High Frequency and Intensity Rehabilitation in 641 Subacute Ischemic Stroke Patients.

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.

[Anal cytology]. / Anális citológia.

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.

[Syphilitic glomerulonephritis: case report and review of the literature]. / Veseérintettség syphilises fertozésben: esetismertetés és a szakirodalom áttekintése.

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.

[Antimicrobal resistance of Neisseria gonorrhoeae strains in Hungary]. / Neisseria gonorrhoeae törzsek rezisztenciaadatai Magyarországon.

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.

[Lymphogranuloma venereum: the first Hungarian cases]. / Lymphogranuloma venereum: elso hazai esetek.

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.

Aliphatic alcohol contaminants of illegally produced spirits inhibit phagocytosis by human granulocytes.

CONTEXT: Unregulated production of spirits in many countries leads to products containing appreciable levels of aliphatic alcohols (AAs) and is the main source of human exposure to these substances worldwide. Previous studies have confirmed that alcohol abuse can lead to ethanol-induced immunosuppression and thereby increased susceptibility to infectious diseases. Granulocytes, as professional phagocytic cells, play a crucial role in engulfment and killing of pathogenic microorganisms. Thus, a decrease in their phagocytic activity has been invoked as a factor in the impaired antimicrobial defense observed in alcoholics. However, AAs consumed as contaminants of illicit spirits may also influence phagocytosis, thereby contributing to a further decrease in microbicidal activity but, so far, this has not been studied. OBJECTIVE: Therefore, the aim of this study was to measure granulocyte phagocytosis following treatment of granulocytes with those higher alcohols found in illegal spirits. MATERIALS AND METHODS: Granulocytes were isolated from human peripheral blood. Then phagocytosis of opsonized zymosan particles by granulocytes treated with AAs individually and in combination was determined. RESULTS: These alcohols inhibited phagocytosis in a concentration-dependent manner and at lower concentrations when combined than when tested individually. DISCUSSION AND CONCLUSION: Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit phagocytosis in a clinically meaningful way in episodic heavy drinkers.

Controlled randomized open label clinical study comparing the safety and efficacy of loading schedules in vitamin D deficient patients.

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.

Cutaneous malignancies in patients with Parkinson's disease at a dermato-oncological university centre in Hungary.

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.

Six years' experience and trends of serum 25-hydroxy vitamin D concentration and the effect of vitamin D3 consumption on these trends.

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.

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma-A Retrospective Single-Center Study.

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.

Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus.

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.

Anti-PD-1 Monotherapy in Advanced Melanoma-Real-World Data from a 77-Month-Long Retrospective Observational Study.

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.

STIs during the COVID-19 Pandemic in Hungary: Gonorrhea as a Potential Indicator of Sexual Behavior.

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.

Role of salsolinol in the regulation of pituitary prolactin and peripheral dopamine release.

(R)-Salsolinol (SAL), a dopamine (DA)-related tetrahydroisoquinoline, has been found in extracts of the neuro-intermediate lobes (NIL) of pituitary glands and in the median eminence of the hypothalamus obtained from intact male rats and from ovariectomized and lactating female rats. Moreover, analysis of SAL concentrations in NIL revealed parallel increases with plasma prolactin (PRL) in lactating rats exposed to a brief (10 min) suckling stimulus after 4-h separation. SAL is sufficiently potent in vivo to account for the massive discharge of PRL that occurs after physiological stimuli (i.e. suckling). At the same time, it was without effect on the secretion of other pituitary hormones. It has been also shown that another isoquinoline derivative, 1-methyldihydroisoquinoline (1MeDIQ), which is a structural analogue of SAL, can dose-dependently inhibit the in-vivo PRL-releasing effect of SAL. Moreover, 1MeDIQ can inhibit the elevation of plasma PRL induced by physiological stimuli, for example suckling, or in different stressful situations also. 1MeDIQ also has a psycho-stimulant action, which is fairly similar to the effect of amphetamine, i.e. it induces an increase in plasma catecholamine concentrations. It is clear from these data that this newly discovered endogenous compound could be involved in regulation of pituitary PRL secretion. It has also been observed that SAL is present in peripheral, sympathetically innervated organs, for example the atrium, spleen, liver, ovaries, vas deferens, and salivary gland. Furthermore, SAL treatment of rats results in dose-dependent and time-dependent depletion of the DA content of the organs listed above without having any effect on the concentration of norepinephrine. More importantly, this effect of SAL can be completely prevented by amphetamine and by 1MeDIQ pretreatment. It is clear there is a mutual interaction between SAL, 1MeDIQ, and amphetamine or alcohol, not only on PRL release; their interaction with catecholamine "synthesis/metabolism" of sympathetic nerve terminals is also obvious.

[Frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples of sexually active individuals]. / Az Ureaplasma urealyticum és a Mycoplasma hominis antibiotikum-érzékenysége és gyakorisága szexuálisan aktív egyének genitális mintáiban.

UNLABELLED: Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. AIM: The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. PATIENTS AND METHODS: Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab®) into Urea-Myco DUO kit (Bio-Rad®) and were incubated for 48 hours at 37 C°. Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad®). RESULTS: Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. CONCLUSIONS: Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the first such a clinical microbiological study in this topic in Hungary.

[Meningovascular neurosyphilis as the cause of ischemic cerebrovascular disease in a young man]. / Meningovascularis neurosyphilis miatti fiatalkori ischaemiás cerebrovascularis betegség.

Authors report a case of a 35-year-old male with right-sided mild paresis, incontinence, dysexecutive syndrome, short-term memory loss and behavioral changes. Bilateral cerebral infarcts in the region of the caudate nuclei and the adjacent white matter were proved by brain MRI and multiple stenoses of the branches of Willis-circle were confirmed by MR angiography. Elevated protein level and pleocytosis were found in the cerebrospinal fluid with intrathecal IgG synthesis. Serum rapid plasma reagin, Treponema pallidum Particle Agglutination test, Treponema pallidum ELISA, liquor Venereal Disease Research Laboratory tests were positive. Meningovascular neurosyphilis was diagnosed. 24M U/day intravenous penicillin-G treatment was given for 14 days. The patient has vascular dementia due to the bilateral strategic infarcts disconnecting the prefrontal circuits; his symptoms are similar to general paresis. Laboratory and radiologic improvement was observed. Still, the patient have severe residual cognitive decline.

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer.

BACKGROUND: Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (SHMT1) C1420T or methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated. METHODS: The SHMT1 and MTHFR genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated. RESULTS: There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for SHMT1 TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for MTHFR CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for SHMT1 with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the SHMT1 T allele/MTHFR CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by SHMT1 polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of SHMT1 1420CC genotypes. CONCLUSIONS: A protective effect of SHMT1 1420T allele or SHMT1 1420 T allele/MTHFR 677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of SHMT1 1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in SHMT1 1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why SHMT1 and MTHFR polymorphisms are associated only with rectal and not colon cancer risk.

Frequent KIT mutations in skin lesions of patients with BRAF wild-type Langerhans cell histiocytosis.

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.

Exercise Effects on Multiple Sclerosis Quality of Life and Clinical-Motor Symptoms.

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.

Transmitted drug resistance in newly diagnosed and treatment-naïve HIV type 1-infected patients in Hungary.

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.