Lege Artis Medicinae

[mRNA technology did not initially appear to be a clear success story]

KATONA Ferenc

JUNE 07, 2021

Lege Artis Medicinae - 2021;31(5-6)

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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

[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.]

Lege Artis Medicinae

[Lipid lowering therapy during COVID-19 pandemic]

MÁRK László

[The COVID-19 pandemic posed significant challenges to all healthcare systems of the world as created a new situations above the large number of people infected, solutions of which were lacking any previous patterns. Former experiences were specifically needed among physicians who practised usually with therapies supported by evidence based clinical experiences thus they were working along the principles of Evidence-Based Medicine. The new observations and recommendations for treating infected patients increased gradually, however they were not always well-founded by the general urgency. In this situation, physicians faced often problems of the patient’s former medications since they had to focus on the therapy of the prevalent life-threatening condition. In such cases, therapy as lipid lowering, which is inherently inimically and lightly taken, may be omitted even more often. Basic drugs of lipid lowering are statins. They are used to reduce cholesterol levels and the risk of cardiovascular events, but they have also been described as having beneficial effect on the new viral infection. In this effect, the statins beyond the well-known anti-inflammatory impact and increasing the expression of angiotensin-converting enzyme-2 further mechanisms can take part as well. These may include among others the promoted breakdown of lipid rafts, which directly inhibits the entry of coronavirus into the cell through the S protein by decreasing the level of cholesterol required for this proceeding. In a group of more than 1200 statin treated and SARS-COV-2 infected patients the overall mortality rate by the 28th day was 48% lower than among the non-statin-users. According to a meta-analysis of nearly nine thousand COVID-19-infected statin users, they had 30% lower mortality rate or serious complications. Up to date observational studies suggest that statin therapy and the administration of other lipid lowering drugs should be continued or initiated according to the guidelines also during the COVID-19 infection.]

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.]

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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.

Clinical Neuroscience

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.

Clinical Neuroscience

Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study

NALBANTOGLU Mecbure, AKALIN Ali Mehmet, GUNDUZ Aysegul, KIZILTAN Meral

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Lege Artis Medicinae

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]

FARSANG Csaba

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

Lege Artis Medicinae

[Second game, 37th move and Fourth game 78th move]

VOKÓ Zoltán

[What has Go to do with making clinical decisions? One of the greatest intellectual challenges of bedside medicine is making decisions under uncertainty. Besides the psychological traps of traditionally intuitive and heuristic medical decision making, lack of information, scarce resources and characteristics of doctor-patient relationship contribute equally to this uncertainty. Formal, mathematical model based analysis of decisions used widely in developing clinical guidelines and in health technology assessment provides a good tool in theoretical terms to avoid pitfalls of intuitive decision making. Nevertheless it can be hardly used in individual situations and most physicians dislike it as well. This method, however, has its own limitations, especially while tailoring individual decisions, under inclusion of potential lack of input data used for calculations, or its large imprecision, and the low capability of the current mathematical models to represent the full complexity and variability of processes in complex systems. Nevertheless, clinical decision support systems can be helpful in the individual decision making of physicians if they are well integrated in the health information systems, and do not break down the physicians’ autonomy of making decisions. Classical decision support systems are knowledge based and rely on system of rules and problem specific algorithms. They are utilized widely from health administration to image processing. The current information revolution created the so-called artificial intelligence by machine learning methods, i.e. machines can learn indeed. This new generation of artificial intelligence is not based on particular system of rules but on neuronal networks teaching themselves by huge databases and general learning algorithms. This type of artificial intelligence outperforms humans already in certain fields like chess, Go, or aerial combat. Its development is full of challenges and threats, while it presents a technological breakthrough, which cannot be stopped and will transform our world. Its development and application has already started also in the healthcare. Health professionals must participate in this development to steer it into the right direction. Lee Sedol, 18-times Go world champion retired three years after his historical defeat from AlphaGo artificial intelligence, be­cause “Even if I become the No. 1, there is an entity that cannot be defeated”. It is our great luck that we do not need to compete or defeat it, we must ensure instead that it would be safe and trustworthy, and in collaboration with humans this entity would make healthcare more effective and efficient. ]