Hypertension and nephrology

[The February 2014 Report on the Situation of Vascular Surgery Care in the Budapest Region]

FEBRUARY 20, 2014

Hypertension and nephrology - 2014;18(01-02)

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Hypertension and nephrology

[Fenestration of endothelium of juxtaglomerular arteriole]

ROSIVALL László

[For the first time, we demonstrated the fenestration in the endothelium of the distal portion of renal afferent arteriole (AA), which is unusual among high pressure vessels. The fenestrae are co-localized with renin producing granular epithelioid cells; this arrangement makes it likely that the relatively large renin molecules may use this path to enter into the plasma. We also demonstrated that the length and area of this fenestrated segment 1) correlates with the activity of the renin-angiotensin system (RAS), 2) may change by age, in response to some stimuli such as thirst and in some diseases, 3) allows filtration of fluid prior to the glomerular filtration, which can be as high as about 30% of GFR. This morphology and the high filtration volume in AA is one of the most striking observations of renal microcirculation, and question several basic renal physiological issues.]

Hypertension and nephrology

[Effect of age on the function of renin-angiotensin system]

VÁMOS Zoltán, CSÉPLÕ Péter, KOLLER Ákos

[Angiotensin II (Ang II) by activating angiotensin type 1 receptors (AT1R) is one of the most potent vasoconstrictors in the regulation of vasomotor tone and thus systemic blood pressure. In this study, we hypothesized that aging alters Ang II - induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from newborn, young, middle age, old and senescent rats and their vasomotor responses were measured in a myograph (DMT-600) to repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by qRT-PCR and the AT1R protein density was measured by Western blot. Contractions of vessels to the first administration of Ang II increased from newborn to young and middle age rats then they decreased to senescent rats. In general, second administration of Ang II elicited reduced contractions, but they also first increased and then they decreased to old age. Similarly, the AT1R mRNA level and the AT1R protein density increased from newborn to young and middle age rats then they decreased to senescent rats. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting that it is - and thus regulation of systemic blood pressure is - determined primarily by genetic programs.]

Hypertension and nephrology

[Physical activity, physical function and exercise in chronic kidney disease]

NAGY Judit, APOR Péter, KISS István

[This review summarize the decreased physical activity and physical function of chronic kidney disease patients from the early stage of their renal disease; the favourable effects of exercise training on physical activity and function as well as on progression of chronic renal diseases. At the end, there is a recommendation for implementation of exercise in this renal patient population. The conclusion is that, on the basis of the evidences patients with chronic renal disease should be advised to increase their physical activity in all stages of their renal disea]

Hypertension and nephrology

[Risk categories, goals and treatment of hypercholesterolemia in Europe and in the recommendations of the AHA/ACC]

PADOS Gyula, KARÁDI István, AUDIKOVSZKY Mária, REIBER István, PARAGH György

[Hypercholesterolemia is one of the most important major risk factors that can be most influenced. Its treatment is based on guidelines. In 2013 in Hungary the common guideline of 17 societies (MKKK) as well as the recommendations of EAS/ESC and those of IAS are at disposal. These recommendations have established similar risk categories and strict LDL-cholesterol goals (<1.8 mmol/l). On 12 November, 2013, in the USA after a long drawn debate the AHA/ACC - without any lipid association - issued a new cholesterol (Ch) guideline, which drasticly differs from the existing national and European recommendations. According to AHA/ACC each patient with cardiovascular disease or diabetes should be treated with statin, irrespective of the Ch value, All patients with a LDL-Ch level over 4.9 mmol/l should also be treated with statin. In primary prevention those with values between 1.8-4.9 (LDL-Ch), or 3.5-8.0 mmol/l (Ch) would also be given statin, if their risk is more than 7.5%, with the new calculator system (“Statin Benefit Groups”). These recommendations would eliminate the classic risk categories (very-high, high, moderate risk), would abolish the system of treatment goals, as well as the regular Ch test. The non-statin therapy is not supported even in combinations. A big part of the population with low Ch level would also receive statin based on the results with the calculator, meaning that in the USA the number of those treated might double. Not only the European (e.g. EAS/,ESC) but even American societies (National Lipid Association 2013-2014) (e.g. NLA) oppose to the new guideline of AHA/ACC.]

Hypertension and nephrology

[Blood presssure paradoxon in very elderly patients]

SZÉKÁCS Béla, BÉKÉSI Gábor, KISS István

[The paper is warning for the necessity of very complex consideration before taking antihypertensive therapeutic decisions (indication, point or points of actiou, blood pressure target levels, dynamics of BP reduction, etc) for elderly hypertensive patients. Blood pressure reduction can mean efficient protection against cardiovascular events also among the elderly hypertensives. However in those old and very old hypertensive patients who have not only severe stiffness of their large vessels but suffer in advanced co-morbidities and integrated pathologic geriatric syndromes, the blood pressure reduction can result in sometimes even life threatening general deterioration. Antihypertensive therapeutic dilemmas of elderly caregivers appear mainly in relation to old hypertensive patients of age over 80 years. For this „very old” age period the HYVET study gave us evidence based conclusions about the cardiovascular protective usefulness of combined antihypertensive treatment resulting in BP reduction to 150 Hgmm systolic BP target levels. However a non-negligable rate of selection of the included patients in HYVET study can weaken the generalizability of the HYVET findings in this age period and the extensibility of its antihypertensive therapeutic conclusions for the entire „very old” population because this population has also a high proportion of patients with chronic progressive illnesses and general decline. Thus the elderly hypertensives’ caregiver must always carefully and critically balance between the messages of the HYVET and the nonselective observational follow up studies among elderlies showing frequently the so-called epidemiologic blood pressure/ mortality paradoxon. The paper is also trying to find potencial pathomechanical interpretations and point of actions for the epidemiologic blood pressure/mortality paradoxon found in the very old population.]

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Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Clinical Neuroscience

Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

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[LAM 30: 1990–2020. Facing the mirror: Three decades of LAM, the Hungarian medicine and health care system]

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Clinical Neuroscience

[The connection between the socioeconomic status and stroke in Budapest]

VASTAGH Ildikó, SZŐCS Ildikó, OBERFRANK Ferenc, AJTAY András, BERECZKI Dániel

[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]