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BACKGROUND: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. METHODS: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. RESULTS: Twenty-five patients were included with a median age of 78 (65-82) years. The median treatment duration was 48 (16-72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. CONCLUSIONS: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.
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Introduction: Vitamin D (vitD) deficiency may have importance in some diseases, but there is a lack of data in our country to clarify the current situation. Our aim was to examine the basic characteristics of patients' vitD status, and the ratio of vitD deficiency and its relation to certain diseases, assess seasonality and trends, and reveal the indirect impact of the COVID-19 pandemic on vitD3 supplementation at the patient population level. Methods: Anonymized data on 25(OH)D test results were obtained from the clinical data registry of a tertiary teaching hospital covering the period between 1 January 2015 and 30 June 2021. VitD consumption (pharmacy sale) data were retrieved from the database of the National Health Insurance Fund of Hungary in order to calculate the defined daily dose (DDD)/1,000 inhabitants/day. Descriptive statistics and odds ratios with their 95% confidence intervals were calculated. The two-sample t-test and F-test were used to analyze our patients' data. Significant differences were considered if p <0.05. Results: Altogether, 45,567 samples were investigated; the mean age was 49 ± 19.1 years and 68.4% of them were female subjects. Overall, 20% of all patients had hypovitaminosis D, and just over 7% of patients had vitD deficiency. Male subjects had higher odds for hypovitaminosis or vitD deficiency (65.4 ± 28.2 nmol/L vs. 68.4 ± 28.4 nmol/L; p <0.0001). The mean 25(OH)D concentration has changed during the year, reaching a peak in September and a minimum in February. Patients with diseases of the circulatory system, genitourinary system, certain conditions originating in the perinatal period, and "sine morbo" (i.e., without a disease; such as those aged over 45 years and female teenagers) had statistically higher odds for lower 25(OH)D concentrations (p <0.00001). VitD consumption showed seasonality, being higher in autumn and winter. A slight increase started in the season of 2017/18, and two huge peaks were detected at the beginning of 2020 and 2021 in association with the COVID-19 waves. Conclusion: Our data are the first to describe data concerning vitD in our region. It reinforces the notion of vitD3 supplementation for some risk groups and also in healthy individuals. To prevent the winter decline, vitD3 supplementation should be started in September. This and the results during the COVID-19 pandemic highlight the importance of health education encouraging vitamin D3 supplementation.
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Background: The possible correlation between melanoma and Parkinson's disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary. Methods: From 2004 to 2017, a retrospective analysis of the centre's database was performed based on International Statistical Classification of Diseases-10 codes. Results: Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47-0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56-0.98, p=0.0392) but not for melanoma. Conclusions: We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population.
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Rapidly restoring vitamin D levels to normal might be desirable in certain clinical situations. Larger doses of supplementation, have been shown to increase bone loss and the risk of falls. The optimal way to perform vitamin D loading safely and effectively is still not well elucidated. Our study was aimed to assess the safety and efficacy of two oral vitamin D loading protocols. Sixty-nine subjects with vitamin D deficiency (25OH-vitamin D (25(OH)D) < 20 ng/ml) were included. Thirty-five participants received 30 000 IU of vitamin D3 per week for 10 weeks (group Slower Loading Dose (SLD)) and thirty-four received 30 000 IU twice weekly for 5 weeks (group Moderate Loading Dose (MLD)) resulting in a loading dose of 300 000 IU for all subjects. Following this initial loading phase, both groups received 30 000 IU biweekly for 4 weeks to test whether the recommended daily vitamin D supplementation in range of 2000 IU dose-equivalent could maintain the achieved levels. Seventy-nine percent of those subjects treated in group SLD and everyone in group MLD achieved a 25(OH)D level of 30 ng/ml, which is the lower limit of the recommended normal range in Hungary. The mean increase in 25(OH)D was significantly higher in group MLD than in group SLD (38.6 ± 1.80 ng/ml vs 46,6 ± 1.80 ng/ml). No significant decrease was observed with the administration of the maintenance dose. There were no clinically significant changes in serum or urine calcium, and bone biomarkers in either group. Both protocols were found to be safe and effective, but the five-week dosing caused a significantly greater increase in 25(OH)D. A maintenance dose applied for four weeks after the loading protocol did not raise 25(OH)D levels further but maintained the achieved increase. The administration of 30 000 IU of vitamin D3 twice weekly for five weeks is a rapid, effective and safe way to treat vitamin D deficiency in vitamin D deficient patients.
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Doenças Ósseas Metabólicas , Deficiência de Vitamina D , Humanos , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D , Colecalciferol/efeitos adversos , Vitaminas/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Suplementos NutricionaisRESUMO
The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%-70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.
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Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Discoide , Antígeno B7-H1/metabolismo , Granzimas/metabolismo , Humanos , Lúpus Eritematoso Cutâneo/metabolismo , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Discoide/metabolismo , Lúpus Eritematoso Discoide/patologia , Receptor de Morte Celular Programada 1/metabolismo , Pele/patologiaRESUMO
The social distancing measures introduced due to the COVID-19 pandemic may have affected the sexual behavior of the population. We collected data retrospectively from the National STD Center of Hungary. The overall patient influx data of the STD Center and the number of patients diagnosed with syphilis, chlamydia, and gonorrhea infections were assessed in the three-month period of 2020 when the strict governmental lockdown was introduced in Hungary. Data were compared to the pre- and post-lockdown quarters of 2020 and matched to the respective quarters of 2018 and 2019. The number of patients diagnosed with syphilis and chlamydia infections in 2020 during the lockdown decreased compared to 2018 and 2019, while the number of gonorrhea cases increased. The lower number of STI screenings resulted in a significant decrease in asymptomatic syphilis and chlamydia case numbers. However, the growing number of gonorrhea cases in 2020 during lockdown highlights that sexual behavior remained unchanged regardless of restrictions. Therefore, gonorrhea may be considered as an indicator of STI incidences during the pandemic.
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COVID-19 , Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Sífilis , COVID-19/epidemiologia , Infecções por Chlamydia/epidemiologia , Controle de Doenças Transmissíveis , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Hungria/epidemiologia , Pandemias , Estudos Retrospectivos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/epidemiologiaRESUMO
Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.
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OBJECTIVES: To determine the effects of exergaming on quality of life (QoL), motor, and clinical symptoms in subacute stroke patients. DESIGN: A pseudorandomized controlled trial, using a before-after test design. SETTING: University hospital. PARTICIPANTS: Subacute, ischemic stroke outpatients (N=3857), 680 of whom were randomized and 641 completed the study. INTERVENTIONS: We determined the effects of 5 times a week twice daily (EX2; 50 sessions; n=286) and once daily (EX1; 25 sessions; n=272) exergaming and low-intensity standard care (control [CON]; 25 sessions; n=83) on clinical, mobility, blood pressure (BP), and QoL outcomes. MAIN OUTCOME MEASURES: The primary outcome was Modified Rankin Scale. Secondary outcomes were activities of daily living, 5 aspects of health-related QoL, Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), and static balance (center of pressure). RESULTS: During exercise, the peak heart rate was 134, 134, and 126 beats per minute in the EX2, EX1, and CON groups, respectively. mRS improved similarly in the EX2 (-1.8; effect size, d=-4.0) and EX1 (-1.4; d=-2.6) groups, but more than in the CON group (-0.7; d=-0.6). QoL, Barthel Index, BBS, 6MWT, and standing posturography improved more in the EX2 group and the same in the EX1 and CON groups. Systolic and diastolic resting BP decreased more in the EX2 and EX1 groups than in the CON group. The intervention effects did not differ between men (n=349) and women (n=292). CONCLUSIONS: Twice daily compared with once daily high-intensity exergaming or once daily lower intensity standard care produced superior effects on clinical and motor symptoms, BP, and QoL in male and female subacute ischemic stroke participants.
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Terapia por Exercício/métodos , AVC Isquêmico/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Jogos de Vídeo , Atividades Cotidianas , Idoso , Pressão Sanguínea , Comorbidade , Feminino , Marcha/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Equilíbrio Postural/fisiologia , Qualidade de Vida , Método Simples-CegoRESUMO
Langerhans cell histiocytosis (LCH) is characterized by mutations of the RAS-RAF-MAPK signaling pathway. We analyzed MAP2K1, NRAS and KIT mutation incidence in skin lesions of BRAF wild-type (wt) LCH patients. We evaluated the occurrence of MAP2K1, NRAS and KIT mutations in seven LCH and one indeterminate cell histiocytosis (ICH) patients. MAP2K1 mutation frequency was found to be 3/7 (42.9%) in LCH and also found in ICH. Similarly, the KIT mutation frequency was found to be equally prevalent (4/7, 57.1%) in LCH and also occurred in ICH. Involvement of KIT exons in LCH-ICH indicated that exon 9/11/18 were equally prevalent followed by exon 13. This exploratory analysis on BRAF-wt LCH revealed a KIT mutation rate comparable to MAP2K1. Although the detected KIT mutations are different from activating mutations found in other KIT-dependent neoplasms, our data suggest that KIT-inhibitors might have a role in treating BRAF-wt LCH patients.
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Histiocitose de Células de Langerhans/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Dermatopatias/genética , Adolescente , Adulto , Idoso , Feminino , GTP Fosfo-Hidrolases/genética , Predisposição Genética para Doença , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/terapia , Humanos , Lactente , MAP Quinase Quinase 1/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Taxa de Mutação , Fenótipo , Prognóstico , Dermatopatias/patologia , Dermatopatias/terapia , Adulto JovemRESUMO
INTRODUCTION: Different therapies can improve clinical and motor symptoms of multiple sclerosis (MS) similarly, but studies comparing the effects of different exercise therapies on clinical and motor outcomes are scant. We compared the effects of exergaming (EXE), balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group (CON) on clinical and motor symptoms and quality of life (QoL) in people with MS (PwMS). METHODS: PwMS (n = 68, 90% female; age, 47.0 yr; Expanded Disability Status Scale score 5-6) were randomized into five groups. Before and after the interventions (five times a week for 5 wk), PwMS were tested for MS-related clinical and motor symptoms (Multiple Sclerosis Impact Scale-29 (MSIS-29), primary outcome), QoL (EuroQol Five Dimensions Questionnaire), symptoms of depression, gait and balance ability (Tinetti Assessment Tool), static and dynamic balance and fall risk (Berg Balance Scale), walking capacity (6-min walk test), and standing posturography on a force platform. RESULTS: EXE, BAL, and CYC improved the MSIS-29 scores similarly. EXE and CYC improved QoL and walking capacity similarly but more than BAL. Only EXE improved gait and balance scores (Tinetti Assessment Tool). EXE and BAL improved fall risk and standing balance similarly but more than CYC. PNF and CON revealed no changes. The EuroQol Five Dimensions Questionnaire moderated the exercise effects on the MSIS-29 scores only in EXE. Changes in QoL and changes in the MSIS-29 scores correlated (R = 0.73) only in EXE. CONCLUSION: In conclusion, BAL and CYC but EXE in particular, but not PNF, can improve clinical and motor symptoms and QoL in PwMS (Expanded Disability Status Scale score 5 to 6), expanding the evidence-based exercise options to reduce mobility limitations in PwMS.
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Terapia por Exercício/métodos , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/reabilitação , Qualidade de Vida , Ciclismo , Depressão , Feminino , Marcha , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Exercícios de Alongamento Muscular , Equilíbrio Postural , Método Simples-CegoRESUMO
OBJECTIVES: Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) may affect the success of first-line antiretroviral treatment. This study aimed to monitor the presence of HIV-1 strains carrying transmitted drug resistance-associated mutations (TDRMs) in newly diagnosed and treatment-naïve patients in Hungary. METHODS: This study included 168 HIV-infected individuals diagnosed between 2013-2017; most of them (93.5%) belonged to the homo/bisexual population. HIV-1 subtypes and TDRMs were determined by analysing the protease and reverse transcriptase coding regions of the pol gene by the Stanford HIV Drug Resistance Database. Transmission clusters among patients were identified using phylogenetic analysis. RESULTS: Although subtype B HIV-1 strains were predominant (87.5%), non-B subtypes including F, A, CRF01_AE, CRF02_AG, D and G were also recorded, especially in young adults. The overall prevalence of TDR was 10.7% (18 of 168; 95% CI: 6.9-16.3%). Subtype B HIV-1 strains carried most of the TDRMs (94.4%). Nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were the most prevalent indicators of TDR (16 of 168; 9.5%; 95% CI: 5.9-14.9%), followed by mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2 of 168; 1.2%; 95% CI: 0.3-4.2%) and protease inhibitors (PIs) (1 of 168, 0.6%; 95% CI: 0.1-3.3%). Phylogenetic analysis revealed that most NRTI-associated resistance mutations were associated with a single monophyletic clade, suggesting early single-source introduction and ongoing spread of this drug-resistant HIV-1 strain. CONCLUSIONS: Onward transmission of drug-resistant subtype B HIV-1 strains accounted for the majority of TDRs observed among treatment-naïve HIV-infected individuals in Hungary.
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Farmacorresistência Viral , Infecções por HIV/transmissão , HIV-1/classificação , Mutação , Adulto , Fatores Etários , Bissexualidade/estatística & dados numéricos , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Adulto JovemRESUMO
INTRODUCTION/PURPOSE: Little is known about the comparative effectiveness of exercise programs, especially when delivered at a high intensity, in mobility-limited older adults. We compared the effects of 25 sessions of high-intensity agility exergaming (EXE) and stationary cycling (CYC) at the same cardiovascular load on measured and perceived mobility limitations, balance, and health-related quality of life in mobility-limited older adults. METHODS: Randomized to EXE (n = 28) and CYC (n = 27), mobility-impaired older adults (age 70 yr) exercised five times per week for 5 wk at 80% of age-predicted maximal heart rate. Waitlisted controls did not exercise (n = 28). RESULTS: Groups did not differ at baseline in any outcomes (P > 0.05). The primary outcomes (The Short Form-36-Health Survey: EXE, 6.9%; effect size, 2.2; CYC, 5.5%, 1.94; Western Ontario and McMaster Universities Osteoarthritis Index: EXE, -27.2%, -3.83; CYC, -17.2, -2.90) improved similarly (P > 0.05). Secondary outcomes, including body mass (-3.7%), depression (-18%), and walking capacity (13.5%) also improved (P < 0.05) similarly after the two interventions. Activities of daily living, Berg Balance Score, BestTest scores, and Dynamic Gait Index improved more (P < 0.05) after EXE than CYC. Center of pressure of standing sway path improved in one of six tests only after EXE (P < 0.05). Postexercise cardiovascular response improved in EXE (P = 0.019). CON did not change in any outcomes (P > 0.05). CONCLUSIONS: When matched for cardiovascular and perceived effort, two diverse high-intensity exercise programs improved health-related quality of life, perceived mobility limitation, and walking capacity similarly and balance outcomes more in mobility-limited older adults, expanding these older adults' evidence-based exercise options to reduce mobility limitations.
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Terapia por Exercício/métodos , Limitação da Mobilidade , Fatores Etários , Idoso , Ciclismo/fisiologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Pesquisa Comparativa da Efetividade , Dieta , Feminino , Frequência Cardíaca/fisiologia , Treinamento Intervalado de Alta Intensidade , Humanos , Masculino , Percepção/fisiologia , Esforço Físico/fisiologia , Equilíbrio Postural/fisiologia , Qualidade de Vida , Velocidade de Caminhada/fisiologiaRESUMO
The incidence of malignant melanoma, one of the deadliest cancers, continues to increase. Here we tested connexin (Cx) expression in primary melanocytes, melanoma cell lines and in a common nevus, dysplastic nevus, and thin, thick, and metastatic melanoma tumor progression series involving the tumor microenvironment by utilizing in silico analysis, qRT-PCR, immunocyto-/histochemistry and dye transfer tests. Primary melanocytes expressed GJA1/Cx43, GJA3/Cx46 and low levels of GJB2/Cx26 and GJC3/Cx30.2 transcripts. In silico data revealed downregulation of GJA1/Cx43 and GJB2/Cx26 mRNA, in addition to upregulated GJB1/Cx32, during melanoma progression. In three melanoma cell lines, we also showed the loss of GJA1/Cx43 and the differential expression of GJB1/Cx32, GJB2/Cx26, GJA3/Cx46 and GJC3/Cx30.2. The dominantly paranuclear localization of connexin proteins explained the ~10â»90 times less melanoma cell coupling compared to melanocytes. In melanocytic tumor tissues, we confirmed the loss of Cx43 protein, fall of cell membrane and elevated paranuclear Cx32 with moderately increased cytoplasmic Cx26 and paranuclear Cx30.2 positivity during tumor progression. Furthermore, we found Cx43, Cx26 and Cx30 proteins upregulated in the melanoma adjacent epidermis, and Cx43 in the tumor flanking vessels. Therefore, differential connexin expression is involved in melanocytic tumor progression where varying connexin isotypes and levels reflect tumor heterogeneity-related bidirectional adaptive interactions with the microenvironment.
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The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3-not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D3. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3 months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D3 provide equal efficacy and safety profiles.
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Colecalciferol/administração & dosagem , Suplementos Nutricionais , Deficiência de Vitamina D/dietoterapia , Adulto , Idoso , Calcifediol/sangue , Colecalciferol/efeitos adversos , Colecalciferol/uso terapêutico , Estudos de Coortes , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Comprimidos , Equivalência Terapêutica , Fatores de Tempo , Deficiência de Vitamina D/sangueRESUMO
Despite experimental findings suggesting the prognostic significance of Aquaporin 1 (AQP1) in human melanoma, no published clinical data are available. We studied the expression of AQP1 protein in cutaneous melanoma, correlated our findings with standard histological and genetic markers, and long-term clinical follow-up. Our study evaluated the AQP1 protein expression in 78 melanoma patients, representing two predefined risk cohorts using the immune labeling technique with commercially available anti-AQP1 antibodies on routinely formalin-fixed and paraffin-embedded tumor tissue samples. BRAF V600E mutation analyses were carried out successfully in 70 patients using PCR and restriction fragment length polymorphism analyses, followed by confirmatory analysis with the Sanger sequencing technique. AQP1-expressing melanoma cells were found in 52 cases (66.7%, median H-score=124.24). Significantly higher AQP1 H-scores (P=0.047) were found in the 'high-risk' patients. No correlations were found with the established histological markers, such as mitotic index (P=0.42), Clark level (P=0.95), and Breslow thickness (P=0.51). BRAF V600 mutation analyses were successful in 89%, and showed a two times higher mutation frequency in the 'high-risk' group. The BRAF V600 mutations were significantly associated with AQP1 expression (P=0.014). Long-term follow-up indicated a reduced progression-free survival (P=0.036) and overall survival (P=0.017) for the AQP1-positive cutaneous melanoma patients. AQP1 expression is likely to be associated with an adverse prognosis in cutaneous melanoma.
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Aquaporina 1/biossíntese , Melanoma/genética , Melanoma/metabolismo , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aquaporina 1/genética , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias Cutâneas/patologia , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Pregnancy associated melanoma (PAM) by definition appears during pregnancy or within 1 year after delivery. In this retrospective study we analysed the pathological characteristics and survival rate of PAM and matched the data with non-pregnant age- and stage-matched control patients. Between 2003 and 2014, 34 pregnant women (aged 32.5 ± 5.6 years) were diagnosed with melanoma at the Department of Dermatology, Venereology and Dermatooncology of the Semmelweis University. During the pathological process histologic subtype, Breslow thickness and Clark level, tumor cell type, mitotic rate, peritumoral inflammation, as well as ulceration, regression, necrosis, vascular invasion and presence of satellite were analyzed and related to clinical data. Primary tumor location and clinical staging, disease course, local recurrence and metastases, 5-year survival rate, other tumor development before or after the diagnosis of melanoma have also been documented. We found no difference in all parameters between pregnant and non-pregnant melanoma cases except peritumoral inflammation which was higher in PAM group, moreover the presence of mild inflammation was significantly higher in PAM group compared to non-pregnancy associated melanoma (NPAM) women group.
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Melanoma/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Inflamação/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Gravidez , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: European guidelines on the treatment of Neisseria gonorrhoeae are based mostly on Western European data, although these recommendations may not be optimised for the circumstances in Hungary. AIM: The aim of the authors was to assess current antimicrobial resistance of Neisseria gonorrhoeae strains in order to enhance gonococcal antimicrobial surveillance in Hungary. Neisseria gonorrhoeae strains were isolated at the National Center of Sexually Transmitted Infections at the Department of Dermatology, Venerology and Dermatooncology of Semmelweis University in the period between January 2011 and June 2014. METHOD: Antimicrobial resistance was determined with minimum inhibitory concentration measurement. Neisseria gonorrhoeae Multiantigen Sequence typing was used as molecular typing method. RESULTS: Resistance to the currently recommended extended spectrum cephalosporins is rare in Hungary, but there is an emerging azithromycin resistance among the Neisseria gonorrhoeae strains. CONCLUSIONS: Revision of the national treatment guideline must consider that the most frequent sequence types of Neisseria gonorrhoeae strains causing infections in Hungary are mainly resistant to azithromycin.
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Antibacterianos/farmacologia , Azitromicina/farmacologia , Cefalosporinas/farmacologia , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Hungria , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificaçãoRESUMO
INTRODUCTION: The incidence of anal cancer has increased in recent decades, particularly among human immunodeficiency virus infected men who have sex with men. Anal intraepithelial neoplasia is a potential precursor lesion of anal cancer. Anal cytology is the primary screening test for anal intraeptithelial neoplasia. AIM: The authors aimed to analyze the results of anal cytology of patients with human immunodeficiency virus infection at the National Centre of STD, Department of Dermatology, Dermatooncology and Venereology, Semmelweis University. METHOD: 155 anal cytological examinations were performed in 140 patients between November 1, 2012 and August 31, 2014. RESULTS: 44% of patients were found to have anal dysplasia, and only 1.6% of patients had high-grade lesions. This rate is lower as compared to published studies including larger number of patients. CONCLUSIONS: The study underlines the necessity of screening for anal lesions in the population at-risk.
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Canal Anal/patologia , Neoplasias do Ânus/diagnóstico , Carcinoma in Situ/diagnóstico , Detecção Precoce de Câncer , Infecções por HIV/complicações , Lesões Pré-Cancerosas/diagnóstico , Adulto , Idoso , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/patologia , Carcinoma in Situ/prevenção & controle , Feminino , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Hungria/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Estudos RetrospectivosRESUMO
Lymphogranuloma venereum is a sexually transmitted infection caused by the Chlamydia trachomatis serovars L1-3. It has been found to be endemic in tropical countries. In the last decades several cases have been reported in Western Europe, particularly in men who have sex with men population infected with human immunodeficiency virus. The authors present three cases of lymphogranuloma venereum infections, observed at their department in 2013 and 2014. The three human immunodeficiency virus infected patients who belonged to men who have sex with men population had casual sexual contacts in Western Europe. The symptoms included urethral discharge, discomfort and inguinal lymphadenomegaly in two patients, and rectal pain, discharge and perianal ulceration in one patient. The diagnosis was confirmed by nucleic acid amplification test performed in samples obtained from urethral discharge and exudate of perianal ulcer; lymphogranuloma venereum 2b serovars were demonstrated in two patients and serovar 2 in one patient. Doxycyclin (daily dose of two times 100 mg for 21 days) resolved the symptoms in all cases. The authors conclude that lymphogranuloma venereum is a diagnostic challenge in Hungary, too. It is important to be aware of the altered clinical features of this disease to prevent complications and spreading.
Assuntos
Chlamydia trachomatis/isolamento & purificação , Infecções por HIV/complicações , Linfogranuloma Venéreo/diagnóstico , Adulto , Fármacos Anti-HIV/uso terapêutico , Chlamydia trachomatis/genética , Diagnóstico Diferencial , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Hungria , Linfogranuloma Venéreo/complicações , Linfogranuloma Venéreo/tratamento farmacológico , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Sorogrupo , Testes Sorológicos , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/diagnóstico , ViagemRESUMO
The authors report the history of a patient with syphilitic glomerulonephritis, a rare complication of syphilis. The patient was admitted to the hospital with clinical symptoms of neurosyphilis. During his hospital stay urine analysis revealed an extremely high proteinuria, that had not been known before. Intravenous penicillin treatment improved the renal protein loss, but it took a total of six months until complete resolution was achieved. The serology that confirmed the syphilis, the concomitant nephrotic syndrome and the improvement after penicillin therapy met the criteria of syphilitic glomerulonephritis. This case prompted the authors to review the literature about this rare complication of syphilis that has a great clinical significance.