Acute tear of the fascia cruris at the attachment to the Achilles tendon: a new diagnosis

BACKGROUND: The fascia cruris encloses the posterior structures of the calf and connects to the paratenon and the Achilles tendon. We describe the clinical presentation, ultrasound imaging characteristics and the time to the recovery of tears of the fascia cruris at the attachment to the Achilles tendon. METHODS: Retrospective review of 11 tears of the fascia cruris in the different legs as separate events in 9 patients (6 male and 3 female, mean age 35.52 years, range 11–48) identified using diagnostic ultrasound, after presenting with Achillodynia. RESULTS: 11 participants presented at a mean of 4.5 weeks (range 0.5–12) after onset of symptoms. The left Achilles was more commonly injured than the right (7 : 4) and the lateral side more than the medial (6 : 4) with one case with medial and lateral presentation. Clinically, there was swelling and tenderness over the medial or lateral border in the mid to upper portion of the Achilles. 7 of the 11 (63.6%) had functional overpronation. Ultrasound appearances of a tear were identified as hypoechoic area extending from the medial or lateral border of the Achilles extending along the anatomical plane of the fascia cruris. Average return to activity was 5.2 weeks (range 1–22). Participants presenting later had longer recovery but all participants returned to full activity (r=0.4). CONCLUSIONS: This is the first description of the clinical details and sonographic findings of a tear to the fascia cruris at its attachment to the Achilles tendon. This needs to be considered as a cause of Achillodynia in athletes as recognition will affect the management

The u-can-act Platform:A Tool to Study Intra-individual Processes of Early School Leaving and Its Prevention Using Multiple Informants

We present the u-can-act platform, a tool that we developed to study the individual processes of early school leaving and the preventative actions that mentors take to steer these processes in the right direction. Early school leaving is a significant problem, particularly in vocational education, and can have severe consequences for both the individual and society. However, the prevention of early school leaving is hampered by a mismatch between research and practice: research tends to focus on identifying risk factors using group averages and cross-sectional studies, while practitioners focus on intervening in individual processes. We aim to help solve this mismatch with our project u-can-act. In this project we have developed a platform that helps to gain insight into both the individual processes that precede early school leaving as well as the actions that mentors take to prevent it. In this paper we introduce the u-can-act platform, which consists of three technology-based, reusable methodological innovations. Specifically, our innovations concern: (i) an open source web application for longitudinal personalized data-collection, (ii) an automated study protocol that optimizes adherence in a difficult target group (adolescents at risk for early school leaving), and (iii) a technologically assisted coupling between mentor and student that allows us to study dyadic interactions over time. We present performance results of our platform, including participant adherence, the behavior of the questionnaire items over time, and the way that our web application is experienced by the participants. We conclude that our innovative platform is successful in collecting multi-informant time-series data on intervention processes among students in vocational education, both for at-risk students and control students, and for their mentors. Moreover, our platform is suitable for broader applications: it can be used to study any malleable individual process including the efforts of a second individual who aims to influence this process. Because of the unique insights that the u-can-act platform is able to generate, the platform may ultimately contribute to solving the mismatch between research and practice, and to more effective interventions in individual processes

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed n

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).</p

The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI): instrument and pre-launch testing

This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI), to be launched onboard of ESA's Herschel Space Observatory, by 2008. It includes the first results from the instrument level tests. The instrument is designed to be electronically tuneable over a wide and continuous frequency range in the Far Infrared, with velocity resolutions better than 0.1 km/s with a high sensitivity. This will enable detailed investigations of a wide variety of astronomical sources, ranging from solar system objects, star formation regions to nuclei of galaxies. The instrument comprises 5 frequency bands covering 480-1150 GHz with SIS mixers and a sixth dual frequency band, for the 1410-1910 GHz range, with Hot Electron Bolometer Mixers (HEB). The Local Oscillator (LO) subsystem consists of a dedicated Ka-band synthesizer followed by 7 times 2 chains of frequency multipliers, 2 chains for each frequency band. A pair of Auto-Correlators and a pair of Acousto-Optic spectrometers process the two IF signals from the dual-polarization front-ends to provide instantaneous frequency coverage of 4 GHz, with a set of resolutions (140 kHz to 1 MHz), better than < 0.1 km/s. After a successful qualification program, the flight instrument was delivered and entered the testing phase at satellite level. We will also report on the pre-flight test and calibration results together with the expected in-flight performance

Systemic versus localized coagulation activation contributing to organ failure in critically ill patients

In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may not only be relevant for vascular atherothrombotic disease in general but has in certain clinical settings considerable consequences, for example in the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on an interleukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by physiological anticoagulant mechanisms and endogenous fibrinolysis. Interestingly, apart from the overall systemic responses, a differential local response in various vascular beds related to specific organs may occur