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1.
Fortschr Neurol Psychiatr ; 91(7-08): 311-318, 2023 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-36599444

RESUMO

Clinical research on the therapeutic efficacy of psychedelics is currently experiencing a renaissance. Available scientific evidence on their efficacy in various psychiatric conditions, as well as their legally approved use in some countries of the world, show the possibility of their future application in clinical practice also in Germany. The field is facing substantial challenges that have to be addressed, such as defining and setting a suitable clinical frame. This manuscript deals with the historical background of the clinical application of psychedelics, as well as the psycho-phenomenology, modes of action, possible indications and aspects of safety. The current research status in Germany and the organization of professional societies are discussed in a historical and international context and attention is drawn to unresolved critical issues in the field.


Assuntos
Alucinógenos , Transtornos Mentais , Psiquiatria , Humanos , Transtornos Mentais/tratamento farmacológico , Alemanha
2.
Int J Gynecol Cancer ; 30(10): 1548-1553, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32938723

RESUMO

BACKGROUND: There is limited information about the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer. OBJECTIVE: To evaluate the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer as a sub-protocol of the prospectively randomized LION trial. METHODS: The Sexual Activity Questionnaire was applied to assess sexual function according to its sub-scales activity, pleasure, and discomfort. The 'orgasm' sub-scale from the Female Sexual Function Index was also added. The questionnaire was administered in combination with the EORTC QLQ-C30 questionnaire at baseline prior surgery, after 6, 12, and 24 months. The primary endpoint was changes in sexual function. RESULTS: Overall, 495 patients received the questionnaires. 254 (51%) responded at baseline. Of these, 55 (22%) patients were sexually active, 182 (72%) were sexually inactive, and for 17 (7%) patients' data were not available. There was a total of 55/495 (11%) patients at 6 months, 139 (28%) patients at 12 months, and 81 (16%) patients at 24 months. Median age was 60.5 years (range 21.4-75.8). At baseline, sexually active responders were significantly younger (median age 51.5 years,) than sexually inactive responders (median age 61.8 years) and tended to have a better performance status. Discomfort evaluated as dryness of the vagina and pain during sexual intercourse was significantly worse at 12 months than at baseline (p<0.001); however, the surgical variable, lymphadenectomy, did not have any impact on this. The orgasm sub-scale showed diverging results with a deterioration from baseline to 12 months in the lymphadenectomy group compared with the no-lymphadenectomy group (p=0.02). CONCLUSION: The majority of patients were sexually inactive; however, in those who were sexually active, pain during intercourse was worse at 12 months. In addition, the orgasm sub-scale demonstrated worse results in patients who underwent complete lymphadenectomy. The study suggests that surgery in the retroperitoneal space may influence sexual function.


Assuntos
Dispareunia/etiologia , Excisão de Linfonodo/efeitos adversos , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Comportamento Sexual/estatística & dados numéricos , Inquéritos e Questionários , Fatores de Tempo
4.
Artigo em Inglês | MEDLINE | ID: mdl-27466220

RESUMO

BACKGROUND: The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known. METHODS: In this randomized crossover, placebo-controlled, and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 substances. RESULTS: We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra. CONCLUSIONS: Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system.


Assuntos
Antipsicóticos/administração & dosagem , Benzotiazóis/administração & dosagem , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/efeitos dos fármacos , Agonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Neurônios Dopaminérgicos/efeitos dos fármacos , Fumarato de Quetiapina/administração & dosagem , Adulto , Velocidade do Fluxo Sanguíneo , Estudos Cross-Over , Neurônios Dopaminérgicos/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Pramipexol , Fluxo Sanguíneo Regional , Suíça , Fatores de Tempo , Adulto Jovem
5.
Eur Arch Psychiatry Clin Neurosci ; 265(1): 45-55, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24902936

RESUMO

Dealing with one's emotions is a core skill in everyday life. Effective cognitive control strategies have been shown to be neurobiologically represented in prefrontal structures regulating limbic regions. In addition to cognitive strategies, mindfulness-associated methods are increasingly applied in psychotherapy. We compared the neurobiological mechanisms of these two strategies, i.e. cognitive reappraisal and mindfulness, during both the cued expectation and perception of negative and potentially negative emotional pictures. Fifty-three healthy participants were examined with functional magnetic resonance imaging (47 participants included in analysis). Twenty-four subjects applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level, both strategies were associated with comparable activity of the medial prefrontal cortex and the amygdala. When expecting negative versus neutral stimuli, the mindfulness group showed stronger activations in ventro- and dorsolateral prefrontal cortex, supramarginal gyrus as well as in the left insula. During the perception of negative versus neutral stimuli, the two groups only differed in an increased activity in the caudate in the cognitive group. Altogether, both strategies recruited overlapping brain regions known to be involved in emotion regulation. This result suggests that common neural circuits are involved in the emotion regulation by mindfulness-based and cognitive reappraisal strategies. Identifying differential activations being associated with the two strategies in this study might be one step towards a better understanding of differential mechanisms of change underlying frequently used psychotherapeutic interventions.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Emoções/fisiologia , Atenção Plena , Adulto , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Hum Brain Mapp ; 35(7): 2966-77, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24039023

RESUMO

Social anxiety disorder (SAD) is the second leading anxiety disorder. On the functional neurobiological level, specific brain regions involved in the processing of anxiety-laden stimuli and in emotion regulation have been shown to be hyperactive and hyper-responsive in SAD such as amygdala, insula and orbito- and prefrontal cortex. On the level of brain structure, prior studies on anatomical differences in SAD resulted in mixed and partially contradictory findings. Based on previous functional and anatomical models of SAD, this study examined cortical thickness in structural magnetic resonance imaging data of 46 patients with SAD without comorbidities (except for depressed episode in one patient) compared with 46 matched healthy controls in a region of interest-analysis and in whole-brain. In a theory-driven ROI-analysis, cortical thickness was increased in SAD in left insula, right anterior cingulate and right temporal pole. Furthermore, the whole-brain analysis revealed increased thickness in right dorsolateral prefrontal and right parietal cortex. This study detected no regions of decreased cortical thickness or brain volume in SAD. From the perspective of brain networks, these findings are in line with prior functional differences in salience networks and frontoparietal networks associated with executive-controlling and attentional functions.


Assuntos
Mapeamento Encefálico , Lobo Frontal/patologia , Rede Nervosa/patologia , Lobo Parietal/patologia , Transtornos Fóbicos/patologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Neuropsychobiology ; 69(2): 95-106, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24577108

RESUMO

BACKGROUND: Self-referential emotions such as shame/guilt and pride provide evaluative information about persons themselves. In addition to emotional aspects, social and self-referential processes play a role in self-referential emotions. Prior studies have rather focused on comparing self-referential and other-referential processes of one valence, triggered mostly by external stimuli. In the current study, we aimed at investigating the valence-specific neural correlates of shame/guilt and pride, evoked by the remembrance of a corresponding autobiographical event during functional magnetic resonance imaging. METHOD: A total of 25 healthy volunteers were studied. The task comprised a negative (shame/guilt), a positive (pride) and a neutral condition (expecting the distractor). Each condition was initiated by a simple cue, followed by the remembrance and finished by a distracting picture. RESULTS: Pride and shame/guilt conditions both activated typical emotion-processing circuits including the amygdala, insula and ventral striatum, as well as self-referential brain regions such as the bilateral dorsomedial prefrontal cortex. Comparing the two emotional conditions, emotion-processing circuits were more activated by pride than by shame, possibly due to either hedonic experiences or stronger involvement of the participants in positive self-referential emotions due to a self-positivity bias. However, the ventral striatum was similarly activated by pride and shame/guilt. In the whole-brain analysis, both self-referential emotion conditions activated medial prefrontal and posterior cingulate regions, corresponding to the self-referential aspect and the autobiographical evocation of the respective emotions. CONCLUSION: Autobiographically evoked self-referential emotions activated basic emotional as well as self-referential circuits. Except for the ventral striatum, emotional circuits were more active with pride than with shame.


Assuntos
Encéfalo/fisiologia , Emoções/fisiologia , Autoimagem , Vergonha , Adolescente , Adulto , Mapeamento Encefálico , Sinais (Psicologia) , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Testes Neuropsicológicos , Inquéritos e Questionários , Estriado Ventral/fisiologia , Adulto Jovem
8.
Brain Topogr ; 27(1): 138-48, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24241476

RESUMO

The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders.


Assuntos
Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico , Emoções/fisiologia , Imageamento por Ressonância Magnética , Inibição Neural , Neurorretroalimentação , Adulto , Regulação para Baixo , Expressão Facial , Estudos de Viabilidade , Feminino , Humanos , Masculino , Adulto Jovem
9.
Eur Arch Psychiatry Clin Neurosci ; 264(1): 45-60, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24100929

RESUMO

Borderline personality disorder (BPD) is associated with disturbed emotion processing, typically encompassing intense and fast emotional reactions toward affective stimuli. In this study, we were interested in whether emotional dysregulation in BPD occurs not only during the perception of emotional stimuli, but also during the anticipation of upcoming emotional pictures in the absence of concrete stimuli. Eighteen female patients with a diagnosis of BPD and 18 healthy control subjects anticipated cued visual stimuli with prior known emotional valence or prior unknown emotional content during functional magnetic resonance imaging. Brain activity during the anticipation of emotional stimuli was compared between both groups. When anticipating negative pictures, BPD patients demonstrated less signal change in the left dorsal anterior cingulate cortex (dACC) and left middle cingulate cortex (MCC), and enhanced activations in the left pregenual ACC, left posterior cingulate cortex (PCC) as well as in left visual cortical areas including the lingual gyrus. During the anticipation of ambiguously announced stimuli, brain activity in BPD was also reduced in the left MCC extending into the medial and bilateral dorsolateral prefrontal cortex. Results point out that deficient recruitment of brain areas related to cognitive-emotional interaction already during the anticipation phase may add to emotional dysregulation in BPD. Stronger activation of the PCC could correspond to an increased autobiographical reference in BPD. Moreover, increased preparatory visual activity during negative anticipation may contribute to hypersensitivity toward emotional cues in this disorder.


Assuntos
Sintomas Afetivos/etiologia , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/psicologia , Motivação/fisiologia , Adulto , Transtorno da Personalidade Borderline/patologia , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Oxigênio/sangue , Estimulação Luminosa , Psicometria , Autorrelato , Adulto Jovem
10.
Psychiatr Prax ; 51(2): 84-91, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-37813364

RESUMO

OBJECTIVE: To establish the effectiveness of Individual Placement and Support (IPS) to integrate people with mental illness into the general labor market, controlled comparisons with usual rehabilitative practice in terms of employment rates and cost-effectiveness are needed. METHODS: 20 IPS participants with psychoses (primarily schizophrenia spectrum disorders) were compared with 20 controls who were offered usual rehabilitative practices in adjacent counties (rehabilitation as usual, RAU) over 18 months. RESULTS: IPS was significantly superior to RAU on all job-related criteria with moderate to high effect sizes, with no differences in absenteeism, hospital days, or dropout rates. IPS was significantly superior to RAU on cost-effectiveness. CONCLUSION: This study provides evidence that IPS is an effective and cost-efficient addition to existing vocational rehabilitation services for people with psychoses.


Assuntos
Readaptação ao Emprego , Transtornos Mentais , Transtornos Psicóticos , Humanos , Análise Custo-Benefício , Alemanha , Transtornos Mentais/reabilitação , Transtornos Psicóticos/terapia , Reabilitação Vocacional
11.
Psychiatr Prax ; 2024 Oct 09.
Artigo em Alemão | MEDLINE | ID: mdl-39384318

RESUMO

AIM: Inpatient-Equivalent Home Treatment (IEHT) for mental health is new in Germany and therefore requires quality development. A best practice model (BPM) for IEHT is being developed from a service user perspective. METHODS: 1. Collection and organization of evidence (literature review; n=55 interviews with service users), 2. qualitative analysis and formulation of criteria; 3. consensus and grouping of criteria (Delphi process). RESULTS: 58 Best practice criteria were developed in 8 groups: 1. Information, access and crisis management; 2. Treatment framework, end of treatment and continuity; 3. Scheduling, organization of contacts and flexibility; 4. Practical support and activation; 5. Treatment and therapy services; 6. Treatment team and staff; 7. Relatives, caregivers and community; and 8. Privacy and behavior in the home environment. CONCLUSION: The BPM provides initial guidance for a user-centered assessment of the implementation of IEHT.

12.
Hum Brain Mapp ; 34(2): 437-46, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22076860

RESUMO

Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies.


Assuntos
Transtornos de Ansiedade/patologia , Lobo Frontal/patologia , Vias Neurais/patologia , Lobo Temporal/patologia , Adulto , Anisotropia , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Variações Dependentes do Observador
13.
Psychiatr Prax ; 50(8): 407-414, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-37683674

RESUMO

AIM: The quasi-experimental AKtiV study investigates the effects inpatient-equivalent home treatment (IEHT). This paper describes the study population based on demographic and clinical parameters at baseline and compares the index treatment. METHODS: Over a period of 12 months 200 IEHT users were included in the intervention group (IG) and 200 inpatients were included in the control group (CG). The comparability of the two groups was ensured by propensity score matching (PSM). RESULTS: In addition to the PSM variables, IG and CG did not differ significantly from each other variables at study inclusion. The duration of the index treatment was significantly longer in the IG (M=37.2 days) compared to the CG (M=27.9 days; p<0.001). CONCLUSION: The similarity of the two groups enables comparisons over 12 months, investigating IEHT effects on long-term outcomes.


Assuntos
Hospitalização , Pacientes Internados , Humanos , Resultado do Tratamento , Alemanha
14.
Eur Psychiatry ; 66(1): e71, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37681407

RESUMO

BACKGROUND: Inpatient equivalent home treatment (IEHT), implemented in Germany since 2018, is a specific form of home treatment. Between 2021 and 2022, IEHT was compared to inpatient psychiatric treatment in a 12-months follow-up quasi-experimental study with two propensity score matched cohorts in 10 psychiatric centers in Germany. This article reports results on the treatment during the acute episode and focuses on involvement in decision-making, patient satisfaction, and drop-out rates. METHODS: A total of 200 service users receiving IEHT were compared with 200 matched statistical "twins" in standard inpatient treatment. Premature termination of treatment as well as reasons for this was assessed using routine data and a questionnaire. In addition, we measured patient satisfaction with care with a specific scale. For the evaluation of patient involvement in treatment decisions, we used the 9-item Shared Decision Making Questionnaire (SDM-Q-9). RESULTS: Patients were comparable in both groups with regard to sociodemographic and clinical characteristics. Mean length-of-stay was 37 days for IEHT and 28 days for inpatient treatment. In both groups, a similar proportion of participants stopped treatment prematurely. At the end of the acute episode, patient involvement in decision-making (SDM-Q-9) as well as treatment satisfaction scores were significantly higher for IEHT patients compared to inpatients. CONCLUSIONS: Compared to inpatient care, IEHT treatment for acute psychiatric episodes was associated with higher treatment satisfaction and more involvement in clinical decisions.


Assuntos
Tomada de Decisão Compartilhada , Pacientes Internados , Humanos , Pacientes Internados/psicologia , Participação do Paciente , Satisfação do Paciente , Satisfação Pessoal , Tomada de Decisões
15.
Psychiatr Prax ; 2023 Nov 21.
Artigo em Alemão | MEDLINE | ID: mdl-37989203

RESUMO

This part of the AKtiV Study focuses on treatment satisfaction of patients and their relatives within Inpatient Equivalent Home Treatment (IEHT) and regular treatment. Stress of relatives and job satisfaction and workload of employees in IEHT is also considered. Relevant Parameters were collected via established as well as newly adapted questionnaires at the end of treatment. Patients and relatives in IEHT are significantly more satisfied. The stress experienced by relatives is reduced in both forms of treatment. Employees in IEHT are generally very satisfied, although there is no correlation with the satisfaction of relatives and patients. Known limitations of satisfaction surveys must be taken into account. In general these results encourage the expansion and continuous development of this new form of treatment in Germany.

16.
BMC Neurosci ; 13: 52, 2012 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-22624857

RESUMO

BACKGROUND: Self-referential cognitions are important for self-monitoring and self-regulation. Previous studies have addressed the neural correlates of self-referential processes in response to or related to external stimuli. We here investigated brain activity associated with a short, exclusively mental process of self-reflection in the absence of external stimuli or behavioural requirements. Healthy subjects reflected either on themselves, a personally known or an unknown person during functional magnetic resonance imaging (fMRI). The reflection period was initialized by a cue and followed by photographs of the respective persons (perception of pictures of oneself or the other person). RESULTS: Self-reflection, compared with reflecting on the other persons and to a major part also compared with perceiving photographs of one-self, was associated with more prominent dorsomedial and lateral prefrontal, insular, anterior and posterior cingulate activations. Whereas some of these areas showed activity in the "other"-conditions as well, self-selective characteristics were revealed in right dorsolateral prefrontal and posterior cingulate cortex for self-reflection; in anterior cingulate cortex for self-perception and in the left inferior parietal lobe for self-reflection and -perception. CONCLUSIONS: Altogether, cingulate, medial and lateral prefrontal, insular and inferior parietal regions show relevance for self-related cognitions, with in part self-specificity in terms of comparison with the known-, unknown- and perception-conditions. Notably, the results are obtained here without behavioural response supporting the reliability of this methodological approach of applying a solely mental intervention. We suggest considering the reported structures when investigating psychopathologically affected self-related processing.


Assuntos
Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Encéfalo/fisiologia , Processos Mentais/fisiologia , Autoimagem , Controles Informais da Sociedade , Adulto , Encéfalo/irrigação sanguínea , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Estimulação Luminosa , Adulto Jovem
17.
Cancers (Basel) ; 14(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35267497

RESUMO

BACKGROUND: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed by carboplatin-paclitaxel chemotherapy +/- nintedanib. METHODS: 103 HGSOC patients' tumor samples from phase III AGO-OVAR-12 were analyzed. A comprehensive analysis of the TME was performed by immunohistochemistry on tissue microarray. Comparative genomic hybridization was carried out to evaluate genomic instability signatures through homologous recombination deficiency (HRD) score, genomic index, and somatic copy number alterations. The relationship between genomic instability and TME was explored. RESULTS: Patients with high intratumoral CD3+ T lymphocytes had longer progression-free survival (32 vs. 19.6 months, p = 0.009) and overall survival (OS) (median not reached). High HLA-E expression on tumor cells was associated with a longer OS (median OS not reached vs. 52.9 months, p = 0.002). HRD profile was associated with high HLA-E expression on tumor cells and an improved OS. In the multivariate analysis, residual tumor, intratumoral CD3, and HLA-E on tumor cells were more predictive than other parameters. CONCLUSIONS: Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup.

18.
BMC Cancer ; 11: 12, 2011 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-21223596

RESUMO

BACKGROUND: Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer. METHODS: Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed. RESULTS: CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p=0.024), advanced tumor stage (p=0.001), greater invasion depth (p=0.025), undifferentiated tumor grade (p<0.001) and high preoperative SCC-Ag values (p=0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p=0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p=0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables. CONCLUSION: CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression.


Assuntos
Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/metabolismo , Anidrases Carbônicas/sangue , Anidrases Carbônicas/metabolismo , Neoplasias do Colo do Útero/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidrase Carbônica IX , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Adulto Jovem
19.
BMC Psychiatry ; 11: 120, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21801366

RESUMO

BACKGROUND: The debate on appropriate financing systems in inpatient psychiatry is ongoing. In this context, it is important to control resource use in terms of length of stay (LOS), which is the most costly factor in inpatient care and the one that can be influenced most easily. Previous studies have shown that psychiatric diagnoses provide only limited justification for explaining variation in LOS, and it has been suggested that measures such as psychopathology might be more appropriate to predict resource use. Therefore, we investigated the relationship between LOS and psychopathological syndromes or symptoms at admission as well as other characteristics such as sociodemographic and clinical variables. METHODS: We considered routine medical data of patients admitted to the Psychiatric University Hospital Zurich in the years 2008 and 2009. Complete data on psychopathology at hospital admission were available in 3,220 inpatient episodes. A subsample of 2,939 inpatient episodes was considered in final statistical models, including psychopathology as well as complete datasets of further measures (e.g. sociodemographic, clinical, treatment-related and psychosocial variables). We used multivariate linear as well as logistic regression analysis with forward selection procedure to determine the predictors of LOS. RESULTS: All but two syndrome scores (mania, hostility) were positively related to the length of stay. Final statistical models showed that syndromes or symptoms explained about 5% of the variation in length of stay. The inclusion of syndromes or symptoms as well as basic treatment variables and other factors led to an explained variation of up to 25%. CONCLUSIONS: Psychopathological syndromes and symptoms at admission and further characteristics only explained a small proportion of the length of inpatient stay. Thus, according to our sample, psychopathology might not be suitable as a primary indicator for estimating LOS and contingent costs. This might be considered in the development of future costing systems in psychiatry.


Assuntos
Hospitais Psiquiátricos/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/economia , Transtornos Mentais/psicologia , Serviços de Saúde Mental/estatística & dados numéricos , Modelos Estatísticos , Adulto , Feminino , Hospitais Psiquiátricos/economia , Humanos , Masculino , Serviços de Saúde Mental/economia , Pessoa de Meia-Idade
20.
J Psychopharmacol ; 35(1): 100-102, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33307959

RESUMO

The aim of this study was to investigate the effect of acute dopamine agonistic and antagonistic manipulation on the visual-cue induced blood oxygen level-dependent signal response in healthy volunteers. Seventeen healthy volunteers in a double-blind placebo-controlled cross-over design received either a dopamine antagonist, agonist or placebo and underwent functional magnetic resonance imaging. Using classical inference and Bayesian statistics, we found no effect of dopaminergic modulation on properties of visual-cue induced blood oxygen level-dependent signals in the visual cortex, particularly on distinct properties of the haemodynamic response function (amplitude, time-to-peak and width). Dopamine-related effects modulating the neurovascular coupling in the visual cortex might be negligible when measured via functional magnetic resonance imaging.


Assuntos
Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Hemodinâmica/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Córtex Visual , Adulto , Estudos Cross-Over , Sinais (Psicologia) , Dopaminérgicos/farmacologia , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Neurotransmissores/farmacologia , Estimulação Luminosa/métodos , Córtex Visual/irrigação sanguínea , Córtex Visual/diagnóstico por imagem , Córtex Visual/efeitos dos fármacos
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