Lege Artis Medicinae

[History and Winners of the LAM Award]

MARCH 21, 2009

Lege Artis Medicinae - 2009;19(01 klsz)

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Lege Artis Medicinae

[THE EPIDEMIOLOGY OF CEREBROVASCULAR DISEASES IN HUNGARY AFTER THE MILLENNIUM]

VOKÓ Zoltán, SZÉLES György, KARDOS László, NÉMETH Renáta, ÁDÁNY Róza

[INTRODUCTION - Here we present the descriptive epidemiology of stroke in Hungary including mortality, morbidity, functional limitation and inpatient care based on the most recent health statistical data. METHODS - Mortality data were analysed by direct and indirect standardisation, and geographical mapping based on empirical Bayesian smoothing. Morbidity data were obtained from the General Practitioners’ Morbidity Sentinel Station Program and the National Health Surveys. The latter also provided data on functional limitation. Data on inpatient service were taken from the European Hospital Morbidity Database of WHO. RESULTS - Hungarian stroke mortality continued to decrease in recent years, and the slope of the decrease was larger than in Western Europe. Stroke mortality was highest in the Northern- Hungarian Region, and in Somogy and Zala counties. The incidence of stroke was 1.5-2 times higher than in the developed countries in most age groups. Over 64 years of age, a decline of stroke incidence was observed, especially in men. In this age group approximately 10% of men and 7% of women had already had a stroke. Of these patients more than 10% needed assistance to get out of the bed, dress up, or eat. Hospitals reported more than 60 000 stroke cases in 2005. CONCLUSION - Despite the promising trends in stroke mortality and now also in morbidity, both indices are still rather high in Hungary compared to those in Western-Europe. The relatively favourable epidemiological changes, however, may be overridden by the increased stroke burden resulting from the aging of the population.]

Lege Artis Medicinae

[STATE-OF-THE ART COMPLEX TREATMENT OF THYROID CANCERS]

LUKÁCS Géza

[Thyroid cancers derived from follicular epithelial cells are histologically classified as papillary, follicular and anaplastic. Cancers that originate from parafollicular, or C-cells, are termed medullary carcinomas. Their annual incidence is fairly low; 3 to 7 cases per 100 000 people. After the Chernobyl disaster, however, thyroid cancers have received much attention. They often occur at young age, and frequently and early give metastases. They typically grow slowly and have a good prognosis even in the metastatic stage. The main prognostic factors include age, tumour size and extent, the completeness of surgical removal, distant metastases and tumour grade. Based on these parameters, they are classified into high-risk and low-risk groups. There are no prospective randomized studies available on the optimal treatment of thyroid cancers. Their biological aggressiveness differs according to geographic location, which explaines why the management of thyroid carcinomas has not been standardized internationally. Contrary to America and Australia, in Europe there are several endemic goitre regions, and background radiation is higher. It is generally accepted that here the standard therapy of choice is total thyreoidectomy with adequate lymph node dissection followed by postoperative radioiodine ablation. It is a reasonable demand to minimize the higher morbidity associated with radical surgery (e.g., recurrent nerve palsy, postoperative hypoparathyroidism) below 1%. It is recommended that such operations are performed by experienced thyroid surgeons in centres with multidisciplinary endocrine teams.]

Lege Artis Medicinae

[STEM CELL THERAPY AFTER ACUTE MYOCARDIAL INFARCTION]

NYOLCZAS Noémi, GYÖNGYÖSI Mariann

[Left ventricular remodelling and chronic heart failure as a consequence of myocardial infarction is a major problem despite of the everimproving therapeutic options. The available treatment methods have fairly limited success in preventing the development of these changes. Myocardial regeneration with stem cell treatment is a promising therapeutic alternative. Although the results should still be confirmed in large, randomised, multicentric controlled trials, data from animal studies and small clinical trials suggest that therapy with stem cells after acute myocardial infarction is safe and feasible, is able to reduce the extent of necrosis, and may improve myocardial perfusion and left ventricular function. This review presents the types of cells that can be used, the ways of application, and the available results of clinical trials of stem cell therapy after acute myocardial infarction.]

Lege Artis Medicinae

[Axillar sentinel node biopsy and surgical treatment of the axilla in breast cancer patients - Evidences and open questions]

CSERNI Gábor

Lege Artis Medicinae

[THE REAL FACE OF JUVENILE POLYPOSIS SYNDROME - MALIGNANCY IN A DISEASE PREVIOUSLY THOUGHT TO BE BENIGN]

TAM Beatrix, SALAMON Ágnes, BAJTAI Attila, NÉMETH Annamária, KISS János, SIMON László

[INTRODUCTION - The majority of colorectal cancer cases is sporadic, but familial and autosomal dominant forms should also be considered. Juvenile polyposis syndrome is an autosomal dominant condition caused by mutations in the SMAD4 or the BMPR1A gene. Typically, numerous hamartomatous polyps develop in the upper gastrointestinal and the colorectal area. In contrast to earlier opinions, some of these polyps may transform malignantly, like in the case presented here, at the age of 34-35 years on average. CASE REPORT - During the eighteen-year continuous care of the young man treated for juvenile polyposis, more than a hundred polyps were resected from the gastrointestinal tract. After an eigth-year intermission of surveillance because of insufficient compliance, the patient presented in a severe clinical condition caused by metastatic colorectal cancer. He died after a short palliative therapy at the age of 31. Based on the family tree, all of his living adult first-degree relatives were subsequently examined and juvenile polyposis syndrome was also diagnosed in his older brother. Genetic testing revealed a mutation in the BMPR1A gene in the clinically affected brother, one of his daughters, and also in the deceased probands child. CONCLUSION - Genetic testing made it possible to relieve the mutation-free relatives of the anxiety and particularly of a number of unnecessary, mainly invasive examinations, while mutation carriers can be given the best possible clinical surveillance.]

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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.

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

[The role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]