Fengerrhodes9336

Members of the International Skeletal Society compiled a glossary of terms for musculoskeletal radiology. The authors also represent national radiology or pathology societies in Asia, Australia, Europe, and the USA. We provide brief descriptions of musculoskeletal structures, disease processes, and syndromes and address their imaging features. Given the abundance of musculoskeletal disorders and derangements, we chose to omit most terms relating to neoplasm, spine, intervention, and pediatrics. Consensus agreement was obtained from 19 musculoskeletal radiology societies worldwide.Objectives To identify the diagnostic performance of magnetic resonance imaging (MRI) in the knee-flexed position for the detection of meniscal ramp lesions in patients with anterior cruciate ligament tears. Materials and methods Forty-three patients (mean age 24.5 ± 9.5 years; 21 males, 22 females) with an arthroscopically proven anterior cruciate ligament tear were included in this retrospective study. The presence of the following two important features on MRI was recorded irregularity of the medial meniscus at the posterior margin, and complete fluid filling between the posterior horn of the medial meniscus and the capsule margin. Findings obtained in arthroscopy served as the reference standard. The diagnostic sensitivity, specificity, and inter-observer agreement were calculated. Results Sixteen ramp lesions were noted on arthroscopy (37.2%). With an irregularity of the medial meniscus at the posterior margin on MRI, the sensitivity and specificity were 87.5 and 59.3% at 10° knee flexion and 93.8 and 85.2% at 90° flexion, respectively. The complete fluid filling sign on MRI showed sensitivity and specificity of 31.3 and 100% at 10° knee flexion and 87.5 and 100% at 90° flexion, respectively. The concordance between the two observers for the two MRI features was very good (k = 0.70-0.88). Conclusion MRI with the knee in the flexed position improves the diagnostic performance of the detection of meniscal ramp lesions compared with MRI with the knee in the extended position.Aim The aim of this article is to understand the pros and cons of various methods involved in first-in-human (FIH) dose calculation and act decisively in dose escalations when calculating the maximum tolerated dose. Subjects and methods We reviewed early phase clinical trials for methods of FIH dose and dose-escalation steps and discuss them in line with existing guidelines. We also reviewed the clinical trial registry to recognize trends in trial registration in recent years and after a massive failure in a few trials. Results Phase 1 trials of TGN 1412 and BIA10-2474 would always be remembered as catastrophes for pharmaceutical development plans. Fluzoparib in vitro Quite often than not, healthy human volunteers are the guinea pigs in this stage of drug development. And, the most important aspect of designing an early phase study is deciding upon the dose to be started with, apart from the selection of cohort and escalation steps. The common principles used for FIH dose calculation include no observed adverse effect level, minimum anticipated biological effect level, pharmacologically active dose, pharmacokinetic/pharmacodynamic approach, and similar drug comparison approach. Conclusion Early phase clinical trials are basically foundation stones on which lies the entire onus of the later stages of development. Deciding FIH dose is a crucial step that necessitates the incorporation of detailed data from the preclinical stages and application of the most conservative approach for the safety/benefit of the volunteers in these studies.Introduction This comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (Cmin) and treatment outcomes. Methods Chronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). Nilotinib Cmin and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months. Results Sixty-eight patients (57.5 ± 15.0 years, 49% female) participated. Median adherence to nilotinib (MEMS and pill count) was ≥ 99% and adherence less then 90% was rare. Self-reported nonadherence (MARS-5) increased in the first year of treatment to a third of patients. In line with the strong beliefs in the necessity of taking nilotinib, forgetting to take a dose was more prevalent than intentionally adjusting/skipping doses. Nilotinib Cmin were generally above the therapeutic target in 95% of patients. Patients reported a variety of side effects, of which fatigue was most frequent. The mean Cmin was higher in patients who reported severe itching and fatigue. The overall 1-year MMR rate ranged from 47 to 71%. Conclusion Substantial nonadherence ( less then 90%) to nilotinib was rare and nilotinib Cmin were generally above the therapeutic target. Lack of response in our group of patients was not related to nonadherence or inadequate Cmin. Nevertheless, a considerable number of patients experienced difficulties in adhering to the twice daily fasted dosing regimen, emphasizing the importance of continuous support of medication adherence in CML. Clinical trial registration NTR3992 (Netherlands Trial Register, www.trialregister.nl).Purpose Fractional doses of proton pump inhibitors (PPIs) more often than once daily (qd) inhibit 24-h acid secretion more effectively than an increase in the standard single daily dose. Although rabeprazole 5 mg qd is covered for prevention of aspirin-induced gastric injury under the Japanese insurance system, it is unclear whether rabeprazole 5 mg twice daily (bid) would more effectively inhibit acid secretion. We compared acid inhibition between rabeprazole 10 mg qd and 5 mg bid in healthy volunteers with different alleles of CYP2C19. Methods Twelve Helicobacter pylori-negative healthy volunteers (CYP2C19 genotypes extensive metabolizer (EM) (n = 6) and poor metabolizer (PM) (n = 6)) received three kinds of regimen for 7 days under a randomized crossover design rabeprazole 5 mg qd (5 mg QD), 10 mg qd (10 mg QD), and 5 mg bid (5 mg BID). A 24-hour pH monitoring was conducted before the trial and on day 7 of each regimen. Results No significant differences in median pH values (4.0 (1.9-5.9)) and (4.4 (2.1-6.5)) or percent time of pH ≥ 4 (50.7% (11.9-86.8%) and 56.8% (19.3-83.9%)) were seen between the 10 mg QD and 5 mg BID regimens. Median pHs and percent time of pH ≥ 4 in CYP2C19 PMs were significantly higher than those in EMs. With 5 mg BID, there was no significant difference in percent-time with pH ≥ 4 between daytime and nighttime, but the 10 mg QD showed a significant difference. Conclusion Rabeprazole 5 mg bid provided no therapeutic advantage for acid inhibition compared with rabeprazole 10 mg qd, regardless of CYP2C19 genotype status.Purpose A Bayesian confidence propagation neural network (BCPNN) is a signal detection method used by the World Health Organization Uppsala Monitoring Centre to analyze spontaneous reporting system databases. We modify the BCPNN to increase its sensitivity for detecting potential adverse drug reactions (ADRs). Method In a BCPNN, the information component (IC) is defined as an index of disproportionality between the observed and expected number of reported drugs and events. Our proposed method adjusts the IC value by borrowing information about events that have occurred in drugs defined as similar to the target drug. We compare the performance of our method with that of a traditional BCPNN through a simulation study. Results The false positive rate of the proposed method was lower than that of the traditional BCPNN method and close to the nominal value, 0.025, around the true difference in ICs between the target drug and similar drugs equal to 0. The sensitivity of the proposed method was much higher than that of the traditional BCPNN method in case in which the difference in ICs between the target drug and similar drugs ranges from 0 to 2. When applied to a database managed by Japanese regulatory authority, the proposed method could detect known ADRs earlier than the traditional method. Conclusions The proposed method is a novel criterion for early detection of signals if similar drugs have the same tendencies. The proposed BCPNN tends to have higher sensitivity when the true difference is greater than 0.Purpose To compare anatomical and functional results between internal limiting membrane (ILM) peeling and non-ILM peeling in macula-off rhegmatogenous retinal detachment (RRD). Methods We completed a retrospective cohort study of patients who underwent pars plana vitrectomy (PPV) due to macula-off RRD. ILM peeling (P) versus non-ILM peeling (NP) groups were compared regarding best-corrected visual acuity (BCVA), anatomical success, endotamponade, concomitant scleral band placement and BCVA gain for epiretinal membranes (ERM) resubjected to PPV. Statistical significance was considered when p less then 0.05. Results PPV was conducted in 352 patients, among which 43.5% (n = 153) were in the P group and 55.6% (n = 196) were in the NP group. Both groups had significant BCVA improvement during the study period (p less then 0.001), but with no significant difference between them. Anatomical success was similar between P (84.2%) and NP (87.2%) groups. No difference was found with regard to endotamponade (p = 0.07) or concomitant scleral band placement (p = 0.43). The NP group developed subsequent ERM more frequently (p = 0.004), but BCVA gains for eyes requiring repeat PPV for ERM were not found (p = 0.14). Conclusions Although ERM formation and greater anatomical success are reasons to support the use of ILM peeling in RRD, we did not observe any anatomical or functional difference regarding ILM peeling or functional gain with secondary ERM peeling.Purpose To examine the structure of photoreceptors surrounding two subtypes of subretinal drusenoid deposits (SDD), namely, dot and ribbon SDD, using multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT). Methods Twenty-six eyes of 13 patients with age-related macular degeneration (AMD) and SDD and 16 eyes of 8 subjects in normal chorioretinal health were studied. SDD presence, stage, and subtype were determined using color fundus photographs, infrared reflectance, autofluorescence imaging, and SD-OCT. SDD and surrounding photoreceptors were imaged using AOSLO. The structure of cone photoreceptors and SDD was examined at the baseline and at 2-year follow-up studies in 6 patients. Results Dot SDD were identified in 18 eyes of 9 patients and coexisting dot and ribbon SDD were observed in 8 eyes of 4 patients. While a characteristic photoreceptor mosaic was clearly revealed by AOSLO in the area unaffected by lesions in those eyes with dot-only SDD, in unaffected areas adjacent to retinal regions with predominantly ribbon SDD, photoreceptors could no longer be visualized. Conclusion The invisibility of the photoreceptor mosaic in unaffected areas adjacent to retinal regions with predominantly ribbon SDD suggests degeneration in the outer segment and the interdigitation zone, which impairs the waveguiding ability of the photoreceptors. Our study implies possible differentiation of disease outcome and functional impact in different types of SDD.