Abductor tendon tears are associated with hypertrophy of the tensor fasciae latae muscle

Objective: To evaluate the association between hypertrophy of the tensor fasciae latae muscle and abductor tendon tears. Materials and methods: Thirty-five patients who underwent MRI of the abductor tendons of the hip were included in this retrospective study. A subgroup of 18 patients was examined bilaterally. The area of the tensor fasciae latae muscle and the area of the sartorius muscle (size reference) were quantified at the level of the femoral head, and a ratio was calculated. Two radiologists assessed the integrity of the gluteus medius and minimus tendon in consensus. Data were analyzed with a Mann-Whitney U test. Results: Sixteen out of 35 patients (46%) had a tear of the gluteus medius or minimus tendon. The ratio of the area of the tensor fasciae latae to the sartorius muscle was significantly higher (p = .028) in the group with an abductor tendon tear (median 2.25; Interquartile Range [IQR] = 1.97-3.21) compared to the group without any tears (median 1.91; IQR = 1.52-2.26). The bilateral subanalysis showed that in patients without a tear, the ratio of the two areas did not differ between each side (p = .966), with a median of 1.54 (primary side) and 1.76 (contralateral side). In patients with an abductor tendon tear the ratio was significantly higher (p = .031) on the side with a tear (median 2.81) compared to the contralateral healthy side (1.67). Conclusion: Patients with abductor tendon tears showed hypertrophy of the tensor fasciae latae muscle when compared to the contralateral healthy side and to patients without a tea

Identification of a New Chemical Class of Antimalarials

The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with half-maximal inhibitory concentration (IC50) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all 3 asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine Plasmodium berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model. ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potentia

Amide Proton Transfer Contrast Distribution in Different Brain Regions in Young Healthy Subjects

ObjectivesTo define normal signal intensity values of amide proton transfer-weighted (APTw) magnetic resonance (MR) imaging in different brain regions.Materials and MethodsTwenty healthy subjects (9 females, mean age 29 years, range 19 – 37 years) underwent MR imaging at 3 Tesla. 3D APTw (RF saturation B1,rms = 2 μT, duration 2 s, 100% duty cycle) and 2D T2-weighted turbo spin echo (TSE) images were acquired. Postprocessing (image fusion, ROI measurements of APTw intensity values in 22 different brain regions) was performed and controlled by two independent neuroradiologists. Values were measured separately for each brain hemisphere. A subject was scanned both in prone and supine position to investigate differences between hemispheres. A mixed model on a 5% significance level was used to assess the effect of gender, brain region and side on APTw intensity values.ResultsMean APTw intensity values in the hippocampus and amygdala varied between 1.13 and 1.57%, in the deep subcortical nuclei (putamen, globus pallidus, head of caudate nucleus, thalamus, red nucleus, substantia nigra) between 0.73 and 1.84%, in the frontal, occipital and parietal cortex between 0.56 and 1.03%; in the insular cortex between 1.11 and 1.15%, in the temporal cortex between 1.22 and 1.37%, in the frontal, occipital and parietal white matter between 0.32 and 0.54% and in the temporal white matter between 0.83 and 0.89%. APTw intensity values were significantly impacted both by brain region (p < 0.001) and by side (p < 0.001), whereby overall values on the left side were higher than on the right side (1.13 vs. 0.9%). Gender did not significantly impact APTw intensity values (p = 0.24). APTw intensity values between the left and the right side were partially reversed after changing the position of one subject from supine to prone.ConclusionWe determined normal baseline APTw intensity values in different anatomical localizations in healthy subjects. APTw intensity values differed both between anatomical regions and between left and right brain hemisphere

Sex and age dependencies of aqueductal cerebrospinal fluid dynamics parameters in healthy subjects

Objectives: To assess the influence of age and sex on 10 cerebrospinal fluid (CSF) flow dynamics parameters measured with an MR phase contrast (PC) sequence within the cerebral aqueduct at the level of the intercollicular sulcus.Materials and Methods: 128 healthy subjects (66 female subjects with a mean age of 52.9 years and 62 male subjects with a mean age of 51.8 years) with a normal Evans index, normal medial temporal atrophy (MTA) score, and without known disorders of the CSF circulation were included in the study. A PC MR sequence on a 3T MR scanner was used. Ten different flow parameters were analyzed using postprocessing software. Ordinal and linear regression models were calculated.Results: The parameters stroke volume (sex: p < 0.001, age: p = 0.003), forward flow volume (sex: p < 0.001, age: p = 0.002), backward flow volume (sex: p < 0.001, age: p = 0.018), absolute stroke volume (sex: p < 0.001, age: p = 0.005), mean flux (sex: p < 0.001, age: p = 0.001), peak velocity (sex: p = 0.009, age: p = 0.0016), and peak pressure gradient (sex: p = 0.029, age: p = 0.028) are significantly influenced by sex and age. The parameters regurgitant fraction, stroke distance, and mean velocity are not significantly influenced by sex and age.Conclusion: CSF flow dynamics parameters measured in the cerebral aqueduct are partly age and sex dependent. For establishment of reliable reference values for clinical use in future studies, the impact of sex and age should be considered and incorporated

Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. METHOD AND FINDINGS: The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study

Consensus guidelines for the definition of time-to-event end points in image-guided tumor ablation: results of the SIO and DATECAN initiative

International audienceThere is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue

Mid-term results of MR-guided high-intensity focused ultrasound treatment for relapsing superficial desmoids

PURPOSE Desmoids are locally infiltrative, nonmalignant soft tissue tumors. Surgery, radiation therapy, and chemotherapy have been the mainstay of treatment, but relapse is common and side effects can result in significant morbidity. MR-HIFU is increasingly recognized as an alternative treatment modality. We assessed the success rate of MR-HIFU for the treatment of extra-abdominal desmoids at our institute. MATERIALS AND METHODS Five patients with relapsing desmoid tumors (three males, two females; age range 40-79 years) were treated using the Sonalleve system in an outpatient setting without general anesthesia. Changes in total tumor volumes were measured with a tumor tracking software. Adverse events were documented. RESULTS MR-HIFU was successful in all patients without severe side effects. Follow up ranged from 13 to 60 months. Three patients required more than one treatment session. In 3 patients with small lesions (mean = 9.7 mL), complete ablation was achieved with no evidence of viable tumor on follow up MRI at an average of 35.7 months, while in two patients with larger lesions (mean = 46 mL) the targeted tumor volumes decreased by 73% at 14 months. Skin injuries comprised first- and second-degree burns and were observed with short distance to skin (mean = 0.9 cm) and proximity to bone (i.e. ribs). Skin burns healed within weeks with topical treatment. CONCLUSION MR-HIFU shows good mid-term result for extra-abdominal desmoids with complete response for small lesions and stabilization of larger lesions. MR-HIFU for desmoids can be performed under regional anesthesia/sedation as outpatients