Lege Artis Medicinae

[Host switching does not need any magic]

KOVÁCS Sándor

JULY 31, 2023

Lege Artis Medicinae - 2023;33(6-7)

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Further articles in this publication

Lege Artis Medicinae

[Ancient Roman medicine in light of recent archeological finds near Jaszbereny, Hungary]

SZABÓ Katalin

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Lege Artis Medicinae

[”Medicine must not be allowed to become a mechanistic process”]

BENCZÚR Béla

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Lege Artis Medicinae

[Evolution in medical therapy of heart failure with reduced left ventricular ejection fraction: clinical importance of the rapid titration strategy]

VARJAS Norbert, HEPP Tamás, BENCZÚR Béla

[Both, mortality and morbidity of chronic heart failure are persistently high, thus its adequate disease management is of pre-eminent importance. For heart failure with reduced ejection fraction (HFrEF) numerous evidence are available to improve its prognosis, including reduction of mortality, sudden cardiac death, and hospitalizations. Large randomized clinical trials have been shown that angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-receptor/neprilysin inhibitor (ARNI), B-blockers, mineralocotricoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) reduce both morbidity and mortality of HFrEF patients. Accordingly, the heart failure recommendation of the European Society of Cardiology (ESC) issued 2021, proposed the basic therapy for HFrEF in 4 pillars: ACEI/ARNI, BB, MRA and SGLT2 inhibitors. 
Instead of the earlier approach of stepwise sequential therapy, the new recommendation advocates for simultaneous initiation of all four drug classes with rapid titration to the target dose. The STRONG-HF clinical trial aimed to compare the rapid titration with its conventional strategy. Con­cer­ning the primary composite endpoint of re­peated heart failure in 180 days with rehospitalization and all-cause mortality compared with changes in quality of life and re­hospitalization by heart failure as separate endpoints, the rapid titration was significantly more efficient solution. 
When optimizing therapy, we have also to pay attention to the comorbidities of HFrEF patients, which may compromise the procedure of titration. The consensus document of the ESC Heart Failure Association recommends special patient profiling by comorbidities and specific hemodynamic parameters, followed by therapeutic re­com­mendations on different patient profiles. Overall, SGLT2 inhibitors have the least limiting factors and contraindications, thus they can be used in all profiles without exception – as early as at initiating the therapy.]

Lege Artis Medicinae

[Type 2 diabetes associated anxiety and affective disorders]

TORZSA Péter, HARGITTAY Csenge, TORZSA Gergely, TRIPOLSZKY Bálint, RIHMER Zoltán, GONDA Xénia

[Type 2 diabetes mellitus, as well as depression and anxiety, are generally prevalent and often occur together. Their relationship is complex with impacts of common aetiological factors, such as genetic background, activation of the stress system and the sympathetic nervous system, dysfunction of the immune system and elevated inflammatory cytokines, changes in the central nervous system, as well as lifestyle and socioeconomic factors. On the other hand, their relationship of the three conditions are bidirectional: diabetes may increase the risk of developing depression and anxiety through the burden of disease and diabetic distress, as well as the negative impact of complications on quality of life, while depression and anxiety may lead to diabetes through their negative impact on self-care, and antidepressants used to treat depression may also affect glycaemic control. It is important to draw the attention of professionals to the interrelations of diabetes, depression and anxiety since by screen­ing of mental symptoms there can be reduced the disease burden of comorbidities. ]

Lege Artis Medicinae

[Bridge over the abyss – Recommendations and reality  of lipid-lowering treatment]

REIBER István, MEZÔ Izabella

[2023-ban evidenciaként kell elfogadunk azt a tényt, hogy az emelkedett LDL-C okozó rizikótényezője az atheroscleroticus érbetegségeknek és a következményként fellépő érkatasztrófáknak (myocardialis infarktus, stroke, perifériás érelzáródás). Intenzív lipidterápiával, azaz intenzív dózisú statin (20–40 mg rosuvastatin vagy 40–80 mg atorvastatin) és ezetimib kombinációjának alkalmazásával 50% feletti mértékben csökkenthető az LDL-C-szint, és így a kezeltek nagy részénél elérhetőek lennének a hazai és a nemzetközi ajánlásokban szereplő LDL-C-célértékek. ]

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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

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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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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.