Leishmaniasis is caused by different species of the protozoa, Leishmania, and frequently found in South-Western Asia, Eastern Africa, Brazil, and Mediterranean countries. Leishmania are transmitted to humans by the bite of sandflies. After weeks to months, unspecific symptoms may occur, accompanied by more specific findings like pancytopenia and organomegaly. We report two children with pancytopenia and hepato-/splenomegaly: a 1-year-old boy was first diagnosed with an Adenovirus-infection, accompanied by fever, pancytopenia, and hepatosplenomegaly who had spent his summer vacation in Spain and a 3-year-old boy of Macedonian origin who was first diagnosed with a Parvovirus B19-infection again accompanied by splenomegaly and pancytopenia. In both children, leukemia was excluded by an initial bone marrow puncture. As fever was still persistent weeks after the children’s first hospital stay, both children received antibiotics empirically without sustainable effect. While different autoantibodies were present in both children, an immunosuppressive therapy was initiated in the younger boy without therapeutic success. A second bone marrow puncture was performed and Leishmania were finally detected morphologically and proven serologically. After weight-adjusted treatment with liposomal Amphotericin B for 10 days, both children recovered completely without relapse. Aim of this report is to broaden the spectrum of differential diagnoses in children with pancytopenia, splenomegaly, and fever to visceral leishmaniasis particularly when travel history is positive for the Mediterranean area. The infection may mimic more common diseases, such as leukemia, viral infections, or autoimmune diseases, because polyclonal B cell activation and other mechanisms may lead to multiple positive serologic tests. Both cases illustrate typical pitfalls and shall encourage taking Leishmaniasis into diagnostic consideration.

Antibody-drug conjugates (ADCs) have changed the treatment of breast cancer (BC) in more recent years. BC is a heterogenous group of malignancies with a broad range of histopathological characteristics. ADCs represent a class of therapeutics that combines an antigen-specific antibody backbone bound to a potent cytotoxic agent (the payload), via a linker, contributing to an improved therapeutic index. Currently, three ADCs received approval by the US Food and Drug Administration (FDA) and are in routine clinical use in different treatment settings; many more ADCs are in earlier and later stages of development, and their future approval will improve treatment options for patients with advanced but potentially also early-stage BC over time. Just recently, the results of three phase 3 trials (ASCENT, TULIP, and DESTINY-Breast03) evaluating sacituzumab govitecan (SG), trastuzumab duocarmazine, and trastuzumab deruxtecan (T-DXd) in different treatment settings were presented and showed promising results. This overview focuses on the newer ADCs, including T-DXd and SG, their pharmacology, mechanisms of action, and relevant studies. In addition, the latest results from trials investigating some newer ADCs, in further stages of development are presented.

Treatment with sotorasib has shown intracranial complete responses and continued intracranial stabilization in <i>KRAS G12C-</i>mutated non-small-cell lung carcinoma (NSCLC) patients with previously treated, stable brain metastases in a post hoc analysis of the ongoing CodeBreaK 100 trial. We present the case of a patient with <i>KRAS G12C-</i>mutant adenocarcinoma of the lung with active untreated brain metastases with a nearly complete intracranial response only 6 weeks after start of sotorasib illustrating the benefit of sotorasib in patients with active, previously untreated brain metastases in <i>KRAS G12C-</i>mutated NSCLC.

Medium-chain acyl-coenzyme-A dehydrogenase (MCAD) catalyzes the first step of mitochondrial beta-oxidation for medium-chain acyl-CoAs. Mutations in the ACADM gene cause MCAD deficiency presenting with life-threatening symptoms during catabolism. Since fatty-acid-oxidation disorders are part of newborn screening (NBS), many novel mutations with unknown clinical relevance have been identified in asymptomatic newborns. Eighteen of these mutations were separately cloned into the human ACADM gene, heterologously overexpressed in Escherichia coli and functionally characterized by using different substrates, molecular chaperones, and measured at different temperatures. In addition, they were mapped to the three-dimensional MCAD structure, and cross-link experiments were performed. This study identified variants that only moderately affect the MCAD protein in vitro, such as Y42H, E18K, and R6H, in contrast to the remaining 15 mutants. These three mutants display residual octanoyl-CoA oxidation activities in the range of 22 % to 47 %, are as temperature sensitive as the wild type, and reach 100 % activity with molecular chaperone co-overexpression. Projection into the three-dimensional protein structure gave some indication as to possible reasons for decreased enzyme activities. Additionally, six of the eight novel mutations, functionally characterized for the first time, showed severely reduced residual activities < 5 % despite high expression levels. These studies are of relevance because they classify novel mutants in vitro on the basis of their corresponding functional effects. This basic knowledge should be taken into consideration for individual management after NBS.

Background Up to now, no prospective cohort study using a validated questionnaire has assessed patients’ expectation and perception of divided anesthesia care and its influence on patient satisfaction. Objective We assessed patient satisfaction with divided anesthesia care in a district general hospital in Switzerland. We hypothesized that patient expectations, combined with their perceptions of the (un)importance of continuous anesthesia care would influence patient satisfaction. Material and methods A total of 484 eligible in-patients receiving anesthesia from October 2019 to February 2020 were included and received preoperative information about divided care via a brochure and face-to-face. The primary outcome was the assessment of patient satisfaction with divided anesthesia care using a validated questionnaire. In group 1 continuity of care was considered important but not performed. In group 2 continuity was ensured. In group 3 continuity was regarded as not important and was not performed. In group 4 patients could not remember or did not answer. A psychometrically developed validated questionnaire was sent to patients at home after discharge. Results A total of 484 completed questionnaires (response rate 81%) were analyzed. In group 1 (n = 110) the mean total dissatisfaction score was 25% (95% confidence interval [CI] 21.8–28.1), in group 2 (n = 61) 6.8% (95% CI 4.8–8.7), in group 3 (n = 223) 12.1% (95% CI 10.7–13.4), and in group 4 (n = 90) 15% (95% CI 11–18); ANOVA: p < 0.001, η = 0.43. Of the patients 286 (59%) considered continuity of care by the same anesthetist relatively unimportant (34%) or not important at all (25%). The other 40% considered it important (22%) or very important (18%). Conclusion Despite receiving comprehensive preoperative information about divided anesthesia care, 40% of patients still considered continuity of care by the same anesthetist important. We recommend further research evaluating whether and how patient expectations can be modified towards the common practice of divided care and patient satisfaction can be increased.

Perioperative anxiety is a widespread complaint. The mutual relation between anxiety and patient satisfaction with anaesthesia is still under debate. We assessed the prevalence and different triggers of perioperative anxiety and the association with patient satisfaction. A psychometric questionnaire1 was sent to patients after discharge. Clinical Data was used from a previous study. Statistical analysis included bivariate and multivariate regression models. 141 patients (30%) reported anxiety regarding anaesthesia before admission to hospital. The prevalence of anxiety was significantly associated with patient age < 54 years (n = 196, prevalence = 37%, p = 0.002), female gender (n = 242, prevalence 39%, p < 0.001) and surgical specialty (gynaecology (n = 61, prevalence = 49%), otolaryngology (n = 56, prevalence = 46%) p < 0.001). The fear of not waking up from anaesthesia (n = 44, prevalence 32%, SD 45.8) and of developing postoperative nausea or vomiting (n = 42, prevalence 30%, SD 46.0) were the most reported triggers of anxiety. The presence of anxiety was associated with impaired overall patient satisfaction (mean dissatisfaction score 23%, SD 16.3, p < 0.001), especially regarding the dimensions “information and involvement in decision-making” (14% of deficits stated in non-anxious group compared to 23% in anxious group, p < 0.001), “respect and trust” (2% vs 6.26%, p < 0.001) and “continuity of care” (50% vs 57%, p < 0.015).

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