[The recombinant human parathyroid hormone, teriparatide as an alternative remedy for the medication-related osteonecrosis of the jaw]. / Humán rekombináns parathormon (teriparatid) mint alternatív megoldás a gyógyszer okozta állcsontnekrózis terápiájára.

In developed countries, osteoporosis is one of the most common debilitating conditions in the population over the age of 50. Unfortunately, the pathomechanism of the disease is still not fully understood. Nowadays, the administration of antiresorptive drugs blocking osteoclastic activity is the most commonly used medication to slow down the speed of the bone loss. One of the uncommon side effects of such drugs is the medication-related osteonecrosis of the jaw (MRONJ). Recently, a number of alternative therapeutic approaches has been tested and published, amongst them the recombinant human parathyroid hormone (rhPTH, teriparatide) use, which is turning into a promising treatment modality. According to certain meta-analyses, its pharmacological effect on increasing bone mineral density and controlling pathological vertebral fractures is superior to antiresorptive drugs; however, the so-called "off-label" application of teriparatide remains controversial. As intermittent administration of teriparatide stimulates bone formation, several animal and clinical studies indicated that systemic application of teriparatide shortened fracture healing time and improved quality of the callus and the newly formed bone. Furthermore, recently several clinical studies showed the beneficial effect of the intermittent rhPTH administration in the management of MRONJ. This article reviews the history of the anabolic effect of the low-dose rhPTH discovery, provides evidence-based data from animal and human studies, summarizes its biological mechanisms and the clinical benefits of the anabolic therapy and also their possible role in the management of MRONJ. The majority of the clinical data indicates that, in the case of therapy-resistant osteonecrosis, it may be worthwhile to apply short-term intermittent teriparatide therapy. Notwithstanding, more randomized clinical trials are necessary in order to confirm the efficacy and the safety of the use of teriparatide in the treatment of MRONJ. Orv Hetil. 2023; 164(36): 1406-1415.

[The role of dietary factors and nutrients in rheumatoid arthritis]. / Étrendi tényezok és tápanyagok szerepe rheumatoid arthritisben.

Rheumatoid arthritis is the most common autoimmune inflammatory joint disease. Internal and external factors may play a role in its development. In recent years, an increasing number of studies highlighted that diet has a central role in the risk and progression of the disease. Several foods and nutrients present anti-inflammatory and antioxidant properties that have protective effects on the development and outcome of rheumatoid arthritis. The aim of this review is to summarize and describe the results of randomized clinical trials or cohorts that have investigated the effects of diet and nutrition in relation to rheumatoid arthritis and the potential role of dietary therapy in the management of rheumatoid arthritis. Certain dietary patterns and components can be used as adjunctive therapies in the treatment of rheumatoid arthritis and may contribute to the effective reduction of disease activity, the induction of remission and its long-term maintenance. At present, there is no nutrition guideline on the dietary management of rheumatoid arthritis and it is therefore important to objectively assess the potential effects and risks of dietary factors and dietary habits. Orv Hetil. 2023; 164(27): 1052-1061.

[Aggressive pituitary adenoma and pituitary carcinoma]. / Agresszív hypophysisadenoma és hypophysiscarcinoma.

Anterior pituitary tumours, once considered benign neoplasms, may rarely have aggressive behaviour and can even metastasize. The current guideline of the European Society of Endocrinology defines aggressive pituitary adenomas as radiologically invasive tumours with an unusually rapid growth rate and frequent relapses despite the optimal use of standard therapies. Currently, there is not any single, well-defined pathological marker of malignancy. Pituitary carcinomas are thus clinically defined by the presence of craniospinal or distant metastases, typically developing several years after the first presentation. Histopathology may predict aggressive behaviour if the Ki67 index and mitotic rate are elevated and in case of positive p53 staining. These patients' short- and long-term therapy should be individualized and regularly discussed by a multidisciplinary pituitary team. Besides standard medical treatment administered in maximally tolerated doses, current recommendations suggest repeated surgery and radiotherapy. If this approach fails, the next choice of treatment is chemotherapy with temozolomide. After that, immune checkpoint inhibitors, bevacizumab, and peptide receptor radiotherapy are emerging therapies that should be used on a case-by-case basis. Orv Hetil. 2023; 164(30): 1167-1175.

[Reducing the risk of infections in hereditary and acquired complement deficiencies.] / Infekciók kockázatának csökkentése veleszületett és szerzett komplementdefektusokban.

Hereditary complement deficiencies are relatively rare worldwide, they account for about 1-10% of primary immunodeficiencies. Acquired complement deficiencies are more prevalent and with the more frequent use of complement inhibitor therapy, the incidence of patients with iatrogenic complement deficiency is increasing. Alike in the inherited forms, patients have a high risk of severe and life-threatening infections caused by encapsulated bacteria (sepsis, meningitis). The most frequent pathogens are Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. C5 and C3 complement inhibitor therapies are available in Hungary, which are mostly indicated in the treatment of paroxysmal nocturnal hemoglobinuria, myasthenia gravis, neuromyelitis optica and atypical haemolytic uremic syndrome. It is of utmost importance to prevent severe, potentially life-threatening bacterial infections in this group of patients. Nevertheless, there is no Hungarian guidance to decrease the risk of infections, preventive measures are incomplete and not standardized posing potential risk of infections for these patients, so far. In this review, we aim to summarize the international clinical practices and guidance on the infection prevention in complement deficient patients. This recommendation might be a source of an evidence-based Hungarian guideline regarding vaccination and antibiotic prophylaxis in this specifically vulnerable group of patients. Orv Hetil. 2023; 164(25): 971-980.

[Recent aspects of pharmaceutical and endoscopic treatment of acute gastroduodenal ulcer bleeding]. / Az akut gastroduodenalis fekélyvérzés gyógyszeres és endoszkópos kezelésének újabb szempontjai.

Acute gastroduodenal ulcer bleeding is a life-threatening condition. Management of the acute gastroduodenal ulcer bleeding requires the cooperation of different specialists. The complex management program includes the immediate control of the hemodynamic status, transfusion and gastric acid inhibition therapy, endoscopic diagnosis, treatment and occasionally the invasive radiological interventions and surgery. According to the recent guidelines, pre-endoscopic parenteral proton-pump inhibitor therapy is recommended only for consideration. Urgent endoscopy (≤12 hours after admission) has no advantage to the early endoscopic (≤24 hours after admission) strategy. For ulcers with high rebleeding risk due to more than 2 cm in diameter, fibrotic base or wide visible vessel, the use of the "over-the-scope clip" is advisable even as a first-line endoscopic hemostatic therapy. Intermittent high-dose parenteral proton-pump inhibitor therapy is a new therapeutical option after endoscopic hemostasis. In patients with acute gastroduodenal bleeding who are taking low dose aspirin for secondary cardiovascular prophylaxis, aspirin should not be interrupted, while low dose aspirin administered for primary prophylaxis may be stopped. Orv Hetil. 2023; 164(23): 883-890.

[Cholangitis and cholecystitis: diagnostic criteria and management]. / Epeút- és epehólyag-gyulladás: diagnosztikus kritériumok és terápia.

In developed countries, diseases of the gallbladder and the biliary tract count as some of the most frequent gastrointestinal disorders. The inflammation of the gallbladder/biliary tree is a potentially severe, even lethal condition that requires rapid diagnosis and early multidisciplinary approach to be treated. Although the frequency of these diseases is high, the treatment is not unified in Hungary yet. The aim of the evidence-based recommendation is to clarify the diagnostic criteria and severity grading of these diseases and to highlight the indications and rules of proper application of the numerous available therapeutic interventions. The recent guideline is based on the consensus of the Board members of the Endoscopic Section of the Hungarian Gastroenterology Society in contribution with renown experts of surgery, infectology as well as interventional radiology and it counts as a clear and easy applicable guide during the all-day healthcare practice. Our guidelines are based on Tokyo guidelines established on the basis of the consensus reached in the International Consensus Meeting held in Tokyo which were revised in 2013 (TG13) and in 2018 (TG18). Orv Hetil. 2023; 164(20): 770-787.

[Current diagnostic and treatment strategies for urachal cancer]. / Az urachuscarcinoma aktuális diagnosztikai és kezelési lehetoségei.

Urachal carcinoma is a rare malignancy that is uniquely associated with the field of urology. Urachal carcinoma is mostly diagnosed in urological care centers due to its most frequently presenting symptom that is hematuria. Currently available diagnostic and therapeutic knowledge is solely based on case reports and single center series, while no prospective clinical studies are carried out due to the modest number of patients. These circumstances have made creating professional guidelines challenging, hence the treatment of urachal carcinoma is commonly based on individual clinical decisions. In this review, we summarize the epidemiology, diagnostic modalities, prognosis as well as local and systemic therapeutic approaches of urachal carcinoma. Furthermore, we aim to draw conclusions from this knowledge base that may guide clinical decision-making. Finally, we highlight some of the novel therapeutic strategies that hold the potential to improve urachal carcinoma patients' prognosis and quality of life. Orv Hetil. 2023; 164(16): 602-609.

[Alectinib and mixed large cell neuroendocrine carcinoma of the lung.] / Az alectinib és a tüdo kevert nagysejtes neuroendokrin carcinomája.

The treatment of mixed large cell neuroendocrine carcinoma is less studied due to its low incidence. However, the presence of anaplastic lymphoma kinase (ALK) fusion gene is rare in such tumours, ALK inhibitors may represent a promising therapeutic option instead of cytostatic therapy. Routine chest X-ray and then computed tomography (CT) examination revealed a pulmonary tumour in a 52-year-old asymptomatic woman. The neoplasm was removed by lobectomy. Histological examination confirmed papillary predominant lung adenocarcinoma. The patient was treated with postoperative chemotherapy and irradiation. 3 years later, neurologic symptoms were observed, therefore, brain CT was performed. The evaluation confirmed brain metastases which were removed. Histological examination identified metastasis of large cell neuroendocrine carcinoma. Revision and molecular examination of the metastasis and lung specimen revealed pulmonary mixed large cell neuroendocrine carcinoma with ALK-rearrangement. Alectinib (Alecensa) treatment was initiated resulting in regression of the previously observed liver metastases. Progression has not occurred in the last 3 years since the start of treatment. Detection of ALK fusion genes and research of ALK inhibitor therapy focus primarily on lung adenocarcinomas. Our case report would like to draw attention to the evaluation of driver mutations in pulmonary mixed neuroendocrine carcinoma with adenocarcinoma component because targeted treatment may be an effective alternative. Orv Hetil. 2023; 164(14): 548-554.

[Our experience with the treatment of Hodgkin lymphoma patients]. / Hodgkin-lymphomás betegek kezelésével szerzett tapasztalataink.

Overall and disease-free survival of Hodgkin lymphoma patients has improved significantly since the 2000s. This is due to the use of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) polychemotherapy and modern radiotherapy. In recent years, further diagnostic and therapeutic changes have been made, which further improve patients' survival. The most significant role in this is the improvement of diagnostics, such as the 18FDG-PET/CT, which is now routinely used repeatedly during treatment, and the response-adapted treatment(s) based on it. The main role of ABVD treatment in first-line treatment is still clear, but the combination of anti-CD30 monoclonal antibody (brentuximab vedotin) and AVD (adriamycin, vinblastine, dacarbazine) is already available as a targeted treatment for patients at higher risk. The role of autologous hematopoietic stem cell transplantation in the treatment of high-risk, relapsing/refractory patients is still clear, but the new, targeted innovative drugs (brentuximab vedotin, pembrolizumab) can already be used in the previous salvage treatments. New therapeutic options have new side effects, which must be taken into account during treatment (and after it). In our summary, we present these new diagnostic and therapeutic approaches, based on our own practice and experience. Orv Hetil. 2023; 164(11): 403-410.

[The role of extracorporeal life support in cardiopulmonary resuscitation]. / Az extracorporalis keringéstámogatás helye az újraélesztésben.

The frequency of the administration of extracorporeal cardiopulmonary resuscitation is increasing both in the treatment of in-hospital and out-of-hospital cardiac arrest. The latest resuscitation guidelines support the use of mechanical circulatory support devices in the cases of prolonged cardiopulmonary resuscitation in certain selected patient groups. However, only little evidence is available regarding the effectiveness of extracorporeal cardiopulmonary resuscitation, and many open questions remained unanswered regarding the adequate conditions of this modality. The timing and location of extracorporeal cardiopulmonary resuscitation are important factors, as well as the appropriate training of the personnel using extracorporeal techniques. Our review briefly summarizes, according to the current literature and recommendations, in which cases extracorporeal resuscitation may be beneficial, which type of mechanical circulatory support is the first choice of extracorporeal cardiopulmonary resuscitation, which factors influence the efficacy of this supportive treatment, and which complications may be expected during mechanical circulatory support during resuscitation. Orv Hetil. 2023; 164(13): 510-514.

[Oncological prehabilitation]. / Onkológiai prehabilitáció.

Cancer is currently the second leading cause of death in developed countries. Precision oncology treatments have significantly improved morbidity and mortality rates, 60% of patients can be cured or the disease can be managed as a chronic condition, so preserving and optimizing quality of life is just as important as successful treatment. The integration of rehabilitation has become generally accepted, however, preparatory treatments prior to oncological interventions should also receive more and more emphasis. In our center, we introduced the so-called oncological prehabilitation program that is a preparation treatment before oncological interventions. The program is popular among patients, and the positive feedback affects team members as well. Our goal is to present the structure and expected benefits of oncology prehabilitation as well as the possibilities of integrating it into the continuum of care, thereby introducing a change of perspective and paradigm shift. With oncological prehabilitation, we can witness a change of attitude and paradigm shift. Additional services supporting successful oncology treatments improve the quality of life, which - if there is an intention and need - could be implemented in oncology centers even with the current human resources. Orv Hetil. 2022; 163(50): 1975-1981.

[Genetic revision of the Hungarian Cystic Fibrosis Registry]. / A magyar Cystás Fibrosis Regiszter genetikai revíziója.

INTRODUCTION: Cystic fibrosis (CF) is one of the most common monogenic diseases. Genetic testing is becoming increasingly reasoned to establish or confirm the diagnosis by detecting abnormal mutations. OBJECTIVE: In order to develop a diagnostic strategy for cystic fibrosis and to facilitate mutation-specific treatments, the genetic revision of the Hungarian Cystic Fibrosis Registry was performed. METHOD: 582 patients' data and samples were used for the revision (528 originally included in the register and 54 received during the revision). First we reviewed the patients' existing genetic findings. Wherever necessary, a comprehensive three-level genetic analysis of the CFTR gene was done. RESULTS: According to our study, of the 528 patients present in the Registry, 395 (74.8%) had 2 pathogenic CFTR mutations. We completed and corrected 94 patients' previously incomplete genetic status. 73 different pathogenic variants were described, in which 1 aberration was not previously reported (c.3130G>A). The 5 most common mutations were: F508del (68.4%); CFTRdele2,3 (3.7%); G542X (3.2%); 2184insA (2.7%); W1282X (2.3%). Based on genotype and age, in Hungary 211 patients are eligible for the available lumacaftor-ivacaftor combination therapy, and 361 patients for the ivacaftor-tezacaftor-elexacaftor therapy. CONCLUSION: Due to the revision, we could identify the patients who can benefit from mutation-specific drugs instead of symptomatic therapy. In addition, the data obtained have been used to map the Hungarian distribution of mutations in the CFTR gene, which will help to develop a diagnostic strategy. Orv Hetil. 2022; 163(51): 2052-2059.

Internet addiction: the medical challenge of the 21st century? br / Internetfüggoség: a 21. század orvosi kihívása?

As a result of digitalisation and the increasing use of the internet, its problematic use is on the rise in the 21st cen-tury, with a predominant impact on minors and a potentially increasing challenge for health care systems in the fu-ture. The main risk factors for this phenomenon are age, inadequate social and family relationships, and can be as-sociated with mental problems such as depression and anxiety, somatic illnesses, often with additional dependencies. Imaging studies can detect abnormally functioning brain areas in the affected individuals, however, there is a signifi-cant heterogeneity among them. Similar to other addictions, extensive internet use negatively affects the individual in all areas of life. We do not have a high level of evidence for treatment yet, but it appears that treatments used in other (classic) addictive diseases may be effective.

Neoadjuvant (preoperative) chemoradiotherapy of advanced rectal tumors / Elorehaladott végbéldaganatok neoadjuváns (preoperatív) kemoradioterápiája

Introduction: There have been significant changes in the treatment protocol for rectal tumors in recent decades, greatly reducing the rate of local recurrence and distant metastasis, thereby increasing overall survival. Method: We performed a retrospective processing and statistical analysis of the data of 362 patients with rectal cancer who underwent local neoadjuvant chemoradiotherapy and then underwent surgical treatment between 1 January 2010 and 31 December 2017 at the Institute of Surgery of the University of Debrecen. We compared the response rate and overall survival results of our patients with local neoadjuvant treatment to the outcomes of total neoadjuvant treatment reported by the recent large international studies. Results: We experienced complete pathological regression in 8.6% of our patients. After neoadjuvant therapy, 10.7% of our patients experienced distant metastasis at the time of the operation or within 3 months period thereafter. In our study, the rate of response to the neoadjuvant treatment was a prognostic factor independent of the stage at di-agnosis and recognition. The groups with better response produced significantly better survival results. Conclusion: The total neoadjuvant treatment doubled the number of patients with complete pathological response, and the incidence of distant metastasis was by 7% lower in both recent international studies compared to the local neoadjuvant group. 85% of our patients were T3-4N+ stage at the time of recognition. Given the 10.7% rate of dis- tant metastases detected at the time of surgery or within 3 months in our patient population, we can state that ap- proximately half of our patients would have benefited from the administration of total neoadjuvant therapy which produced better outcomes. Based on this conclusion, we decided to introduce the total neoadjuvant therapy protocol in our department for treatment of patients with advanced rectal tumors.

Clinical risk assessment in decision making for hospital discharge of patients with pulmonary embolism / Klinikai kockázatbecslésen alapuló döntéshozatal a tüdoemboliás betegek kórházi elbocsátása során

Introduction: There are a vast number of studies that analyze the safest possible way of early at-home treatment of patients with pulmonary embolism after diagnosis. Objective: Our study aimed to find out how many patients could be discharged safely and without complications, if using the three validated score systems of the 2019 European Society of Cardiology guideline regarding pulmonary embolism. Method: Throughout our retrospective, quantitative study, we gathered data from the 2015-2018 period before the establishment of the new, 2019 guideline. We assessed patients who had a diagnosis of pulmonary embolism at the emergency room in the given period. With the help of the prognostic score systems, we retrospectively made a risk stratification using the main symptoms and vital parameters. We analyzed the categorical variables with chi-square test. For assessing two continuous variables, we used Pearson's correlation. We defined our level of significance at p<0,05. Results: 374 (199 female and 175 male) patients were enrolled in our study. Our retrospective calculation had the following results: based on the PESI score 151 patients, on the basis of the sPESI 101 patients and according to the Hestia criteria 50 patients could have been discharged, treated at home without complications and increasing the mortality. The negative predictive value (PESI: 98%, sPESI: 100%, Hestia: 100% with CI: 95%) and sensitivity (PESI: 91%, sPESI: 100%, Hestia: 100%) of the three prognostic scores showed applicable efficiency. Conclusion: We concluded that all three prognostic criteria can be used safely taking the local clinical experience and preference into consideration, aiming at early discharge. Adapting them nationally could decrease hospital load.

Short term results of the FLOT neoadjuvant therapy on the surgical management of advanced gastro-oesophageal junction adenocarcinoma / A neoadjuvans FLOT-terápia hatása az elorehaladott gyomor-cardia tumorok rövid távú onkológiai és sebészi kezelés eredményeire

Introduction. Recently the therapeutic treatment for advanced, stage T2-T4 gastro-oesophageal junction cancer and those adjacent to the regional lymph nodes involves neoadjuvant chemotherapy with subsequent surgical intervention. Method. Neoadjuvant oncological treatment for gastro-oesophageal junction cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group I). In the course of the new protocol (FLOT-, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), patients were included with resectable gastro-oesophageal junction cancer who had a clinical-stage cT2 or higher nodal positive cN+ disease (Group II). Between 31st of December 2013 and 1st of June 2021 we retrospectively analyzed the effect of these FLOT oncological protocols in terms of surgical outcomes in cases of T2-T4 tumors (n = 9). We compared the results of the randomly assigned nine patients from earlier ECF/ECX protocol (Group I). We analyzed the effect of the different neoadjuvant therapy on tumor regression, and evaluated the types of possible side effects, type of surgery, and the oncological radicality of surgical procedures (number of removed regional lymph nodes, resection margins). Results. Comparing the two groups we found that in cases of FLOT neoadjuvant chemotherapy complete regression was achieved significantly a higher number like in earlier ECX/ECF therapy. Furthermore, the average number of removed lymph nodes, and the safety resection margins (distal, circumferential) no significant difference was found between the two groups. Neutropenia was the most frequently encountered side effect. Leukopenia, neutropenia and nausea occurred more frequently in cases of the old protocol (Group I). Conclusions. As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-oesophageal junction cancer, the number of cases with complete tumor regression has significantly increased. The present results strongly suggest a significant advantage in favor of FLOT neoadjuvant treatment following surgery. The prevalence of side effects was also appreciably lower in cases of the FLOT protocol.