Low frequency of AIP mutations in patients with young-onset sporadic pituitary macroadenomas.

PURPOSE: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene cause familial isolated pituitary adenomas (FIPA). AIP mutations have also been found in patients with apparently sporadic pituitary adenomas, particularly in young patients with large adenomas. The aim of this study was to determine the frequency of AIP germline mutations in patients with young-onset sporadic pituitary macroadenomas. METHODS: The AIP gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years. RESULTS: Heterozygous rare sequence variants in AIP were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25 years. The frequency of AIP pathogenic or likely pathogenic variants in patients under the age of 30 and 18 years was 3.4% and 5.0%, respectively. CONCLUSION: The frequency of AIP mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of AIP mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel AIP mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of AIP mutations in the molecular mechanisms underlying pituitary tumorigenesis.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Central systolic blood pressure (cSBP) to brachial systolic blood pressure (brachSBP) ratio reproducibility during antihypertensive therapy.

OBJECTIVES: Higher CSBP than brachial SBP in individual patient increases cardiovascular (CV) risk. For follow-up it is important to assess the reproducibility of such measurements. The aim of this study was to assess the reproducibility of these differences, expressed as a CSBP/BrachSBP ratios. SUBJECTS AND METHODS: Eighty-three patients on antihypertensive therapy were analysed for the reproducibility of such ratios after time interval of several month up to several years. For CSBP estimation, we used the Arteriograph (Tensiomed Ltd.), based on blood pressure measurements by cuff on oscillometric principle, using pulse wave analysis (PWA) for assessment of CSBP. RESULTS: The proportion of patients retained the same characteristics (either higher central or higher peripheral SBP) between the first and second measurement was 71.1 %. The association between 1st and 2nd measurement, was statistically significant, p < 0.001. CONCLUSION: In our study, a high proportion (60 %) of treated hypertensive patients had CSBP higher than brachial SBP, which may adversely influence their prognosis. This characteristic is highly reproducible. Taking into the account these differences may increase the exactness of CV risk estimation and may contribute to explanation of residual risk of individual patient (Tab. 3, Fig. 1, Ref. 28).

Holter ECG findings in diabetics with medial arterial calcification.

OBJECTIVES: Medial arterial calcification (MAC) is a nonobstructive condition leading to reduced arterial compliance. The disease most commonly occurs in diabetes mellitus. Decreased ankle-brachial pressure index (ABI) is a well-known marker of increased cardiovascular mortality. However, also the values of ABI above 1.3, typical in MAC, are associated with increased mortality. METHODS: By means of Holter ECG monitoring, we investigated 41 patients (25 men, 16 women) with mean age of 59±8 years, suffering of type 2 diabetes mellitus and identified as having MAC, and Holter ECG monitoring with an average duration of recording 22.36 hours, was carried out by GE-Marquette MARS ECG Holter system. RESULTS: We found frequent incidence of cardiac arrhythmias and myocardial ischemia in 22 patients (53.7 %). Only 19 patients (46.3 %) had normal Holter ECG recordings. ABI values were significantly higher in patients with abnormal ECG Holter recordings. CONCLUSION: Our results confirm the importance of ABI estimation in clinical practice. As the central goal of therapy for patients with myocardial ischemia and/or complex forms of cardiac arrhythmias is the reduction or elimination of these episodes. Ambulatory Holter ECG monitoring plays an important role in the management of these patients (Tab. 7, Ref. 16).

Central systolic blood pressure increases with aortic stiffness.

OBJECTIVES: Central systolic blood pressure (CSBP) is the pressure in the root of aorta, which directly influences organs such as brain, heart and kidneys and is related to organ damage. Its value increases with the aortic stiffness. The aim of this study was to analyze the relationships of CSBP to aortic stiffness parameters. METHODS: Central blood pressure (BP) and related parameters were measured by Arteriograph, working based on oscillometric principle, using pulse wave analysis (PWA) approach. We examined 123 patients (69 females, 54 males) with a primary hypertension. RESULTS: Using a linear correlation analysis, we found that CSBP was correlated to aortic pulse wave velocity (PWV), aortic and brachial pulse pressure (PP), aortic augmentation index, return time of reflected pressure wave (RT) and aortic and brachial augmentation indexes. Multivariate analysis defines the aortic pulse pressure (PPao) as the most powerful parameter influencing CSBP. By an individual analysis of BP in each patient separately, we defined two different types of central hemodynamics; those with a higher CSBP than brachial SBP occur in stiffer aorta. CONCLUSION: The CSBP increases with aortic PP, the most powerful stiffness parameter of aorta. Higher CSBP than brachial SBP usually accompanies a stiffer aorta (Tab. 5, Ref. 19).

[Multiple cephalic deep granuloma annulare of children]. / Granulomes annulaires profonds multiples céphaliques de l'enfant.

BACKGROUND: Deep granuloma annulare is a fairly rare variety of granuloma annulare. It is seen predominantly in children and mainly affects the anterior aspect of the legs and the top of the feet; cephalic presentation is rare. Below, we report three cases of deep granuloma annulare in children presenting solely at the cephalic extremity. PATIENTS AND METHODS: Case 1: a six-year-old boy presented 7 cutaneous nodules measuring 1 to 2cm that were flesh-coloured, insensitive to palpation, of hard consistency and deeply attached. The lesions were grouped together on the anterior half of the left temporal fossa. While spontaneous regression of the three nodules was noted in the month following cutaneous biopsy, these nodules recurred a few months later. Case 2: a four-year-old girl with five deep cephalic nodules measuring around one centimetre and the colour of normal skin were seen on her right temporal fossa. The child was lost to follow-up after biopsy. Case 3: a four-month-old infant was presenting some 15 deep cutaneous nodules arranged in linear fashion on the forehead next to the left temporal fossa. These nodules regressed spontaneously one month after biopsy. In all three cases, histological examination confirmed the diagnosis of deep granuloma annulare. DISCUSSION: There have been few published cases of multiple, cephalic, deep granuloma annulare at a single site in children. The condition has an extensive differential diagnosis that includes malignant tumours; in addition, histological confirmation is normally essential. Treatment is not qualified and therapeutic extension with clinical monitoring alone may frequently be recommended.

[Specifics of using ambulatory blood pressure monitoring in the elderly]. / Specifiká vyuzitia ambulantného monitorovania krvného tlaku u starsích osôb.

Arterial hypertension is a chronic disease which represents a major risk factor for damage of cardiovascular system. Insufficient control of elevated blood pressure is associated with the development of target organ damage, increased cardiovascular morbidity and mortality with a adverse prognostic value. Using ambulatory blood pressure monitoring (ABPM) we can improve the overall management of elderly patients at which the prevalence of arterial hypertension is particularly high.

[Epidemiologic data of hyperuricaemia prevalence in the conditions of primary care in Slovakia]. / Epidemiologické údaje o výskyte hyperurikémie u muzov a u zien v podmienkach primárnej liecebnej starostlivosti na Slovensku.

Hyperuricaemia represents nowaday the new risk factor for cardiovascular diseases. Prevalence data and its treatment in our patient's population are still missing. Literature data shows, that its prevalence differs in various populations significantly from 4% up to 40% with race and geographical means. In the hospital population its prevalence is about 7% and represents the important predictor of hospital mortality, e.i with heart failure. From the Framingham data relative risk was estimated of 25% for cardiovascular diseases, coronary heart disease and all-course mortality. From the epidemiologic survey Mirror Slovakia hyperuricaemia was evaluated from the sample of 20 000 patients from the primare care physicians in order to see the picture on this newer risk factor.

[Arterial hypertension--multicirculus vitiosus vasorum]. / Artériová hypertenzia--viacnásobný cievny bludný kruh.

AIM: The aim of this review is to address documents and a number of studies on hypertension published in the last years in order to assess their contribution to our expanding knowledge of arterial hypertension. DISCUSSION: Arterial hypertension is not defined by symptoms and signs but by numbers of blood pressure values. Arterial hypertension is vascular disease (vascular risk factor) of many vascular diseases (atherosclerosis; arteriolosclerosis/arteriolonecrosis/arteriolocalcinosis; arterial thrombosis; arterial embolism; arterial thromboembolism; arterial dissection; complicated arterial aneurysm) and other. CONCLUSION: Arterial hypertension is cause and consequence of functional (endothelial dysfunction) and of structural organovascular injury (multiorganomultivascular disease). Blood vessels are culprits, implements and victims of arterial hypertension and of organovascular arterial diseases.

Risk factors in diabetic nephropathy progression at present.

Diabetic nephropathy is becoming an increasingly important cause of morbidity and mortality worldwide as a consequence of increasing prevalence of type 2 diabetes and obesity. The glomeruli of patients with diabetes are characterized by glomerular hypertrophy, widening of the glomerular basement membrane, mesangial expansion, podocytopenia leading to nodular (Kimmelstiel-Wilson) glomerulosclerosis. Many studies have reported the initiation and progression of incipient nephropathy in type 1 diabetes patients, but only limited data are available in type 2 diabetes patients. The information on the risk factors and conversion rate of normal renal function to proteinuria in type 2 diabetes patients is sparse. In this report, we review risk factors of diabetic nephropathy progression in type 2 diabetes patients (Ref. 50).

Vasculitides as a rare cause of intermittent claudication.

Intermittent claudication of the lower extremities is a common symptom described in older patients with atherosclerotic peripheral arterial disease. Peripheral arterial disease due to atherosclerosis is known to be associated with a higher risk of myocardial infarction, stroke and all-cause mortality. However, if intermittent claudication appears in a younger group of patients or older patients in absence of traditional risk factors for atherosclerosis such as smoking, dyslipidemia, arterial hypertension and diabetes mellitus other causes than atherosclerosis must be considered. These conditions include vasculitides, fibromuscular dysplasia, cystic adventitial disease, excentric vascular compression by tumor, popliteal artery entrapment syndrome, trauma or dissection. Vasculitides present a heterogenous group of disorders characterized by inflammatory destruction of blood vessels. Although often not a leading symptom intermittent claudication could be a part of a clinical picture in giant-cell arteritis, Takayasu´s arteritis, Buerger´s disease, polyarteritis nodosa or Behçet disease. Limb claudication is usually of rapid onset, progressive and bilateral. Each of the mentioned vasculitides is specific in ethiology and clinical manifestation with a variable prognosis for the patient. Increased awareness of the presence of different causes of limb claudication and their early diagnosis with a prompt initiation of appropriate treatment may help to avoid clinical progression that can lead to vascular surgery or even limb loss (Ref. 37).

[Resistant hypertension in the elderly]. / Rezistentná hypertenzia v starsom veku.

The issue of resistant hypertension is complex and from the clinical aspect very current, especially in the elderly. For the diagnosis of resistant hypertension in routine practice, ambulatory blood pressure monitoring is a proven method to distinguish it from the white coat hypertension. Fixed combinations of antihypertensive drugs helps to improve compliance not only in geriatric patients, but are also indicated in hypertensive patients with diabetes mellitus, metabolic syndrome, in patients with target organ damage, renal disease, coronary heart disease and post stroke conditions. Especially in the population of older hypertensive patients, listed diseases with polymorbidity are frequently present.

[Management of superficialis thrombophlebitis. Guidelines of the Angiologiy Section of the Slovak Medical Chamber (2013)]. / Manazment povrchovej tromboflebitídy. Odporúcania Angiologickej sekcie Slovenskej lekárskej komory (2013).

UNLABELLED: The aim of Guidelines of the Angiology Section of the Slovak Medical Chamber (AS SMC) is to address a last european guidelines for the management of thrombophlebitis superficialis, as well as results in evidence based  medicine (EBM) in order to assess their contribution to our expanding knowledge on rational management of thrombophlebitis superficialis. DISCUSSION: Superficial thrombophlebitis is a common disease, usually considered to be benign. However, the practice of systemic duplex ultrasonography has revealed a large number of cases of deep vein thrombosis concomitant with superficial thrombophlebitis. Assessment of clinical probability of deep vein thrombosis and venous tromboembolism and systematic duplex ultrasound investigation has been proposed in the initial management of superficial thrombophlebitis, to detect the presence of any underlying deep vein thrombosis. In contrast with extensive information on the management of deep vein thrombosis, there is little knowledge about the most appropriate treatment of the superficial thrombophlebitis. CONCLUSION: The treatment of superficial thrombophlebitis should improve local symptoms while preventing the development of complications such as venous thromboembolism. The most effective therapeutic approach to superficial thrombophlebitis seems to be represented by fondaparinux (a synthetic selective indirect inhibitor of factor Xa) which have been shown to prevent VTE events and the extension and/ or recurrence of superficial thrombophlebitis.

[Present and future of pharmaco-arteriothromboprophylaxis in clinical practice. Guidelines of Angiology Section of Slovak Medical Chamber]. / Súcasnost a budúcnost farmako-artériotromboprofylaxie v klinickej praxi. Odporúcania Angiologickej sekcie Slovenskej lekárskej komory.

Antiplatelet therapy by acetylsalicylic acid (aspirin) provided pivotal advances in the prevention and treatment of organovascular (cardiovascular, cerebrovascular, extremitovascular, renovascular, genitovascular, mesenteriovascular, bronchopulmovascular, oculovascular, otovascular and other) arterial ischemic diseases. Currently available antiplatelet drugs have some limitations which might be overcomed by improved dosing regimens, use of combination of agents affecting different platelet functions and, in particular, by the new antiplatelet drugs (new arterial antithrombotics) with distinct pharmacodynamic properties offering new advantages, including faster onset of action, greater potency, and reversibility of effects. Document (Guidelines) of the Angiology Section of the Slovak Medical Chamber (AS SMS, 2013).

[Management of dyslipidaemias -  present and future. Guidelines of the Angiology Section of the Slovak Medical Chamber (2013)]. / Manazment dyslipidémií -  prítomnost a budúcnost. Odporúcania Angiologickej sekcie Slovenskej lekárskej komory (2013).

AIM: The aim of Guidelines of the Angiology Section of the Slovak Medical Chamber is to address a last European guidelines for the management of dyslipidaemias, as well as results in evidencebased medicine (EBM) in order to assess their contribution to our expanding knowledge on reducing of residual organovascular risk. DISCUSSION: Lipid metabolism can be disturbed in different ways, leading to changes in plasma lipoprotein function and/ or levels. This by itself and through interaction with other vascular risk factors and endothelial dysfunction may affect the development of atherosclerosis and other vascular diseases. Therefore, dyslipidaemias cover a broad spectrum of lipid abnormalities, some of which are of great importance in organovascular prevention. Dyslipidaemias may be related to other diseases (secondary dyslipidaemias) or to the interaction between genetic predisposition and environmental factors. Dyslipidaemias may also have a different meaning in certain subgroups of patients which may relate to genetic predisposition and/ or co morbidities. This requires particular attention complementary to the management of the total CV risk. Optimal LDLcholesterol levels are the primary strateging task in the therapeutical preventive approaches. However, at present increasing attention has focused on the role of inflamation, levels of HDLcholesterol and triglycerides in the process of atherosclerosis. Statins represent basic pillar in dyslipidemia treatment. Despite the intensive management of all conventional vascular risk factors and the intensified treatment with statins, residual organovascular risk remains high. Therefore the interest is focused on finding the place of combined antidyslipidemic treatment and the development of new antidyslipidemics. CONCLUSION: Strategies for preventing of organovascular diseases have emphasized vascular risk factors effective modification using treatment approaches supported by evidencebased medicine (EBM).

[The impact of a 14- day regular physical exercise regime on the concentration of the classes and subclasses of lipoprotein particles in young subjects with a sedentary lifestyle]. / Vplyv 14 dní trvajúcej pravidelnej telesnej zátaze na koncentrácie tried a podtried lipoproteínových partikúl u mladých probandov so sedavým spôsobom zivota.

Recommendations from the cardiological professional companies working in the area of primary prevention of cardiovascular diseases put an emphasis on regular aerobic physical activity. Its positive effect on both cardiovascular and overall mortality has repea-tedly been proven by the observations of prospective and cross sectional epidemiological studies. One of the possible explanations of this positive effect is a change in the concentration of lipoprotein classes and their subclasses, which is expressed as a change in their average size. In a group of young healthy men and women with a sedentary lifestyle we observed the effect of medium intensive physical exercise in the form of a 30- minute slow run per day lasting for 14 days. The concentration of lipoprotein classes and subclasses were determined through the method of a linear electrophoresis in polyacrylamide gel. In the observed group we found a statistically significant decrease of VLDL, large IDL particles, medium sized LDL, small dense LDL, and medium sized HDL particles. In the light of current knowledge all these lipoprotein particles are deemed as atherogenic. Thus, as little as 14 days of regular exercising has a positive effect on the concentration of plasmatic lipoproteins, and emphasises the role of regular physical activity in the primary prevention of cardiovascular diseases.