Drawing as a Way of Knowing: How a Mapping Model Assists Preoperative Evaluation of Patients with Thyroid Carcinoma.

Background: Effective pre-surgical planning is crucial for achieving successful outcomes in endocrine surgery: it is essential to provide patients with a personalized plan to minimize operative and postoperative risks. Methods: Preoperative lymph node (LN) mapping is a structured high-resolution ultrasonography examination performed in the presence of two endocrinologists and the operating surgeon before intervention to produce a reliable "anatomical guide". Our aim was to propose a preoperative complete model that is non-invasive, avoids overdiagnosis of thyroid microcarcinomas, and reduces medical expenses. Results: The use of 'preoperative echography mapping' has been shown to be successful, particularly in patients with suspected or confirmed neoplastic malignancy. Regarding prognosis, positive outcomes have been observed both post-surgery and in terms of recurrence rates. We collected data on parameters such as biological sex, age, BMI, and results from cytologic tests performed with needle aspiration, and examined whether these parameters predict tumor malignancy or aggressiveness, calculated using a multivariate analysis (MVA). Conclusions: A standard multidisciplinary approach for evaluating neck lymph nodes pre-operation has proven to be an improved diagnostic and preoperative tool.

Self-reported treatment effectiveness for Crohn's disease using a novel crowdsourcing web-based platform.

BACKGROUND AND AIMS: Internet and social media platforms have become an unprecedented source for sharing self-experience, potentially allowing the collection and integration of health data with patient experience. StuffThatWorks (STW) is an online open platform that applies machine learning and the power of crowdsourcing, where patients with chronic medical conditions can self-report and compare their individual outcomes using a structured online questionnaire. We aimed to conduct a cross-sectional, international, crowdsourcing, artificial-intelligence (AI) web-based study of patients with Crohn's disease (CD) self-reporting their outcomes. METHODS: A proprietary STW Bayesian inference model was built to measure improvement in CD severity (on scale of 1-5) for each treatment and ranked treatments using effectiveness. The effectiveness of first-line biological treatments was analyzed by multiple comparisons and by calculating odds ratios and 95% confidence intervals for each treatment pair. RESULTS: We included 7593 self-reported CD patients for the analysis. Most of the participants were female (75.8%) and from English-speaking countries (95.7%). Overall, anti-TNF drugs were the most reported tried treatment (52.8%). Infliximab (IFX) was ranked as the most effective treatment by the STW effectiveness model followed by bowel surgery (second), adalimumab (ADA, third), ustekinumab (UST, 4rd), and vedolizumab (VDZ, fifth). In paired comparison analyses, IFX was most effective, ADA had similar effectiveness compared to UST and all three were more effective than VDZ. CONCLUSION: We present the first online crowdsourcing AI platform-based study of self-reported treatment effectiveness in CD. Net-based crowdsourcing patient-reported outcome platforms can potentially help both clinicians and patients select the best treatment for their condition.

Combined 3D Endoanal Ultrasound and Transperineal Ultrasound Improves the Detection of Anal Sphincter Defects.

INTRODUCTION: Anal sphincter injury, mainly due to obstetric or iatrogenic etiology, is the most common cause of fecal incontinence (FI). Three-dimensional endoanal ultrasound (3D EAUS) is used for assessment of the integrity and the degree of anal muscle injury. However, 3D EAUS accuracy may be hampered by regional acoustic effects, such as intravaginal air. Therefore, our aim was to examine whether a combination of transperineal ultrasound (TPUS) and 3D EAUS would improve the accuracy of detection of anal sphincter injury. METHODS: We prospectively performed 3D EAUS followed by TPUS in every patient evaluated for FI in our clinic between January 2020 and January 2021. The diagnosis of anal muscle defects was assessed in each ultrasound technique by two experienced observers that were blinded to each other's assessments. Interobserver agreement for the results of the 3D EAUS and the TPUS exams was examined. A final diagnosis of anal sphincter defect was based on the results of both ultrasound methods. Discordant results were re-analyzed by the two ultrasonographers for a final consensus on the presence or absence of defects. RESULTS: A total of 108 patients underwent ultrasonographic assessment due to FI (mean age 69 ± 13). Interobserver agreement for the diagnosis of tear on EAUS and TPUS was high (83%) with Cohen's kappa of 0.62. EAUS confirmed anal muscle defects in 56 patients (52%), while TPUS confirmed them in 62 patients (57%). The final consensus agreed on the diagnosis of 63 (58%) muscular defects and 45 (42%) normal exams. The Cohen's kappa coefficient of agreement between the results of the 3D EAUS and the final consensus was 0.63. CONCLUSIONS: The combination of 3D EAUS and TPUS improved the detection of anal muscular defects. The application of both techniques for the assessment of the anal integrity should be considered in every patient going through ultrasonographic assessment for anal muscular injury.

Disproportionately Low Albumin and High Neutrophil-to-Lymphocyte Ratio in Small Bowel Adenocarcinoma Patients With Long-Duration Crohn's Disease.

INTRODUCTION: Although Crohn's disease (CD) is a known risk factor of small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge. Identification of biomarkers for SBA may lead to early detection. METHODS: This is a retrospective study comparing albumin levels and neutrophil-to-lymphocyte ratio (NLR) of patients with long-standing CD who underwent small bowel resection with and without malignancy. RESULTS: Forty-two patients with CD were included in this study (11 with SBA). Median NLR before surgery was 8.5 (interquartile range 6.2-31.3) in patients with SBA and 3.8 (interquartile range 2.8-5.3) for patients without SBA ( P < 0.05). Mean albumin levels before surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL vs 3.5 ± 0.6 g/dL, respectively, P < 0.05), despite patients with SBA being under longer total parenteral nutrition treatment duration. DISCUSSION: CD patients with SBA diagnosis have increased NLR and lower albumin before surgery compared with CD patients without detection of SBA.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Serum Syndecan-1: A Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design. Serum SDC1 was measured by enzyme-linked immunoassay. The diagnostic accuracy of SDC1 levels for diagnosing PDAC was computed. A unified cohort enriched with additional early-stage patients with PDAC was used to evaluate the association of SDC1 with survival outcomes and patient characteristics. RESULTS: In the derivation cohort, serum SDC1 levels were significantly higher in patients with PDAC (n = 39) compared with healthy controls (n = 20) (40.1 ng/mL, interquartile range 29.8-95.3 vs 25.6 ng/mL, interquartile range 17.1-29.8, respectively; P < 0.001). The receiver operating characteristic analysis area under the curve was 0.847 (95% confidence interval 0.747-0.947, P < 0.001). These results were replicated in a separate age-matched validation cohort (n = 38 PDAC, n = 38 controls; area under the curve 0.844, 95% confidence interval 0.757-0.932, P < 0.001). In the combined-enriched PDAC cohort (n = 110), using a cutoff of 35 ng/mL, the median overall 5-year survival between patients below and above this cutoff was not significantly different, although a trend for better survival after 1 year was found in the lower level group (P = 0.06). There were 12 of the 110 patients with PDAC (11%) who had normal CA 19-9 in the presence of elevated SDC1. DISCUSSION: These findings suggest serum SDC1 as a promising novel biomarker for early blood-based diagnosis of pancreatic cancer.

Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.

Effectiveness and safety of Ustekinumab for Crohn's disease; systematic review and pooled analysis of real-world evidence.

BACKGROUND: Ustekinumab [UST] is effective in Crohn's disease (CD) in the UNITI studies. Several real-world experience (RWE) studies with UST have been published to date. Our aim was to summarize the available RWE data for UST effectiveness and safety. METHODS: A systematic review of the available RWE studies of UST for CD and pooled analysis of the available effectiveness and safety data was performed. RESULTS: Eight relevant studies of 6 RWE were included for analysis. Data from 578 patients were pooled for analysis. Most patients (97.7%) were anti-TNF experienced. Pooled clinical response rate was 60%, 62%, 49% at 12, 24 and 52 weeks respectively (95% CI (0.42-0.77), (0.48-0.75), (0.37-0.62)). Pooled remission rate was 39% (95% CI (0.18-0.65)) at 24 weeks and pooled endoscopic response rate was 63% (95% CI (0.53-0.72)) after approximately one year of UST; 134 adverse events (AE) were reported in total, pooled proportion 21% (95% CI (0.12-0.35)). Serious AE were reported in 19 patients, pooled proportion 5% (95% CI (0.03-0.08)). Infections were reported in 38, pooled proportion 6% (95% CI (0.04-0.11)). CONCLUSION: Pooled analysis of the RWE data suggests that the real-world effectiveness and safety are comparable to that reported in the randomized control trials.

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Vedolizumab in IBD-Lessons From Real-world Experience; A Systematic Review and Pooled Analysis.

BACKGROUND: Vedolizumab [VDZ] is an anti-integrin monoclonal antibody effective in ulcerative colitis [UC] and Crohn's disease [CD]. Several real-world experience [RWE] studies with VDZ have been published to date. The aim of this systematic review was to summarise the available real-life experience with VDZ. METHODS: We performed a systematic review of the available RWE studies of VDZ in CD and UC. We performed a pooled analysis of the available efficacy and safety data for induction and maintenance treatment in adult cohorts. A narrative review of VDZ use in special clinical settings was also performed. RESULTS: Nine studies including 1565 [571 UC, 994 CD] adult patients were identified. In CD, clinical response and remission were achieved in 54% (95% confidence interval [CI] 41-66%) and 22% [95% CI 13-35%] by Week 6 and in 49% [95% CI 37-51%] and 32% [95% CI 23-42%] by Week 14; at Week 52, 45% [95% CI 28-64%] and 32% [95% CI 12-62] of the patients responded, and were in clinical remission, respectively. In UC, clinical response and remission were achieved in 43% [95% CI 37-49] and 25% [95% CI 12-45] by Week 6, respectively, and in 51% [95% CI 43-61%]and 30% [95% CI 24-36%] by Week 14/22, respectively; at week 52, clinical response and remission were achieved in 48% and 39% of the patients, respectively. Adverse effects were mostly minor and occurred in 30.6% of the patients; infections were reported in 3.4% of the patients. CONCLUSIONS: VDZ is efficacious in CD and UC and has a favourable safety profile in RWE studies.

Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases.

BACKGROUND: Studies have confirmed an increased risk of colorectal cancer in patients with ulcerative colitis; hence, surveillance is recommended. Optional modalities include white light endoscopy (WLE) or dye-spray chromoendoscopy. However, narrow-band imaging (NBI) is still not considered comparable to chromoendoscopy. AIM: The aim of this study was to compare the diagnostic yield (DY) of WLE, chromoendoscopy, NBI for detection of neoplasia in patients with inflammatory bowel disease (IBD) by performing a meta-analysis of the existing literature. METHODS: We searched databases for prospective studies. For each modality, we performed comparative per-lesion analysis (any neoplasia detection) and per-patient analysis (patient with neoplastic lesions). Meta-analysis was performed using fixed-effect model unless heterogeneity was high. Odds ratios (ORs) with 95% CIs were calculated and pooled. RESULTS: Five studies compared chromoendoscopy to WLE. Chromoendoscopy (n = 361) was superior to WLE (n = 358) with per-patient analysis OR 2.05 (95% CI 1.26, 3.35) and per-lesion analysis OR 2.79 (95% CI 2.08, 3.73). High-definition (HD) chromoendoscopy was superior to HD-WLE with per-lesion analysis OR 2.48 (95% CI 1.55, 3.97). In four studies comparing NBI to WLE (n = 305), no difference was found in per-patient analysis OR 0.97 (95% CI 0.62, 1.53) and per-lesion analysis OR 0.94 (95% CI 0.63, 1.4). In two studies comparing CE to NBI (n = 104), no difference was found in per-patient analysis OR 1.0 (95% CI 0.51, 1.95) and per-lesion analysis OR 1.29 (95% CI 0.69, 2.41). CONCLUSION: Chromoendoscopy is superior to WLE for detection of dysplasia in IBD, even with HD endoscopy. No difference in DY could be demonstrated for NBI in comparison with other modalities.

Diagnostic yield of capsule endoscopy versus magnetic resonance enterography and small bowel contrast ultrasound in the evaluation of small bowel Crohn's disease: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Capsule endoscopy (CE), magnetic resonance enterography (MRE) and small bowel (SB) intestinal contrast ultrasound (SICUS) are the modalities of choice for SB evaluation. This study aimed to compare the diagnostic yield (DY) of CE to MRE and SICUS in detection and monitoring of SB CD through meta-analysis of the available literature. METHODS: We performed a systematic literature search for trials comparing the accuracy of CE, MRE and SICUS for detection of active SB inflammation in patients with suspected and/or established CD. Only prospective studies comparing CE with another additional diagnostic modality were included in the final analysis. Pooled odds ratios (ORs) for the DY of the three modalities were calculated. RESULTS: A total of 112 studies were retrieved; following selection, 13 studies were eligible for analysis. The DY of CE for detection of active SB CD was similar to that of MRE (10 studies, 400 patients, OR 1.17; 95% CI 0.83-1.67) and SICUS (5 studies, 142 patients, OR 0.88; 95% CI 0.51-1.53). The outcomes were similar for the subgroups of suspected versus established CD and adult versus pediatric patients. CE was superior to MRE for proximal SB CD (7 studies, 251 patients, OR 2.79; 95% CI 1.2-6.48); the difference vs SICUS was not significant. CONCLUSION: CE, MRE and SICUS have similar DY for detection of SB CD in both suspected and established CD. CE is superior to MRE for detection of proximal SB disease, however the risk of capsule retention should be considered.

Fecal calprotectin for the prediction of small-bowel Crohn's disease by capsule endoscopy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Fecal calprotectin is a well-established marker of mucosal inflammation. Although the correlation of elevated calprotectin levels with colonic inflammation has been confirmed repeatedly, it is less established for the small bowel. The aim of the current study was to assess the diagnostic accuracy of calprotectin for the prediction of active small-bowel disease on capsule endoscopy by performing a diagnostic test meta-analysis. MATERIALS AND METHODS: A comprehensive search was performed using PubMed/Embase. Studies addressing patients with suspected/established Crohn's disease (CD) evaluated with calprotectin and videocapsule were included. A diagnostic meta-analysis was carried out; pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each cut-off. RESULTS: Seven studies (463 patients) were entered into the final analysis. The DOR was significant for all the evaluated FC cut-offs (50 µg/g: sensitivity 0.83, specificity 0.53, DOR-5.64; 100 µg/g: sensitivity 0.68, specificity 0.71, DOR-5.01; 200 µg/g: sensitivity 0.42, specificity 0.94, DOR-13.64). On sensitivity analyses, when only studies addressing suspected Crohn's or retrospective studies were included, the results did not change significantly. For studies including patients with suspected CD only, the overall accuracy for FC cut-off 50 µg/g was further increased (sensitivity 0.89, specificity 0.55, DOR-10.3), with a negative predictive value of 91.8%. SUMMARY AND CONCLUSION: Fecal calprotectin has a significant diagnostic accuracy for the detection of small-bowel CD. Our results suggest that in patients with suspected CD with calprotectin <50 µg/g, the likelihood of positive diagnosis is very low.

Ustekinumab in Crohn's disease: evidence to date and place in therapy.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) with uncertain etiology. Biologic agents have revolutionized the treatment of CD but nonresponders remain a challenge. Ustekinumab is an interleukin 12/23p40 inhibitor that was recently found effective in treating CD. We reviewed the current literature regarding the efficacy of ustekinumab in treating CD and concluded that ustekinumab is a novel, promising and relatively safe agent for the treatment of moderate to severe CD. Additional data from randomized controlled studies and real-life cohorts are pending.

Combination of Corticosteroids with 5-Aminosalicylic Acids Compared to Corticosteroids Alone for Hospitalized Patients with Active Ulcerative Colitis.

BACKGROUND: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. OBJECTIVES: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. METHODS: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. RESULTS: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13-0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. CONCLUSIONS: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment.

Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease.

BACKGROUND: Autonomic dysfunction has been implicated in Crohn's disease (CD). We aimed to investigate heart rate variability (HRV) as a marker of possible autonomic imbalance in patients with CD. METHODS: Thirty patients with CD and 30 age- and gender-matched healthy controls were enrolled in a prospective cohort study and underwent HRV study. Anxiety level was scored using the STAI questionnaire and CD clinical activity was assessed by Harvey-Bradshaw index. Blood tests including inflammatory markers were obtained for all participants. RESULTS: CD subjects had lower mean blood pressure (85.51 ± 11.07 mm Hg, 91.51 ± 6.99, P = 0.015) and albumin and significantly higher CRP and IL-6 compared with controls (P < 0.002 for all comparisons). Mean HRV values of very low-frequency power and low-frequency power components were significantly lower among CD subjects (P = 0.038 and 0.027, respectively), implying a predominant sympathetic tone. Anxiety level scores were significantly higher among patients with CD for both state anxiety (P = 0.001) and trait anxiety (P < 0.0001). However, patients with active disease had similar anxiety scores as patients in remission, yet had a significantly lower BMI, lower albumin level, and higher CRP and IL-6 levels (P < 0.05 for all comparisons). Moreover, despite similar anxiety scores, patients with active disease had higher pulse rate (P = 0.02) and lower HRV indexes, which correlated with albumin levels(r = 0.7, P = 0.001). CONCLUSIONS: Although patients with CD have higher anxiety levels compared with controls, they exhibit depressed HRV independent of this anxiety state and in direct correlation with disease activity and inflammatory markers. These observations suggest an inherent imbalance of autonomic function associated with active inflammation.

Nilotinib-associated acute pancreatitis.

OBJECTIVE: To report a case of acute pancreatitis in a patient receiving nilotinib for chronic myelogenous leukemia (CML). CASE SUMMARY: A 69-year-old man recently diagnosed with chronic phase CML received nilotinib 300 mg twice daily and was admitted with acute pancreatitis that appeared the day after the first dose. The patient had normal levels of triglycerides and denied alcohol use. Serum pancreatic enzymes were within normal limits the day before nilotinib initiation. Abdominal computed tomography demonstrated a normal liver, bile duct without stones, and findings that were consistent with focal pancreatitis. The patient's history was significant for concomitant use of enalapril and simvastatin; both have been associated with pancreatitis, but the patient had been taking these medications for at least 5 years without adverse effects. Nilotinib was immediately discontinued. Abdominal pain resolved and serum pancreatic enzymes levels returned to normal 2 weeks later. DISCUSSION: One of the adverse effects of some tyrosine kinase inhibitors is increased levels of serum pancreatic enzymes. Accordingly, nilotinib labeling includes "high lipase levels in serum" as an adverse event. There are few case reports of acute pancreatitis associated with nilotinib in the literature and some are incomplete. We present a well-documented case of nilotinib-associated acute pancreatitis. Consistent with Badalov's new classification system for drug-induced acute pancreatitis and with the Naranjo probability scale, this case represents a possible adverse reaction of pancreatitis associated with nilotinib therapy. As rechallenge is unethical, treatment with nilotinib has not been resumed. CONCLUSIONS: This case demonstrates a possible association between acute pancreatitis and nilotinib use. Although a rare phenomenon, clinicians should be alert for signs and symptoms of pancreatitis, as treatment with nilotinib for CML is becoming more common.

Low admission Norton scale scores are associated with falls long after rehabilitation in the elderly with hip fractures.

BACKGROUND: In this study, we investigated if low admission Norton scale scores (ANSS) are associated with falls, fractures, hospitalizations, and death, after rehabilitation in the elderly with hip fractures. METHODS: This prospective historical study followed consecutive elderly patients (≥65 years) who were admitted for rehabilitation following hip fracture surgery during 2009 and followed up in January or February 2012. The incidence of falls, number of falls, incidence of fractures, number of hospitalizations, and death rates were compared between patients with low (≤14) and high (≥15) ANSS. RESULTS: The final cohort included 174 patients of mean age 83.6 ± 6.2 years, with 133 (76.4%) being women. Fifty-seven (27.0%) patients died during follow-up. Of the remaining 127 patients, 44 (34.6%) fell at least once and 15 (11.8%) suffered fractures. Overall, 81 (46.6%) patients had a low ANSS. Relative to patients with a high ANSS, they had a higher incidence of falls (odds ratio 3.3, 95% confidence interval 1.5-7.1; P = 0.002) and fell more times (1.2 ± 1.8 versus 0.6 ± 1.7; P = 0.002). Regression analysis showed that ANSS (as a parametric variable) as well as a low ANSS (as a nonparametric variable) were independently associated with falls (P = 0.002 and P = 0.009, respectively). There were no differences between patients with low and high ANSS in terms of incidence of fractures, number of hospitalizations, and death rates. CONCLUSION: The Norton scoring system may be used for predicting falls long after rehabilitation in the elderly with hip fractures.

Cytomegalovirus-associated cerebral sinus vein thrombosis.

Cytomegalovirus (CMV)-associated thrombosis has been reported many times in the medical literature, and most patients had deep vein thrombosis and/or pulmonary embolism. CMV-associated cerebral sinus vein thrombosis has been reported only twice. We present an immunocompetent patient with CMV-associated cerebral sinus vein thrombosis and no other thrombosis risk factors. This is another example of the pro-thrombotic features of CMV. Physicians should be alert for symptoms and signs of acute CMV infection in patients with thrombosis.