Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy

OBJECTIVE: Prediction of the clinical course of Crohn's disease (CD) is difficult in the long term. Our aim was to determine whether the presence of severe endoscopic lesions (SELs) may predict a higher risk of colectomy and penetrating complications. METHODS: All patients at our institution with active ileocoIonic CD who had colonoscopies between 1990 and 1996 were included in the study. SELs were defined as extensive and deep ulcerations covering more than 10% of the mucosal area of at least one segment of the colon. RESULTS: Among the 102 patients included, 53 had SELs at index colonoscopy. During the follow-up (median = 52 months), 37 patients underwent colonic resection. Probabilities of colectomy at 1, 3, and 8 yr were 20%, 26%, and 42%. Risk of colectomy was independently affected by the presence of SELs at index colonoscopy (relative risk [RR] = 5.43, 95% CI = 2.64-11.18), a Crohn's Disease Activity Index level greater than 288 (RR = 2.21, 95% CI = 1.09-4.47), and the absence of immunosuppressive therapy during the follow-up (RR = 2.44, 95% CI = 1.20-5.00). Probabilities of colectomy were, respectively, 31% and 6% at 1 yr, 42% and 8% at 3 yr, and 62% and 18% at 8 yr in patients with and without SELs. We performed a second analysis excluding the 14 patients operated on within the 3 months after the index colonoscopy: presence of SELs remained the only significant factor predictive of colectomy (RR = 6.72, 95% CI = 2.26-20.03). All six patients with penetrating complications during the follow-up had SELs at index colonoscopy. CONCLUSIONS: Patients with CD exhibiting deep and extensive ulcerations at colonoscopy have a more aggressive clinical course with an increased rate of penetrating complications and surgery.     

Nocturnal pain correlates with effusions in diseased hips.

Thirty-five of 50 patients with different hip joint disease had sonographic evidence of joint effusion. Arthrocentesis confirmed effusions in 30 of these 35 patients. Thirty-two of the 35 patients had nocturnal pain. Both nocturnal pain and sonographic evidence of effusion decreased after aspiration (15 patients) and aspiration and injection of corticosteroids (15 patients). In a further group of 61 patients who subsequently had Charnley arthroplasties, 35 had positive sonograms before operation. Of these, 25 had effusions confirmed at operation, the remaining 10 having synovitis and capsule thickening. Again a correlation was found with nocturnal pain. The sensitivity of sonography in detecting hip joint effusion was 92% with a specificity of 70%. Nocturnal pain had a lower sensitivity, 85%, but higher specificity, 94%.     

The Extent of Late Gadolinium Enhancement Can Predict Adverse Cardiac Outcomes in Patients with Non-Ischemic Cardiomyopathy with Reduced Left Ventricular Ejection Fraction: A Prospective Observational Study

ObjectiveThe clinical course of an individual patient with heart failure is unpredictable with left ventricle ejection fraction (LVEF) only. We aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived myocardial fibrosis extent and to determine the cutoff value for event-free survival in patients with non-ischemic cardiomyopathy (NICM) who had severely reduced LVEF.Materials and MethodsOur prospective cohort study included 78 NICM patients with significantly reduced LV systolic function (LVEF < 35%). CMR images were analyzed for the presence and extent of late gadolinium enhancement (LGE). The primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, heart transplantation, implantable cardioverter-defibrillator discharge for major arrhythmia, and hospitalization for congestive heart failure within 5 years after enrollment.ResultsA total of 80.8% (n = 63) of enrolled patients had LGE, with the median LVEF of 25.4% (19.8–32.4%). The extent of myocardial scarring was significantly higher in patients who experienced MACE than in those without any cardiac events (22.0 [5.5–46.1] %LV vs. 6.7 [0–17.1] %LV, respectively, p = 0.008). During follow-up, 51.4% of patients with LGE ≥ 12.0 %LV experienced MACE, along with 20.9% of those with LGE ≤ 12.0 %LV (log-rank p = 0.001). According to multivariate analysis, LGE extent more than 12.0 %LV was independently associated with MACE (adjusted hazard ratio, 6.71; 95% confidence interval, 2.54–17.74; p < 0.001).ConclusionIn NICM patients with significantly reduced LV systolic function, the extent of LGE is a strong predictor for long-term adverse cardiac outcomes. Event-free survival was well discriminated with an LGE cutoff value of 12.0 %LV in these patients.     

Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

Purpose

Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.

Materials and Methods

We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).

Results

Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0±10.2% versus 11.8±9.7%, p=0.61, and 286.3±54.7 versus 295.7±53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5±17.9% versus 28.3±16.6%, p=0.02, and 207.3±68.2 versus 241.3±76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7±8.7% to 15.8±18.4%, p=0.08, and from -18.6±58.0 to -61.9±84.3, p=0.08).

Conclusion

Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.     

Noroviruses and histo‐blood groups: the impact of common host genetic polymorphisms on virus transmission and evolution

Noroviruses (NoVs) are recognized as a leading cause of human gastroenteritis worldwide. Infection occurs following the ingestion of contaminated food or, most often, through direct contact from person to person. However, not all individuals are equally sensitive to these viruses. Indeed, NoVs use glycans of the ABH and Lewis histo‐blood group antigen family (HBGAs) as attachment factors. At the epithelial level, the synthesis of these HBGAs requires the action of several glycosyltransferases that are encoded by the ABO, FUT2, and FUT3 genes. The combined polymorphism at these three loci dictates sensitivity to NoV infection because the attachment profile to these glycans varies among strains. Structural analysis of the capsid protein interaction with HBGAs reveals distinct modes of binding for strains of genogroups I and II but high conservation within each genogroup, whereas minor amino acid changes are sufficient to generate modifications of HBGA‐binding specificities or affinities. Such modifications therefore induce changes in the spectrum of susceptible individuals. Studies of NoV–HBGA interactions together with phylogenetic analyses and the epidemiologic survey of strains indicate that NoV transmission and evolution depend on both the establishment of herd immunity and the genetic resistance of many individuals, which confers herd innate protection by restricting NoV circulation. Copyright © 2013 John Wiley & Sons, Ltd.     

Dissecting the Structure and Mechanism of a Complex Duplication–Triplication Rearrangement in the DMD Gene

Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event.     

Early imaging signs of the use of antiresorptive medication and MRONJ: a systematic review

Objective

The main aim is to identify, by means of different imaging modalities, the early bone changes in patients “at risk” and in stage 0 MRONJ.

Materials and methods

A search of the literature was performed on PubMed, Embase, Web of Science, and Cochrane Library databases, until June 9, 2020. No language or year restrictions were applied. Screening of the articles, data collection, and qualitative analysis was done. The Newcastle-Ottawa Scale (NOS) was used for observational studies, and the Systematic Review Centre for Laboratory Animal Experimentation’s (SYRCLE) risk of bias tool for the animal studies.

Results

A total of 1188 articles were found, from which 47 were considered eligible, whereas 42 were suitable for the qualitative analysis. They correspond to 39 human studies and 8 animal studies. Radiographic findings such as bone sclerosis, osteolytic areas, thickening of lamina dura, persisting alveolar socket, periapical radiolucency, thicker mandibular cortex, widening of the periodontal ligament space, periodontal bone loss, and enhancement of the mandibular canal were identified as early bone changes due to antiresorptive therapy. All those findings were also reported later in Stage 0 patients.

Conclusion

The main limitations of these results are the lack of prospective data and comparisons groups; therefore, careful interpretation should be made. It is a fact that radiographic findings are present in antiresorptive-treated patients, but the precise timepoint of occurrence, their relation to the posology, and potential risk to develop MRONJ are not clear.

Clinical relevance

The importance of a baseline radiographic diagnosis for antiresorptive-treated patients.