The importance of socio-economic determinants of health in the care of patients with peripheral artery disease: A narrative review from VAS.

Socio-economic determinants of health (SDoH) include various nonmedical factors in the socio-economic sphere with a potentially significant impact on health outcomes. Their effects manifest through several mediators/moderators (behavioral characteristics, physical environment, psychosocial circumstances, access to care, and biological factors). Various critical covariates (age, gender/sex, race/ethnicity, culture/acculturation, and disability status) also interact. Analyzing the effects of these factors is challenging due to their enormous complexity. Although the significance of SDoH for cardiovascular diseases is well documented, research regarding their impact on peripheral artery disease (PAD) occurrence and care is less well documented. This narrative review explores to what extent SDoH are multifaceted in PAD and how they are associated with its occurrence and care. Additionally, methodological issues that may hamper this effort are addressed. Finally, the most important question, whether this association may contribute to reasonable interventions aimed at SDoH, is analyzed. This endeavor requires attention to the social context, a whole systems approach, multilevel-thinking, and a broader alliance that reaches out to more stakeholders outside the medical sphere. More research is needed to justify the power in this concept to improve PAD-related outcomes like lower extremity amputations. At the present time, some evidence, reasonable consideration, and intuitive reasoning support the implementation of various interventions in SDoH in this field.

Genetic Etiology of Nonsyndromic Hearing Loss in Hungarian Patients.

Hearing loss is the most prevalent sensory disorder worldwide. The majority of congenital nonsyndromic hearing loss (NSHL) cases are caused by hereditary factors. Previously, the majority of NSHL studies focused on the GJB2 gene; however, with the availability of next-generation sequencing (NGS) methods, the number of novel variants associated with NSHL has increased. The purpose of this study was to design effective genetic screening for a Hungarian population based on a pilot study with 139 NSHL patients. A stepwise, comprehensive genetic approach was developed, including bidirectional capillary sequencing, multiplex ligation-dependent probe amplification (MLPA), and an NGS panel of 108 hearing loss genes. With our results, a genetic diagnosis was possible for 92 patients. Sanger sequencing and MLPA identified the genetic background of 50% of these diagnosed cases, and the NGS panel identified another 16%. The vast majority (92%) of the diagnosed cases showed autosomal recessive inheritance and 76% were attributed to GJB2. The implementation of this stepwise analysis markedly increased our diagnostic yield and proved to be cost-effective as well.

Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.

BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.

Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies.

Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. All patients demonstrated undetectable baseline anti-SARS-CoV-2 immunoglobulin levels before CP. Each patient received at least a complete course of remdesivir and at least one unit of CP. Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of B-cell lymphopenia (p = 0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p = 0.017), length of hospital stay (p = 0.007), and PCR positivity (p = 0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p < 0.001) and hospital stay (p < 0.0001). In those cases where there were at least 10 days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p = 0.006). In conclusion, the combination of inhibition of viral replication with passive immunization was proved to be efficient and safe. Our results suggest the clear benefit of early, combined administration of remdesivir and CP to avoid protracted COVID-19 disease among patients with HMs and B-cell lymphopenia.

High Level of Unwarranted Clinical Variation in the Use of Lower Extremity Revascularisation Procedures in Hungary (2013-2017).

OBJECTIVE: Assessment of variations in the use of lower extremity open vascular surgical procedures (LEOPEN) and lower extremity endovascular procedures (LEENDO) across small geographic areas in Hungary from 2013 to 2017. Introduction of a new metric giving a rough estimate of unwarranted clinical variation in revascularisation practice. METHODS: Spatial variation (at local administrative unit level) of referral for LEOPEN and LEENDO was evaluated through a retrospective analysis using healthcare administrative data of all beneficiaries in Hungary. The same assessment was performed for percutaneous coronary intervention in acute myocardial infarction (PCIAMI). The latter was considered a reasonable comparator (similar at risk population, well organised, guideline driven patient pathways, small room for referral discretion). Consequently, the ratio of spatial variations of LEOPEN and LEENDO to PCIAMI (as a reference) are thought to reflect unwarranted clinical variation. RESULTS: A total of 109 882 procedures were identified in the database (LEOPEN, LEENDO, PCIAMI) affecting 85 083 patients. While estimates of spatial variations for LEOPEN and LEENDO turned out to be high (systematic component of variation [SCV] 0.09 and 0.21, respectively), PCIAMI showed a low SCV value of 0.02. Consequently, the ratios of SCVs were SCV/SCVref = 4.67 (LEOPEN) and SCV/SCVref = 10.3 (LEENDO), indicating high levels of unwarranted clinical variation. CONCLUSION: The analysis showed that patients living in different locations of Hungary face very different odds of having lower extremity revascularisation procedures (open or endovascular). This spatial variation is thought to be related mainly to the failure in vascular service organisation. The newly introduced numerical estimate of unwarranted clinical variation may support within, and also between, system comparisons.

Spatial analysis of factors impacting lower limb major amputation rates in Hungary: Is geography partially destiny?

Background: Lower limb major amputations represent a substantial public health burden in Hungary, where previous research revealed markedly high rates with significant spatial variations. Therefore, we aimed to assess to what extent healthcare and socio-economic factors in the local environment explain the regional disparity. Patients and methods: In a retrospective cohort analysis, based on the healthcare administrative data of the Hungarian population, lower limb major amputations were identified from 1st of January 2017 to 31st of December 2019. The permanent residence of the amputees on the local administrative level (197 geographic units) was used to identify potential healthcare (outpatient care, revascularisation activity) and socio-economic (educational attainment, local infrastructure and services, income and employment) determinants of amputations. Spatial effects were modelled using the spatial Durbin error regression model. Results: 10,209 patients underwent 11,649 lower limb major amputations in the observational period. In our spatial analysis, outpatient care was not associated with local amputation rates. However, revascularisation activity in a geographic unit entailed an increased rate of amputations, while revascularisations in the neighbouring areas were associated with a lower rate of amputations, resulting in an overall neutral effect (ß=-0.002, 95% CI: -0.05 - 0.04, p=0.96). The local socio-economic environment had a significant direct inverse association with amputations (ß=-7.45, 95% CI: -10.50 - -4.42, p<0.0001) . Our spatial model showed better performance than the traditional statistical modelling (ordinary least squares regression), explaining 37% of the variation in amputations rates. Conclusions: Regional environmental factors explain a substantial portion of spatial disparities in amputation practice. While the socio-economic environment shows a significant inverse relationship with the regional amputation rates, the impact of the local healthcare-related factors (outpatient care, revascularisation activity) is not straightforward. Unravelling the impact of the location on amputation practice requires complex spatial modelling, which may guide efficient healthcare policy decisions.

Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial. We aimed at investigating the effects of losartan in a rat model of RIHD. Male Sprague-Dawley rats were studied in three groups: (1) control, (2) radiotherapy (RT) only, (3) RT treated with losartan (per os 10 mg/kg/day), and were followed for 1, 3, or 15 weeks. At 15 weeks post-irradiation, losartan alleviated the echocardiographic and histological signs of LVH and fibrosis and reduced the overexpression of chymase, connective tissue growth factor, and transforming growth factor-beta in the myocardium measured by qPCR; likewise, the level of the SMAD2/3 protein determined by Western blot decreased. In both RT groups, the pro-survival phospho-AKT/AKT and the phospho-ERK1,2/ERK1,2 ratios were increased at week 15. The antiremodeling effects of losartan seem to be associated with the repression of chymase and several elements of the TGF-ß/SMAD signaling pathway in our RIHD model.

Identification of putative phenotype-modifying genetic factors associated with phenotypic diversity in Brooke-Spiegler syndrome.

Brooke-Spiegler syndrome (BSS, OMIM 605041) is a rare monogenic skin disease characterized by the development of skin appendage tumors caused by mutations in the cylindromatosis gene. We recently investigated a Hungarian and an Anglo-Saxon pedigrees affected by Brooke-Spiegler syndrome. Despite carrying the same disease-causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene, the affected family members of the two pedigrees exhibit striking differences in their phenotypes. To identify phenotype-modifying genetic factors, whole exome sequencing was performed and the data from the Hungarian and Anglo-Saxon BSS patients were compared. Three putative phenotype-modifying genetic variants were identified: the rs1053023 SNP of the signal transducer and activator of transcription 3 (STAT3) gene, the rs1131877 SNP of the tumor necrosis factor receptor-associated factor 3 (TRAF3) gene and the rs202122812 SNP of the neighbour of BRCA1 gene 1 (NBR1) gene. Our study contributes to the accumulating evidence for the clinical importance of phenotype-modifying genetic factors, which are potentially important for the elucidation of disease prognosis.

Lower Limb Amputations and Revascularisation Procedures in the Hungarian Population: A 14 Year Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to assess the long term trends of lower limb amputation and revascularisation in Hungary over 14 years. METHODS: This was a retrospective cohort study that included all patients who underwent lower limb amputation or revascularisation over a 14 year period (2004-2017) in Hungary. Inpatient administrative data claims covering the entire beneficiary population were incorporated. Lower limb amputations (both minor and major) and revascularisation procedures (both open and endovascular) were identified in the claims files. Incidence rates were calculated and time trends were assessed via a generalised additive model. RESULTS: From 2004 to 2017, a total of 121 351 lower limb amputations (61 154 minor; 60 197 major) and 149 355 revascularisation procedures (89 243 open; 60 112 endovascular) were detected in 140 581 patients. The number of minor amputations decreased moderately in the last few years of the study period, while major amputations showed a slight decline (15%) beginning after 2013, which was more marked (22%) following adjustment for age. While the crude incidence of open vascular surgery procedures decreased by 31% (from 74.5/105 to 51.4/105), endovascular procedures showed growth by 79% (from 33.7/105 to 60.4/105) over the whole observation period. CONCLUSION: Observed amputation and revascularisation trends in Hungary are similar to the international experience. The major difference is a more than one decade lag in the starting point of the decline of amputations and in the move towards endovascular procedures. The number of amputations is more than twofold higher and the number of revascularisations is close to half that reported internationally. This comprehensive report of two vascular care performance indicators reveals an east/west vascular health divide in Europe and indicates the need to improve amputation prevention.

Simple assessment of quality of life and lower limb functional capacity during cilostazol treatment - results of the SHort-tERm cIlostazol eFFicacy and quality of life (SHERIFF) study.

Background: Symptomatic peripheral arterial disease (intermittent claudication) is a major cause of disability and mobility loss in older men and women and thus has a significant negative impact on the patients' quality of life. Both surgical and endovascular revascularization procedures and noninvasive medical therapies, such as supervised training and drug treatment, can improve walking capacity. Cilostazol is the only drug having a class I (level of evidence A) recommendation for the treatment of intermittent claudication (IC). The aim of this study was to evaluate the effect of three-month cilostazol treatment on the health-related quality of life and on the lower limb functional capacity in patients with IC in the clinical practice. Patients and methods: The study was a multicenter, non-interventional trial, performed in Hungary in 2018. 812 PAD patients (Fontaine II stage, mean age: 67.17 years, male/female: 58.25/41.75 %) were enrolled, who received cilostazol (50 or 100 mg b.i.d.) for 3 months. 802 patients completed the study. Quality of life was evaluated with the EQ-5D-3L questionnaire functional capacity with the WELCH (Walking Estimated-Limitation Calculated by History) questionnaire. Pain-free and maximal walking distance, ankle-brachial index (ABI) were measured at baseline and after 3-month treatment. Results: Upon conclusion of the study, the EQ-5D-3L index improved (baseline: -0.46 ± 0.22, 3rd month: -0.26 ± 0.18; p < 0.0001) and there was a significant increase in the WELCH score as well (19 ± 14, 31 ± 18; respectively, p < 0.0001). Both pain-free and maximal walking distance improved significantly by 54.52 % (median: 53.85 %) and 42.5 % (median: 34.68 %); respectively (p < 0.001). Adverse events occurred in 10 patients, 1 patient stopped cilostazol treatment because of side effects. Conclusions: Three months cilostazol treatment significantly improved quality of life and lower limb functional capacity in patients with intermittent claudication. The WELCH questionnaire is a useful tool for the evaluation of intermittent claudication treatment in the clinical practice.

Regional variation of lower limb major amputations on different geographic scales - a Hungarian nationwide study over 13 years.

Background: The incidence of lower limb major amputations is an important healthcare quality indicator, as it reflects all efforts aimed to prevent limb loss. Analysis of within-country regional variations in incidence may reveal the sources of disparities in care. Materials and methods: Based on the data of the Hungarian healthcare beneficiary population from 2004 to 2016, the incidence of lower limb major amputations and its spatial variations was determined regionally on four levels of geographic resolution. Variability and autocorrelation were quantified on different resolutions. Results: A total of 56,468 lower limb major amputation procedures were identified in 49,528 patients over the observation period. Marked regional variations were detected at all geographic scale levels. In the case of county-level and local administrative level, the systematic component of variation was 0.03 and 0.09, respectively. Only half of the variation at local administrative level was explained by county. Conclusions: Lower limb major amputations show marked regional variations on the different geographic levels of resolution. The more granular the assessment, the higher the regional variation was. Assumingly, this observation is partially a mathematical necessity but may also be related to the different characteristics of care at a given level of spatial aggregation. The decomposition of the variance of amputation rates indicates that the potential explanatory factors contributing to spatial variability are multiple and may be interpreted on different levels of geographic resolution. Addressing the unwarranted variations and resolving the issues that contribute to high lower limb major amputation rates needs further explorative analysis.

Clinical and genetic differences between pustular psoriasis subtypes.

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10-15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10-14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

Genetic investigation confirmed the clinical phenotype of congenital chloride diarrhea in a Hungarian patient: a case report.

BACKGROUND: Congenital chloride diarrhea (CCD, OMIM 214700) is a rare autosomal recessively inherited condition characterized by watery diarrhea, hypochloremia and metabolic alkalosis. Mutations of the solute carrier family 26, member 3 (SLC26A3, OMIM 126650) gene are responsible for the disease. The gene encodes a transmembrane protein, which is essential for intestinal chloride absorption. CASE PRESENTATION: Here we report a Hungarian boy, presenting the clinical phenotype of CCD. The patient born at 32 weeks of gestation and underwent surgery for abdominal distension and intestinal obstruction related to malrotation. After recovery, electrolyte replacement therapy was necessary due to several periods of diarrhea. After exclusion of other possible causes, increased chloride concentration in the feces supported the diagnosis of CCD. The diagnosis was confirmed by molecular genetic testing. Direct sequencing revealed compound-heterozygosity for a frameshift mutation c.1295delT (p.Leu432Argfs*11) and the known Polish founder mutation c.2024_2026dupTCA (p.Ile675_Arg676insLeu). CONCLUSIONS: Here we present the clinical symptoms of the first patient in Hungary diagnosed with CCD. Based on the clinical symptoms, stool analysis and genetic testing, the diagnosis of CCD was established. Our study provides expansion for the mutation spectrum of the SLC26A3 gene and the genetic background of CCD.

[The potential role of oscillometric devices for ankle-brachial index measurements in clinical practice]. / A boka-kar index oszcillometriás elven muködo meghatározásának helye a klinikai gyakorlatban.

INTRODUCTION: Oscillometric devices in contrast to the traditional Doppler based method for ankle-brachial index measurements have promising advantages like no need for special training, faster performance, and operator independence. AIM: Comparative assessment of the oscillometric and Doppler-based ankle-brachial index measurement. METHOD: Ankle-brachial index measurements were performed by continuous wave Doppler and an automatic oscillometric device (BOSO ABI-system 100) in consecutive subjects. The comparative assessment was performed by Bland-Altman and ROC analysis. RESULTS: The two kinds of measurements (734 measurements) showed a good agreement in the ankle-brachial index spectrum close to the cut-off value of 0.9. The agreement diminished below or above this value. The optimal oscillometric ankle-brachial index diagnostic cut-off value was 0.96. CONCLUSIONS: The oscillometric device is not interchangeable for Doppler devices in the whole ankle-brachial index spectrum. Nevertheless, owing to its discriminative power, the oscillometric measurement potentially has an efficient role in the screening of asymptomatic patients. Orv Hetil. 2018; 159(5): 176-182.

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

BACKGROUND: Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities. OCA type IV (OCA4, OMIM 606574) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene. This gene encodes a membrane-associated transport protein, which regulates tyrosinase activity and, thus, melanin content by changing melanosomal pH and disrupting the incorporation of copper into tyrosinase. METHODS: Here we report two Hungarian siblings affected by an unusual OCA4 phenotype. After genomic DNA was isolated from peripheral blood of the patients, the coding regions of the SLC45A2 gene were sequenced. In silico tools were applied to identify the functional impact of the newly detected mutations. RESULTS: Direct sequencing of the SLC45A2 gene revealed two novel, heterozygous mutations, one missense (c.1226G > A, p.Gly409Asp) and one nonsense (c.1459C > T, p.Gln437*), which were present in both patients, suggesting the mutations were compound heterozygous. In silico tools suggest that these variations are disease causing mutations. CONCLUSIONS: The newly identified mutations may affect the transmembrane domains of the protein, and could impair transport function, resulting in decreases in both melanosomal pH and tyrosinase activity. Our study provides expands on the mutation spectrum of the SLC45A2 gene and the genetic background of OCA4.

[Cilostazol is effective and safe option for the treatment of intermittent claudication. Results of the NOCLAUD study]. / A cilostazol hatékony és biztonságos lehetoség a claudicatio intermittens kezelésére. A NOCLAUD vizsgálat eredményei.

Intermittent claudication can seriously impair the patients' quality of life. Cilostazol was registered in Hungary in 2014. This study aimed to evaluate the efficacy and safety of cilostazol in patients with intermittent claudication. 1405 patients were enrolled to the 6 months, multicenter, non-interventional trial. From the 1331 patients, who completed the study, the data of 674 patients were subjected to efficacy analysis. Pain free and maximal walking distance and the 6 minute walking test improved significantly at 3 months (78.65%, 65.23%, 56.09%; respectively, p<0.001), and a further increase was observed after 6 months treatment (129.74%, 107.2, 80.38% respectively, p<0.001). Adverse events occured in 7.26% of the patients. The most frequent adverse events were headache, diarrhea, dizziness, tachycardia or palpitation. 24 patients (1.7%) stopped cilostazol treatment because of side effects. 6 month cilostazol treatment significantly increased the walking distance in patients with intermittent claudication, without important safety problems. Orv. Hetil., 2017, 158(4), 123-128.

[Ischemic origin of diabetic foot disease. Epidemiology, difficulties of diagnosis, options for prevention and revascularization]. / A diabeteses láb ischaemiás eredete. Epidemiológia, a diagnózis nehézségei, prevenciós és revascularisatiós lehetoségek.

"Diabetic foot" as definition covers a multifactorial clinical condition. According to the recent epidemiological data, the role of lower limb ischemia is getting more influential over other pathological causes, like neuropathy, infections and bone or soft tissue deformity. In diabetes, vascular disease leads to increased risk for leg ulcers and minor or major amputations. The traditional diagnostic tools for recognition of peripheral arterial disease have limited value because of diabetes specific clinical manifestations. Available vascular centers with special expertise and diagnostic tools are the prerequisite for efficient diagnosis supporting timely recognition of peripheral arterial disease. In course of treatment of diabetic foot with ischemic origin, beyond effective medical treatment revascularization (open vascular surgery or endovascular procedures) has paramount importance for prevention of limb loss. Vascular teams of vascular specialists, vascular surgeons and interventional radiologist in dedicated centers in multidisciplinary cooperation with other professions represent public health issue in effective prevention. Orv. Hetil., 2017, 158(6), 203-211.

The CYLD p.R758X worldwide recurrent nonsense mutation detected in patients with multiple familial trichoepithelioma type 1, Brooke-Spiegler syndrome and familial cylindromatosis represents a mutational hotspot in the gene.

BACKGROUND: Multiple familial trichoepithelioma type 1 (MFT1; MIM 601606), a rare monogenic skin disease with autosomal dominant inheritance, is characterized by the development of multiple skin-colored papules on the central area of the face, frequently occurring in the nasolabial area. The disease is associated with various mutations in the cylindromatosis (CYLD; MIM 605018) gene that are also responsible for familial cylindromatosis (FC) and Brooke-Spiegler syndrome (BSS). METHODS: Recently we have identified a Spanish MFT1 pedigree with two affected family members (father and daughter). Direct sequencing of the CYLD gene revealed a worldwide recurrent heterozygous nonsense mutation (c.2272C/T, p.R758X) in the patients. RESULTS: This mutation has already been detected in patients with all three clinical variants - BSS, FC and MFT1 - of the CYLD-mutation spectrum. Haplotype analysis was performed for the Spanish patients with MFT1, Dutch patients with FC and an Austrian patient with BSS, all of whom carry the same heterozygous nonsense p.R758X CYLD mutation. CONCLUSIONS: Our results indicate that this position is a mutational hotspot on the gene and that patients carrying the mutation exhibit high phenotypic diversity.

[Peripheral arterial disease and diabetes related lower limb amputations. Presentation of the epidemiological data and the analysis of potentialities in preventive strategy]. / A perifériás veroérbetegséggel és a cukorbetegséggel összefüggo alsó végtagi amputációk. Epidemiológiai adatok bemutatása és a megelozo stratégia lehetoségeinek elemzése.

Lower limb amputation as one of the most devastating consequences of peripheral arterial disease and diabetes mellitus needs peculiar attention. This review aims at comparing Hungarian and international amputation data. Realizing the great variability of the global amputation incidence and trends data, the main determinants of this variety are assessed. These factors involve methodological differences in reporting, demographic, epidemiological, economic, societal and cultural variation of the affected populations and differences in the health care service. The amputation hazard can be considered as an example of lifetime risk that can be characterized by complex interaction of contionuously changing risk factor pattern. In that sense an effective preventive strategy planning needs complex measure implementations that associate with multidisciplinary approach, timely complex preventive interventions and centralized vascular care. Research and development on amputation field shows clear priority that can contribute to the better understanding of this extremely complex scenario with significant public health consequences. Orv. Hetil., 2016, 157(32), 1266-1274.

[Recurrent European missense mutation in a Hungarian pedigree with Papillon-Lefèvre syndrome]. / Rekurrens európai misszensz mutáció egy magyar Papillon-Lefèvre szindrómában szenvedo családban.

Papillon-Lefèvre syndrome, a rare disease with autosomal recessive inheritance, is characterized by aggressive periodontitis and palmoplantar hyperkeratosis. Mutations of the cathepsin C gene are responsible for the development of the disease. In this study, we aimed to describe in details the clinical symptoms and to determine the underlying genetic abnormality in two Hungarian siblings affected by Papillon-Lefèvre syndrome. The siblings are under regular dental and dermatological care since their symptoms appeared, but, due to the fact that genetic analysis of Papillon-Lefèvre syndrome has been available for one or two years in Hungary, their mutation screenings were just recently performed. We have identified a homozygous missense mutation on the cathepsin C gene, which is an already published mutation and was originally reported from Germany. Our investigations would like to draw attention to a rare disease, Papillon-Lefèvre syndrome, in which first symptom can be the aggressive periodontitis, and in which genetic testing and for helping child-bearing and family planning is now available.