Long-standing Disease Research Articles

Site-specific assessment of spinal radiographic progression improves detection of TNF blocker-associated disease modification in axial spondyloarthritis: longitudinal observational data from the Swiss Clinical Quality Management Registry

ObjectivesTo analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine).MethodsPatients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years.ResultsMean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively).ConclusionDisease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Surgical Treatment of Decompensated Cicatricial Stricture of the Esophagus, Grade III-IV Dysphagia, and Compression Syndrome Caused by Nontoxic Multinodular Goiter: A Case Report

Objective: Long-standing gastroesophageal reflux disease is the most common cause of a cicatricial stricture of the esophagus. The treatment of this pathology involves a wide range of methods including conservative and surgical options. Surgeons can encounter technical difficulties in case of concomitant neck and chest pathology.Clinical case: We report a case of a decompensated cicatricial stricture of the esophagus with concomitant paraesophageal hiatal hernia, refractory gastroesophageal reflux disease, and nontoxic multinodular goiter (166.9 cm3). Selecting the optimal management for such patients is often a challenge. Staged treatment significantly improves postoperative quality of life, but the increased length of hospital stay can negatively impact patient compliance.

The Role of Neutrophils in Spondyloarthritis: A Journey across the Spectrum of Disease Manifestations.

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils' role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets.

Outcomes of Multidisciplinary and Evidence-Based Management of Chronic Limb Threatening Ischemia Patients: The Impacts of Protocol-Based Care Processes

Background: Chronic limb-threatening ischemia (CLTI) represents the late stage of atherosclerotic peripheral arterial disease (PAD). Similar to atherosclerosis in other vascular beds, it is preceded by a long-standing early disease and pre-disposing conditions. Thus, the care of this patient population is theoretically best delivered by a multidisciplinary team. The authors studied the outcomes of a multidisciplinary, well-structured, and evidence-based protocol that might influence better outcomes for CLTI patients. Materials and Methods: The present study was a retrospective study done in a single center. Between January 2018 and December 2020, data were reviewed from CLTI patients that received the multidisciplinary, well-structured, and evidence-base protocol for the treatment of CLTI. The primary outcome was the perioperative clinical outcome of the patients. The secondary outcomes were the 1-year clinical outcome and the admission cost for vascular operation. Results: Two hundred thirty CLTI cases between January 2018 and December 2020 were retrospectively reviewed. Of the 230 cases, 87.9% were elderly (older than 60-years-old) with significant comorbidities including diabetes (74.3%) and hypertension (74.8%). The protocol implementation resulted in clinical outcomes in terms of both major adverse cardiac event (MACE) and major adverse limb event (MALE) at 1.3% and 6.52%, respectively. The survival rates at 1-and 2-years post-revascularization were 84.3% and 74.1%, and the 1-year follow-up MACE and MALE were 6.08% and 12.2%, respectively. Moreover, the protocol statistically improved the quality of life as measured by EuroQoL group-5 Dimensions-5 Levels (EQ-5D-5L) utility score. The median 1-year mean EQ-5D-5Q score increased from 0.332 to 0.863. The cost of the treatments was significantly higher with the increasing severities of CLTI. Conclusion: A multidisciplinary, well-structured, and evidence-based protocol may potentially be effective in improving the quality of care among CLTI patients, both in terms of clinical outcomes and overall health status. Keywords: Peripheral arterial disease (PAD); Chronic limb-threatening ischemia (CLTI); Multidisciplinary and evidence-based protocol

Multiple Sclerosis: Inflammatory and Neuroglial Aspects.

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease's natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells.

Failure and multiple failure for disease modifying antirheumatic drugs in rheumatoid arthritis: Real-life evidence from a tertiary referral center in Italy.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments' clinical response. Goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. To investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors' according to RA patient characteristics in a real-world setting. 718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. Patients failing to at least two csDMARDs or bDMARDs' drug for inefficacy were defined "csDMARDs multifailure" and "bDMARDs multifailure", respectively. Discontinuation of at least two cs- and bDMARDs was termed "global multifailure". In total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. Reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. Longstanding disease (≥ 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). Thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). Different causes of drug discontinuation were observed on DMARDs treatments. Demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets.

P201 Assessment of factors associated with cumulative bowel damage in surgically naïve patients using Lemann index and global MaRIA index in Crohn’s disease

Abstract Background The Lémann index (LI) is a unique tool that measures cumulative bowel damage in Crohn’s disease (CD) and is composed of surgical procedures and severity and extent of bowel lesions according to endoscopy and MR enterography (MRE). Since there is a significant contribution of previous surgery in LI calculation, our aim of this study is to investigate factors associated with cumulative bowel damage using LI in both total population and surgically naïve patients. Methods In this cross-sectional study, LI was calculated evaluating 20 small bowel, 7 large bowel and 3 upper GI segments. For each segment bowel resections, inflammatory, stricturing or penetrating lesions were considered using MRE and upper and lower endoscopy. Global MaRIA (gMaRIA) index was calculated using following parameters on 6 bowel segments on MRE: bowel wall thickness, ulcers, edema, and relative contrast enhancement. Longstanding disease was ≥10-year duration. Disease activity was defined as CRP>5 or HBI≥5. Extent and disease behavior were assessed using Montreal classification. Multivariate logistic regression adjusted for confounders was performed (age, gender, BMI, smoking status, CRP, disease behavior and extension, biological therapy, gMaRIA score, and HBI). Results This study included 320 CD patients [age 36 (24-46), 54.6% males, disease duration 7.2 (1-14) years, BMI 21.3 (17.4-24.8) kg/m2]. There were 142 (44.4%) surgically naïve and 128 (40%) patients with longstanding disease. In total population, higher LI values were observed among those with longstanding disease (10.31 vs 5.35 years, p<0.001), patients treated with biological therapy (9.7 vs. 6.4, p=0.005) and prior surgery (11.81 vs. 1.62, p<0.005). There was no difference in LI according to activity (p=0.921) and smoking status (p=0.336). Multivariate analysis on total population revealed independent predictors of elevated LI which were BMI (β=-0.268, p<0.02), disease duration (β=0.120, p=0.041) and prior surgery (β=5.42, p<0.001). Hence, separate multivariate analysis was performed on surgically naïve which revealed following predictors of LI (other than surgery): current smoking (β=1.14, p=0.010), perianal disease (β=1.39, p=0.02) and gMaRIA score (β=0.093, p<0.001). Conclusion Positive predictors of cumulative bowel damage in surgically naïve patients were smoking, perianal disease, and radiological activity (gMaRIA), while in total population longer disease duration, BMI and prior surgery. There are several important contributing variables on cumulative bowel damage which were revealed after removing previously operated patients, which would otherwise remain unrecognized. This risk factors in CD could stratify patients at high risk for complicated course of disease.

P377 Changes over time in the Lémann Index and the Inflammatory Bowel Disease-Disability Index in patients with Crohn’s disease

Abstract Background Crohn’s disease (CD) is a progressive, transmural disorder that leads to intestinal damage (fistula, abscesses, stenosis) and worsens the patient’s quality of life. The Lémann Index (LI, assessing cumulative bowel damage in CD) and the Inflammatory Bowel Disease-Disability Index (IBD-DI) have recently been validated. The objective of the present study was to assess changes over time in the LI and the IBD-DI and to identify factors associated with these changes. Methods In a cohort of 130 patients with CD being followed up prospectively at Lille University Hospital (Lille, France), the LI and the IBD-DI were evaluated first in 2016 (assessment #1, results previously published) and then again between September 2020 and October 2021 (assessment #2). Factors associated with the differences in the LI and IBD-DI were probed with a Mann-Whitney test or a bivariate analysis of variance. Survival curves for the progression of CD (surgery, drug-related events) were plotted according to the Kaplan-Meier method. Spearman’s coefficient was calculated as a guide to the strength of the correlation between the LI and the IBD-DI. Results 101 patients were included. More than half of the included patients had a long-standing disease (>15 years), 35% had ano-perineal involvement and 56% had a history of resection. Clinical activity was reported in 40% of patients at assessment#2. The median time interval between the two evaluations was 4.2 years. The LI (assessed in 61 patients) did not change significantly (median: 9.6 at #1 vs. 9.3 at #2; p = 0.14). The LI increased for 16 patients (26%), decreased for 26 (43%) and was stable for 19 (31%). Persistent clinical activity was the only factor significantly associated with worsening of the LI (p=0.01). A LI >7.9 was not associated with CD progression. The IBD-DI score (assessed in 98 patients), decreased significantly over time (median: 23.2 at #1 vs. 21.4 at #2; p = 0.006). The IBD-DI decreased for 59 patients (60.2%), increased for 37 (37.8%) and was stable for two (2%). Factors associated with improvement in the IBD-DI were younger age at diagnosis, a longer time interval before initiation of the first biologic, drug optimization, and exposure to combination therapy. There was no correlation between LI and the IBD-DI (r 0.125, p=0.27). Conclusion This is the first cohort study assessing changes over time in both the LI and the IBD-DI in CD patients. After more than 4 years of follow-up, the LI appeared to be stable and the IBD-DI decreased, without correlation between the indices. Persistent clinical activity was associated with worsening LI reinforcing the interest in monitoring these patients.

The Occurrence of Gallbladder Carcinoma in Yemeni Patients Undergoing Cholecystectomy in Two Hospitals

Background: Primary cancer of the gallbladder has wide 
 geographical, ethnic and cultural variations with poor prognosis. 
 Currently, there is no study about gallbladder carcinoma in Yemen. 
 The aim is to detect the occurrence of gallbladder carcinoma in 
 Yemeni patients undergoing cholecystectomy. 
 Patients and Methods: A descriptive retrospective study of data of 
 940 patients operated for gallstones in two university hospitals in 
 Yemen between 2002 and 2006 was carried out with respect to results 
 of histopathological analysis of gallbladder specimens. There were 
 872 women and 68 men. Patients who have no histopathological 
 reports in their files were excluded. Histopathological reports of 838 
 patients were retrospectively investigated for gallbladder malignancy. 
 Results: Gallbladder carcinoma was detected in 4 female patients of 
 median age 66 years. No male patient was affected. Adenocarcinoma 
 was the variety found in all four cases. All four patients with 
 gallbladder cancer have history of longstanding gallstone disease. 
 Conclusion: The study supports the hypothesis that gallbladder 
 carcinoma is rare and mostly affects elder women with long-standing 
 gallbladder stones. The occurrence of gallbladder carcinoma in the 
 targeted sample is significantly less than that of the western countries. 
 Cooperation between surgeon, sonographist and histopathologist is 
 strongly advised, particularly when gallbladder malignancy is 
 suspected 

Post-endoscopy colorectal cancer after colectomy in inflammatory bowel disease patients: a population-based register study.

Long-standing inflammatory bowel disease (IBD) colitis is an indication for endoscopic surveillance. Postcolonoscopy colorectal cancer (PCCRC), cancer detected after a negative colonoscopy, is a quality indicator for colonoscopy. In analogy with PCCRC, we aimed to assess postendoscopy CRC (PECRC) in individuals with IBD who had undergone colectomy. This register study included Swedish adults with an IBD diagnosis who had undergone colectomy and later were examined by either colonoscopy or sigmoidoscopy during 2001-2012. The final study population had a CRC diagnosis within 36 months of the index examination. Poisson regression was used to assess the relative risks (RR) of PECRC. A total of 33 individuals, 12 with an ileorectal anastomosis and 21 with a rectal remnant, had a CRC diagnosis within 36 months of the index endoscopy. Eleven cancers were detected as CRCs, and 22 (67%) were PECRCs. Compared with individuals aged >70 years, individuals aged <30 years had an RR of 3.1 (P = 0.054) and individuals aged 30-50 years had a RR of 2.6 (P = 0.030). A longer interval between colectomy and index endoscopy (>10 vs. <10 years) was associated with a lower risk of PCCRC (RR = 0.5; P = 0.007). There was no significant difference between the risk for Crohn's disease vs. ulcerative colitis, or between ileorectal anastomosis and rectal remnant risks. Continuous surveillance of IBD patients after colectomy is important. In the postcolectomy context, PECRC may be used as a quality indicator.

Factors Associated With Household Work Limitations in Mexican Patients With Rheumatoid Arthritis: The Impact of the Disease on Women's Life.

Little attention has been given to the impact of rheumatoid arthritis (RA) on domestic work, which remains the domain of women, particularly in the Latin American region. The study identified factors associated with RA-related household work limitations (HOWL) in Mexican for women with long-standing disease. This cross-sectional study was performed between September 2020 and April 2022, in patients from the recent-onset RA cohort (initiated in 2004). At study entry, patients had standard rheumatic assessments and were administered the HOWL questionnaire, a survey to assess family responsibilities, household work characteristics, and the patient's economic dependency, and the family APGAR index to assess family function. Multiple logistic regression analysis identified variables associated with RA-related HOWL. Data from 114 female RA patients were analyzed. Overall, at cohort entry, patients were middle-aged (median, 37.5 years), with 12 years of education, and the minority (n = 42 [39.3%]) were married or living together. Patients were representative of typical patients with recent-onset disease and had significant disease activity. At study entry, the patients had 12 (7-16) years of disease duration, and their disease was under control. The median (interquartile range) HOLW-Q score was 0.67 (0-3.33), and 33 patients (28.9%) had RA-related HOWL. Receiving financial support for family living expenses, requiring assistance for activities of daily living, and DAS28 (Disease Activity Score, 28 joints evaluated) were associated with RA-related HOWL; meanwhile, a better Short-Form 36 score at disease onset was protective. Domestic work in Mexican RA women might be impacted by social determinants, health-related quality of life at disease onset, and current disease activity status.

Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study.

Kidney complications are common in patients with long-standing inflammatory bowel disease (IBD). Whether kidney complications, defined as low estimated glomerular filtration rate (eGFR), may predispose to later IBD is unknown. We analyzed the association between eGFR and the risk of being subsequently diagnosed with IBD among 1 612 160 adults from Stockholm. The exposure was categories of eGFR, with 90 to 104 mL/min/1.73 m2 as the reference. Cox regression models were used to investigate the association between eGFR, IBD, and IBD subtypes. Subgroup analyses included age strata, sex, education, and comorbidities. To explore the possibility of detection bias or reverse causation, we estimated IBD hazard ratios (HRs) after excluding cases and individuals censored during early years of follow-up. During a median of 9 years of follow-up, we detected 9663 cases of IBD (3299 Crohn's disease, 5072 ulcerative colitis, 1292 IBD unclassified). Lower eGFR levels were associated with higher IBD risk (for eGFR 30-59 mL/min/1.73 m2: adjusted HR, 1.15; 95% confidence interval [CI], 1.01-1.33; and for eGFR <30 mL/min/1.73 m2: adjusted HR, 1.65; 95% CI, 1.16-2.37). This association was stronger in magnitude for Crohn's disease (for eGFR 30-59 mL/min/1.73 m2: HR, 1.33, 95% CI, 1.04-1.72; and for eGFR <30 mL/min/1.73 m2: HR, 2.25; 95% CI, 1.26-3.99). Results were consistent across strata of age, comorbidities, and attained education but suggested the association between eGFR and IBD to be stronger in women (P for interaction <.05). Results attenuated but were robust to exclusion of early IBD cases. We observed an association between reduced eGFR and the risk of developing IBD, which was stronger in magnitude for Crohn's disease.

Prognostic Value of CD8+ Lymphocytes in Hepatocellular Carcinoma and Perineoplastic Parenchyma Assessed by Interface Density Profiles in Liver Resection Samples.

Hepatocellular carcinoma (HCC) often emerges in the setting of long-standing inflammatory liver disease. CD8 lymphocytes are involved in both the antitumoral response and hepatocyte damage in the remaining parenchyma. We investigated the dual role of CD8 lymphocytes by assessing density profiles at the interfaces of both HCC and perineoplastic liver parenchyma with surrounding stroma in whole-slide immunohistochemistry images of surgical resection samples. We applied a hexagonal grid-based digital image analysis method to sample the interface zones and compute the CD8 density profiles within them. The prognostic value of the indicators was explored in the context of clinicopathological, peripheral blood testing, and surgery data. Independent predictors of worse OS were a low standard deviation of CD8+ density along the tumor edge, high mean CD8+ density within the epithelial aspect of the perineoplastic liver-stroma interface, longer duration of surgery, a higher level of aspartate transaminase (AST), and a higher basophil count in the peripheral blood. A combined score, derived from these five independent predictors, enabled risk stratification of the patients into three prognostic categories with a 5-year OS probability of 76%, 40%, and 8%. Independent predictors of longer RFS were stage pT1, shorter duration of surgery, larger tumor size, wider tumor-free margin, and higher mean CD8+ density in the epithelial aspect of the tumor-stroma interface. We conclude that (1) our computational models reveal independent and opposite prognostic impacts of CD8+ cell densities at the interfaces of the malignant and non-malignant epithelium interfaces with the surrounding stroma; and (2) together with pathology, surgery, and laboratory data, comprehensive prognostic models can be constructed to predict patient outcomes after liver resection due to HCC.

Endoscopic treatment of Mirizzi syndrome

Mirizzi syndrome is a complication of cholelithiasis occurring in 0.25-6% of cases [1]. Clinical pattern includes jaundice due to prolapse of a large calculus into the common bile duct following cholecystocholedochal fistula. Ultrasound, CT, MRI, MRCP data, as well as some pathognomonic signs provide preoperative diagnostics of Mirizzi syndrome. In most cases, treatment of this syndrome requires open surgery. We report successful endoscopic treatment of a patient with long-standing bile stone disease complicated by Mirizzi syndrome. Postoperative complications of surgery performed in acute period of disease and further staged treatment using retrograde access are illustrated. Endoscopic treatment demonstrated minimally invasive management of disease presenting diagnostic and technical difficulties.

Extrahepatic portal vein occlusion presenting with vascular, biliary, and visceral complications evaluated on multidetector computed tomography

Extrahepatic portal venous obstruction, predominantly a disease of childhood, is a chronic and long-standing disease characterized by thrombosis of the portal vein, leading to multiple collateral formation and other associated complications owing to long-standing nature of the disease. We present the case of a 22-year-old male with symptoms and signs of gastrointestinal bleed and pain in the left upper abdomen with similar episodes in the past.

An Unusual Sequela of Longstanding Gallstone Disease

An Unusual Sequela of Longstanding Gallstone Disease

Bait microalga harboring antimicrobial peptide for controlling Vibrio infection in Argopecten irradians aquaculture

Vibrio infection is a longstanding and serious bacterial disease of various shellfish species that has caused high mortality rates for many decades. Antibiotics can effectively prevent and control bacterial diseases. However, the long-term abuse of antibiotics exacerbates the risk of environmental pollution, which also poses a threat to food safety. In this study, transgenic lines of the marine microalga Tetraselmis subcordiformis harboring antimicrobial peptide NZ2114 were attempted to be created as an oral drug-delivery system in shellfish aquaculture. Toward this, codon-optimized nz2114 was respectively assembled into nuclear and chloroplast expression vectors of T. subcordiformis. After particle bombardment, two stable transgenic lines Y1 (with nuclear transformation) and Y2 (with chloroplast transformation) were selected, each expressing a stable transgene inheritance for at least 12 months. In vitro experiments demonstrated the significant inhibition of total protein containing NZ2114 from transgenic lines on two marine Vibrio species and Staphylococcus aureus. To test the efficacy of transgenic baits, pathogen-infected scallops (Argopecten irradians) were fed with transgenic T. subcordiformis via oral delivery. The results showed that the survival rate (after 20 days of infection) of the scallops fed transgenic T. subcordiformis was much higher than that of scallop fed with wild-type algae (95.92% versus 80.41%). In summary, this strategy offers a new, efficient, and low-cost method for controlling Vibrio in scallop aquaculture through oral drug-delivery system, which is a promising step toward the development of safe and environment-friendly antimicrobial baits.

Body impedance analysis to estimate malnutrition in inflammatory bowel disease patients - A cross-sectional study.

Malnutrition is a common clinical problem in patients with inflammatory bowel diseases (IBD). However, a gold standard for the detection of malnutrition in IBD patients is lacking. A cross-sectional study to assess malnutrition in patients with IBD and healthy controls (HCs). Clinical characteristics (Montreal classification, disease activity, previous surgery) and mutations in the NOD2 gene in patients with Crohn's disease (CD) were obtained. We performed a nutritional assessment with screening for nutritional risk and diagnosis for malnutrition (Malnutrition Universal Screening Tool [MUST]) score, NRS-2002, European Society for Clinical Nutrition and Metabolism (ESPEN), and Global Leadership Initiative on Malnutrition (GLIM) criteria and performed body impedance analysis (BIA). 101 IBD patients (57 CD and 44 ulcerative colitis (UC) and 50 HC were included in a single northern German tertiary center. GLIM criteria detected malnutrition significantly more often compared to the ESPEN criteria. Active disease, a long-standing disease course, and previous surgery were associated with reduced muscle mass. IBD patients had a higher fat mass index compared to HC. Mutations in the NOD2 gene had no effect on nutritional status. The GLIM criteria detect malnutrition at a higher rate compared to ESPEN. Specific disease factors might put IBD patients at a higher risk for the development of malnutrition, so these patients might benefit from a frequently performed screening, which might result in a favorable disease course.

Screening of Venturia inaequalis virulence and resistance of Malus genotypes to apple scab using in vitro methodology

Abstract The apple scab induced by Venturia inaequalis is an economically significant disease of apples worldwide and is predominantly controlled by multiple fungicide applications. Therefore, resistant apple cultivation is important for long-standing disease control. The knowledge about cultivar resistance is mainly founded on their evaluation in orchard conditions and testing in a greenhouse that is laborious and requires a large space. This study evaluated apple cultivar resistance and the virulence of V. inaequalis strains by inoculating detached leaves and immature fruits. Nine V. inaequalis strains originating from different apple-growing regions and host genotypes were tested on eight apple genotypes. Microscopic and macroscopic symptom development and host tissue reactions were monitored during the experiments. The tested V. inaequalis strains and cultivars showed different levels of virulence and resistance, respectively. Cultivar ‘Lobo’ was scored as partially susceptible, with almost all strains tested. The incompatible interaction with or without host tissue reactions was observed only on the cultivar ‘Priscilla’ with all the strains and field populations tested. The results of this study using detached leaves and immature fruits were concordant with the data obtained in the cultivar evaluation trials in the orchards.

Uricase-Deficient Larval Zebrafish with Elevated Urate Levels Demonstrate Suppressed Acute Inflammatory Response to Monosodium Urate Crystals and Prolonged Crystal Persistence.

Gout is caused by elevated serum urate leading to the deposition of monosodium urate (MSU) crystals that can trigger episodes of acute inflammation. Humans are sensitive to developing gout because they lack a functional urate-metabolizing enzyme called uricase/urate oxidase (encoded by the UOX gene). A hallmark of long-standing disease is tophaceous gout, characterized by the formation of tissue-damaging granuloma-like structures ('tophi') composed of densely packed MSU crystals and immune cells. Little is known about how tophi form, largely due to the lack of suitable animal models in which the host response to MSU crystals can be studied in vivo long-term. We have previously described a larval zebrafish model of acute gouty inflammation where the host response to microinjected MSU crystals can be live imaged within an intact animal. Although useful for modeling acute inflammation, crystals are rapidly cleared following a robust innate immune response, precluding analysis at later stages. Here we describe a zebrafish uox null mutant that possesses elevated urate levels at larval stages. Uricase-deficient 'hyperuricemic' larvae exhibit a suppressed acute inflammatory response to MSU crystals and prolonged in vivo crystal persistence. Imaging of crystals at later stages reveals that they form granuloma-like structures dominated by macrophages. We believe that uox-/- larvae will provide a useful tool to explore the transition from acute gouty inflammation to tophus formation, one of the remaining mysteries of gout pathogenesis.