact of SD on the prognosis of patients with UTUC undergoing radical nephroureterectomy (RNU). Methods: Among the 244 consecutive patients who underwent RNU at our single institution from May 2005 to October 2019, only patients who had histologically confirmed pure UC or UC with SD (UCSD) were included. SD required the presence of intercellular bridges or keratinization for diagnosis. Metastasis-free survival (MFS) and overall survival (OS) rates were retrospectively evaluated using Kaplan–Meier analysis and Cox regression analysis. Results: We identified 197 (87.9%) and 27 (12.1%) patients with pure UC and UCSD, respectively. No significant differences in age, sex, concomitant carcinoma in situ and tumour grade were observed between the groups. UCSD was significantly associated with an advanced tumour stage and a higher rate of lymphovascular invasion. With a median follow-up time of 58 months, the pure UC and UCSD groups had a 5-year MFS rate of 65.2% and 40.9% ( p=0.005) and a 5-year OS rate of 74.4% and 49.0% ( p=0.002), respectively. Multivariate analyses revealed that the presence of SD was significantly associated with MFS [hazard ratio (HR), 1.88; p=0.027] and OS (HR, 1.70; p=0.048). Conclusions: The patients with UCSD are at high risk for disease metastasis and short-term survival. SD in UC could be an independent predictor of poor prognosis after RNU for UTUC.

P928 Identification of mucosal microbiome-host gene interactions in ulcerative colitis patients

Abstract Background With the development of NGS analysis, many studies have been performed on the role of gut microbiota in the pathogenesis of inflammatory bowel disease and the possibility of gut bacteria as a diagnosis and treatment modality for IBD. However, the role of gut microbiota in clinical applications such as markers for diagnosis, prognosis prediction and the therapeutic agents is still unclear, and further studies on host-microbe interactions are still needed. In this study, we tried to detect mucosal bacterial species which can discriminate between ulcerative colitis and normal control and the correlations between the microbiome and gene expression through integrated analysis of metagenomic sequencing and RNA-sequencing in the colonic mucosa of UC patients and normal controls. Methods Colonic tissues obtained from UC patients (n = 7) and normal control (n = 13) were subjected to 16S rRNA sequencing of the microbiome and next-generation sequencing (NGS) RNA-seq. The differentially expressed genes (DEGs) and DEGs-based enrichment terms were obtained. Gene set enrichment analysis (GSEA) and PathfindR were also used to reveal significant differences of meaningful gene sets. The datasets were analyzed individually and integrated including sociomedical factors for combined analysis using bioinformatics approaches. Correlation analyses were performed between microbiome and gene expression and network analysis were presented. Results From DEG results, 28 and 18 genes were higher expressed in the UC and normal groups, respectively. GSEA provided total 1,857 gene sets enriched in the UC group. We identified that patients with UC show decreased species such as Bacteroides coprocola, Bacteroides phlebeius, Parabacteroides merdae and increased abundance of other species, such as Eubacterium._eligens, Clostridium_clostridioforme, Faecalibacterium_prausnitzii. An integrative analysis identified immunomodulatory genes including HLA-G, PSMA4 for which gene expression is negatively correlated with Bacteroides species. Conclusion In addition to identifying mucosal microbiome and host-genes expression patterns in the UC patients, we showed the potential role of host-microbe interactions in the development of UC. These findings provided the integrated analysis of microbe- host gene can be served as a biomarker for diagnosis and treatment target in patients with UC.

Assessment of clinical and epidemiological data of inflammatory bowel disease in Egyptian children attending Mansoura University Children Hospital

Context Existing literature is poor with epidemiological studies handling Egyptian paediatric patients diagnosed with inflammatory bowel disease (IBD). Herein, we describe the epidemiological and clinical features of paediatric IBD cases (PIBD) attending Mansoura University Children Hospital (MUCH). Aim To evaluate epidemiological and clinical data of (PIBD) in Egyptian children. Settings and design This retrospective study included the data of Thirty-nine paediatric patients (age&lt;18 years) admitted to the gastroenterology ward of MUCH and divided into two groups; ulcerative colitis group (UC 32 cases) and Crohn disease group (CD 7 cases). Methods and material Data were retrospectively reviewed, including history, examination, biochemical, endoscopic, and pathological findings. Statistical analysis used: SPSS software (version 26 for macOS) to tabulate and analyse the collected data Results UC group had a mean age of 10.73 years compared to 13.2 years in the CD group (P=0.01). The prevalence of anoperineal disease significantly increased with CD. The age of symptom onset and diagnosis confirmation were insignificant between the same groups. Laboratory parameters were also comparable. Pancolitis and ileocolitis were the most common involvement patterns in the UC and CD groups, respectively. Pathologically, UC was distinguished by crypt abscess, while CD was distinguished by granulomas. Conclusions PIBD was related to the male sex, with early diagnosis and a low prevalence of the early-onset disease. Although it is crucial to exclude common infections causing similar manifestations, the paediatrician should consider the possibility of IBD.

Effectiveness of a Community-Based Structured Physical Activity Program for Adults With Type 2 Diabetes

The efficacy of physical activity interventions among individuals with type 2 diabetes has been established; however, practical approaches to translate and extend these findings into community settings have not been well explored. To test the effectiveness of providing varying frequencies of weekly structured exercise sessions to improve diabetes control. The IMPACT (Initiate and Maintain Physical Activity in Communities Trial) study was a controlled randomized clinical trial (randomization occurred from October 2016 to April 2019) that included a 6-month, structured exercise intervention either once or thrice weekly vs usual care (UC; advice only). The exercise intervention was conducted at community-based fitness centers. Follow-up visits were conducted in a university research clinic. Participants included adults with type 2 diabetes (hemoglobin A1c [HbA1c] 6.5%-13.0%, not taking insulin, and no precluding health issues). Data analysis was performed from January to April 2022. A once-weekly structured exercise group, a thrice-weekly structured exercise group, or UC. The primary outcome was HbA1c at 6 months. A total of 357 participants (143 women [40.1%]) with a mean (SD) age of 57.4 (11.1) years were randomized (119 each to the UC, once-weekly exercise, and thrice-weekly exercise groups). There was no significant difference in HbA1c change by study group in the intention-to-treat analysis at 6 months. Specifically, HbA1c changed by -0.23% (95% CI, -0.48% to 0.01%) in the thrice-weekly exercise group and by -0.16% (95% CI, -0.41% to 0.09%) in the once-weekly exercise group. A total of 62 participants (52.1%) in the once-weekly exercise group and 56 participants (47.1%) in the thrice-weekly exercise group were at least 50% adherent to the assigned structured exercise regimen and were included in the per-protocol analysis. Per-protocol analysis showed that HbA1c changed by -0.35% (95% CI, -0.60% to -0.10%; P = .005) at 3 months and by -0.38% (95% CI, -0.65% to -0.12%; P = .005) at 6 months in the thrice-weekly exercise group compared with UC. There was no significant decrease in HbA1c in the once-weekly exercise group. The exercise intervention was effective in improving self-reported minutes of metabolic equivalent tasks per week for participants in the thrice-weekly exercise group (both overall and per protocol). Although the intervention was not effective in the intention-to-treat analysis, participants in the thrice-weekly exercise group who attended at least 50% of the sessions during the 6-month exercise intervention program improved HbA1c levels at 6 months. Future efforts should focus on improving adherence to thrice-weekly structured exercise programs to meet exercise guidelines. ClinicalTrials.gov Identifier: NCT02061579.

Flavonoid Baicalein Suppresses Oral Biofilms and Protects Enamel Hardness to Combat Dental Caries.

The objectives of this study were to investigate the effects of a novel method using flavonoids to inhibit Streptococcus mutans (S. mutans), Candida albicans (C. albicans) and dual-species biofilms and to protect enamel hardness in a biofilm-based caries model for the first time. Several flavonoids, including baicalein, naringenin and catechin, were tested. Gold-standard chlorhexidine (CHX) and untreated (UC) groups served as controls. Optimal concentrations were determined by cytotoxicity assay. Biofilm MTT, colony-forming-units (CFUs), biofilm biomass, lactic acid and polysaccharide production were evaluated. Real-time-polymerase-chain reaction (qRT-PCR) was used to determine gene expressions in biofilms. Demineralization of human enamel was induced via S. mutans-C. albicans biofilms, and enamel hardness was measured. Compared to CHX and UC groups, the baicalein group achieved the greatest reduction in S. mutans, C. albicans and S. mutans-C. albicans biofilms, yielding the least metabolic activity, polysaccharide synthesis and lactic acid production (p < 0.05). The biofilm CFU was decreased in baicalein group by 5 logs, 4 logs, 5 logs, for S. mutans, C. albicans and S. mutans-C. albicans biofilms, respectively, compared to UC group. When tested in a S. mutans-C. albicans in vitro caries model, the baicalein group substantially reduced enamel demineralization under biofilms, yielding an enamel hardness that was 2.75 times greater than that of UC group. Hence, the novel baicalein method is promising to inhibit dental caries by reducing biofilm formation and protecting enamel hardness.

ISB clinical biomechanics award winner 2021: Tibio-femoral kinematics of natural versus replaced knees – A comparison using dynamic videofluoroscopy

BackgroundA comparison of natural versus replaced tibio-femoral kinematics in vivo during challenging activities of daily living can help provide a detailed understanding of the mechanisms leading to unsatisfactory results and lay the foundations for personalised implant selection and surgical implantation, but also enhance further development of implant designs towards restoring physiological knee function. The aim of this study was to directly compare in vivo tibio-femoral kinematics in natural versus replaced knees throughout complete cycles of different gait activities using dynamic videofluoroscopy. MethodsTwenty-seven healthy and 30 total knee replacement subjects (GMK Sphere, GMK PS, GMK UC) were assessed during multiple complete gait cycles of level walking, downhill walking, and stair descent using dynamic videofluoroscopy. Following 2D/3D registration, tibio-femoral rotations, condylar antero-posterior translations, and the location of the centre of rotation were compared. FindingsThe total knee replacement groups predominantly experienced reduced tibial internal/external rotation and altered medial and lateral condylar antero-posterior translations compared to natural knees. An average medial centre of rotation was found for the natural and GMK sphere groups in all three activities, whereas the GMK PS and UC groups experienced a more central to lateral centre of rotation. InterpretationEach total knee replacement design exhibited characteristic motion patterns, with the GMK Sphere most closely replicating the medial centre of rotation found for natural knees. Despite substantial similarities between the subject groups, none of the implant geometries was able to replicate all aspects of natural tibio-femoral kinematics, indicating that different implant geometries might best address individual functional needs.

Acute And Chronic Learning Impairment Following Seizures In Larval Zebrafish

Early‐life seizures (ELS) can disrupt brain development, often leading to cognitive impairments in humans and rodents. Here, we investigated whether seizures in larval zebrafish (Danio rerio) lead to acute and long‐term learning deficits. Based on ELS studies in rodents, we hypothesized that seizures in larval zebrafish would impair their performance in declarative memory tasks. To test this, we induced seizures in larval zebrafish using pentylenetetrazole (PTZ), which causes behavioral and electrical seizures in zebrafish. We modified the existing PTZ seizure model, exposing zebrafish to PTZ daily from 5‐7 days post‐fertilization (dpf). We then compared later‐life learning through short‐term memory tasks that lacked external punishment or motivation and focused on conscious recognition and interest in novel stimuli. To test learning and memory acutely after seizures, we used the visual lateralization novel object recognition (VLNOR) test, based on the novel object recognition test frequently used in rodents. Zebrafish show asymmetries in the use of left (LES) and right eye systems (RES), and will initially use LES to observe novel objects and RES to view familiar objects. We found that, when tested for recall of a previously novel object one hour after initially viewing it, 12‐14 dpf unhandled controls (UC group) reached a statistically significant majority of RES approaches by the end of the 8‐minute recall test (p=0.048). The PTZ group did not, and trended towards a significant decrease from 50% in the first 2 minute bin of the recall test (p=0.054). Taken together, these data indicate that the PTZ fish were not able to recall a previously viewed object, and when the object was reintroduced 1 hour later, responded as if the object were novel. We next used a y‐maze task to assess memory 3 months after seizures. In this task, fish had to recall the novel arm of the maze 90 minutes after being removed from the maze. The PTZ group spent significantly less time in the novel arm of the y‐maze during the recall test compared to their UC clutchmates (mean % time in novel arm +/‐ SE = 44.0+/‐3.2 for UC, 29.7+/‐2.1 for PTZ; p=0.002 by t‐test). Furthermore, our preliminary molecular studies show distinct expression profiles of synaptic plasticity genes between PTZ and UC groups by qPCR. Taken together, these results imply that inducing seizures in larval zebrafish leads to both acute and chronic learning and memory impairments. These findings expand the behavioral characterization of the larval zebrafish seizure model, strengthening the power of this model for researching the cognitive consequences of ELS.