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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. METHODS: We screened fourteen patient-derived PDAC cultures which reflect the intra- and intertumoural heterogeneity of PDAC for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H-1PV. Live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays and titration of viral progeny were conducted. Transcriptome profiling was employed to identify potential predictive biomarkers for response to OV treatment. FINDINGS: Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the classical molecular subtype, the quasi-mesenchymal or basal-like subtype of PDAC was found to be more sensitive to H-1PV, jin-3, and T-VEC. Generally, expression of viral entry receptors did not correlate with sensitivity to OV treatment, with one exception: Expression of Galectin-1 (LGALS1), a factor involved in H-1PV entry, positively correlated with H-1PV induced cell killing. Rather, cellular pathways controlling immunological, metabolic and proliferative signaling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas low cyclic GMP-AMP synthase (cGAS) expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures and cells overexpressing cGAS were found to be less sensitive to MV oncolysis. INTERPRETATION: Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments. FUNDING: German National Science Foundation (Deutsche Forschungsgemeinschaft, DFG), German Cancer Aid (Deutsche Krebshilfe), German National Academic Scholarship Foundation (Studienstiftung des deutschen Volkes), Survival with Pancreatic Cancer Foundation.
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Biomarcadores de Tumor , Viroterapia Oncolítica , Virus Oncolíticos , Neoplasias Pancreáticas , Humanos , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/metabolismo , Perfilación de la Expresión Génica , Línea Celular Tumoral , Supervivencia Celular , Células Tumorales CultivadasRESUMEN
Introduction: Downhill Mountain Biking is an extreme sport requiring high mental strength to perform on the best level in a competition with only one run to win the race. The substantial challenge here is to control automatic processes like competitive anxiety and stress. Hypnosis can address these automatic processes. We developed and evaluated a hypnosis audio-intervention to activate the optimal racing mindset. Methods: In our study, 19 elite Downhill Mountainbike athletes registered at two consecutive races of the IXS Downhill Cup. After the first race, athletes listened to the hypnosis audio-intervention. In this intervention, we instructed the athletes how to activate their optimal mental state before the second race. At both races, we measured competitive anxiety, stress, self-confidence, state resilience, and flow with validated questionnaires and assessed resting heart rate variability as physiological measure of resilience. Results: Race-related somatic anxiety and subjective stress decreased significantly while self-confidence increased significantly from first to second race after athletes listened to the hypnosis. Heart rate variability was significantly increased at the second race indicating elevated vagal activity. When comparing race results of our participants to a control group of other elite athletes competing in the races but not listening to the hypnosis, we found that our study participants generally performed better in both races. Conclusion: The study shows that our hypnosis intervention was effective in reducing competitive anxiety and stress while increasing perceived resilience and self-confidence: After a self-administered hypnosis session, athletes were able to improve automatic processes responsible for putting them in their mental pole position.
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BACKGROUND: Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. CASE PRESENTATION: Here, we report the new case of a 40 - 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. RESULTS: Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. CONCLUSION: This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.
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BACKGROUND: Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as severe encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and central nervous viral infections is increasing and specific inhibitors are available as therapeutic options. METHODS: In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to non-inflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using post-mortem brain tissue samples. RESULTS: We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent and C3 complement deposits were detected in post-mortem brain sections. Intrathecal complement levels were negatively correlated with survival. CONCLUSION: Further investigations are warranted to clarify, whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.
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In our study, we use the post-hypnotic suggestion of easy remembering to improve memory with long-lasting effects. We tested 24 highly suggestible participants in an online study. Participants learned word lists and recalled them later in a recognition memory task. At the beginning of the study, participants were hypnotized and the post-hypnotic suggestion to remember easily was associated with a cue that participants used during the recognition memory task. In a control condition, the same participants used a neutral cue. One week later, participants repeated both conditions with new word lists. Participants were significantly faster and more confident in their recognition ratings in the easy-remembering condition compared to the control condition, and this effect persisted over one week. Crucially, the increased speed and confidence in the easy-remembering condition did not affect memory accuracy. That makes our hypnosis intervention promising for patients experiencing subjective memory impairments. APA PSYCINFO CODES: 2343 (Learning and Memory), 2380 (Consciousness States), 3351 (Clinical Hypnosis).
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Hipnosis , Sugestión , Humanos , Aprendizaje , Recuerdo MentalRESUMEN
Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.
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Enterocolitis Necrotizante , Leche Humana , Niño , Lactante , Recién Nacido , Femenino , Humanos , Masculino , Recien Nacido Extremadamente Prematuro , Fórmulas Infantiles , Peso al Nacer , Método Doble Ciego , Enterocolitis Necrotizante/epidemiología , Unidades de Cuidado Intensivo NeonatalRESUMEN
In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 d106S with replication-competent T-VEC. High infectious doses of HSV-1 d106S killed melanoma (n = 10), head-and-neck squamous cell carcinoma (n = 11), and chondrosarcoma cell lines (n = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time. HSV-1 d106S and, to a lesser extent T-VEC, triggered caspase-dependent early apoptosis as shown by pan-caspase inhibition and specific induction of caspases 3/7, 8, and 9. HSV-1 d106S induced a higher ratio of apoptosis-inducing infected cell protein (ICP) 0 to apoptosis-blocking ICP6 than T-VEC. T-VEC was oncolytic for an extended period of time as viral replication continued, which could be partially blocked by the antiviral drug aciclovir. High doses of T-VEC, but not HSV-1 d106S, increased interferon-ß mRNA as part of the intrinsic immune response. When markers of immunogenic cell death were assessed, ATP was released more efficiently in the context of T-VEC than HSV-1 d106S infection, whereas HMGB1 was induced comparatively well. Overall, the early oncolytic effect on three different tumour entities was stronger with the non-replicative strain, while the replication-competent virus elicited a stronger innate immune response and more pronounced immunogenic cell death.
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Apoptosis , Herpesvirus Humano 1 , Viroterapia Oncolítica , Virus Oncolíticos , Replicación Viral , Herpesvirus Humano 1/fisiología , Humanos , Viroterapia Oncolítica/métodos , Línea Celular Tumoral , Virus Oncolíticos/genética , Virus Oncolíticos/fisiología , Caspasas/metabolismo , Animales , Melanoma/terapia , Melanoma/inmunologíaRESUMEN
BACKGROUND: Zoonotic Borna disease virus 1 (BoDV-1) causes fatal encephalitis in humans and animals. Subsequent to the detection of two paediatric cases in a Bavarian municipality in Germany within three years, we conducted an interdisciplinary One Health investigation. We aimed to explore seroprevalence in a local human population with a risk for BoDV-1 exposure as well as viral presence in environmental samples from local sites and BoDV-1 prevalence within the local small mammal population and its natural reservoir, the bicoloured white-toothed shrew (Crocidura leucodon). METHODS: The municipality's adult residents participated in an anonymised sero-epidemiological study. Potential risk factors and clinical symptoms were assessed by an electronic questionnaire. Small mammals, environmental samples and ticks from the municipality were tested for BoDV-1-RNA. Shrew-derived BoDV-1-sequences together with sequences of the two human cases were phylogenetically analysed. RESULTS: In total, 679 citizens participated (response: 41 %), of whom 38 % reported shrews in their living environment and 19 % direct shrew contact. No anti-BoDV-1 antibodies were detected in human samples. BoDV-1-RNA was also undetectable in 38 environmental samples and 336 ticks. Of 220 collected shrews, twelve of 40 C. leucodon (30%) tested BoDV-1-RNA-positive. BoDV-1-sequences from the previously diagnosed two paediatric patients belonged to two different subclades, that were also present in shrews from the municipality. INTERPRETATION: Our data support the interpretation that human BoDV-1 infections are rare even in endemic areas and primarily manifest as severe encephalitis. Sequence analysis linked both previous paediatric human infections to the local shrew population, but indicated independent infection sources. FUNDING: The project was partly financed by funds of the German Federal Ministry of Education and Research (grant numbers: 01KI2005A, 01KI2005C, 01KI1722A, 01KI1722C, 01KI2002 to MaBe, DR, RGU, DT, BS) as well as by the ReForM-A programme of the University Hospital Regensburg (to MaBa) and by funds of the Bavarian State Ministry of Health, Care and Prevention, project "Zoonotic Bornavirus Focal Point Bavaria - ZooBoFo" (to MaBa, MaBe, BS, MMB, DR, PS, RGU).
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Enfermedad de Borna , Virus de la Enfermedad de Borna , Encefalitis , Salud Única , Animales , Humanos , Niño , Virus de la Enfermedad de Borna/genética , Enfermedad de Borna/epidemiología , Musarañas/genética , Estudios Seroepidemiológicos , ARN Viral/genética , Alemania/epidemiologíaRESUMEN
Missing outcome data in clinical trials may jeopardize the validity of the trial results and inferences for clinical practice. Although sick and preterm newborns are treated as a captive patient population during their stay in the NICUs, their long-term outcomes are often ascertained after discharge. This greatly increases the risk of attrition. We surveyed recently published perinatal and neonatal randomized trials in 7 high-impact general medical and pediatric journals to review the handling of missing primary outcome data and any choice of imputation methods. Of 87 eligible trials in this survey, 77 (89%) had incomplete primary outcome data. The missing outcome data were not discussed at all in 9 reports (12%). Most study teams restricted their main analysis to participants with complete information for the primary outcome (61 trials; 79%). Only 38 of the 77 teams (49%) performed sensitivity analyses using a variety of imputation methods. We conclude that the handling of missing primary outcome data was frequently inadequate in recent randomized perinatal and neonatal trials. To improve future approaches to missing outcome data, we discuss the strengths and limitations of different imputation methods, the appropriate estimation of sample size, and how to deal with data withdrawal. However, the best strategy to reduce bias from missing outcome data in perinatal and neonatal trials remains prevention. Investigators should anticipate and preempt missing data through careful study design, and closely monitor all incoming primary outcome data for completeness during the conduct of the trial.
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Trastorno de Personalidad Antisocial , Líquidos Corporales , Recién Nacido , Femenino , Embarazo , Humanos , Niño , Unidades de Cuidado Intensivo Neonatal , Alta del Paciente , Proyectos de InvestigaciónRESUMEN
Effective coping with acute stress is important to promote mental health and to build stress resilience. Interventions improving stress coping usually require long training periods. In this study, we present a hypnosis-based intervention that produces long-term effects after a single hypnosis session. In that session, we established a post-hypnotic safety suggestion that participants can activate afterwards with a cue, the Jena Safety Anchor. We tested 60 participants in our study who all received the hypnosis session and a stress task. The safety group used the Jena Safety Anchor during acute stress (Trier Social Stress Test, TSST). The control group used a neutral anchor. We measured subjective stress responses via self-reports and physiological stress responses via saliva and blood samples as well as heart rate. One week later, all participants filled in an online survey to measure long-term effects of the post-hypnotic safety suggestion. We found that participants using the Jena Safety Anchor during the TSST reported significantly lower stress compared to the control group. The safety group also reported significantly fewer negative thoughts concerning their TSST performance than the control group during the stress recovery phase and 1 week later. All participants indicated that the Jena Safety Anchor still worked 1 week after its establishment. Suggestibility did not affect the efficacy of the Jena Safety Anchor. Our findings demonstrate that post-hypnotic safety suggestions improve stress coping with long-lasting effects, which makes it a promising intervention to promote mental health and establish stress resilience in just one hypnosis session.
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Hipnosis , Sugestión , Humanos , Encuestas y Cuestionarios , Autoinforme , Habilidades de AfrontamientoRESUMEN
Patients undergoing challenging medical procedures often suffer from high levels of anxiety and stress. Their most important need is a feeling of control and safety. Hypnotic communication provides a means of addressing these feelings without medication. The core technique is to use the perceived stimuli, like beeping sounds or the pressure of the ventilation mask and re-evaluate them as helpful signs. For example, the beeping sounds can be an indicator of the optimal treatment with the highest level of medical equipment in the intensive care unit and the pressure of the ventilation mask might feel like a tight hug of a friend that wants to help. Positive suggestions work even better when patients are in a trance state. In the intensive care unit, you can use the natural trance state instead of inducing a formal hypnotic trance. Positive suggestions can even help to prevent negative emotions before the challenging medical procedure starts. It greatly improves patients' well-being to replace common phrases in the everyday medical practice. This article gives examples of better phrasings and elaborates the scientific evidence of positive suggestions that can even stop bleeding. The goal is to show simple ways to improve communication with patients and induce feelings of control and safety.
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Anestesia , Anestesiología , Hipnosis , Humanos , Ansiedad , Hipnóticos y SedantesRESUMEN
BACKGROUND: Borna disease virus 1 (BoDV-1) causes rare human infections within endemic regions in southern and eastern Germany. The infections reported to date have been linked to severe courses of encephalitis with high mortality and mostly irreversible symptoms. Whether BoDV-1 could act as a trigger for other neurological conditions, is, however, incompletely understood. OBJECTIVES AND METHODS: In this study, we addressed the question of whether the presentation of a clinically isolated syndrome (CIS) or of multiple sclerosis (MS) might be associated with a milder course of BoDV-1 infections. Serum samples of 100 patients with CIS or MS diagnosed at a tertiary neurological care center within an endemic region in southern Germany and of 50 control patients suffering from headache were retrospectively tested for BoDV-1 infections. RESULTS: In none of the tested sera, confirmed positive results of anti-BoDV-1-IgG antibodies were retrieved. Our results support the conclusion that human BoDV-1 infections primarily lead to severe encephalitis with high mortality.
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Enfermedad de Borna , Virus de la Enfermedad de Borna , Encefalitis , Esclerosis Múltiple , Animales , Humanos , Virus de la Enfermedad de Borna/genética , Enfermedad de Borna/epidemiología , Enfermedad de Borna/complicaciones , Estudios Retrospectivos , Proyectos Piloto , Esclerosis Múltiple/epidemiología , Anticuerpos AntiviralesAsunto(s)
Estimulantes del Sistema Nervioso Central , Enfermedades del Recién Nacido , Enfermedades del Prematuro , Recién Nacido , Humanos , Cafeína/uso terapéutico , Apnea/tratamiento farmacológico , Recien Nacido Prematuro , Estimulantes del Sistema Nervioso Central/efectos adversos , Enfermedades del Prematuro/tratamiento farmacológicoRESUMEN
Hand fractures represent commonly encountered injuries in pediatric patients. However, due to modern means of mobility and product safety, the occurrence and distribution of these fractures have changed during the last decades. Therefore, it was the aim of this study to present an update of the epidemiology, pattern, and treatment of hand fractures in a large pediatric cohort. All patients aged between 0 and 17 years treated in our Department in 2019 with fractures of the phalanges, metacarpus, or carpus were included. The medical records were reviewed for age, gender, injury mechanism, fracture localization, season, and treatment. Patients were divided into three different age groups (0-5, 6-12, and 13-17 years). A total of 731 patients with 761 hand fractures were treated during the 1-year study period. The mean age was 11.1 ± 3.5 years, and the majority was male (65%). Male patients were significantly older compared to female patients (p = 0.008). Also, 78.7% of the fractures affected the phalanges, 17.6% the metacarpals, and 3.7% the carpal bones. The proximal phalanges were the most commonly fractured bones (41.5%). Patients with fractures of the carpus were significantly older compared to children sustaining fractures of the metacarpus or phalangeal bones (p < 0.001). Sixteen percent of our patients were treated surgically; these patients were significantly older compared to conservatively treated patients (p = 0.011). Conclusion: The epidemiology, mechanisms of injury, distribution, and treatment of hand fractures significantly varies among different age groups. This knowledge is of importance for educational purposes of younger colleagues entrusted with care of children and adolescents as well as development of effective prevention strategies. What is Known: ⢠Pediatric hand fractures represent the second most common fractures in children. ⢠The epidemiology of pediatric hand fractures has changed during the last decades and therefore there is a need for an update regarding distribution and epidemiology of pediatric hand fractures. What is New: ⢠In this retrospective cohort study, 761 pediatric hand fractures of 731 patients were analyzed in detail. ⢠The main mechanisms of younger patients were entrapment injuries, older children most commonly sustained their fractures due to ball sport injuries. There was an increasing rate of metacarpal and carpal fractures with increasing age, and these fractures had to be treated operatively more often than phalangeal fractures.
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Falanges de los Dedos de la Mano , Fracturas Óseas , Traumatismos de la Mano , Huesos del Metacarpo , Niño , Humanos , Masculino , Adolescente , Femenino , Recién Nacido , Lactante , Preescolar , Estudios Retrospectivos , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Fracturas Óseas/terapia , Huesos del Metacarpo/lesiones , Falanges de los Dedos de la Mano/diagnóstico por imagen , Falanges de los Dedos de la Mano/lesiones , Falanges de los Dedos de la Mano/cirugía , Traumatismos de la Mano/epidemiología , Traumatismos de la Mano/etiología , Traumatismos de la Mano/terapiaRESUMEN
OBJECTIVE: Surgical treatment of venous malformations (VMs) of the hand is challenging. The hand's small functional units, dense innervation, and terminal vasculature can be easily compromised during invasive interventions like surgery or sclerotherapy, leading to an increased risk of functional impairment, cosmetic consequences, and negative psychological effects. METHODS: We have conducted a retrospective review of all surgically treated patients diagnosed with VMs of the hand between 2000 and 2019 and evaluated their symptoms, diagnostic investigations, complications, and recurrences. RESULTS: Twenty-nine patients (females, n = 15) with a median age of 9.9 years (range, 0.6-18 years) were included. Eleven patients presented with VMs involving at least one of the fingers. In 16 patients, the palm and/or dorsum of the hand was affected. Two children presented with multifocal lesions. All patients presented with swelling. Preoperative imaging was done in 26 patients and consisted of magnetic resonance imaging in nine patients, ultrasound in eight patients, and both modalities in nine patients. Three patients underwent surgical resection of the lesions without any imaging. Indications for surgery were pain and restriction of function (n = 16), and when lesions were preoperatively evaluated as completely resectable (n = 11). In 17 patients, a complete surgical resection of the VMs was performed, whereas in 12 children, an incomplete resection of VM was deemed due to nerve sheath infiltration. At a median follow-up of 135 months (interquartile range, 136.5 months; range, 36-253 months), recurrence occurred in 11 patients (37.9%) after a median time of 22 months (range, 2-36 months). Eight patients (27.6%) were reoperated because of pain, whereas three patients were treated conservatively. The rate of recurrences did not significantly differ between patients presenting with (n = 7 of 12) or without (n = 4 of 17) local nerve infiltration (P = .119). All surgically treated patients who were diagnosed without preoperative imaging developed a relapse. CONCLUSIONS: VMs in the region of the hand are difficult to treat, and surgery is associated with a high recurrence rate. Accurate diagnostic imaging and meticulous surgery may contribute to improve the outcome of the patients.
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Malformaciones Vasculares , Niño , Femenino , Humanos , Lactante , Preescolar , Adolescente , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/cirugía , Malformaciones Vasculares/complicaciones , Venas/diagnóstico por imagen , Venas/cirugía , Venas/anomalías , Escleroterapia/efectos adversos , Dolor , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study ("BoDV-1 after solid-organ transplantation") to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.
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Enfermedad de Borna , Virus de la Enfermedad de Borna , Encefalitis Transmitida por Garrapatas , Encefalitis Viral , Encefalitis , Infecciones por Flavivirus , Animales , Humanos , Virus de la Enfermedad de Borna/genética , Enfermedad de Borna/epidemiología , Enfermedad de Borna/genética , Encefalitis Viral/epidemiología , Encefalitis Transmitida por Garrapatas/diagnóstico , Encefalitis Transmitida por Garrapatas/epidemiología , Alemania/epidemiologíaRESUMEN
More than 40 human infections with the zoonotic Borna disease virus 1 (BoDV-1) have been reported to German health authorities from endemic regions in southern and eastern Germany. Diagnosis of a confirmed case is based on the detection of BoDV-1 RNA or BoDV-1 antigen. In parallel, serological assays such as ELISA, immunoblots, and indirect immunofluorescence are in use to detect the seroconversion of Borna virus-reactive IgG in serum or cerebrospinal fluid (CSF). As immunopathogenesis in BoDV-1 encephalitis appears to be driven by T cells, we addressed the question of whether an IFN-γ-based ELISpot may further corroborate the diagnosis. For three of seven BoDV-1-infected patients, peripheral blood mononuclear cells (PBMC) with sufficient quantity and viability were retrieved. For all three patients, counts in the range from 12 to 20 spot forming units (SFU) per 250,000 cells were detected upon the stimulation of PBMC with a peptide pool covering the nucleocapsid protein of BoDV-1. Additionally, individual patients had elevated SFU upon stimulation with a peptide pool covering X or phosphoprotein. Healthy blood donors (n = 30) and transplant recipients (n = 27) were used as a control and validation cohort, respectively. In this pilot study, the BoDV-1 ELISpot detected cellular immune responses in human patients with BoDV-1 infection. Its role as a helpful diagnostic tool needs further investigation in patients with BoDV-1 encephalitis.
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Enfermedad de Borna , Virus de la Enfermedad de Borna , Encefalitis , Animales , Humanos , Virus de la Enfermedad de Borna/genética , Proyectos Piloto , Leucocitos Mononucleares/metabolismo , Enfermedad de Borna/epidemiología , Enfermedad de Borna/patología , Interferón gammaRESUMEN
Borna disease virus 1 (BoDV-1) has been recognized as a rare cause of very severe encephalitis with rapid onset in central Europe. Data on cerebrospinal fluid (CSF) analysis have not yet been analyzed in detail. Here, we present the first study on CSF changes in BoDV-1 encephalitis. We retrospectively analyzed CSFs from 18 BoDV-1 encephalitis cases from Bavaria, Germany, an endemic region, from 1996 to 2021. Data were obtained through review of medical records and institutional databases. We found that white blood cell count (WBC) in CSF is elevated in 13 of our 18 patients at first examination (average 83.2 ± 142.3 leukocytes/µl) and cytology showed predominance of lymphocytes. Patients with typical symptoms of meningoencephalitis had higher WBC in first CSF analyzation (133.5 ± 163.1 vs 4.0 ± 3.2/µl; p = 0.065). BoDV-1 PCR of CSF is not always positive when tested (7 of 9 cases). Four of five patients tested showed a polyvalent reaction against multiple viruses in the CSF suggesting that BoDV-1 may trigger autoimmune mechanisms. CSF changes in BoDV-1 encephalitis seem similar to those of other viral encephalitis and at the beginning WBC can be normal in up to 28%, making the diagnosis even more challenging. All in all, BoDV-1 should be included in the diagnostic workup of patients with rapidly evolving and/or severe encephalitis and patients with severe neuropathy and secondary encephalopathy with and without CSF changes. Repeated CSF examinations as well as BoDV-1 serology and CSF PCR have to be considered in endemic areas.