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Objectives To assess the immediate and three days postintervention effect of one dry needling session compared to one sham needling session on pain, central pain processing, muscle co-contraction and spatiotemporal parameters during gait in knee osteoarthritis patients. Methods A double-blind randomized controlled trial was conducted. Sixty-one knee osteoarthritis patients were randomly assigned to the dry needling or sham needling group. Primary outcomes were pain and central pain processing. Secondary outcomes included muscle co-contraction and spatiotemporal parameters during gait. Patients were assessed at baseline and 15 min after the intervention, and pain also three days after the intervention. Linear mixed models were used to examine between- and within-group differences. Results No significant between-group differences for pain were found, but within-group scores showed a significant decrease 15 min after sham needling and three days after dry needling. The mean conditioned pain modulation effect measured at the m. Trapezius worsened significantly 15 min after sham needling compared to after dry needling (between-group difference). However, individual conditioned pain modulation percentage scores remained stable over time. Various significant within-group differences were found 15 min after sham needling: a decrease of conditioned pain modulation measured at m. Quadriceps and m. Trapezius and stride- and step-time scores, and an increase in step length and widespread pain pressure threshold. A significant decrease in muscle co-contraction index of the m. Vastus Medialis and Semitendinosus was found as within-group difference 15 min after dry needling. Conclusions Dry needling has no larger effect on pain, central pain processing, muscle co-contraction and gait pattern 15 min and three days postintervention compared to sham needling. Mean conditioned pain modulation scores worsened after sham needling compared to after dry needling. Further research remains necessary.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

BACKGROUND AND AIMS: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series. METHODS: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination. RESULTS: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients. CONCLUSIONS: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:9 issue:10 pages:1136-1147 ispartof: location:England status: published

Background: Cognitive–motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty. Objective: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC). Methods: Nine cognitive–motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively. Results: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task ( p Conclusion: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

Hereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC).We performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values 75% as normal (group A), 55-75% as reduced (group B) and 55% as low (group C). Complications were classified according to the Clavien-Dindo Classification, class III-V complications were defined as severe.347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery ( 285 min.) were significant predictive factors for severe complications.FXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy.

Background Adequate neuromuscular control of the knee could be one element to prevent secondary injuries after an anterior cruciate ligament (ACL) injury. To assess neuromuscular control in terms of time, amplitude and activity, electromyography (EMG) is used. However, it is unclear which assessments using EMG could be used for a safe return to sports (RTS). Therefore, we aimed to summarize EMG-related assessments for neuromuscular control of the knee in adult patients after an ACL injury to decide upon readiness for RTS. Methods This systematic review followed guidelines of Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane recommendations. MEDLINE/PubMed, EMBASE, CINAHL, Cochrane Library, Physiotherapy Evidence Database (PEDro), SPORTDiscus and the Web of Science were searched from inception to March 2019 and updated in November 2020. Studies identifying electromyographic assessments for neuromuscular control during dynamic tasks in adult, physically active patients with an anterior cruciate ligament injury were eligible and qualitatively synthesized. Two independent reviewers used a modified Downs and Black checklist to assess risk of bias of included studies. Results From initially 1388 hits, 38 mainly cross-sectional, case-controlled studies were included for qualitative analysis. Most studies provided EMG outcomes of thigh muscles during jumping, running or squatting. Outcomes measures described neuromuscular control of the knee in domains of time, amplitude or activity. Risk of bias was medium to high due to an unclear description of participants and prior interventions, confounding factors and incompletely reported results. Conclusions Despite a wide range of EMG outcome measures for neuromuscular control, none was used to decide upon return to sports in these patients. Additional studies are needed to define readiness towards RTS by assessing neuromuscular control in adult ACL patients with EMG. Further research should aim at finding reliable and valid, EMG-related variables to be used as diagnostic tool for neuromuscular control. Moreover, future studies should aim at more homogenous groups including adequately matched healthy subjects, evaluate gender separately and use sport-specific tasks. Registration The protocol for this systematic review was indexed beforehand in the International Prospective Register of Systematic Reviews (PROSPERO) and registered as CRD42019122188.

Background & Aims: Crohn's disease (CD) patients included in the Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX) trial started infliximab in combination with an immunosuppressant for 1 year. The aim of the present study was to determine the long-term disease course beyond the study period. Methods: We compared the outcomes of patients who did or did not reach the primary end point of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up study was the progression-free survival of CD defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Results: The 95 patients (median disease duration, 4.5 mo; interquartile range, 1.0–56.6 mo) analyzed, including 45 (47%) who achieved the primary end point, were followed up for a median duration of 64.2 months (interquartile range, 57.6–69.9 mo) after the end of the study period. There was no significant difference in CD progression-free survival at 1, 3, and 5 years between patients who achieved the TAILORIX primary end point and patients who did not (P =.64). No difference was observed between both groups for each component of CD progression: anal surgery, major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Conclusions: Achieving a sustained clinical remission off steroids with complete endoscopic remission in this cohort of 95 patients with early CD was not associated with less disease progression. Prospective trials to define the therapeutic goals that change the natural history of CD and prevent complications are needed.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Background We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. Methods This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min−1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min−1) or nasopharyngeal tube (5 L min−1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. Results In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, –23.4% [95% confidence interval (CI), –28.9 to –16.7]; P 1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P Conclusions In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. Clinical trial registration NCT03829293.

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%]. Conclusions Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn’s disease, with no new safety signals. Clinical trial registration number: NCT02513459

Objective To compare the outcomes of different treatments for spontaneous intra-abdominal abscesses (IAA) in active Crohn's disease (CD). Methods A retrospective analysis of patients with CD between January 2007 and December 2018 was performed in two Belgian inflammatory bowel disease centers. Successful conservative management was defined as complete resolution of abscesses without the need for bowel resection. The primary outcome was suboptimal evolution, defined as a composite outcome of recurrence of abscess, postoperative complications or the need for a non-elective resection. Results Forty CD patients presenting with 43 independent episodes of spontaneous IAA development were included. One underwent immediate bowel resection. In all other 42 cases a conservative approach was taken, which led to a complete abscess resolution rate of 28.6% (12/42). The remaining abscesses required bowel resection. Anti-tumor necrosis factor (TNF) agent use was associated with successful conservative management (odds ratio [OR] 13.36, 95% confidence interval [CI] 11.19-15.52, P = 0.006), while the opposite trend was found for corticosteroids (OR 0.14, 95% CI 0.02-1.26, P = 0.055). There was a trend towards suboptimal evolution in case of previous bowel resection (OR 4.77, 95% CI 0.77-29.66, P = 0.094) or in patients aged above 50 years (OR 5.17, 95% CI 0.86-30.91, P = 0.072). Conclusions Bowel resection appears to be inevitable in most CD patients presenting with IAA. An attempt at conservative treatment may be particularly successful with anti-TNF agents in younger patients who have not undergone previous bowel resection. Large-scale prospective studies are needed to confirm these findings.

The chemotherapy response score (CRS) is a histopathological tool to evaluate response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (OC). We critically evaluated the clinical value of CRS and compared its predictive power to standard serological (CA125) and radiological response. A retrospective analysis of 277 OC patients, who received primary chemotherapy, was performed. CRS, serological, and radiological findings were correlated with progression-free (PFS) and overall survival (OS). CRS could be determined in 172 of 277 patients (62.1%). In patients with CRS3, a longer median PFS and OS was observed compared with CRS1/2 patients (31.2 vs. 18.9, P

Dysphagia is a frequent symptom in Parkinson's disease (PD). Thickening liquids facilitates safe swallowing, however, low treatment compliance is a major issue, due to patients' dislike of thickened liquids. Some studies suggest a negative impact of gum-based thickeners, currently most used in clinical practice, on sensory properties compared to starch-based thickeners. This has not yet been investigated in PD. This study's aim was to compare taste, texture, and aroma of gum-based and starch-based thickened soups in participants with PD. Gum-based resource thicken up clear (RTUC) and starch-based kitchen products potato starch (PS) and quinoa flour (QF) were evaluated in broccoli soup. Texture, aroma, and taste were characterized by rheology, volatile, and sensory profiling. Thickened soups were evaluated in participants with PD and controls through a paired comparison test. Reduced release of 61.4%, 46.2%, and 38.5% of volatiles was observed after thickening with RTUC, PS, and QF, respectively. Overall taste intensity was reduced in RTUC- and PS-thickened soup, respectively. Taste and aroma of PS-thickened soup were considered more intense by 70.3% and 63.8% of all participants, respectively (n = 36 PD, n = 41 controls), 56.3% preferred the PS-thickened soup's texture . Taste and aroma of QF-thickened soup were considered more intense by 68.1% and 65.6% of all participants, respectively (n = 47 PD, n = 31 controls), 58.0% preferred the QF-thickened soup's texture. Starch-based thickeners demonstrated higher taste and aroma intensity. However, volatile and sensory profiling demonstrated reduced taste and aroma in all thickeners. Combining kitchen products with flavor enhancers may increase palatability of thickened beverages.

Background: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. Methods: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). Results: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. Conclusions: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. Significance: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.

Objective To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. Results CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. Conclusions The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Background. Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective. To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods. A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results. For DTCmotor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTCcognitive, ICCs ranged from −0.18 to 0.49 and Spearman correlations from −0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion. Reliability of the DTCmotor was, overall, good, whereas that of the DTCcognitive was poor. The “walking” and “cup” dual-task conditions were the most reliable regardless of the integrated cognitive task. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by RIMS by Novartis AG, MS Society Flanders, Swedish Promobilia Foundation, and SailingChallenge4MS.

INTRODUCTION: The impact of severity and location of Crohn's disease (CD) endoscopic ulcers on endoscopic remission in patients treated with antitumor necrosis factor is poorly known. We aimed to describe the endoscopic evolution of CD lesions in a prospective cohort of patients treated with infliximab (IFX) in combo therapy. METHODS: We conducted a post hoc analysis of the TAILORIX randomized controlled trial, which studied biologic-naïve patients with active CD and endoscopic ulcers receiving IFX combo therapy. Ileocolonoscopies were performed at week 0, 12, and 54. Endoscopic healing was defined as the absence of ulcers and complete endoscopic remission as CD Endoscopic Index of Severity (CDEIS)

Background Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3–4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a “delayed” interval debulking surgery (DID) is poorly defined. Methods We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. Results 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5–9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34–561), the median surgical complexity score was 4 (range 1–16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0–5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1–10 mm) compared to residual disease >1 cm. Conclusion Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Background BRCA1/2 mutations are the leading cause of hereditary epithelial ovarian cancer (EOC). The German Consortium for Hereditary Breast and Ovarian Cancer has defined inclusion criteria, which are retrievable as a checklist and facilitate genetic counselling/testing for affected persons with a mutation probability of ≥ 10%. Our objective was to evaluate the prevalence of the BRCA1/2 mutation(s) based on the checklist score (CLS). Methods A retrospective data analysis was performed on EOC patients with a primary diagnosis treated between 1/2011 – 5/2019 at the Central Essen Clinics, where a BRCA1/2 genetic analysis result and a CLS was available. Out of 545 cases with a BRCA1/2 result (cohort A), 453 cases additionally had an extended gene panel result (cohort B). Results A BRCA1/2 mutation was identified in 23.3% (127/545) in cohort A, pathogenic mutations in non-BRCA1/2 genes were revealed in a further 6.2% in cohort B. In cohort A, 23.3% (127/545) of patients had a BRCA1 (n = 92) or BRCA2 (n = 35) mutation. Singular EOC (CLS 2) was present in 40.9%. The prevalence for a BRCA1/2 mutation in cohort A was 10.8%, 17.2%, 25.0%, 35.1%, 51.4% and 66.7% for patients with CLS 2, 3, 4, 5, 6 and ≥ 7 respectively. The mutation prevalence in cohort B was 15.9%, 16.4%, 28.2%, 40.4%, 44.8% and 62.5% for patients with CLS 2, 3, 4, 5, 6 and ≥ 7 respectively. Conclusions The BRCA1/2 mutation prevalence in EOC patients positively correlates with a rising checklist score. Already with singular EOC, the prevalence of a BRCA1/2 mutation exceeds the required 10% threshold. Our data support the recommendation of the S3 guidelines Ovarian Cancer of offering genetic testing to all patients with EOC. Optimisation of the checklist with clear identification of the testing indication in this population should therefore be aimed for.

Background. In the general population, trajectories of walking capacity is accelerated and nonlinear with advanced age. Whether this is more pronounced in persons with multiple sclerosis (pwMS), along with the prevalence of dismobility (ie, slow gait speed), are currently unknown. Our objective was to investigate trajectories of walking capacity and prevalence of dismobility across the adult life span in pwMS versus healthy controls (HC). Methods. Data on maximal timed 25-foot walk test (T25FWT), 2-minute walk test (2MWT), and 6-minute walk test (6MWT) along with prevalence of dismobility were assembled from 2 RIMS multicenter studies (n = 502 pwMS; age range 21-77 years, 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years). HC data were extracted from studies containing normative reference values (n = 1070-3780 HC). Results. Age trajectories of walking capacity was nonlinear and accelerated in pwMS versus HC. While measures of walking capacity in pwMS were suppressed already early in life, the gap between pwMS and HC significantly widened across the 6 age groups (pwMS performed 64%, 70%, 57%, 59%, 51%, and 37% of HC, respectively). This coincided with high prevalences of dismobility in pwMS across the 6 age groups when using usual gait speed cut-point values

SALIHOGLU, ZIYA/0000-0002-6905-2664 WOS:000521719800002 PubMed ID: 32207048 Purpose LSG surgery is used for surgical treatment of morbid obesity. Obesity, anesthesia, and pneumoperitoneum cause reduced pulmoner functions and a tendency for atelectasis. The alveolar "recruitment" maneuver (RM) keeps airway pressure high, opening alveoli, and increasing arterial oxygenation. The aim of our study is to research the effect on respiratory mechanics and arterial blood gases of performing the RM in LSG surgery. Materials and Methods Sixty patients undergoing LSG surgery were divided into two groups (n = 30) Patients in group R had the RM performed 5 min after desufflation with 100% oxygen, 40 cmH(2)O pressure for 40 s. Group C had standard mechanical ventilation. Assessments of respiratory mechanics and arterial blood gases were made in the 10th min after induction (T1), 10th min after insufflation (T2), 5th min after desufflation (T3), and 15th min after desufflation (T4). Arterial blood gases were assessed in the 30th min (T5) in the postoperative recovery unit. Results In group R, values at T5, PaO2 were significantly high, while PaCO2 were significantly low compared with group C. Compliance in both groups reduced with pneumoperitoneum. At T4, the compliance in the recruitment group was higher. In both groups, there was an increase in PIP with pneumoperitoneum and after desufflation this was identified to reduce to levels before pneumoperitoneum. Conclusion Adding the RM to PEEP administration for morbidly obese patients undergoing LSG surgery is considered to be effective in improving respiratory mechanics and arterial blood gas values and can be used safely.

Objectives To determine the impact of incidental parathyroidectomy and mediastinal-recurrent cellular and lymph-node dissection on parathyroid function after total thyroidectomy. Material and methods A single-center retrospective study was conducted for a 5-year period in a university hospital center, including 605 patients undergoing total thyroidectomy, 52 of whom had mediastinal-recurrent cellular and lymph-node dissection. Endpoints The main endpoint was intraoperative number of parathyroid glands as predictor of parathyroid hormone (PTH) level and postoperative hypocalcemia. The secondary endpoint was the correlation between associated mediastinal-recurrent cellular and lymph-node dissection and incidental parathyroidectomy and its impact on PTH level and calcemia in the immediate postoperative period and at 1 month. Results 161 patients (26.61%) showed hypocalcemia in the immediate postoperative period and 12 (1.98%) at 1 month. Mediastinal-recurrent cellular and lymph-node dissection increased incidental parathyroidectomy risk 4.6-fold. Mediastinal-recurrent cellular and lymph-node dissection was associated with a statistically “suggestive” decrease in day-1 calcemia (P = 0.03), and no significant decrease at 1 month (P = 0.52). Incidental parathyroidectomy (6.7% of cases with parathyroidectomy versus 1.3% without) did not significantly increase the rate of early hypocalcemia (P = 0.28), but was associated with a “suggestive” worsening at 1 month (P = 0.02). Conclusion Hypocalcemia after total thyroidectomy is a complex, probably multifactorial issue. Systematic parathyroid gland identification is not recommended due to the increased risk of gland lesion, mainly by devascularization. Incidental parathyroidectomy may induce hypocalcemia at 1 month postoperatively (statistically “suggestive” association).

Background and Aims To report results from VISIBLE 2, a randomised, double-blind, placebo-controlled, phase 3 trial evaluating a new subcutaneous [SC] vedolizumab formulation as maintenance treatment in adults with moderately to severely active Crohn’s disease [CD]. Methods Following open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2, Week 6 clinical responders (≥70-point decrease in CD Activity Index [CDAI] score from baseline) were randomised 2:1 to receive double-blind maintenance vedolizumab 108 mg SC or placebo every 2 weeks until Week 50. Assessments at Week 52 included clinical remission [primary endpoint; CDAI ≤150], enhanced clinical response [≥100-point decrease in CDAI from baseline], corticosteroid-free clinical remission among patients using a corticosteroid at baseline, clinical remission in anti-tumour necrosis factor [anti-TNF]-naïve patients, and safety. Results Following vedolizumab intravenous induction, 275 patients were randomised to vedolizumab SC and 135 to placebo maintenance. At Week 52, 48.0% of patients receiving vedolizumab SC versus 34.3% receiving placebo were in clinical remission [p = 0.008]. Enhanced clinical response at Week 52 was achieved by 52.0% versus 44.8% of patients receiving vedolizumab SC versus placebo, respectively [p = 0.167]. At Week 52, 45.3% and 18.2% of patients receiving vedolizumab SC and placebo, respectively, were in corticosteroid-free clinical remission, and 48.6% of anti-TNF-naïve patients receiving vedolizumab SC and 42.9% receiving placebo were in clinical remission. Injection site reaction was the only new safety finding observed for vedolizumab SC [2.9%]. Conclusions Vedolizumab SC is an effective and safe maintenance therapy in patients with CD who responded to two infusions of vedolizumab intravenous induction therapy.

Shallow-depth sequencing of cell-free DNA, an inexpensive and standardized approach to obtain molecular information on tumors non-invasively, has been insufficiently explored for the diagnosis of lymphoma and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively- recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non-HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed. At diagnosis, liquid biopsies showed detectable copy number alterations in 84.2% of HL patients (88.6% for classical HL) and 74.1% of DLBCL patients. Of the DLBCL patients, copy number profiles between liquid-solid pairs were highly concordant (r=0.815±0.043); and, compared to tissue, HL liquid biopsies had abnormalities with higher amplitudes (P=0.010). This implies that tumor DNA is more abundant in plasma. Additionally, 39.5% of HL and 13.6% of DLBCL cases had a significantly elevated number of plasma Epstein-Barr virus DNA fragments, achieving a sensitivity of 100% compared to the current standard. A longitudinal analysis determined that, when detectable, copy number patterns were similar across (re)staging moments in refractory or relapsed patients. Further, the overall profile anomaly correlated highly with the total metabolic tumor volume (P

The indication for staging lymphadenectomy in patients with ovarian cancer (both early- and late-stage disease) has been a major topic of debate in the last decades. Because the Lymphadenectomy in Ovarian Neoplasms (LION) study has recently demonstrated that systematic lymphadenectomy is not beneficial to patients with advanced ovarian cancer, the discussion has become more complex for patients with early-stage ovarian cancer. Further factors, such as differences in the lymph node metastasis rates of different histologic subtypes, which were not known in the past, need to be taken into account. This review is focused on the available evidence concerning lymphadenectomy in patients with newly diagnosed ovarian cancer.

BACKGROUND AND OBJECTIVE To describe the clinical characteristics and the outcomes of a group of elderly patients referred to a liaison psychiatry department in the emergency department of an Academic University Hospital. METHODS A group of 39 patients aged over 65 years (mean age: 70. years, 56% male), consecutively referred to a liaison psychiatry department between March 2017 and December 2020, was compared to a group of 613 patients aged under 65 years (mean age: 42.0 years, 69% male) following their admission to the emergency department of the Amiens University Hospital, France. RESULTS AND CONCLUSIONS The main reasons for admission in the emergency department were alcohol intoxication (54%), depressive symptoms (23%), and suicidal ideas or behaviors (24%), without significant difference with the group of patients aged under 65 years of age. The rate of patients smoking tobacco on a daily basis was lower in the group of patients over 65 years of age (respectively 28% versus 71%, P

Simple Summary The immune system plays an important role in the development and progression of cancer. The current treatments for ovarian cancer (surgery and chemotherapy) create changes in the immune system, but it is not clear how. Nevertheless, if immunotherapy is associated on top of this, then it seems crucial to understand what is changing in the current state of the art. In this study, we measured immune-related proteins in the serum of ovarian cancer patients throughout their treatment. We discovered that carboplatin-paclitaxel as a chemotherapeutic treatment reduces immunosuppression and promotes immunostimulation, meaning that the immune system be-comes less hostile and more in favour of the patient. Therefore, chemotherapy seems to induce a temporary window of opportunity to insert immunotherapy during the current treatment of ovarian cancer patients. In monotherapy, immunotherapy has a poor success rate in ovarian cancer. Upgrading to a successful combinatorial immunotherapy treatment implies knowledge of the immune changes that are induced by chemotherapy and surgery. Methodology: Patients with a new ovarian cancer diagnosis underwent longitudinal blood samples at different time points during primary treatment. Results.: Ninety patients were included in the study (33% primary debulking surgery (PDS) with adjuvant chemotherapy (ACT), 61% neo-adjuvant chemotherapy (NACT) with interval debulking surgery (IDS), and 6% debulking surgery only). Reductions in immunosuppression were observed after NACT, but surgery reverted this effect. The immune-related proteins showed a pronounced decrease in immune stimulation and immunosuppression when primary treatment was completed. NACT with IDS leads to a transient amelioration of the immune microenvironment compared to PDS with ACT. Conclusion: The implementation of immunotherapy in the primary treatment schedule of ovarian cancer cannot be induced blindly. Carboplatin-paclitaxel seems to ameliorate the hostile immune microenvironment in ovarian cancer, which is less pronounced at the end of primary treatment. This prospective study during primary therapy for ovarian cancer that also looks at the evolution of immune-related proteins provides us with an insight into the temporary windows of opportunity in which to introduce immunotherapy during primary treatment.

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed an early stress response in brain macrophages in NAWM and identified specific macrophage subsets that associate with different stages of demyelinating lesions. These early changes associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination.

Introduction/Background* The vascular endothelial growth factor (VEGF) plays an import role in emergence and spread of high-grade serous tubo-ovarian carcinoma (HGSTOC). Bevacizumab, a monoclonal antibody targeting VEGFA, has therefore been added to first-line treatment of advanced HGSTOC. We here map the dynamics of different stromal components of the tumour microenvironment under chemotherapy with or without bevacizumab. Methodology We performed single-cell RNA-sequencing on 62,461 cells sampled from 6 HGSTOC patients before and after neo-adjuvant platin-based chemotherapy with or without bevacizumab. We identified 44 stromal cell subclusters on which we applied Mixed-effects modelling of Associations of Single Cells to identify cell populations associated with bevacizumab exposure and pathological response using the chemotherapeutic response score. Result(s)* Our study revealed diverse stromal cell subsets associated with bevacizumab exposure. The addition of bevacizumab to frontline chemotherapy increased the odds of endothelial cell (ECs) prevalence by a 3-fold (OR 2.91, 95%CI:2.36-3.58; p Conclusion* We here provide initial evidence on the mechanisms underlying early response to bevacizumab and frontline chemotherapy in HGSTOC, including tip cell impairment, reduced hypoxia and a decrease in regulatory T cells. However, bevacizumab exposure increased the influx of PDGFC-expressing macrophages capable to bypass VEGFA-dependent angiogenesis.

The potential effects of a 24 or 72‐h delay in post‐mortem inspection (PMI) of ungulates on public health and monitoring of animal health and welfare was evaluated. The assessment used a survey of meat inspectors, expert opinion, literature search and a stochastic model for Salmonella detection sensitivity. Disease detection sensitivity at a delayed PMI is expected to reduce detection sensitivity to a variable extent, depending on the hazard and on the signs/lesions and organs involved. No reduction is expected for Trichinella detection in meat from susceptible animal species and any decrease in detection of transmissible spongiform encephalopathies (TSEs) will not exceed the current tolerance for fallen stock. A 24‐h delay in PMI could result in a small reduction in sensitivity of detection for tuberculosis, echinococcosis and cysticercosis. A greater reduction is expected for the detection of pyaemia and Rift valley fever. For the detection of Salmonella, the median model estimates are a reduction of sensitivity of 66.5% (90% probability interval (PI) 0.08–99.75%) after 24‐h delay and 94% (90% PI 0.83–100%) after 72‐h delay of PMI. Laboratory testing for tuberculosis following a sampling delay of 24–72 h could result in no, or a moderate, decrease in detection depending on the method of confirmation used (PCR, culture, histopathology). For chemical contaminants, a delay in meat inspection of 24 or 72 h is expected to have no impact on the effectiveness of detection of persistent organic pollutants and metals. However, for certain pharmacologically active substances, there will be a reduced effectiveness to detect some of these substances due to potential degradation in the available matrices (tissues and organs) and the non‐availability of specific preferred matrices of choice. info:eu-repo/semantics/publishedVersion

Background CALM was a randomized phase 3 trial in patients with Crohn’s disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS), A post hoc analysis of a phase 3 trial in Crohn’s disease showed that a fecal calprotectin cutoff of

Transient Receptor Potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasticity is essential for normal functioning. However, it is unknown whether TRP channel expression is subject to the phenotypic switching that occurs during epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), and whether TRP channel expression is associated with aggressive phenotypes in endometrial cancer (EC). Here, we induced EMT and MET in vitro using in primary EEC and ESC, respectively, and analyzed expression and functionality of TRP channels using RT-qPCR and intracellular Ca2+ imaging. The outcome of these experiments showed a strong association between TRPV2 and TRPC1 expression and the mesenchymal phenotype, whereas TRPM4 expression correlated with the epithelial phenotype. In line herewith, increased TRPV2 and TRPC1 expression levels were observed in both primary and metastatic EC biopsies and in primary EC cells with a high EMT status, indicating an association with an aggressive tumor phenotype. Remarkably, TRPV2 expression in primary EC biopsies was associated with tumor invasiveness and cancer stage. In contrast, increased TRPM4 expression was observed in EC biopsies with a low EMT status and less aggressive tumor phenotypes. Taken together, this dataset demonstrated for the first time that TRP channel expression is strongly linked to cellular phenotypes of the endometrium, and that phenotypic transitions caused by either experimental manipulation or malignancy could alter this expression in a predictable manner. These results implicate that TRP channels are viable biomarkers to identify high-risk EC, and potential targets for EC treatment.

A proliferation inducing ligand (APRIL) mediates a key role in the generation and survival of antibody-inducing plasmocytes. Based on this, APRIL has been targeted in autoimmune diseases including multiple sclerosis (MS) and optic neuritis (ON). In MS lesions, APRIL has a new cellular target, the reactive astrocyte and mediates an immunosuppressive activity. Here, we analyzed APRIL expression in a case of neuromyelitis optica (NMO), another autoimmune neurodegenerative disease, showing selective aquaporin-4 depletion in the spinal cord, complement deposition and infiltration of polymorphonuclear cells. We analyzed by immunohistochemistry the presence of APRIL-producing cells, plasmocytes, astrocytes and the localization of secreted APRIL in a lesion from NMO. Plasmocytes were present close to APRIL-producing cells in meninges. However, our main observation was that APRIL targets reactive astrocytes in this lesion of NMO similarly to MS.

In this case report we present a Family cluster of amoebiasis in a nonendemic region. A 46-year-old women, diagnosed with Crohn's disease for which she received no maintenance therapy, was evaluated for the suspicion of a flare. At colonuscopy however, atypical findings for Crohn's disease were seen. Histopathologic examination revealed micro-organisms compatible with amoebiasis. Interestingly, 4 years before this event she started a new relationship with a 38-year-old man who was diagnosed with liver-amoebiasis 3 months after the start of their start of their relationship. On top of this, her 18-year-old daughter was diagnosed with amoebiasis 2 years after her diagnosis. The source of the infection remains unknown, but we speculate that the infection was transmitted feco-orally between the different members of this family. These cases illustrate that we should be aware of parasitological causes of colitis, especially in patients with atypical endoscopic images or when a close "relative" is diagnosed with amoebiasis.

International audience; France and Canada prehospital systems and care delivery in out-of-hospital cardiac arrests (OHCAs) show substantial differences. This article aims to describe the rationale, design, implementation and expected research implications of the international, population-based, France-Canada registry for OHCAs, namely ReACanROC, which is built from the merging of two nation-wide, population-based, Utstein-style prospectively implemented registries for OHCAs attended to by emergency medical services. Under the supervision of an international steering committee and research network, the ReACanROC dataset will be used to run in-depth analyses on the differences in organisational, practical and geographic predictors of survival after OHCA between France and Canada. ReACanROC is the first Europe-North America registry ever created to meet this goal. To date, it covers close to 80 million people over the two countries, and includes approximately 200 000 cases over a 10-year period.

BACKGROUND: Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks. OBJECTIVE: To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder. METHOD: We searched the PubMed and Web of Science databases for studies that had been published up to January 16th, 2019. Studies investigating the neural correlates of cognitive-motor dual task performance in individuals with a variety of neurologic disorders were included, independently from whether the study included healthy controls. Clinical and imaging data were abstracted for the comparison between single tasks and a dual task in the individuals with a neurologic disorder and for the comparison between the healthy controls and the individuals with a neurologic disorder. RESULTS: Eighteen studies met the inclusion criteria. Study populations included individuals with Parkinson disease, multiple sclerosis, mild cognitive impairment, Alzheimer disease, traumatic brain injury, and stroke. Neuroimaging types used to study the neural correlates of cognitive-motor dual tasking during upper limb or gait tasks included fMRI, functional near-infrared spectroscopy, EEG, and PET. CONCLUSION: Despite large heterogeneity in study methodologies, some recurrent patterns were noted. Particularly, in neurologic patients, an already higher brain activation during single tasks was seen compared with healthy controls, perhaps compromising the patients' ability to further adapt brain activation with increasing load during dual tasking and resulting in reduced behavioral dual task performance. ispartof: COGNITIVE AND BEHAVIORAL NEUROLOGY vol:34 issue:2 pages:79-95 ispartof: location:United States status: published

Background Few data are available regarding the combination of biological therapies (anti-TNF, anti-integrin, anti-interleukins (IL4, 12/23, 17A, 23)) or with a small molecule in patients with IBD. We here report the safety and efficacy of combining these drugs through a national retrospective multicenter case series. Methods Cases were extracted from local databases within the last 3 years. Combined therapy was defined as the concomitant use for a minimum of 1 day of 2 biologics or 1 biologic with a small molecule. Patients’ demographics, disease’ characteristics and types of combined therapies were recorded. Safety was defined as the occurrence of any serious adverse event (SAE): serious infection, opportunistic infection, any hospitalisation, cancer and death, whereas the efficacy of combination was clinically appreciated by physicians. Results From 8 centres, 23 combined therapies were observed in 19 IBD patients (74% Crohn’s disease, 21% ulcerative colitis and 5% IBD type unclassified). Median age at combination was 43.0 years ([IQR]: 31.5–59.0). Seventeen patients presented with a minimum of 1 concomitant IMID (ankylosing spondylitis (n = 11), psoriasis or psoriatic arthritis (n = 5) and other conditions (n = 5)). Reasons for starting a combination were active IBD (57%), another active IMID (30%) or both (13%). Anti-TNF and anti-integrin were combined in 11 cases, anti-TNF and anti-ILs in 5, anti-integrin and anti-ILs in 4 and other combinations in 3 (anti-TNF+rituximab+methotrexate; anti-IL4+anti-IL12/23; anti-IL12/23+methotrexate+leflunomide). The median duration of combined therapies was 5 months ([IQR]: 2–9). During 15.8 patients/years of combined therapy, 11 adverse events (AE) including 9 SAE were recorded in 8 patients. Eight infections were reported with various combinations: anti-TNF and anti-IL in 4 cases, anti-TNF and anti-integrin in 3 and anti-TNF+rituximab+methotrexate in 1. Two infections (both anti-TNF+ anti-integrin) were graded severe leading to hospitalisation, 6 were graded mild or moderate. Cancer and death were not observed. After combined therapy, IBD disease activity was clinically improved in 44% and remained stable in 50% of patients, whereas clinical improvement of IMID was observed in 25% of patients. Overall, the combination of treatments was withdrawn due to ineffectiveness or serious adverse events in 39% and 4%, respectively. Conclusion In our experience, the combination of biologics in patients with IBD ±. another IMID was associated with short term increased efficacy in almost half of patients but also with a risk of infections in one third. No new safety signals were observed in this difficult to treat patients but extensive data are urgently needed.

Background Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNFα and vedolizumab. Methods This is an observational, national, retrospective multicentre study including all UC active patients started on tofacitinib (10 mg BID) from 25 centres in Belgium between November 2018 and August 2019. Prospectively collected data were retrospectively analysed according to intention to treat. Primary endpoints were clinical and endoscopic response and remission rates at weeks 8 and 16. Clinical response and remission were defined as a reduction in the Modified Clinical Mayo score (rectal bleeding, stool frequency) of ≥2 and ≤1, respectively. Endoscopic response and remission were defined as a reduction in Endoscopic Mayo score of ≥1 and ≤1, respectively. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed-rank test were calculated using Medcal 19.1. Results Demographic and baseline data of the 70 included patients are presented in Table 1. Of note is that nearly all patients were refractory to at least one anti-TNF and vedolizumab. Median follow-up was 16 weeks (IQR 13–26). Fifty-four per cent (38/70) of patients required prolonged induction at 10mg BID. Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission, and endoscopic response and remission at weeks 8 and 16 are presented in Figures 1 and 2. Fifty per cent (21/42) of the patients under steroids at baseline could have stopped steroids at 16 weeks. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5–8) to 4 (IQR 2–7) after 8 weeks (n = 49) (p < 0.0001), and down to 2 (IQR 1–5) at week 16 (n = 40) (p < 0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5–6.2) (n = 49) (p = 0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism. Conclusion Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.

Background The optimal endoscopic target in early Crohn’s disease (CD) that limits long-term disease complications is unknown. Methods We analysed medical records from patients who had follow-up data since the end of CALM. Patients with Crohn’s disease endoscopic index of severity (CDEIS) scores at the end of CALM were included. The primary outcome was a composite of major adverse outcomes reflecting CD progression: new internal fistula/abscess, stricture, perianal fistula/abscess, CD hospitalisation, or CD surgery since the end of CALM. We compared median CDEIS and per cent improvement from baseline CDEIS. Youden index analysis was used to identify optimal CDEIS cut-off score associated with CD progression. Kaplan–Meier and Cox regression methods were used to compare rates of progression by different CDEIS targets. Multivariable models were adjusted for age, prior surgery, and stricturing behaviour. Results 110 patients with median age 28 (IQR 22–38) years, disease duration 0.2 (0.1–0.5) years, and median follow up of 3.1 (1.9–4.4) years were included. Eleven per cent had a history of stricture, 5.5% history of surgery, and 52% were originally in the tight control arm of the CALM study. Median CDEIS score at end of CALM was 3 (0–5.4) and 32 (29%) patients had disease progression. Baseline median CDEIS score was similar between those with and without progression [10.9 (7.5–15.5) vs. 11.9 (8–17.5)]. Median CDEIS score at the end of CALM was higher among those with progression [1.3 (0–5.1) vs. 4.9 (3–9.1), p < 0.001)]. Patients within higher quartiles of CDEIS score had higher rates of progression over time (Figure 1). Patients without disease progression had a greater median decrease in CDEIS score from baseline to end of CALM [90% (60–100%) vs. 50% (30–80%), p < 0.001]. The optimal CDEIS score cut-off was 2 with sensitivity 84%, specificity 60% and NPV 90% for progression. Patients with CDEIS ≤ 2 had less progression over time compared with patients with > 50% improvement from baseline CDEIS (not reaching CDEIS ≤ 2) and those not meeting either endpoint (Figure 2). On adjusted analysis, CDEIS score ≤ 2 was associated with a decreased risk of progression (aHR 0.23, 95% CI 0.09–0.56). Conclusion In early CD, a CDEIS score ≤ 2 is optimal cut-off associated with a lower risk of disease progression.

BACKGROUND: Budesonide has been proven to be an effective treatment for microscopic colitis (MC). However, the two current commercially available preparations are released in the ileum. Beclomethasone dipropionate (Clipper®) is a synthetic corticosteroid with topical colonic release. OBJECTIVE: This study aimed to explore whether an open-label treatment with beclomethasone dipropionate is an effective treatment for MC. METHODS: Prospectively collected data of 30 patients from six centres were retrospectively analysed. All patients had a confirmed diagnosis of idiopathic MC (lymphocytic and collagenous colitis) and were symptomatic (i.e. ≥ 21 loose stools over a seven-day period). Treatment consisted of 10 mg beclomethasone daily for four weeks, followed by 5 mg daily for another four weeks. The primary end point was the proportion of patients in remission (i.e. a mean of

Objectives To assess the rate of second (or more) primaries after treatment for head and neck squamous cell carcinoma (HNSCC), and survival compared to patients with a single head and neck cancer. Material and method A single-center retrospective study was performed in a University Hospital Center in 541 patients between 2002 and 2010. Results One hundred and forty-one patients (26.06%) presented 172 metachronous cancers. Overall 5-year survival was 20.3% with and 38.1% without metachronous cancer. Median and mean survival were respectively 21.9 and 51 months in patients with a single cancer, versus 13.9 and 26.5 months in case of metachronous cancer. Specific survival was comparable to overall survival. All-cause and specific survival were significantly poorer in metachronous cancer ( P = 0.001; log-rank α = 0.05). Conclusion At least a quarter of HNSCC patients go on to develop a metachronous second primary. These are of poor prognosis, whatever their location.

Purpose of review Central sensitization (CS) is present in a variety of chronic pain conditions including rheumatoid arthritis (RA). An overview of the treatment options for desensitizing the central nervous system in RA patients, with CS as their dominant pain mechanism, is provided. Recent findings The treatment of pain in RA patients has mostly focused on treating inflammation to indirectly treat pain. Unfortunately, little research has focused on treating CS, which appears to be present in some patients with RA. Summary “Treating the brain without ignoring the joints” should be the leading principle in the management of CS in RA patients. Pain neuroscience education, graded activity, and a time-contingent exercise approach are important interventions to implement in clinical practice. Further research is necessary to evaluate the effectiveness of these promising treatments for diminishing hyperexcitability of the central nervous system in RA patients with CS as their dominant pain mechanism.

Objective To determine whether an ENT clinical screening examination done on all patients chronically addicted to alcohol or tobacco would allow the early diagnosis of cancer of the upper aerodigestive tract. Study design Case series with chart review. Setting Non-university general hospital. Subjects and methods A total of 159 patients presenting chronic addiction to alcohol or tobacco hospitalized in an addiction center or a comprehensive medical clinic were included in this study covering the period 2011-2016. All patients systematically benefitted from an ENT clinical examination to detect mucous membrane lesions. The lesions were categorized as: cancerous, pre-cancerous, or benign. The patients were divided into two groups for comparison: 1) patients with symptoms (dysphagia, dysphonia, dyspnea upon inhalation, cervico-facial pain, secondary otalgia, pharyngeal discomfort unrelated to deglutition, presence of a cervical swelling, or weight loss), and 2) asymptomatic patients. Results The ENT exam was normal in 121 patients (76.1%). Fifty-two patients (32.7%) had at least one symptom. The ENT exam allowed us to detect a benign lesion in 11 patients, a pre-cancerous lesion in 11 patients, and a cancer in 16 (13.22%) patients. All patients with cancer had at least one symptom. Conclusion An ENT clinical screening examination done on patients chronically addicted to alcohol or tobacco can allow early diagnosis of cancer, particularly in patients with at least one symptom.

OBJECTIVE The effect of CSF on blood coagulation is not known. Enhanced coagulation by CSF may be an issue in thrombotic complications of ventriculoatrial and ventriculosinus shunts. This study aimed to assess the effect of CSF on coagulation and its potential effect on thrombotic events affecting ventriculovenous shunts. METHODS Two complementary experiments were performed. In a static experiment, the effect on coagulation of different CSF mixtures was evaluated using a viscoelastic coagulation monitor. A dynamic experiment confirmed the amount of clot formation on the shunt surface in a roller pump model. RESULTS CSF concentrations of 9% and higher significantly decreased the activated clotting time (ACT; 164.9 seconds at 0% CSF, 155.6 seconds at 9% CSF, and 145.1 seconds at 32% CSF). Increased clot rates (CRs) were observed starting at a concentration of 5% (29.3 U/min at 0% CSF, 31.6 U/min at 5% CSF, and 35.3 U/min at 32% CSF). The roller pump model showed a significantly greater percentage of shunt surface covered with deposits when the shunts were infused with CSF rather than Ringer’s lactate solution (90% vs 63%). The amount of clot formation at the side facing the blood flow (impact side) tended to be lower than that at the side facing away from the blood flow (wake side; 71% vs 86%). CONCLUSIONS Addition of CSF to blood accelerates coagulation. The CSF-blood–foreign material interaction promotes clot formation, which might result in thrombotic shunt complications. Further development of the ventriculovenous shunt technique should focus on preventing CSF-blood–foreign material interaction and stagnation of CSF in wake zones.

BACKGROUND & AIMS: Higher infliximab trough levels are associated with clinical and endoscopic remission in patients with Crohn's disease (CD). We investigated pharmacodynamic features of infliximab and radiological healing. METHODS: We performed a substudy of the TAILORIX trial (patients with active luminal CD in Europe, treated with infliximab), analyzing baseline and week 54 magnetic resonance enterography (MRE) data. MREs were scored using the MaRIA score by blinded central readers. Radiologic response and remission were defined, based on MaRIA criteria in all segments, as scores below 11 and 7, respectively. We collected data on infliximab trough levels, biomarkers, and endoscopic findings. Our primary aim was to evaluate pharmacodynamic features associated with radiologic response and remission, based on MRE assessments at baseline and at 54 weeks after initiation of infliximab therapy. RESULTS: We analyzed data from 36 patients (50% female; median age 35.7 years; interquartile age range, 25.6-48.6 years; median disease duration, 1.5 months; interquartile duration range, 0.6-22.4 months). At week 54 of treatment, 36.4% of patients had a radiologic response, 30.3% of patients were in remission, and 71% had endoscopic features of remission. At baseline, there was a correlation between the CD endoscopic index of severity and MaRIA scores (κ = 0.46; P = .008), but we found no correlation at week 54 (κ = 0.06; P = .75). Radiologic remission correlated with infliximab trough level at week 14 (P = .049) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.74; 75% sensitivity; 86% specificity; 90% negative predictive value; 57% positive predictive value). Radiologic response correlated with infliximab trough levels at week 14 (P = .048) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.73; 70% sensitivity; 90% specificity; 86% negative predictive value; 78% positive predictive value) and with continuous pharmacologic evidence of response (infliximab trough levels above 5.0 μg/mL at all time points) (P = .034). CONCLUSIONS: In a substudy of data from the TAILORIX trial of patients with active luminal CD, we identified a relationship between exposure to infliximab and radiologic evidence of outcomes. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:19 issue:5 pages:947-+ ispartof: location:United States status: published

Background Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD. Methods Data were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD Results Linear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively. Conclusions Model-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.