Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Exp Dermatol ; 33(3): e15034, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38459631

RESUMEN

Polymorphic light eruption (PLE) has been mechanistically linked to cytokine abnormalities. Emerging preclinical evidence posits the skin microbiome as a critical modulator of ultraviolet (UV)-induced cytokine expression, thereby influencing subsequent immune responses. This intricate relationship remains underexplored in the context of PLE. Hence, we investigated the differential responses between disinfected and non-disinfected skin following both single and repetitive exposures to solar-simulated UV radiation in patients with PLE. An experimental, half-body pilot study was conducted involving six PLE patients and 15 healthy controls. Participants' skin was exposed to single and multiple doses of solar-simulated UV radiation, both in disinfected and in non-disinfected skin areas. The co-primary outcomes were PLE score and cytokine expression in blister fluid analysed through OLINK proteomic profiling. Secondary outcomes were erythema, pigmentation, induction of apoptotic cells in vacuum-generated suction blisters, and density of infiltrate in skin biopsies of PLE patients. Among the 71 cytokines analysed, baseline expression levels of 20 specific cytokines-integral to processes such as apoptosis, inflammation, immune cell recruitment, cellular growth, and differentiation-were significantly impaired in PLE patients compared with healthy controls. Notably, skin disinfection reversed the observed cytokine imbalances following a single UV exposure at the minimal erythema dose (MED) level and exhibited even more pronounced effects after multiple UV exposures. However, no significant differences were evident in PLE score, erythema, pigmentation, or rates of apoptotic cell induction upon UV radiation. These findings provide evidence for UV-driven cytokine regulation by the skin microbiota and imply microbiome involvement in the PLE immune response.


Asunto(s)
Dermatitis por Contacto , Trastornos por Fotosensibilidad , Humanos , Trastornos por Fotosensibilidad/metabolismo , Proyectos Piloto , Proteómica , Piel/patología , Rayos Ultravioleta , Citocinas , Eritema
2.
Hum Reprod ; 38(10): 2028-2038, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37553222

RESUMEN

STUDY QUESTION: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? SUMMARY ANSWER: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. WHAT IS KNOWN ALREADY: Anecdotal evidence suggests an association of ART with RT. STUDY DESIGN, SIZE, DURATION: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART. WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

3.
Acta Derm Venereol ; 103: adv9403, 2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37358394

RESUMEN

Narrowband-ultraviolet B has shown increased efficacy over broadband-ultraviolet B in pruritic skin diseases, such as psoriasis and atopic dermatitis. In patients with chronic pruritus, e.g. in end-stage renal disease, broadband-ultraviolet B is recommended, but narrowband-ultraviolet B has also shown efficacy in reducing pruritus. This randomized, single blinded, non-inferiority study investigated the effects of narrowband-ultraviolet B compared with broadband-ultraviolet B. Patients with chronic pruritus were treated with either broadband- or narrowband-UVB 3 times a week for 6 weeks and clinical response was monitored. Pruritus, sleep disturbance, and the patients' subjective overall response to treatment were evaluated by the patients on a visual analogue scale (0-10). Skin excoriations were evaluated by investigators on a 4-point scale (0-3). Both phototherapeutic modalities showed significant antipruritic activity (itch reduction 48% and 66.4%, respectively) by broadband-ultraviolet B and narrowband-ultraviolet B. Narrowband-ultraviolet B proved to be not inferior to broadband-ultraviolet B in treating pruritus in patients with chronic pruritus, assuming a 20% non-inferiority margin.


Asunto(s)
Dermatitis Atópica , Psoriasis , Terapia Ultravioleta , Humanos , Terapia Ultravioleta/efectos adversos , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Prurito/etiología , Psoriasis/terapia , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/radioterapia , Dermatitis Atópica/etiología , Recolección de Datos , Resultado del Tratamiento
4.
J Dtsch Dermatol Ges ; 21(12): 1513-1523, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37907427

RESUMEN

BACKGROUND AND OBJECTIVES: This study analyzed the extent to which the recent introduction of more effective treatments has led to an improvement in real-world psoriasis patients. PATIENTS AND METHODS: Patient characteristics and the first-year treatment effectiveness in biologic-naive patients have been analyzed since 2004 until now, irrespective of treatment switches. RESULTS: Data from 2,729 patients were eligible for this analysis. The proportion of female patients increased significantly over the years from 29.9% to 36.2% (p < 0.028), while the number of patients with psoriatic arthritis declined from 36.6% to 30.0% (p < 0.001). Moreover, the duration of psoriatic disease and PASI at the start of the treatment significantly decreased. Last observation carrief forward (LOCF) analysis indicated that PASI 90 response increased from 18.9 to 44.6% at 3 months and from 32.9 to 66.8% at 12 months after treatment started. Similary, the PASI ≤ 3 rates increased from 33.2% to 66.0% at 3 months and from 41.9% to 78.9% at 12 months after the treatment started. CONCLUSIONS: The continuous introduction of more efficient biologics has led to significant improvements in patient care and clinical outcomes. Though one out of three to five patients, depending on the endpoint selected, nowadays still does not achieve an entirely satisfactory treatment response (i.e., PASI 90 or PASI ≤ 3).


Asunto(s)
Productos Biológicos , Psoriasis , Humanos , Femenino , Austria/epidemiología , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Resultado del Tratamiento , Productos Biológicos/uso terapéutico , Sistema de Registros , Índice de Severidad de la Enfermedad
5.
J Clin Immunol ; 42(3): 484-498, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34797428

RESUMEN

Quantifying the phenotypic features of rare diseases such as inborn errors of immunity (IEI) helps clinicians make diagnoses, classify disorders, and objectify the disease severity at its first presentation as well as during therapy and follow-up. Furthermore, it may allow cross-sectional and cohort comparisons and support treatment decisions such as an evaluation for transplantation. On the basis of a literature review, we provide a descriptive comparison of ten selected scores and measures frequently used in IEI and divide these into three categories: (1) diagnostic tools (for Hyper-IgE syndrome, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome), (2) morbidity and disease activity measures (for common variable immune deficiency [CVID], profound combined immune deficiency, CTLA-4 haploinsufficiency, immune deficiency and dysregulation activity [IDDA], IPEX organ impairment, and the autoinflammatory disease activity index), and (3) treatment stratification scores (shown for hypogammaglobulinemia). The depth of preclinical and statistical validations varies among the presented tools, and disease-inherent and user-dependent factors complicate their broader application. To support a comparable, standardized evaluation for prospective monitoring of diseases with immune dysregulation, we propose the IDDA2.1 score (comprising 22 parameters on a 2-5-step scale) as a simple yet comprehensive and powerful tool. Originally developed for use in a retrospective study in LRBA deficiency, this new version may be applied to all IEI with immune dysregulation. Reviewing published aggregate cohort data from hundreds of patients, the IDDA kaleidoscope function is presented for 18 exemplary IEI as an instructive phenotype-pattern visualization tool, and an unsupervised, hierarchically clustered heatmap mathematically confirms similarities and differences in their phenotype expression profiles.


Asunto(s)
Inmunodeficiencia Variable Común , Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Proteínas Adaptadoras Transductoras de Señales , Estudios Transversales , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/terapia , Estudios Prospectivos , Estudios Retrospectivos
6.
Clin Chem Lab Med ; 59(3): 541-546, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33064668

RESUMEN

OBJECTIVES: Data on the clinical importance of the detection of anti-dsDNA antibodies in patients with negative indirect immunofluorescence on the HEp-2 cell (IIF) are sparse and are especially not available for all common commercially available assays. This study aimed to assess the clinical significance of anti-dsDNA antibodies determined by the Elia™ dsDNA assay in patients with negative IIF. METHODS: We retrospectively examined the medical records of 234 consecutive subjects with detectable anti-dsDNA antibodies determined by the Elia™ dsDNA assay. RESULTS: A total of 124 subjects with detectable anti-dsDNA autoantibodies were IIF-negative, but yielded positive or borderline results in the Elia™ CTD screen assay for antinuclear antibodies (ANA). Within this group, 6/49 IIF-negative patients (12%) with ANA-associated systemic autoimmune rheumatic disorders (AASARD) and 118/185 subjects (64%) with various other diseases (Non-AASARD) were identified. There was no statistically significant difference with regard to the concentrations of anti-dsDNA antibodies (p=0.53) between the AASARD and the Non-AASARD group. Within the AASARD group, four patients diagnosed with systemic lupus erythematosus (SLE, treated), discoid lupus erythematosus (untreated), indetermined connective tissue disease (untreated) and polymyositis (treated) had positive anti-dsDNA autoantibodies, whereas two patients with treated SLE, thereby one in remission, had borderline concentrations of anti-dsDNA antibodies. CONCLUSIONS: Our findings suggest that the detection of anti-dsDNA antibodies in IIF-negative patients can be of clinical relevance in some cases. Our results further support the combined use of IIF and solid-phase assays in screening algorithms for ANA, in order to avoid overlooking potentially important autoantibody entities.


Asunto(s)
Técnica del Anticuerpo Fluorescente Indirecta , Anticuerpos Antinucleares , Autoanticuerpos , ADN , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Estudios Retrospectivos
7.
Haematologica ; 105(2): 375-386, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31097632

RESUMEN

RAS-signaling mutations induce the myelomonocytic differentiation and proliferation of hematopoietic stem and progenitor cells. Moreover, they are important players in the development of myeloid neoplasias. RAF kinase inhibitor protein (RKIP) is a negative regulator of RAS-signaling. As RKIP loss has recently been described in RAS-mutated myelomonocytic acute myeloid leukemia, we now aimed to analyze its role in myelomonocytic differentiation and RAS-driven leukemogenesis. Therefore, we initially analyzed RKIP expression during human and murine hematopoietic differentiation and observed that it is high in hematopoietic stem and progenitor cells and lymphoid cells but decreases in cells belonging to the myeloid lineage. By employing short hairpin RNA knockdown experiments in CD34+ umbilical cord blood cells and the undifferentiated acute myeloid leukemia cell line HL-60, we show that RKIP loss is indeed functionally involved in myelomonocytic lineage commitment and drives the myelomonocytic differentiation of hematopoietic stem and progenitor cells. These results could be confirmed in vivo, where Rkip deletion induced a myelomonocytic differentiation bias in mice by amplifying the effects of granulocyte macrophage-colony-stimulating factor. We further show that RKIP is of relevance for RAS-driven myelomonocytic leukemogenesis by demonstrating that Rkip deletion aggravates the development of a myeloproliferative disease in NrasG12D -mutated mice. Mechanistically, we demonstrate that RKIP loss increases the activity of the RAS-MAPK/ERK signaling module. Finally, we prove the clinical relevance of these findings by showing that RKIP loss is a frequent event in chronic myelomonocytic leukemia, and that it co-occurs with RAS-signaling mutations. Taken together, these data establish RKIP as novel player in RAS-driven myeloid leukemogenesis.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas de Unión a Fosfatidiletanolamina , Animales , Diferenciación Celular , Leucemia Mieloide Aguda/genética , Ratones , Monocitos/metabolismo , Proteínas de Unión a Fosfatidiletanolamina/genética , Proteínas de Unión a Fosfatidiletanolamina/metabolismo , Transducción de Señal
8.
Am J Hematol ; 95(10): 1148-1157, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32602117

RESUMEN

Persistent measurable residual disease (MRD) is an increasingly important prognostic marker in acute myeloid leukemia (AML). Currently, MRD is determined by multi-parameter flow cytometry (MFC) or PCR-based methods detecting leukemia-specific fusion transcripts and mutations. However, while MFC is highly operator-dependent and difficult to standardize, PCR-based methods are only available for a minority of AML patients. Here we describe a novel, highly sensitive and broadly applicable method for MRD detection by combining MFC-based leukemic cell enrichment using an optimized combinatorial antibody panel targeting CLL-1, TIM-3, CD123 and CD117, followed by mutational analysis of recurrently mutated genes in AML. In dilution experiments this method showed a sensitivity of 10-4 to 10-5 for residual disease detection. In prospectively collected remission samples this marker combination allowed for a median 67-fold cell enrichment with sufficient DNA quality for mutational analysis using next generation sequencing (NGS) or digital PCR in 39 out of 41 patients. Twenty-one samples (53.8%) tested MRD positive, whereas 18 (46.2%) were negative. With a median follow-up of 559 days, 71.4% of MRD positive (15/21) and 27.8% (5/18) of MRD negative patients relapsed (P = .007). The cumulative incidence of relapse (CIR) was higher for MRD positive patients (5-year CIR: 90.5% vs 28%, P < .001). In multivariate analysis, MRD positivity was a prominent factor for CIR. Thus, MFC-based leukemic cell enrichment using antibodies against CLL-1, TIM-3, CD123 and CD117 followed by mutational analysis allows high sensitive MRD detection and is informative on relapse risk in the majority of AML patients.

9.
Pediatr Blood Cancer ; 67(1): e28022, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31571386

RESUMEN

BACKGROUND: Case reports have portrayed spinal cord atypical teratoid/rhabdoid tumor (spATRT) as an aggressive form of ATRT. We conducted a retrospective European survey to collect data on clinical characteristics, molecular biology, treatment, and outcome of children with intramedullary spATRT. METHODS: Scrutinizing a French national series and the European Rhabdoid Registry database, we identified 13 patients (median age 32 months; metastatic disease at diagnosis, n = 6). Systemic postoperative chemotherapy was administered to all patients; three received intrathecal therapy and six were irradiated (craniospinal, n = 3; local, n = 3). RESULTS: Median observation time was 8 (range, 1-93) months. Progression-free and overall survival rates at 1 and (2 years) were 35.2% ± 13.9% (26.4% ± 12.9%) and 38.5% ± 13.5% (23.1% ± 11.7%). Four patients (ATRT-SHH, n = 2; ATRT-MYC, n = 1; DNA methylation subgroup not available, n = 1) achieved complete remission (CR); two of them are alive in CR 69 and 72 months from diagnosis. One patient relapsed after CR and is alive with progressive disease (PD) and one died of the disease. Three patients (ATRT-MYC, n = 2; subgroup not available, n = 1) died after 7 to 22 months due to PD after having achieved a partial remission (n = 1) or stabilization (n = 2). Five patients (ATRT-MYC, n = 2; subgroup not available, n = 3) developed early PD and died. One patient (ATRT-MYC) died of intracerebral hemorrhage prior to response evaluation. CONCLUSIONS: Long-term survival is achievable in selected patients with spATRT using aggressive multimodality treatment. Larger case series and detailed molecular analyses are needed to understand differences between spATRT and their inracranial counterparts and the group of extradural malignant rhabdoid tumors.


Asunto(s)
Biomarcadores de Tumor/genética , Tumor Rabdoide/mortalidad , Neoplasias de la Médula Espinal/mortalidad , Teratoma/mortalidad , Niño , Preescolar , Terapia Combinada , ADN Helicasas/genética , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Proteínas Nucleares/genética , Pronóstico , Estudios Retrospectivos , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Tumor Rabdoide/terapia , Proteína SMARCB1/genética , Neoplasias de la Médula Espinal/genética , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/terapia , Tasa de Supervivencia , Teratoma/genética , Teratoma/patología , Teratoma/terapia , Factores de Transcripción/genética
10.
Scand J Gastroenterol ; 55(2): 248-250, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31928091

RESUMEN

Background: Basophilia of the peripheral blood (PBB) has rarely been described in patients with ulcerative colitis (UC).Objective: This study aimed to determine the frequency of PBB in patients with UC and to examine a potential correlation of PBB with markers of inflammation.Methods: We compared retrospectively the basophil counts and the occurrence of basophilia (>200 basophils/µL) between 165 patients with UC and 35 controls, and analysed the correlation between the basophil count and the C-reactive protein (CRP).Results: Within the study period, data from 1750 leukocyte differential count determinations of UC patients and 158 results from control subjects were available in the medical records and were statistically analysed. The differences in the basophil counts between the UC and the control group were not statistically significant (60/µL (0-351) vs. 49/µL (0-184), p = .26). Basophilia was apparent in 23 measurements of 10 patients with UC, but was not observed in the controls (p = .30). The basophil count was not significantly correlated with the CRP (p = .065, r = 0.04).Conclusions: Our findings suggest that PBB represents an uncommon and not disease-specific laboratory feature of UC. It is not correlated with the CRP and may not represent a useful biomarker for disease monitoring in UC.


Asunto(s)
Basófilos/citología , Colitis Ulcerosa/sangre , Recuento de Leucocitos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
11.
Br J Nutr ; 122(1): 78-85, 2019 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-31006393

RESUMEN

Nutrition plays a crucial role in the pathophysiology and management of peripheral arterial disease (PAD) and periodontal disease (PD). As PD can have profound effects on an individual's functional ability to eat and can affect nutrient intake, we aimed to evaluate the role of PD severity on dietary intake (DI) and quality in PAD patients and compare it with current dietary recommendations for CVD. PD stages of 421 consecutive PAD patients were determined according to a standardised basic periodontal examination (Periodontal Screening and Recording Index) ('healthy', 'gingivitis', 'moderate periodontitis' and 'severe periodontitis'). Dietary intake (24-h recall), dietary quality (food frequency index (FFI)) and anthropometrical data were assessed. Nutritional intake was stratified according to the severity of PD. No significant differences in DI of macronutrients, nutrients relevant for CVD and FFI were seen between the PD stages. Only median alcohol intake was significantly different between gingivitis and severe periodontitis (P = 0·001), and positively correlated with PD severity (P = 0·001; r 0·159). PD severity and the patient's number of teeth showed no correlation with investigated nutritional parameters and FFI. Few subjects met the recommended daily intakes for fibre (5 %), SFA (10 %), Na (40 %) and sugar (26 %). Macronutrient intake differed from reference values. In our sample of patients with PAD and concomitant PD, we found no differences in DI of macronutrients, nutrients relevant for CVD and diet quality depending on PD severity. The patients' nutrition was, however, poor, deviating seriously from dietary guidelines and recommendations.


Asunto(s)
Dieta/efectos adversos , Enfermedades Periodontales/etiología , Enfermedad Arterial Periférica/complicaciones , Anciano , Registros de Dieta , Femenino , Alimentos/clasificación , Humanos , Masculino , Persona de Mediana Edad , Valor Nutritivo
12.
Skin Pharmacol Physiol ; 32(2): 65-71, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30612131

RESUMEN

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.


Asunto(s)
Antioxidantes/análisis , Carotenoides/análisis , Huevos/análisis , Administración Cutánea , Animales , Pollos , Almacenamiento de Alimentos , Luz , Espectrometría Raman , Temperatura
13.
Am J Hematol ; 93(1): 23-30, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28960408

RESUMEN

Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty-seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1-5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0-3). The most frequent noncleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non-DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; P = .013) and with a shorter relapse-free survival (333 days vs. not reached; log-rank P = .0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML.


Asunto(s)
Biomarcadores de Tumor/genética , Citogenética/métodos , Leucemia Mieloide Aguda/diagnóstico , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven
14.
Wound Repair Regen ; 26(1): 64-68, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29381242

RESUMEN

Patients suffering from pressure ulcers remain to be a challenging task for nursing staff and doctors in the daily clinical management, putting-notably in the case of recurrences-additional strain on the constantly reduced resources in public healthcare. We aimed to assess the risk factors for the recurrence of pressure ulcers at our institution, a tertiary referral center. In this retrospective analysis of patients admitted to our division we identified risk factors for pressure ulcer recurrence. The hospital patient database search included all patients with a diagnosis of pressure ulcers of the torso and lower extremity. One hundred sixty-three patients were diagnosed with pressure ulcers and 55 patients with 63 pressure ulcers met our inclusion criteria. The 17 recurrences (27%) had an average follow-up of 728 days. Most presented with lesions of the ischial tuberosity (n=24). Recurrence was statistically associated with defect size (p = 0.013, Cox regression analysis), and serum albumin levels (p = 0.045, Spearman correlation), but no association was found for body mass index, bacterial profile, comorbidities, localization, previous surgery, or time-to-admission for reconstruction (all p > 0.05). Supported by the recent literature we identified factors like defect size to be associated with pressure ulcer recurrence, but not with time-to admission for reconstruction or number of previous debridements. Whether laboratory values like serum albumin levels were the cause, the result or associated with pressure ulcer recurrence warrants further investigation.


Asunto(s)
Antibacterianos/uso terapéutico , Procedimientos de Cirugía Plástica/métodos , Úlcera por Presión/epidemiología , Úlcera por Presión/fisiopatología , Albúmina Sérica Humana/metabolismo , Adulto , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Terapia Combinada , Comorbilidad , Desbridamiento/métodos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Úlcera por Presión/tratamiento farmacológico , Úlcera por Presión/cirugía , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria , Factores de Tiempo , Cicatrización de Heridas , Adulto Joven
15.
Curr Opin Pediatr ; 30(6): 855-863, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30124581

RESUMEN

PURPOSE OF REVIEW: The risk of cancer is higher, and its outcome is worse in patients with primary immunodeficiency (PID) than in members of the general population. Thus, the inter-relationship of malignant diseases with PIDs requires more study. RECENT FINDINGS: Large genetic screens identified a vast number of germline mutations in childhood cancer patient samples. Although TP53 was the most frequent single gene identified as mutated, many PID disorders like DNA repair defects are among the inborn causes of childhood cancer. We provide a comprehensive analysis of compiled data from seven recent studies that focused on germline genetic landscapes and preexisting conditions in pediatric oncology. As potentially causal germline variants were identified in ≈8% of malignancies in children and adolescents, we visualized this proportion as the 'tips of the icebergs'. The results of additional network analyses showed the shared patterns of germline mutations in various malignancies and yielded a spatial distribution of the 'icebergs'. SUMMARY: The 'iceberg map of germline mutations in childhood cancers' was created to increase the awareness of the inborn genetic underpinnings of childhood malignancies and their relationships with immunodeficiencies. Needs and perspectives of clinical immunologists and pediatric oncologists to both improve patient care and guide research at this critical interface are discussed. VIDEO ABSTRACT.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Mutación de Línea Germinal/genética , Síndromes de Inmunodeficiencia/genética , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Causalidad , Niño , Análisis Mutacional de ADN , Manejo de la Enfermedad , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/fisiopatología , Neoplasias/inmunología , Neoplasias/fisiopatología , Pediatría , Fenotipo
16.
Clin Chem Lab Med ; 56(2): 323-326, 2018 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-28731851

RESUMEN

BACKGROUND: Red blood cells (RBC) resembling the silhouette of a fish are rarely observed in peripheral blood (PB) smears. In this study, we determined the frequency of occurrence of fish-shaped RBC in different haematologic diseases. METHODS: We examined PB smears of patients with iron deficiency anaemia (IDA) (n=23), ß-thalassaemia minor (BTM) (n=30), sickle cell disease (SCD) (n=7), autoimmune haemolytic anaemia (AIHA) (n=13), microangiopathic haemolytic anaemia (MAHA) (n=11), hereditary sphaerocytosis (HS) (n=4), hereditary elliptocytosis (HE) (n=3), vitamin B12 and folate deficiency (n=15), anaemia in liver disease (LD) (n=17), myelodysplastic syndrome (MDS) (n=15), acute myeloid leukaemia (AML) (n=29), chronic myeloid leukaemia (CML) (n=18), primary myelofibrosis (PMF) (n=12), chronic myelo-monocytic leukaemia (CMML) (n=15) and 21 healthy controls by light microscopy for the occurrence of fish-shaped erythrocytes. The fish-shaped RBC were counted as cells per 20 high-power fields (HPF) at 1000-fold magnification, and slides containing ≥1 fish-shaped RBC/20 HPF were regarded as positive. RESULTS: Fish-shaped RBC were significantly found in HE, iron deficiency, vitamin B12/folate deficiency, LD and PMF. The highest numbers of fish-shaped RBC were seen in HE and vitamin B12/folate deficiency. In patients with BTM, MDS, AML and CMML, this RBC anomaly was only occasionally observed. Furthermore, a statistically significant negative correlation of haemoglobin with the occurrence of fish-shaped RBC was apparent (p<0.014). CONCLUSIONS: Our data show that the occurrence of fish-shaped RBC is suggestive of a pathologic condition, especially IDA, HE, vitamin B12 or folate deficiency, primary mylofibrosis or LD, and is significantly associated with severity of anaemia.


Asunto(s)
Eritrocitos Anormales , Enfermedades Hematológicas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia/patología , Niño , Preescolar , Recuento de Eritrocitos , Eritrocitos Anormales/clasificación , Femenino , Enfermedades Hematológicas/patología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto Joven
17.
J Dtsch Dermatol Ges ; 16(8): 981-991, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30117699

RESUMEN

HINTERGRUND: Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschränkung ihrer Lebensqualität konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt. PATIENTEN UND METHODIK: Wir führten einen bundesweiten Querschnitt-Survey in Österreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualität und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit überwiegend tertiären Versorgungsaufgaben durch. ERGEBNISSE: 70,2 % der 1184 befragten Patienten berichtete über eine eingeschränkte Lebensqualität (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16-20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Fälle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewünschten Ausmaß erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45), dem Ausmaß des psoriatischen Körperoberflächenbefalls (p = 3.2e-11) und Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant höheren Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16). SCHLUSSFOLGERUNGEN: Die Lebensqualität der meisten österreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeinträchtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.

18.
J Dtsch Dermatol Ges ; 16(8): 981-990, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30117711

RESUMEN

BACKGROUND: Patients with psoriasis experience impairment in quality of life. Thus, high-quality dermatological care is of particular importance. PATIENTS AND METHODS: We performed a nationwide cross-sectional survey in Austria (BQSAustria Psoriasis 2014/2015) with a special focus on quality of life and satisfaction with treatment among psoriasis patients predominantly treated at tertiary care centers. RESULTS: Overall, 70.2 % of 1,184 patients reported impaired quality of life (DLQI 2-5: 29.4 %; 6-10: 19.3 %; 11-15: 11.5 %; 16-20: 5.2 % and > 20: 4.9 %) despite treatment over the preceding four weeks (topical treatment in 88.2 % of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined subjective treatment goals was achieved to a sufficient degree. In particular, 82.2 % of patients continued to have pruritus despite treatment, which was highly significantly associated with a poor general health status over the preceding week (Spearman's rank correlation; p  =  1.1e-45), the extent of body surface area (p  =  3.2e-11) and scalp area (p  =  3.2e-11) affected, as well as pain (p  =  2.3e-22). Treatment with a biologic was significantly correlated with higher patient satisfaction (Wilcoxon-Test, p  =  2.0e-16). CONCLUSIONS: Despite dermatological care, the majority of Austrian psoriasis patients continues to experience impaired quality of life; there is potential for improvement in the achievement of treatment goals.


Asunto(s)
Psoriasis , Austria , Estudios Transversales , Humanos , Dolor , Prurito , Psoriasis/complicaciones , Psoriasis/terapia , Calidad de Vida
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA