Lege Artis Medicinae

[Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 19]

TEREBESSY András

JUNE 07, 2021

Lege Artis Medicinae - 2021;31(05-06)

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Lege Artis Medicinae

[Hypertension, COPD and COVID-19. Focus on antihypertensive therapy]

FARSANG Csaba

[Chronic obstructive pulmonary disease is a very common comorbidity of hypertension and it is often unrecognised by physicians. The factors involved in the pathomechanism of both diseases should be realised when choosing treatment. Among factors, hypoxia, increased tone of sympathetic nervous system and activation of renin-angiotensin-aldosterone system should primarily be considered. Vascular wall damage and endothelial dysfunction has an important role in both conditions. The goals of treatment are elimination of risk factors, optimizing the blood pressure, the consequential prevention of cardio-cerebrovascular, renal and pulmonary damage; finally prolonging the patients’ life and improving their quality of life as well. Both hypertension and COPD significantly worsen the condition of COVID-19 patients since they increase the severity of the disease and the rate of in-patients’ and their mortality. In the treatment of hypertension among COPD and COVID-19 patients there must be emphasized the medication inhibiting of renin-angiotensin-aldosterone system, such as angiotensin-converting en­zyme inhibitors or angiotensin-II AT1 re­cep­tor antagonists. Special attention concerned the beneficial effect of mineralocorticoid receptor antagonist spironolactone. Other antihypertensive drugs (calcium channel blockers, thiazide-like diu­retics, high selectivity β1 receptor antagonists) may supplement the treatment if necessary. Long-acting β2 receptor agonists, muscarinic receptor antagonists and inhalation corticosteroids may be administered in double or triple combination also in hypertension and COPD as well. It is important to note, that statin therapy and also vitamin D3 improve the condition of COVID-19 patients.]

Lege Artis Medicinae

[COVID-19 and Parkinson’s disease]

TÓTH Adrián, TAKÁTS Annamária

[Parkinson’s disease is the elderly people’s condition which increases the risk of infections in the upper airways in its ad­vanced stages. Specific diseases (as hypertension, diabetes mellitus), older age and the male sex are significantly worsening the course of COVID-19. It would be challenging to examine parallel these diseases, since they are raising two important ques­tions. First, if Parkinson’s disease be a risk factor of COVID-19 morbidity and mortality. Se­condly, how the COVID-19 pandemic can influence the Parkinson’s disease patients. The authors are seeking answers to these questions based on the published results in the topic concerned.]

Lege Artis Medicinae

[Epilepsy in coronavirus pandemic]

SZŰCS Anna, HALÁSZ Péter, NARULA Lalit

[We aim to review the impact of COVID-19 pandemic on epilepsy and epilepsy-care. While the virus has no specific link with epilepsy, it may affect the nervous system both directly and indirectly, leading to seizures in several ways. The hyper-coagulable state occurring with the infection may cause strokes leading to seizures. The infection may first manifest in the form of disturbances of consciousness and behaviour, seizures, and even status epilepticus. The interactions of antiviral/antiepileptic drugs need to be taken into account during treatment. The hypercoagulable state induced by COVID-2 infection may cause stroke, which leads to seizures. The infection can occur also as an impaired consciousness of non-epileptic origin. Interactions of antiviral/antiepileptic drugs have also to be taken into account. The pandemic itself as well as quarantines and social distancing may cause anxiety and insomnia, challenge continuous antiepileptic supply; each one carrying the risk of seizing. Young epilepsy patients with learning disabilities and mental health issues are most vulnerable, justifying their hyper-protection. The danger of infection has highlighted the role of telemedicine. Internet-based video communication may ensure full care for chro­nic patients. Those methods favour bes­­ted patients with higher education. Epilepsy does not increase directly the risk of infection, but its comorbidities may worsen the course of the disease. Brain lesions and hypoxia, stress, insomnia and fever joining the infection increase seizure susceptibility. Because the danger of infection ma­de telemedicine an essential tool of pa­tient care, education and better computer supply for those in need is crucial. ]

Lege Artis Medicinae

[Inflammation and autoimmunity in COVID-19]

SZEKANECZ Zoltán, SZAMOSI Szilvia, SZŰCS Gabriella

[The course of COVID-19 has several stages according to the elapsed time and severity. Cytokine storm-induced multisystemic inflammatory syndrome (MIS) and consequent multiorgan failure occur in severe and critical phases. From a pathological point of view, there is important the co-presenting of inflammation (endothelitis) and microthrombotic events. Beyond respiratory failure, they may harm the cardiovascular and nervous system, the liver and the kidneys. COVID-19 may be associated also with production of autoantibodies and development of autoimmune diseases. Multisystemic inflammatory syndrome can be attenuated by corticosteroids, anti-cytokine antibodies and JAK inhibitors (“repurposing”). Most IL-6 inhibitors, and barici­tinib proved to be effective in several stu­dies, when applied in appropriate stage by MIS identification.]

Lege Artis Medicinae

[Practical aspects of anticoagulant treatment during the COVID-19 pandemic]

KOMÓCSI András

[Coronavirus infection has a multiple im­pact on the coagulation system and anti­coagulant therapies. Patients admitted with COVID-19 have un­usually high incidence of coagulation ab­normalities. The incidence of atrial fibrillation (AF) seems also to be more frequent among COVID-19 out- and especially in-patients. Among COVID-19 patients receiving oral anticoagulant therapy, for minimizing the risk of bleeding or thromboembolic complications there should also be considered the renal and hepatic functions and drug-drug interactions of oral anticoagulant and COVID-19 therapy. In case of direct anticoagulants, in addition to the benefits of better safety, more favorable treatment ad­he­rence, and fixed dosing, the use of this class of drugs does not require laboratory mo­nitoring of efficacy, which may be of exp­licit benefit in terms of social distancing and health network burdens. This study reviews the possible interactions of drugs used for viral infection and anticoagulation, and in addition to the issues of coagulopathy associated with COVID-19, we discuss also the concerning difficulties of continued anticoagulant therapy related to the social distancing measures.]

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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

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

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[The role of sleep in the relational memory processes ]

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[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.]