Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

Neorickettsia helminthoeca associated lymphoid,enteric, and pulmonary lesions in dogs from Southern Brazil: An immunohistochemical study

Neorickettsia helminthoeca (NH), the agent of salmon poisoning disease or canine neorickettiosis (CN), is a bacterial endosymbiont of the nematode Nanophyetus salmincola, and infections are spreading among specific fish‐eating mammalians. This article describes the pathologic and immunohistochemical findings associated with spontaneous NH‐induced infections in dogs from Southern Brazil. The principal pathologic findings were hypertrophy of Peyer patches and lymphadenopathy with lymphocytic proliferation, chronic interstitial pneumonia, and chronic enteritis associated with positive intralesional immunoreactivity to antigens of NH within macrophages and histiocytes. Positive immunoreactivity against canine parvovirus‐2 (CPV‐2) or/and canine distemper virus was not detected in the evaluated intestinal segments or in the samples from the cerebellum and lungs, respectively, from the dogs evaluated. These findings demonstrated that NH was involved in the enteric, pulmonary, and lymphoid lesions herein described, and provide additional information to confirm the occurrence of this bacterial endosymbiont within this geographical location. It is proposed that chronic pneumonia should be considered as a pathologic manifestation of NH‐induced infections. Additionally, our results show that the occurrences of CN seem to be underdiagnosed in Southern Brazil due to the confusion with the incidence of CPV‐2.