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BackgroundPD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia.Patients and methodsWe retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab ± ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and if indicated, rheumatologic consultation.Results26 of 195 patients (13.3%) developed arthralgia. The median onset of symptoms was 100 days (7–780 days). Most frequently, arthralgia involved large joints (shoulders, knees) in a predominantly symmetrical pattern. Only two patients were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients developed the clinical picture of arthritis, with seven of them showing synovitis in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by osteoarthritis. In 11 patients arthralgia could not be specified. The majority of patients was satisfactorily treated with non-steroidal anti-inflammatory drugs (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our patients received further immunosuppressive treatment. Patients with arthralgia showed a better treatment response and improved PFS and OS.ConclusionArthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.

Two surgical options are available for cystic echinococcosis (CE). The two principal approaches are radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule). Here, we describe a standardized endocystectomy technique for hepatic echinococcosis. Twenty-one patients (male/female: 4/3; median age: 28 years) with uncomplicated, isolated hepatic CE (cyst stages WHO CE1, 2, 3a, and 3b) that were treated with the standardized endocystectomy described in this paper. Before the operation and during the follow-up period (mean: 33.8 months, median: 24 months), patients underwent clinical and sonographical and/or magnetic resonance imaging assessment during regular visits managed by an interdisciplinary team. Forty-seven cysts were treated with the standardized endocystectomy technique. The median number of cysts per patient was two (range: 1-8). Nine patients (43%) had a single cystic lesion. The median operation time was 165 minutes and the median intraoperative bleeding volume was 200 mL. The median hospital stay was nine days (range: 6-28 days). Morbidity (Clavien-Dindo III) occurred in four patients (19%). No mortality and no recurrence were found during the median follow-up time of 24 months. The standardized endocystectomy technique presented is a safe procedure with acceptable morbidity, no mortality, and without recurrences in our patient series. Important components of our CE management are interdisciplinary patient care, adequate diagnostic work-ups, and regular pre- and postoperative visits, including long-term follow-up for early and reliable capture of recurrences.

Biosensors are an integral part of modern medicine, are used in basic research, and are increasingly used by consumers as point‐of‐care and wearable devices. Meanwhile, the underlying technological approaches are rapidly expanding, including spectroscopic sensing, artificial bioreceptors, synthetic biological approaches, whole‐cell biosensors, and artificial intelligence. With these diversifications in applications as well as technology, the scope and meaning of the term biosensor is blurring. This paper attempts to give an overview of the sensing approaches, with their physical, chemical, biochemical, and biological principles, and an overview of the fields of application, including nonliving systems and living systems. This leads to a comprehensive overview and a reappreciation of the term biosensor, including not only devices with a molecular biorecognition element and physico‐chemical readout but also the sensing of living biological systems using physical and chemical methods, and the use of living biological systems for sensing purposes.

Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments.

In patients with hepatic cystic echinococcosis (CE), treatment effectiveness, outcomes, complications, and recurrence rate are controversial. Endocystectomy is a conservative surgical approach that adequately removes cyst contents without loss of parenchyma. This conservative procedure has been modified in several ways to prevent complications and to improve surgical outcomes. This systematic review aimed to evaluate the intraoperative and postoperative complications of endocysectomy for hepatic CE as well as the hepatic CE recurrence rate following endocystectomy. A systematic search was made for all studies reporting endocystectomy to manage hepatic CE in PubMed, Web of Science, and Cochrane CENTRAL databases. Study quality was assessed using the methodological index for non-randomized studies (MINORS) criteria and the Cochrane revised tool to assess risk of bias in randomized trials (RoB2). The random-effects model was used for meta-analysis and the arscine-transformed proportions were used to determine complication-, mortality-, and recurrence rates. This study is registered with PROSPERO (number CRD42020181732). Of 3,930 retrieved articles, 54 studies reporting on 4,058 patients were included. Among studies reporting preoperative anthelmintic treatment (31 studies), albendazole was administered in all of them. Complications were reported in 19.4% (95% CI: 15.9-23.2; I2 = 84%; p-value <0.001) of the patients; biliary leakage (10.1%; 95% CI: 7.5-13.1; I2 = 81%; p-value <0.001) and wound infection (6.6%; 95% CI: 4.6-9; I2 = 27%; p-value = 0.17) were the most common complications. The post-endocystectomy mortality rate was 1.2% (95% CI: 0.8-1.8; I2 = 21%; p-value = 0.15) and the recurrence rate was 4.8% (95% CI: 3.1-6.8; I2 = 87%; p-value <0.001). Thirty-nine studies (88.7%) had a mean follow-up of more than one year after endocystectomy, and only 14 studies (31.8%) had a follow-up of more than five years. Endocystectomy is a conservative and feasible surgical approach. Despite previous disencouraging experiences, our results suggest that endocystectomy is associated with low mortality and recurrence.

Neutrino detectors, particle calorimeters and some dark matter detectors require dense and massive active materials. An extremely fine segmentation is desirable to achieve precise three-dimensional particle tracking. However, such systems introduce significant challenges in construction and demand a large number of readout electronics channels, leading to extremely high costs. In this article, we propose an alternative approach to elementary particle detection that enables ultrafast three-dimensional high-resolution imaging in large volumes of unsegmented scintillator. Enabling technologies are plenoptic systems and time-resolving single-photon avalanche diode array imaging sensors. Together, they enabled us, using a plenoptic camera, to reconstruct the origin of single photons in the scintillator. A case study focused on neutrino detection demonstrates full event reconstruction with a spatial resolution of two hundred micrometres. This work paves the way for a class of particle detectors whose capabilities should be further enhanced through future developments and expanded to Cherenkov light detection, medical imaging and neutron detection. We propose an alternative approach to elementary particle detection: a plenoptic system combined with time-resolving single-photon avalanche diode array sensors leads to ultrafast three-dimensional high-resolution imaging in unsegmented scintillator.

Biliary vessel pathology due to alveolar echicococcosis (AE) results in variable combinations of stenosis, necrosis and inflammation. Modern management strategies for patients with cholestasis are desperately needed. The aim is proof of principle of serial ERC (endoscopic retrograde cholangiography) balloon dilation for AE biliary pathology. Retrospective case series of seven consecutive patients with AE-associated biliary pathology and ERC treatment in an interdisciplinary endoscopy unit at a University Hospital which hosts a national echinococcosis treatment center. The AE patient cohort consists of 106 patients with AE of the liver of which 13 presented with cholestasis. 6/13 received bilio-digestive anastomosis and 7/13 patients were treated by ERC and are reported here. Biliary stricture balloon dilation was performed with 18-Fr balloons at the initial and with 24-Fr balloons at subsequent interventions. If indicated 10 Fr plastic stents were placed. Six patients were treated by repeated balloon dilation and stenting, one by stenting only. After an acute phase of 6 months with repeated balloon dilation, three patients showed \"sustained clinical success\" and four patients \"assisted therapeutic success,\" of which one has not yet reached the six month endpoint. In one patient, sustained success could not be achieved despite repeated insertion of plastic stents and balloon dilation, but with temporary insertion of a fully covered self-expanding metal stent (FCSEMS). There was no loss to follow up. No major complications were observed. Serial endoscopic dilation is a standard tool in the treatment of benign biliary strictures. Serial endoscopic intervention with balloon dilation combined with benzimidazole treatment can re-establish and maintain biliary duct patency in AE associated pathology and probably contributes to avoid or postpone bilio-digestive anastomosis. This approach is in accordance with current ERC guidelines and is minimally disruptive for patients.

This multicenter imaging study aimed to establish and validate automated radiomics models predicting therapy response (TR) and minimal residual response (MRD) in newly diagnosed multiple myeloma (MM) from baseline MRI. Retrospectively, 118 MM patients from the GMMG-HD7 trial (EudraCT: 2017-004768-37) with data on TR and/or MRD after induction therapy and baseline MRI were included. Data were split by center into a training set (center 1–2; n  = 79) and a test set (center 3–10; n  = 39). TR was classified as very good partial response or better versus other. An in-house developed nnU-Net was used to automatically segment pelvic bone marrow for the subsequent extraction of 245 radiomics features and piriformis muscle for normalization. Random forest classifiers were trained using radiomics features only (I), radiomics features with additional confounders (II) or myeloma-relevant clinical features (III), or only clinical features (IV) to predict TR or MRD status. The area under the receiver operating characteristic curve (AUROC) was calculated to assess prediction performance. The prediction model using only radiomics features (I) showed the highest predictive performance for TR on the test set with an AUROC of 0.70. AUROC values for radiomics-based prediction of the MRD status (I-III) ranged from 0.54 to 0.52. In conclusion, our study demonstrated the potential of automated radiomics models from baseline MRI to non-invasively predict TR in MM on an independent, multicentric test set.

Electrocatalyst degradation, often caused by oxidative processes, forms a large barrier for the wide-spread application of electrolysers and fuel cells, which are crucial for a sustainable energy society. A detailed understanding of the catalyst surface structure under oxygen evolution reaction (OER) conditions is, therefore, required to design more stable catalysts. Here, we study the oxidation of a Pt(111) model electrode under operando conditions combining High-Energy Surface X-ray Diffraction (HE-SXRD) with a Rotating Disk Electrode (RDE) in a unique experimental setup. This approach allows us to follow the atomic structure of the electrode-electrolyte interface under oxygen evolution reaction conditions under hitherto unexplored potential regimes. We find that the Pt(111) surface gets electro-oxidized in a layer-by-layer fashion. From ex situ X-ray Reflectivity (XRR) and X-ray Photoelectron Spectroscopy (XPS) measurements we find that a sub-nm thick, PtO 2 oxide film is forming, which deactivates the surface and leads to surface roughening. Our results provide important insights into the electrochemical oxidation of platinum electrocatalysts and resolves crucial differences to thermal oxidation processes. Electrocatalyst degradation driven by oxidation is a major barrier to a sustainable energy society. Here, the authors study the oxidation of Pt(111), a prominent model system, under oxygen evolution conditions, resolving self-limiting layer-by-layer growth of a sub-nanometer disordered PtO 2 film.

Keywords: Extracellular vesicles, Protein signature, Molecular risk stratification, Early response prediction, Colorectal liver metastases