A simple clinical score to stratify the risk of procedure-related adverse events in ERCP procedures with trainee involvement.

BACKGROUND : Optimal training strategies in endoscopic retrograde cholangiopancreatography (ERCP) remain controversial despite the shift toward competence-based training models, with limited data available on patient safety during training. We aimed to assess whether pre-procedural clinical predictors could identify patients at low risk of developing procedure-related adverse-events (AEs) in a training environment. METHODS : We performed a prospective, multicenter, cohort study in five training centers. A data collection system documenting indication, clinical data, trainee performance (assessed using a validated competence assessment tool), technical outcomes, and AEs over a 30-day follow-up was utilized. We developed a clinical risk score (Trainee Involvement in ERCP Risk Score [TIERS]) for patients undergoing ERCP and compared the rate of AEs in a training environment between low-risk and high-risk groups. The association between trainee performance and AE rate was also evaluated. RESULTS : 1283 ERCPs (409 [31.9 %, 95 %CI 29.3 %-34.4 %] with trainee involvement) performed by 11 trainers and 10 trainees were analyzed. AEs were more frequent in the high-risk compared with the low-risk group: 26.7 % (95 %CI 20.5 %-34.7 %) vs. 17.1 % (95 %CI 12.8 %-22.2 %). TIERS demonstrated a high negative predictive value for AEs (82.9 %, 95 %CI 79.4 %-85.8 %) and was the only predictor of AEs on multivariable analysis (odds ratio 1.38, 95 %CI 1.09-1.75). Suboptimal trainee performance was associated with an increase in AE rates. CONCLUSION : Simple, clinical-based predictive tools could improve ERCP training by selecting the most appropriate cases for hands-on training, with the aim of increasing patient safety.

Large Intron Inversions in Romanian Patients with Hemophilia A-First Report.

Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophilia A (HA), large intron inversions represent a major cause of disease, accounting for almost half of the cases of severe HA worldwide. We investigated the intron 22 and intron 1 inversion status in a cohort of Romanian unrelated patients with severe HA. Moreover, we evaluated the role of these inversions as relative risk factors in inhibitor occurrence. Materials and Methods: Inverse shifting-a polymerase chain reaction method was used to detect the presence of intron 22 and intron 1 inversions in 156 Romanian patients with HA. Results: Intron inversion 22 was found in 41.7% of the patients, while intron 1 inversion was detected in 3.2% of the patients. Overall, large intron inversions represented the molecular defect in 44.9% of the studied patients. Our findings are in accord with previously published reports from Eastern Europe countries and with other international studies. The risk of inhibitor development was higher in patients with inversion 1 compared to the patients with HA without any inversion detected. Conclusions: The current study demonstrates the major causative role of large intron inversions in severe HA in Romanian patients. Moreover, our study confirms the contribution of intron 1 inversion in inhibitor development.

Immunosuppressive therapy of systemic lupus erythematosus associated peripheral neuropathy: A systematic review.

INTRODUCTION: Peripheral neurologic manifestations may be associated with most of the collagen vascular diseases including systemic lupus erythematosus (SLE), yet most of the times it is not clear what therapy should be prescribed. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations suggest the use of glucocorticoids and immunosuppressive agents for the treatment of SLE associated peripheral neuropathy (PN) (strength of statement A, category of evidence 1), however these recommendations are based on studies that did not focus specifically on PN but rather on neuropsychiatric manifestations of SLE out of which only one was a randomized controlled clinical trial that included 7 patients with peripheral neuropathy. The objective of this systematic review is to determine whether the pathogenic treatments (corticosteroids, immunosuppressive agents, intravenous immunoglobulins, plasmapheresis) are effective for SLE associated PN. METHODS: We searched MEDLINE for all the studies that included the pathogenic treatment of SLE associated PN. The purpose was to identify randomized clinical trials, and in the absence of these, we included observational studies and case reports or case series. RESULTS: The search returned only retrospective case reports or case series. Only one prospective study, a randomized controlled study, was focused on neuropsychiatric SLE and included few patients with PN (7). Some studies reported cases of PN responsive to glucocorticoids (GC), cyclophosphamide (CYC), rituximab (RTX), azathioprine (AZA), plasmapheresis (PPH), intravenous immunoglobulin (IVIG), mycophenolate mofetil (MMF) or different combinations of these immunosuppressive agents, whereas others noticed effectiveness of sequential treatments (i.e. administration of a therapeutic agent after another single agent or a combination of agents had previously failed). Many studies did not mention how the outcomes were objectively measured. CONCLUSIONS: There are no interventional studies dedicated to the SLE associated PN, only retrospective case reports or case series which not only did they show contradictory results, but they also represent the lowest level of evidence. There is a strong need for new analytical studies dedicated to SLE associated PN.Protocol registered with PROSPERO (number CRD42019121748).

Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. OBJECTIVE: The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. METHODS: Medline and Embase databases were searched from inception to December 2014. RESULTS: A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. CONCLUSION: Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study.

BACKGROUND: Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression. METHODS: 40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits. RESULTS: Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype. CONCLUSIONS: RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.

Endocan, Novel Potential Biomarker for Systemic Sclerosis: Results of a Pilot Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by vascular alterations of small arteries and microvessels with subsequent tissue fibrosis. Endocan is expressed by endothelial cells and associated with endothelial dysfunction; therefore it could be a potential biomarker for Ssc patients. METHODS: Twenty-one Ssc patients and 20 sex- and age-matched healthy controls were recruited for the study. Serum endocan levels were determined using ELISA method in all patients and controls. RESULTS: Serum endocan levels were superior in Ssc patients (median 2.53 (1.10-7 ng/ml)) compared with controls (0.79 (0-2 ng/ml), P < 0.05). Higher serum endocan expression was seen in diffuse Ssc subset and associated with the presence of digital ulcers and daily Raynaud's phenomenon (P < 0.05). Higher serum endocan levels were associated with a modified Rodnan skin score >14 and longer disease duration (P < 0.05). Values of areas under the receiver operating curves showed that serum endocan had good discriminative power for Ssc diagnosis, differentiating diffuse from limited subset type and differentiating patients with modified Rodnan skin score above and under 14 (area under curve: 0.94, 0.81, 0.75, respectively). CONCLUSION: The results of this pilot study suggest endocan as a potential biomarker for microvascular manifestations and complications in Ssc patients. These encouraging results could promote future prospective studies in order to determine the exact role played by endocan as a biomarker for Ssc.

Association of anti phosphatidyl ethanolamine antibodies and low complement levels in systemic sclerosis patients--results of a cross-sectional study.

Some systemic sclerosis (Ssc) patients express antiphospholipid antibodies and their percentage varies within studies in the literature. The particular role of these antibodies in clinical manifestations of Ssc is still unknown. The aim of the study was to examine an extended panel of antiphospholipid antibodies in Ssc patients who did not have any clinical features of antiphospholipid antibody syndrome. A cross-sectional study was designed and 36 consecutive patients with Ssc were recruited. A relatively high proportion of patients (14 patients - 38.9%) had antiphospholipid antibody presence. Most Ssc patients (11 patients - 30.6%) had IgM anti phosphatidyl ethanolamine antibodies. Serum IgM anti phosphatidyl ethanolamine antibodies, IgM anti prothrombin and IgG anti ß2 glycoprotein 1 antibodies were associated with low complement levels in Ssc patients. In multivariate analysis, only serum IgM anti phosphatidyl ethanolamine antibodies concentration and serum IgG anti ß2 glycoprotein 1 antibodies concentration were independently associated with hypocomplementemia after adjusting for age and gender. No other correlations with Ssc clinical characteristics were found. In conclusion, antiphospholipid antibodies are present in a large proportion of Ssc patients who do not have clinical features or a history of antiphospholipid antibodies. IgM anti phosphatidyl ethanolamine antibodies seem to be more frequent and the dominant antiphospholipid antibody type in the group recruited from the Romanian Ssc population.

Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

CONTEXT: Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. OBJECTIVE: To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. METHODS: Medline and Embase databases were searched in February 2014. RESULTS: Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. CONCLUSION: Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

Serum endocan levels are increased in patients with inflammatory bowel disease.

BACKGROUND: Endocan is a marker of angiogenesis previously studied in various types of cancer and inflammatory conditions. Its expression is influenced by vascular endothelial growth factor A (VEGF A) and tumor necrosis factor alpha (TNF alpha), cytokines involved in pathogenetic pathways in inflammatory bowel disease (IBD). The aim of this study was to determine whether serum endocan levels were increased in IBD patients. METHODS: We conducted an exploratory pilot study. Serum endocan levels were determined in a group of 33 consecutive IBD patients from an observational cohort study ongoing at Colentina Hospital and compared to levels determined in two control groups: healthy controls and stage IV cancer patients. RESULTS: Endocan levels were significantly higher in the IBD group as compared to both healthy controls (p < 0.001) and cancer patients (p < 0.01). There was no correlation found between endocan levels and disease activity as assessed by clinical or endoscopical activity scores. CONCLUSIONS: There is a potential role for endocan in future biomarker studies in IBD patients.

Systematic review of self-assembling peptides as topical agents for treatment and prevention of gastrointestinal bleeding.

Background/Aims: Gastrointestinal bleeding is a significant and potentially lethal event. We aimed to review the efficiency and safety of self-assembling peptides for the treatment and prevention of gastrointestinal tract bleeding. Methods: We conducted a systematic search for studies describing the endoscopic use of self-assembling peptides for treatment or prevention of bleeding in the gastrointestinal tract in a parallel, independent fashion. The primary outcomes were rates of successful initial hemostasis, delayed bleeding, and rebleeding. The secondary outcomes were adverse events and ease and volume of gel used. Results: Seventeen studies were analyzed. Overall success rate of self-assembling peptides in gastrointestinal bleeding was 87.7% (38%-100%), regardless of etiology or associated treatments. Rebleeding rate ranged from 0% to 16.2%, with a mean of 4.7%, and overall delayed bleeding rate was 5% (range, 0%-15.9%). Only three adverse events were reported in a pooled number of 815 patients. The volume of gel used varied (0.43 to 3.7 mL) according to indication and type of bleeding. Conclusions: The limited available data on the use of self-assembling peptides in gastrointestinal endoscopy suggest a high efficiency and good safety profile.

Exploring the Role of Serum Osteonectin and Hsp27 in Pediatric MAFLD Diagnosis and Cardiometabolic Health.

BACKGROUND: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. METHODS: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. RESULTS: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. CONCLUSIONS: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

Markers of cardiac dysfunction associated with inflammation in a cohort of patients with acute decompensation of cirrhosis.

BACKGROUND AND AIMS: Inflammation underpinning acute decompensation (AD) of liver disease is an important driver for the development of acute-on-chronic liver failure or death. We aimed to investigate associations between inflammatory biomarkers and impaired cardiac function in patients admitted for AD of cirrhosis. METHODS: This is a retrospective analysis of a well-characterized prospective cohort of patients with AD of liver disease admitted to a tertiary referral center. All patients had echocardiographic assessment of cardiac function and serum samples at admission. We reclassified patients according to the CLIF-C AD score, measured inflammatory (IL-6, IL-8, TNF-ɑ, CD206) and cardiac-specific (NT-proBNP, troponin T) biomarkers and tested for associations with echocardiographic parameters of cardiac function. We explored the impact on outcome of these factors in multivariate analysis. RESULTS: We included 70 patients (58 ±â€…10 years, 28 women), with a mean CLIF-C AD score of 47 ±â€…7. Thirty-nine patients (56%) fulfilled the echocardiographic criteria for cardiac dysfunction. We found associations between parameters of diastolic dysfunction and serum concentrations of IL-6 and CD206. Echocardiographic parameters of cardiac function were not associated with markers of liver dysfunction such as the CLIF-C AD score. In multivariate analysis higher MELD, higher NT-proBNP, and IL-8 concentrations as well as the absence of echocardiographic criteria for cardiac dysfunction significantly associated with death during follow-up. CONCLUSION: We found evidence in favor of a clinically relevant link between serum biomarkers of inflammation (IL-6, CD206) and echocardiographic signals of cardiac dysfunction in patients with acutely decompensated cirrhosis.

Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study.

BACKGROUND: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. METHODS: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. RESULTS: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). CONCLUSIONS: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.

Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients.

Introduction: Systemic sclerosis (Ssc) is a multiorgan debilitating autoimmune disease that associates the triad: vascular involvement, tissue fibrosis and profound immune response alterations. Numerous previous studies focused on identification of candidate proteomic Ssc biomarkers using mass-spectrometry techniques and a large number of candidate Ssc biomarkers emerged. These biomarkers must firstly be confirmed in independent patient groups. The aim of the present study was to investigate the association of cytokeratin 17 (CK17), marginal zone B1 protein (MZB1) and leucine-rich α2-glycoprotein-1 (LRG1) with clinical and biological Ssc characteristics. Material and methods: Serum CK17, MZB1 and LRG1 were assessed in samples of the available Ssc biobank comprising of samples from 53 Ssc patients and 26 matched age and gender controls. Results: Circulatory CK17, LRG1 and MZB1 concentrations were increased in Ssc patients. Cytokeratin 17 is independently associated with Ssc disease activity. Patients with pulmonary fibrosis expressed higher LRG1 and MZB1 concentrations. Serum MZB1 concentrations were also associated with extensive skin fibrosis. Conclusions: Serum CK17, MZB1 and LRG1 were confirmed biomarkers for Ssc. LRG1 seems a good biomarker for pulmonary fibrosis, while MZB1 is a good biomarker for extensive skin fibrosis. CK17 proved to be independently associated with Ssc disease severity, higher CK17 values being protective for a more active disease.

Shared Molecular Targets in Parkinson's Disease and Arterial Hypertension: A Systematic Review.

(1) Background: Parkinson's disease and arterial hypertension are likely to coexist in the elderly, with possible bidirectional interactions. We aimed to assess the role of antihypertensive agents in PD emergence and/or progression. (2) We performed a systematic search on the PubMed database. Studies enrolling patients with Parkinson's disease who underwent treatment with drugs pertaining to one of the major antihypertensive drug classes (ß-blockers, diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium-channel blockers) prior to or after the diagnosis of parkinsonism were scrutinized. We divided the outcome into two categories: neuroprotective and disease-modifying effect. (3) We included 20 studies in the qualitative synthesis, out of which the majority were observational studies, with only one randomized controlled trial. There are conflicting results regarding the effect of antihypertensive drugs on Parkinson's disease pathogenesis, mainly because of heterogeneous protocols and population. (4) Conclusions: There is low quality evidence that antihypertensive agents might be potential therapeutic targets in Parkinson's disease, but this hypothesis needs further testing.

S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease with incomplete known physiopathology. There is a high number of candidate proteomic biomarkers for Ssc that have not yet been confirmed on independent Ssc cohorts. The aim of the study was to confirm circulating S100A6, calumenin, and cytohesin 2 as biomarkers for Ssc. METHODS: 53 Ssc patients and 26 age- and gender-matched controls were included. Serum S100A6, calumenin, and cytohesin 2 were evaluated with commercial ELISA kits. Associations between serum expression and clinical Ssc characteristics were evaluated. RESULTS: Serum calumenin, S100A6, and cytohesin 2 were higher in Ssc patients compared to controls. Calumenin associated with extensive cutaneous fibrosis, frequency of Raynaud phenomenon, and low complement level, and had a tendency to be higher in Ssc patients with pulmonary fibrosis. S100A6 correlated with the number of active digital ulcers. Serum cytohesin 2 levels were higher in patients with teleangiectasia and associated with pulmonary artery pressure. CONCLUSIONS: Serum calumenin, S100A6, and cytohesin 2 were confirmed as biomarkers on an independent group of Ssc patients. Calumenin had the best predictive capacity for cutaneous Ssc manifestations. Future studies are needed to evaluate the prognostic value of these biomarkers and evaluate them as possible therapeutic targets.

Candidate proteomic biomarkers in systemic sclerosis discovered using mass-spectrometry: an update of a systematic review (2014-2020).

Background. Systemic sclerosis (Ssc) is an autoimmune disease characterized by graduate cutaneous and tissue fibrosis development and irreversible fibroproliferative vascular changes.The aim of the current systematic review was to update the list of proteomic candidate biomarkers identified from Ssc samples with mass spectrometry techniques.Methods. Medline and Scopus databases were searched on 1st September 2020. Relevant articles were searched from March 2014 until September 2020. Two independent reviewers evaluated the retrieved articles.Results. From a total of 97 articles, 9 articles were included in the final analysis summarizing 539 candidate proteomic biomarkers from various samples from Ssc patients (a larger number compared to the previous systematic review). Most biomarkers were identified from cutaneous biopsies. Only 5 articles included a validation step of the findings with only 13 biomarkers being validated.Conclusions. Although many candidate biomarkers were additionally identified, independent validation studies are needed in order to evaluate the importance of these biomarkers for Ssc patients.

Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review.

BACKGROUND: Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable. AIM: To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients. METHODS: We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH. RESULTS: We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn's disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein. CONCLUSION: Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.

Blood Pressure Patterns in Patients with Parkinson's Disease: A Systematic Review.

(1) Background: Cardiovascular autonomic dysfunction is a non-motor feature in Parkinson's disease with negative impact on functionality and life expectancy, prompting early detection and proper management. We aimed to describe the blood pressure patterns reported in patients with Parkinson's disease, as measured by 24-h ambulatory blood pressure monitoring. (2) Methods: We conducted a systematic search on the PubMed database. Studies enrolling patients with Parkinson's disease undergoing 24-h ambulatory blood pressure monitoring were included. Data regarding study population, Parkinson's disease course, vasoactive drugs, blood pressure profiles, and measurements were recorded. (3) Results: The search identified 172 studies. Forty studies eventually fulfilled the inclusion criteria, with 3090 patients enrolled. Abnormal blood pressure profiles were commonly encountered: high blood pressure in 38.13% of patients (938/2460), orthostatic hypotension in 38.68% (941/2433), supine hypertension in 27.76% (445/1603) and nocturnal hypertension in 38.91% (737/1894). Dipping status was also altered often, 40.46% of patients (477/1179) being reverse dippers and 35.67% (310/869) reduced dippers. All these patterns were correlated with negative clinical and imaging outcomes. (4) Conclusion: Patients with Parkinson's disease have significantly altered blood pressure patterns that carry a negative prognosis. Ambulatory blood pressure monitoring should be validated as a biomarker of PD-associated cardiovascular dysautonomia and a tool for assisting therapeutic interventions.

Motion training on a validated mechanical ERCP simulator improves novice endoscopist performance of selective cannulation: a multicenter trial.

Background and study aims Current data show that traditional training methods in endoscopic retrograde cholangiopancreatography (ERCP) fall short of producing competent trainees. We aimed to evaluate whether a novel approach to simulator-based training might improve the learning curve for novice endoscopists training in ERCP. Methods We conducted a multicenter, randomized controlled trial using a validated mechanical simulator (the Boskoski-Costamagna trainer). Trainees with no experience in ERCP received either standard cannulation training or motion training before undergoing standard cannulation training on the mechanical simulator. Trainees were timed and graded on their performance in selective cannulation of four different papilla configurations. Results Thirty-six trainees (16 in the motion training group, 20 in the standard group) performed 720 timed attempts at cannulating the bile duct on the simulator. Successful cannulation was achieved in 698 of 720 attempts (96.9 %), with no significant difference between the two study groups ( P  = 0.37). Trainees in the motion training group had significantly lower median cannulation times compared to the standard group (36 vs. 48 seconds, P  = 0.001) and better technical performance on the first papilla type ( P  = 0.013). Conclusions Our findings suggest that motion training could be an innovative method aimed at accelerating the learning curve of novice trainees in the early phase of their training. Future studies are needed to establish its role in ERCP training programs.