Background. Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup. Methods. Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE ₂ and then loaded with 4 HLA class I and 6 class II–restricted tumor peptides were injected intradermally in high doses over 2 years. We performed serial immunomonitoring in all 53 evaluable patients. Results. Vaccine-specific immune responses including high-affinity, IFNγ-producing CD4 ⁺ and lytic polyfunctional CD8 ⁺ T cells were de novo induced or boosted in most patients. Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not further enhance such immune responses, while keyhole limpet hemocyanin (KLH) pulsing to provide unspecific CD4 ⁺ help promoted CD8 ⁺ T cell responses — notably, their longevity. An unexpected 19% of nonresectable metastatic melanoma patients are still alive after 11 years, a survival rate similar to that observed in ipilimumab-treated patients and achieved without any major (>grade 2) toxicity. Survival correlated significantly with the development of intense vaccine injection site reactions, and with blood eosinophilia after the first series of vaccinations, suggesting that prolonged survival was a consequence of DC vaccination. Conclusions. Long-term survival in advanced melanoma patients undergoing DC vaccination is similar to ipilimumab-treated patients and occurs upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine injection site reactions occurring after the initial vaccinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT00053391. FUNDING. European Community, Sixth Framework Programme (Cancerimmunotherapy LSHC-CT-2006-518234; DC-THERA LSHB-CT-2004-512074), and German Research Foundation (CRC 643, C1, Z2).

To assess the value of a score-based system which allows standardized evaluation of pulmonary edema on bedside chest radiographs (CXRs) under routine clinical conditions. Seven experienced readers assessed bedside CXRs of ten patients with an extravascular lung water (EVLW)-value of ≤ 8 mL/kg (range: 4–8 mL/kg; indicates no pulmonary edema) and a series of ten patients with an EVLW-value of ≥ 15 mL/kg (range: 15–21 mL/kg; = indicates a pulmonary edema) with and without customized software which would permit a standardized assessment of the various indications of pulmonary edema. The software provides a score that identifies patients with and without pulmonary edema. EVLW-values were measured instantly after bedside CXR imaging using a pulse contour cardiac output (PiCCO) system and served as a reference standard. The patients were non-traumatic and not treated with diuretics or dobutamine during bedside CXR imaging and the PiCCO measurements. Mean sensitivity, specificity, positive and negative predictive value, the percentage of overall agreement and the free-marginal multirater kappa value was calculated for both the standard and the standardized score-based approach. The net reclassification index was calculated for each reader as well as for all readers. Evaluation of bedside CXRs by means of the score-based approach took longer (23 ± 12 seconds versus 7 ± 3 seconds without the use of the software) but improved radiologists’ sensitivity (from 57 to 77%), specificity (from 90 to 100%) and the free-marginal multirater kappa value (from 0.34 to 0.68). The positive predictive value was raised from 85 to 100% and the negative predictive value from 68 to 81%. A net reclassification index of 0.3 (all readers) demonstrates an improvement in prediction performance gained by the score-based approach. The percentage of overall agreement was 67% with the standard approach and 84% with the software-based approach. The diagnostic accuracy of bedside CXRs to discriminate patients with elevated EVLW-values from those with a normal value can be improved with the use of a standardized score-based approach. The investigated system is freely available as a web-based application (accessible via: http://www.radiologie.uk-erlangen.de/aerzte-und-zuweiser/edema ).

Proprioceptive neuromuscular stimulating insoles are increasingly applied in treating functional complaints, chronic pain, foot disorders and so on. To evaluate rasterstereography as a tool in objectifying postural changes resulting from neuromuscular afferent stimulation and proprioceptive neuromuscular stimulating insoles and to compare the respective effects on posture. This is a prospective experimental study. A total of 27 healthy volunteers were consecutively exposed to six different varying intense neuromuscular afferent stimulating test conditions at three different times. One test condition featured proprioceptive neuromuscular stimulating insoles. In each test condition, a sequence of 12 rasterstereographic recordings of back shape was documented. Changes between six different test conditions and over time for 14 posture characterising parameters were investigated, for example, trunk inclination, pelvic torsion, lateral deviation of the spine’s amplitude or sagittal spinal curve. Standard deviation of our rasterstereographic measurements (±2.67 mm) was better than in most comparable reference values. Different neuromuscular stimuli were found to provoke significant changes to various posture parameters, including trunk inclination, pelvic torsion and so on ( each p < 0.001, F-tests). Proprioceptive neuromuscular stimulating insoles induced significant changes for parameter lateral deviation of the spine’s amplitude (p = 0.03). Neuromuscular afferent stimulation and proprioceptive neuromuscular stimulating insoles induce postural changes, which can be detected reliably by rasterstereography. We demonstrated that rasterstereography – a radiation-free imaging modality – enables visualisation and documentation of subtle postural changes induced by varying intense neuromuscular afferent stimulation and the application of proprioceptive neuromuscular stimulating insoles.

To evaluate the reader’s diagnostic performance against the ground truth with and without the help of a novel content-based image retrieval system (CBIR) that retrieves images with similar CT patterns from a database of 79 different interstitial lung diseases. We evaluated three novice readers’ and three resident physicians‘ (with at least three years of experience) diagnostic performance evaluating 50 different CTs featuring 10 different patterns (e.g., honeycombing, tree-in bud, ground glass, bronchiectasis, etc.) and 24 different diseases (sarcoidosis, UIP, NSIP, Aspergillosis, COVID-19 pneumonia etc.). The participants read the cases first without assistance (and without feedback regarding correctness), and with a 2-month interval in a random order with the assistance of the novel CBIR. To invoke the CBIR, a ROI is placed into the pathologic pattern by the reader and the system retrieves diseases with similar patterns. To further narrow the differential diagnosis, the readers can consult an integrated textbook and have the possibility of selecting high-level semantic features representing clinical information (chronic, infectious, smoking status, etc.). We analyzed readers’ accuracy without and with CBIR assistance and further tested the hypothesis that the CBIR would help to improve diagnostic performance utilizing Wilcoxon signed rank test. The novice readers demonstrated an unassisted accuracy of 18/28/44%, and an assisted accuracy of 84/82/90%, respectively. The resident physicians demonstrated an unassisted accuracy of 56/56/70%, and an assisted accuracy of 94/90/96%, respectively. For each reader, as well as overall, Sign test demonstrated statistically significant (p < 0.01) difference between the unassisted and the assisted reads. For students and physicians, Chi²-test and Mann-Whitney-U test demonstrated statistically significant (p < 0.01) difference for unassisted reads and statistically insignificant (p > 0.01) difference for assisted reads. The evaluated CBIR relying on pattern analysis and featuring the option to filter the results of the CBIR by predominant characteristics of the diseases via selecting high-level semantic features helped to drastically improve novices’ and resident physicians’ accuracy in diagnosing interstitial lung diseases in CT.

Early detection of loco-regional breast cancer recurrence improves patients’ overall survival, as treatment can be initiated or active treatment can