Lege Artis Medicinae

[Without COVID-19 maybe we should not concern the monkeypox]

VARGA János

JULY 18, 2022

Lege Artis Medicinae - 2022;32(06-07)

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Lege Artis Medicinae

[Attitudes towards end-of-life decisions among neonatology intensive care workers – Legal aspects behind decisions ]

FEITH Helga Judit, SALLAI Eszter Zsófia, SOÓSNÉ Kiss Zsuzsanna, GÉZSI András, GRADVOHL Edina, KOVÁCS Aranka, BERBIK István, SZABÓ Miklós

[Minors’ end-of-life dilemmas are among the most difficult decisions. Premature infants’ chance of survival has greatly improved thanks to the development of technology. Under-age children’s quality of life, as an aspect, does not appear in the effective Hungarian legislation. The aim of our study is to survey the change in NICU (neonatology intensive care unit) workers’ opinions/attitudes after a 20-year-period about restrictions in severely impaired new-borns’ intensive cares. Quantitative, complete sociological surveys in the Hungarian NICUs using self-administered, anonymous questionnaires (n = 728). Cross-Tabulation analysis and Pearson chi-squared test have been used for the data evaluation. In both studies, the majority of participants agreed that if the condition is fatal, it may be appropriate to limit the intensive care. Acceptance of treatment withdrawal has increased, but active euthanasia is still not accepted. Most healthcare workers are unsatisfied with the current legal order and there is a need for change, especially in cases of fatal and poor prognosis. Despite the fact that the effective Hungarian health care regulation does not allow withdrawal of treatment even in severe conditions, a significant number of those working at Hungarian NICUs would consider it as acceptable in some cases, moreover the share of acceptance has in­creased in the last two decades. Comparing the results with the current regulations, it can be suggested that it is necessary to increase the sensitivity of the legislators and to change the related legislation.]

Lege Artis Medicinae

[Herbs and natural substances used in Covid-19 caused by Wuhan and Delta variants of SARS-Cov-2 in the light of clinical trials]

CSUPOR Dezsô

[The use of medicinal plants in the preven­tion and treatment of Covid-19 started soon after the pandemic began. In some countries (e.g. China), the use of medicinal plants for this purpose was an officially declared goal. The plants used in therapy were selected on the basis of in silico studies, preclinical data or extrapolation of folk medicinal experience. In other parts of the world, the majority of medicinal plants are used by Covid patients outside of formal medicine, typically as food supplements. In this article, we review randomised controlled clinical trials of herbal preparations, indtoducing the potential place of herbal preparations in the therapy of Covid-19. A total of 17 trials were identified, most of which studied the effect on disease symptoms. Although most of the products tested were shown to be effective in at least one endpoint, the quality of the studies (mostly open-label, using non-standardised formulations) does not allow positive conclusions on efficacy. ]

Lege Artis Medicinae

[Dual incretin therapy – a novel approach in the antidiabetic therapy of type 2 diabetes ]

WINKLER Gábor, KIS János Tibor

[The introduction of incretin-based blood glucose lowering drugs, the dipeptidyl peptidase inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have opened up new perspectives in the antidiabetic treatment of type 2 diabetes. Beneficial properties of these drugs have directed the attention to study further enterohormones with potentially favourable effects on carbohydrate metabolism. Since the point of attack of these hormones is partly different partly identical, based on theoretical considerations, activating simultaneously their receptors in terms of glycemic control may result in synergistic and additive effects. This study reviews the concept of lowering the blood sugar level in type 2 diabetes based on multiagonistic receptor stimulation further the potential benefits of co-stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. It also briefly discusses the first data on tirzepatide as the first representative of dual receptor agonists accepted for clinical use by the FDA.]

Lege Artis Medicinae

[Modern approach and advanced treatment of obesity ]

SIMONYI Gábor, BEDROS J. Róbert, WITTMANN István

[Obesity is a recurrent, progressive chronic disease associated with body fat accumula­tion the body. Due to the nature of the dis­ease, its treatment and care is a life-long program. Elements of therapy: lifestyle modification (diet and exercise), psychological treatment, medication and if necessary, surgery. The Hungarian Society of Obesity and Exercise, recommends a low-carbohydrate and high-protein diet in the first half year of the weight loss program. During physical activity, dynamic, aerobic forms of movement (e.g. walking, jogging, swimming, cycling, etc.) are preferred. The options of drug treatment in Hungary are orlistat, naltrexone/bupropion fixed dose combination and liraglutide sc (3.0 mg) and bariatric surgery, which all can contribute successfully to the weight loss program.]

Lege Artis Medicinae

[Clinical protocol of the early childhood eating and sleep disorders outpatient clinic ]

SCHEURING Noémi, GULÁCSI Ágnes, ÁGOSTON Olga, SIBA Mónika, STADLER Judit, BALÁZS Krisztina, EGYED Katalin, KECSKEMÉTI Judit, HOLLÓSI Lilla Eszter, DANIS Ildikó, GERVAI Judit, SZABÓ László

[In a three-part article series, we present (1) the clinical protocol used by the Early Childhood Eating and Sleep Disorders Outpatient Clinic of the Heim Pál National Pediatric Institute; (2) the follow-up monitoring methodology of treatment efficacy; and (3) the first results obtained by this moni­toring program in a three-part ar­ticle. The Clinic with in-patient background was the first in the Hungarian health care system to provide organized care by interdisciplinary methods for families of infants and young children struggling with early child­hood emotional and behavioural regulation problems. The present first article concerns the clinical protocol of our facility based on the international literature and our own prior experiences. In the literature review, we emphasize especially the early childhood range of care for eating and sleep disorders. Thus, we justify the rationale of structure and activities of our Outpatient Clinic launched in 2017 by a brief summary of the international literature. Our aim is to inspire further health care providers to set up similar interdisciplinary services by a detailed description of our facility. ]

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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.

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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.

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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.

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Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.