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The article describes the induction of melanoma-associated chondroitin sulfate proteoglycan (MCSP)-specific CD4+ T cell clones from the peripheral blood of a healthy human donor and the subsequent identification of the T cell epitope which is located in the core protein. It discusses how the T cells directly recognized HLA-matched MCSP-expressing melanoma cells and produced high amounts of IFNgamma, a cytokine with important antitumoral effects.

Dopamine-based reward and learning mechanisms have been suggested to contribute to placebo effects. However, the exact role of dopaminergic neurotransmission in their generation and maintenance is still unclear. This study aimed to shed light on the causal role of dopamine in establishing positive treatment expectations, as well as on the magnitude and duration of their effect on pain. To this end, we used an established placebo analgesia paradigm in combination with 2 opposing pharmacological modulations of dopaminergic tone, i.e., the dopamine antagonist sulpiride and the dopamine precursor L-dopa which were both applied in an experimental, double-blind, randomized, placebo-controlled trial with a between-subject design in N = 168 healthy volunteers. The study medication successfully altered dopaminergic tone during the conditioning procedure. Contrary to our hypotheses, the medication did not modulate the formation of positive treatment expectation and placebo analgesia tested 1 day later. Placebo analgesia was no longer detectable on day 8 after conditioning. Using a combined frequentist and Bayesian approach, our data provide strong evidence against a direct dopaminergic influence on the generation and maintenance of placebo effects. Further exploration of the neurochemical mechanisms underlying placebo analgesia remains paramount in the quest to exploit these effects for optimal treatment outcomes. Trial registration: ClinicalTrials.gov German Clinical Trials Register, ID: DRKS00029366, https://drks.de/search/en/trial/DRKS00029366., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kunkel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The primary objective was to determine whether obliteration of the epitympanic area and mastoid cavity during canal wall up (CWU) cholesteatoma surgery reduces the rate of recurrent and residual cholesteatoma compared to not obliterating the same area. The secondary objective was to compare postoperative hearing outcomes between both techniques., Methods: A retrospective cohort study was conducted in a tertiary referral center. One-hundred-fourty-three ears were included of patients (≥18y) who underwent a CWU tympanomastoidectomy for cholesteatoma with or without bony obliteration between January 2015 and March 2020 in the University Medical Center Utrecht. The median follow-up was respectively 1.4 (IQR 1.1-2.2) vs. 2.0 years (IQR 1.2-3.1) ( p  = 0.013)., Interventions: All patients underwent CWU tympanomastoidectomy for cholesteatoma. For 73 ears bone dust, Bonalive® or a combination was used for obliteration of the mastoid and epitympanic area, the rest of the ears ( n  = 70) were not obliterated. In accordance with the Dutch protocol, included patients are planned to undergo an MRI scan with diffusion-weighted imaging (DWI) one, three and five years after surgery to detect recurrent or residual cholesteatoma., Main Outcome Measures: The primary outcome measure was recurrent and residual cholesteatoma as evaluated by MRI-DWI and/or micro-otoscopy and confirmed by micro-otoscopy and/or revision surgery. The secondary outcome measure was the postoperative hearing., Results: In this cohort, the group treated with canal wall up tympanomastoidectomy with subsequent bony obliteration (73 ears, 51.0%) had significantly lower recurrent (4.1%) and residual (6.8%) cholesteatoma rates than the group without obliteration (70 ears, 25.7% and 20.0%, respectively; p  < 0.001). There was no significant difference between both groups in postoperative bone conduction thresholds (mean difference 2.7 dB, p  = 0.221) as well as the mean air-bone gap closure 6 weeks after surgery (2.3 dB in the non-obliteration and 1.5 dB in the obliteration group, p  = 0.903)., Conclusions: Based on our results, a canal wall up tympanomastoidectomy with bony obliteration is the treatment of choice, since the recurrent and residual disease rate is lower compared to the group without obliteration. The bony obliteration technique does not seem to affect the perceptive or conductive hearing results, as these are similar between both groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Erfurt, Westerhout, Straatman, Smit, Stokroos and Thomeer.)

A 74-year-old woman presented herself at the outpatient clinic for dermatology with three temporoparietal ulcers on her scalp which are diagnosed as complications of temporal arteritis. The core symptoms of temporal arteritis are often non-specific, causing diagnostic delay. This dermatological complication can be an important clinical clue urging the physician to start treatment.

Aim of the Study: Because of significant changes in recent years, cases of illicit drug exposure reported to the Poisons Information Centre (PIC) Erfurt during the last 10 years were investigated., Methods: Retrospective analysis of above-mentioned cases from 2011 to 2020 according to substance classes, symptom severity, age groups, and gender., Results: Cases of illicit drug exposure (4,963, 2.8% of all exposures) increased from 316 in 2011 to 614 in 2015, decreased to 514 in 2017, and rose again to 578 in 2019. In 2020, a drop to 549 cases was observed. The ratio of multiple to single drug exposure cases, however, increased from 1.0 to 1.7 in 2020. Cases of exposure to psychostimulants almost doubled from 168 in 2011 to 319 in 2020. Cases of exposure to new psychoactive substances (NPS) rose from 21 in 2011 to 126 in 2015 and fell to 16 in 2020. 320 cases (6.5%) of illicit drug exposures resulted in severe, 1902 cases (38.3%) in moderate and 2139 cases (43.1%) in minor or no symptoms. Age groups mainly involved were adults of middle age (72.7%) and unknown age (12.7%) as well as adolescents (12.1%). Men (69.9%) were more often involved than women (26.9%)., Conclusions: Illicit drug exposures reported to the Poisons Information Centre (PIC) Erfurt discontinuously increased from 2011 to 2020 mainly by increase in mixed consumption. The intermittent decrease in 2016 and 2017 was caused by the fall of NPS exposures. Data of substance abuse from PICs could supplement official annual drug reports in aspects of Clinical Toxicology., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The inclusion of facial and bodily cues (clinical gestalt) in machine learning (ML) models improves the assessment of patients' health status, as shown in genetic syndromes and acute coronary syndrome. It is unknown if the inclusion of clinical gestalt improves ML-based classification of acutely ill patients. As in previous research in ML analysis of medical images, simulated or augmented data may be used to assess the usability of clinical gestalt. Objective: To assess whether a deep learning algorithm trained on a dataset of simulated and augmented facial photographs reflecting acutely ill patients can distinguish between healthy and LPS-infused, acutely ill individuals. Methods: Photographs from twenty-six volunteers whose facial features were manipulated to resemble a state of acute illness were used to extract features of illness and generate a synthetic dataset of acutely ill photographs, using a neural transfer convolutional neural network (NT-CNN) for data augmentation. Then, four distinct CNNs were trained on different parts of the facial photographs and concatenated into one final, stacked CNN which classified individuals as healthy or acutely ill. Finally, the stacked CNN was validated in an external dataset of volunteers injected with lipopolysaccharide (LPS). Results: In the external validation set, the four individual feature models distinguished acutely ill patients with sensitivities ranging from 10.5% (95% CI, 1.3-33.1% for the skin model) to 89.4% (66.9-98.7%, for the nose model). Specificity ranged from 42.1% (20.3-66.5%) for the nose model and 94.7% (73.9-99.9%) for skin. The stacked model combining all four facial features achieved an area under the receiver characteristic operating curve (AUROC) of 0.67 (0.62-0.71) and distinguished acutely ill patients with a sensitivity of 100% (82.35-100.00%) and specificity of 42.11% (20.25-66.50%). Conclusion: A deep learning algorithm trained on a synthetic, augmented dataset of facial photographs distinguished between healthy and simulated acutely ill individuals, demonstrating that synthetically generated data can be used to develop algorithms for health conditions in which large datasets are difficult to obtain. These results support the potential of facial feature analysis algorithms to support the diagnosis of acute illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Forte, Voinea, Chichirau, Yeshmagambetova, Albrecht, Erfurt, Freundt, Carmo, Henning, Horst, Sundelin, Wiering, Axelsson and Epema.)

Introduction: It can be observed that there is an increase in the methamphetamine (MA) consumption in Saxony (Federal Republic of Germany). There is so far no data available in German speaking countries about the risk of MA consumption in pregnancy or delivery., Methods: The data from all pregnant women who were examined or delivered at the Clinic for Obstetrics and Gynaecology between 2010-2015 were retrospectively searched for MA consumption. 119 pregnancies with 113 deliveries of 115 women consuming MA could be evaluated. 88 women admitted the consumption according to the history, 28 women denied it and there was no information available in the records of 3 cases. 113 women agreed to test MA in blood and 93 cases were positive (28 cases of them with low-dose consumption). The statistical analysis was performed by the Institute for Medical Informatics and Biometry. The data driven from the quality control report of the department of Gynaecology in 2015 was used as a control group., Results: MA-consumers are significantly younger, without a permanent relationship, without a job and have a low education level. The first detection of the pregnancy was late and the number of performed routine examinations including ultrasound assessment was lower compared to the controls. 7 women had no routine examination. The number of premature contractions, cervical insufficiency and gestational diabetes were significantly higher. The number of patients needing tocolysis, antenatal glucocorticoid treatment for prevention of neonatal respiratory distress syndrome or in-patient care was significantly higher in patients consuming MA. The number of amniotic infection syndrome and premature rupture of membranes were higher. The rate of intrauterine fetal death was 3,5% which was much higher than the rate of control group (0,2%)., Discussion: The MA-consumption increases the risk for mother and child significantly during the pregnancy and delivery (pregnancy complications, premature delivery, increased rate of abortion, intrauterine death). A special attention must be taken for the young pregnant, non-working women without a partner who do not take the routine examinations in account or start having them late., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim of the Study: Poisoning due to substance abuse has changed significantly during the last few years. Therefore, developments of substance abuse reported to the Poisons Information Centre Erfurt were investigated and compared to other circumstances of human exposures during the last 15 years., Methods: Retrospective analysis of all cases of human exposures (intentional abuse, accidental and unknown circumstances, and suicide attempts) for the period 2002-2016 according to substance classes, reasons of exposures, symptom severity, age groups, and gender., Results: Cases of substance abuse (n=7,237, 3.5% of all exposures) continuously increased from 250 (159 with one and 91 with multiple substances) in 2002 to 830 in 2016 (398 with one and 432 with multiple substances). Cases of exposure to metamphetamine strongly increased from 10 in 2003 to 100 in 2012 and dropped to 52 in 2016. Cases of exposure to new psychoactive substances (NPS) rose from 1 in 2008 to 130 in 2015 and fell to 90 in 2016. Substance abuse significantly (p<0.001) more often caused moderate (29.1%) and severe symptoms (5.8%) than suicide attempts (11.6%; 4.9%). NPS and their subgroup synthetic cannabinoids led significantly (p<0.001 and 0.025) more frequently to moderate and severe symptoms (46.9% and 43.6%; 7.9% and 6.0%) than cannabis exposure (19.7%; 2.1%)., Conclusions: Clinical significance of substance abuse is shown by the fact that it resulted more often in moderate and severe symptoms than suicide attempts. Data of substance abuse from PICs could supplement those on clinical toxicology in official annual drug reports., Competing Interests: Die Autoren erklären, dass kein Interessenskonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim of the Study: Exposures in suicide attempts are demanding for hospitals and poisons information centres (PICs). Therefore, the time characteristics of their frequency were studied. Methods: A retrospective analysis was undertaken of all human exposures reported to Centre Erfurt from the beginning of 2004 to the end of 2013 according to their frequency in the respective year, season, month, weekday, time of the weekday, circumstances of exposure, age and gender. Results: 59.7% of all exposures (n=137 104) were accidental, 23.4% occurred in suicide attempts and 3.3% in substance abuse. 0.3% of the suicide attempts resulted in death. Their number continuously increased from n=2 422 in 2004 to n=3 458 in 2013, but their relative frequency remained almost constant at 23.4%. Their highest numbers were reached in the spring and summer with maxima in July and August and minima in February and September. During the week, the most suicide attempts were observed between Sunday and Tuesday and the least on Friday. Highest rate of suicide attempts was seen at 10 pm and lowest at 6 am. The median of age was 39 years (first quartile 24 years, third quartile 50 years). The female proportion was almost twice as high as the male. Conclusions: Hospitals the Centre Erfurt is serving should be particularly prepared for exposures in suicide attempts in the spring and summer (especially in July and August), at the beginning of the week and shortly before midnight., Competing Interests: Interessenkonflikt:: Die Autoren erklären, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim of the Study: Because of their frequency, non-opioid analgesics (NOA) single drug exposures registered by Poisons Information Centre (PIC) Erfurt have been studied over a decade., Methods: A retrospective analysis of frequencies, circumstances of exposure, symptom severity, and age groups in NOA single drug exposures received by the PIC Erfurt from the beginning of 2003 to the end of 2012 was undertaken., Results: Of all 4749 NOA single drug exposures, the 10 most frequent were caused by paracetamol (n=1 686), ibuprofen (n=1 439), acetylsalicylic acid (n=456), dipyrone (n=274), diclofenac (n=267), flupirtine (n=138), naproxen (n=41), etoricoxib (n=36), indomethacin (n=24), and dexketoprofen (n=19). Paracetamol single drug exposures increased from 158 in 2003 to 216 in 2007 and fell afterwards to 133 in 2012. Ibuprofen single drug exposures continously rose from 57 in 2003 to 258 in 2012. Adults were more often involved in NOA (53.8%) and all single drug exposures (54.1%) than children (45.9% and 45.6%, respectively). Suicidal attempts were more frequent in NOA (43.1%) than in all single drug exposures (34.2%), whereas accidental exposures or exposures in abuse were less often (33.4 and 0.2%, 46.0 and 0.9% respectively). NOA single drug exposures resulted mostly in none to minor symptoms (77.0%) and rarely in moderate (2.1%) or severe symptoms (1.0%). One adult was found dead after probable ingestion of 32 g of acetylsalicylic acid in suicidal intention., Conclusions: Because many NOA are over-the-counter drugs, it is difficult to obtain data on their use. PIC data could provide information on the NOA use in the population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim of the Study: The purpose of this study was to get information on all human exposures to veterinary medicines (HEVM) reported to the Poisons Information Centre (PIC) over a 10-year period., Methods: A retrospective analysis of all HEVM was undertaken and a comparison was made to all human exposures (HE) registered by the PIC from the beginning of 2003 to the end of 2012 according to frequencies, circumstances of exposure, symptom severity, age groups, and substances involved in HEVM., Results: In total, 389 cases of HEVM with 409 veterinary medicines were registered (0.30% of all HE, 360 monoexposures). The relative frequency of children and adults in HEVM (children: 52.4%, adults: 46.0%) and all HE (children: 48.7%, adults 48.7%) was the same with significant (p<0.05) differences in some age subgroups. The portion of accidental exposures was significantly (p<0.05) higher in HEVM (83.3%) than in all exposures (59.3%), whereas the portion of suicidal exposures was significantly (p<0.05) lower (HEVM: 6.4%, all exposures: 23.6%). Most frequent veterinary medicines (ATCvet) in HEVM were antiparasitic substances, insecticides and repellents (n=185), substances for the nervous system (n=48), substances for the cardiovascular system (n=35), and immunologicals (n=35). HEVM mostly resulted in no or mild symptoms (83.8%) and rarely in moderate (10/389, 2.6%) or even severe symptoms (5/389, 1.3%). In 4 of 5 cases of HEVM with severe symptoms, veterinary surgeons used products for animal euthanasia (n=3) or methadone (n=1). Once, self-medication with anthelmintics for several days by a goatherd resulted in transient blindness., Conclusions: In comparison to other HE, HEVM are rare. Most accidental HEVM in laymen result only in none to mild symptoms. If veterinary surgeons, however, swallow or inject products for animal euthanasia or opioids in suicidal intention, severe symptoms can be expected., (© Georg Thieme Verlag KG Stuttgart · New York.)

Advanced and specialized radiological diagnostics are essential in the case of clinical suspicion of pediatric injuries to the head, thorax, abdomen, and extremities when there is no case history or when "battered child syndrome" is assumed on the basis of inadequate trauma. In particular, the aim of this sophisticated diagnostic procedure is the detection of lesions of the central nervous system (CNS) in order to initiate prompt medical treatment. If diagnostic imaging shows typical findings of child abuse, accurate documented evidence of the diagnostic results is required to prevent further endangerment of the child's welfare.

Melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high molecular weight-melanoma-associated antigen) represents an interesting target antigen for cancer immunotherapy which is expressed on human melanomas and other tumors such as breast carcinomas, gliomas, neuroblastomas and acute leukemias. MCSP seems to play an important functional role in melanoma as it is involved in tumor cell migration, invasion and angiogenesis. In this study, we isolated CD4(+) T helper cells from the blood of a healthy donor, recognizing a peptide from the MCSP core protein presented by HLA-DBR1*1101 molecules. T cell reactivity against the identified peptide could be detected in the blood of healthy donors and melanoma patients. MCSP specific T cells from the blood of a patient could be readily expanded by repeated peptide stimulation and recognized MCSP and HLA-DR expressing tumor cells. Our findings suggest that vaccination against MCSP helper T cell epitopes might be a promising approach to fight melanoma., ((c) 2009 Wiley-Liss, Inc.)