Treatment of type 2 diabetes mellitus in the elderly - Special considerations.

Type 2 diabetes is a frequent chronic disease. Given its strong positive association with older age, it is a significant public health issue in elderly populations. Furthermore, the aging of the population, driven by increasing life expectancy in high and middle-income countries leads to an increasing prevalence of diabetes.Although the same diagnostic criteria apply to the elderly and to younger people, there are unique aspects to the care for elderly type 2 diabetes patients. Both treatment goals and preferred medications, as well as non-pharmacological approaches should be adjusted in the elderly. For example, increasing the amount of physical activity may encounter difficulties, while introducing an appropriate diet may be more challenging. The patients' therapeutic adherence requires special attention due to cognitive and physical limitations. The most important treatment goal is to avoid hypoglycemia. Frailty, social and economic issues, comorbidities and the consequent polypharmacy frequently causing drug-drug interactions, as well as the increased danger of drug toxicity due to renal failure are only some of the problems that make the health care for old diabetes patients extremely difficult. Adequate care requires cooperation from a multidisciplinary team of health care professionals.Acute diabetes complications have a higher mortality in the elderly, thus close attention must be paid to avoid them. Family members should be involved in the care of elderly diabetes patients, and it is recommended to educate them on clinical signs of complications. Regular care for the patients including feedback on quality of life and early signs of health issues are essential.

Anemia of geriatric patients.

Anemia is a common finding in the elderly. Approximately 10 percent of the elderly suffers from anemia. Anemia per se is an independent factor of mortality in older patients regardless its cause. Frailty is also frequent in geriatric patients. That means that there is a decreased reserve capacity to react to different stress factors including anemia. The frequent presence of heart failure and also impaired cerebrovascular circulation makes more difficult to tolerate anemia in older age. Anemia is a symptom, finding and treating the underlying cause is also important. Treatment always depends on clinical findings: the more severe the symptoms, the more important to treat them. Severity of anemia depends not only the underlying cause, degree of anemia, co-morbidities and frailty of the patients, but also the speed of its development. Sudden blood loss due to an accident is less well tolerated than the same degree of anemia due to B12 deficiency. Main causes of anemia in the elderly include nutritional deficiencies, chronic diseases, tumors, and certain hematological malignancies such as chronic lymphocytic leukemia, multiple myeloma, myelodysplastic syndrome.

COVID-19 and the elderly.

COVID-19 has become a great burden of the world in respect of health care, social, and economical reason. Several million people died worldwide so far and more and more mutants are generated and spread. Older people with co-morbidities and frailty syndrome have a significantly higher risk to get the infection and also higher the risk of a more serious disease process. Mortality of COVID-19 is also higher in case of geriatric patients. In this review we attempted to summarize the factors of the higher susceptibility for more serious disease, what actions need to be taken for defending older patients and also special aspects of clinical presentation including ophthalmic symptoms.

[Importance of thromboprophylaxis in hospitalized non-surgical patients]. / A thromboprophylaxis jelentosége nem sebészeti fekvobeteg-osztályokon.

Venous thromboembolism (including deep vein thrombosis and pulmonary embolism) is a group of diseases with high morbidity. Mortality caused by venous thromboembolism is also highly significant. It is one of the most frequent preventable causes of death in hospital treated patients. It is not easy to assess the real prevalence of the disease because of the frequent symptomless manifestations (as autopsies become less and less frequent, the number of post-mortem diagnoses also decreases) and also because the disease often generates after hospital discharge. There are a number of factors contributing to the development of venous thromboembolism in hospital treated patients. The significance of risk factors differs in the case of patients treated in surgical and medical departments. In this review, the thromboprophylaxis of mainly medical inpatients are discussed. Though there are guidelines about indications and methods of venous thromboprophylaxis, yet it is an unsolved problem to enforce them worldwide and also in Hungary. Despite the effective prophylactic methods, results cannot be considered satisfactory. The number of days spent in hospital and also the number of re-admisson are elevated because of venous thromboembolism. Beside this, the complications also lead to the worsening of the quality of life of these patients, moreover, to disability or death. The financial burden of the health system is also significant. Improvement of the efficacy of the prevention of venous thromboembolism is a highly important issue of health policy. Orv Hetil. 2019; 160(17): 654-661.

[Problem solving care models for Parkinson's disease]. / Problémamegoldó ápolási-gondozási modell Parkinson-kórban.

INTRODUCTION: Parkinson's disease affects more than 6,3 million people worldwide. Most patients and relatives are left alone to struggle with the symptoms associated with fluctuations in drug levels and the psychotic side effects of the anti-Parkinson's medications. Moreover, quite often even health providers may find difficult to interpret and manage the problems that have been encountered. AIM: The aims of the authors were to analyze systematically the biopsychosocial needs of Parkinson's patients, and to develop a complex, evidence-based Parkinson's-nursing-care model. METHOD: Patients' needs were assessed based on an observational study involving an old patient with Parkinson's disease for more than 28 years. The model has been specified as a multidisciplinary care framework adapted to the special characteristics of Parkinson's disease which transcends the limitations of different standard nursing models. RESULTS: The elaborated model contains a detailed description of cooperative problem solving, which is organized around individual patients along with recommendations for addressing various potential problems that might be encountered. CONCLUSIONS: Implementation of the presented model can improve the life quality of Parkinson's patients and can facilitate the life of affected families provided that these families are well aware about the potential benefits of the novel care delivery system.

[Antimicrobial effect on some zoonotic bacteria, of the cell-free fermentation fluid and purified peptide fraction of the entomopathogenic bacterium, Xenorhabdus budapestensis]. / A Xenorhabdus budapestensis entomopatogén baktérium sejtmentes fermentlevének és tisztítottfehérje-frakciójának antimikrobiális hatása néhány zoonoticus baktériumra.

INTRODUCTION: Many multi-resistant patogens appear continuously resulting in a permanent need for the development of novel antibiotics. A large number of antibiotics introduced in clinical and veterinary practices are not effective. Antibacterial peptides with unusual mode of action may represent a promising option against multi-resistant pathogens. The entomopathogenic Xenorhabdus budapestensis bacteria produce several different antimicrobial peptides compounds such as bicornutin-A and fabclavin. AIM: The aim of the authors was to evaluate the in vitro antibacterial effect of Xenorhabdus budapestensis using zoonotic patogen bacteria. METHOD: Cell-free conditioned media and purified peptide fractions of Xenorhabdus budapestensis were tested on Gram-positive (Rhodococcus equi, Erysipelothrix rhusiopathia, Staphylococcus aureus, Streptococcus equi, Corynebacterium pseudotuberculosis, Listeria monocytagenes) and Gram-negative bacteria (Salmonella gallinarum, Salmonella derbi, Bordatella bronchoseptica, Escherichia coli, Pasteurella multocida, Aeromonas hydrophila) using agar diffusion test on blood agar plates. RESULTS: It was found that Xenorhabdus budapestensis bacteria produced compounds with strong and dose-dependent effects on the tested organisms. Purified peptid fraction exerted a more marked effect than cell free conditioned media. Gram-positive bacteria were more sensitive to this antibacterial effect than Gram-negative bacteria. CONCLUSIONS: Antibacterial peptide compound from Xenorhabdus budapestensis exert marked antibacterial effect on zoonotic patogen bacteria and they should be further evaluated in future for their potential use in the control or prevention of zoonoses.

[Drug compliance of patients on anticoagulant treatment]. / Alvadásgátló kezelésben részesülo betegek gyógyszer-adherenciája.

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura.

INTRODUCTION: Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement- and neutrophil activation are parallel, characteristic processes in acute TTP. MATERIALS AND METHODS: Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany). RESULTS: Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r=-0.349, p=0.032) and hemoglobin levels (p=-0.382 p=0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p=0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb. CONCLUSIONS: We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.

[Thrombocytopenia]. / Thrombocytopeniák.

Thrombocytopenia means low platelet count. This is the most frequent cause of bleeding abnormalities. Petechias, purpuras, mucosal bleeding are typical clinical findings. Severe, even life threatening gastrointestinal or intracranial bleeding may also occur. Diagnostic laboratory finding is the prolonged bleeding time. There are several causes of thrombocytopenia. The major mechanisms for a reduced platelet count are decreased production and increased destruction of platelets, or both. The major task is to reveal the underlying cause. Examination of the bone marrow and the peripheral blood smear can be helpful as well as special diagnostics of the assumed disease. Therapy targets the underlying disease, and also involves platelet transfusion. However, in case of diseases with increased platelet activation and consumption, platelet transfusion is contraindicated because it may lead to aggravation of the pathologic process.

[Wegener's granulomatosis]. / Wegener-granulomatosis.

Wegener's granulomatosis is a necrotizing inflammation of small and medium size vessels with granuloma formation. It is a very heterogeneous disease in respect of severity and clinical manifestation. While it can be a rapidly progressive disease with fatal ending, there are forms limited only to one organ. Diagnosis is supported by the positivity of anti-neutrophil cytoplasmatic antibody and the presence of the typical histological findings. Unfortunately, these examinations cannot confirm clinical suspicion relatively frequently. In addition, there may be only symptoms related to one single organ for a long time at the beginning of the disease and, therefore, one have to be aware of the clinical signs and symptoms of the different organ systems. This may allow us to make an early diagnosis and start treatment in time.

Long lasting complete molecular remission after suspending dasatinib treatment in chronic myeloid leukemia.

Tyrosine kinase inhibitors specific for BCR-ABL, were a major breakthrough in CML therapy. Second generation tyrosine kinase inhibitors (dasatinib, nilotinib) are indicated for imatinib resistant and intolerant patients. Present guidelines recommend continuous drug dosing for maintaining remission. There is no available data concerning the optimal duration of dasatinib therapy. We report the case of an imatinib intolerant patient who succeeded a complete molecular remission with dasatinib. Dasatinib was stopped bacause of intolerance, but complete molecular remission was sustained for one year and minor molecular remission for 27 months after discontinuation of dasatinib.

[Antiphospholipid syndrome and pregnancy]. / Antifoszfolipid-szindróma és a terhesség.

Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems.

[Thromboembolic events in malignant diseases]. / Thromboembolia malignus betegségekben.

There is a bidirectional connection between tumors and thrombosis. On one hand, thromboembolic events are more frequent in cases of malignancies, on the other hand, proliferation of tumor cells, progression of the malignant process and metastasis formation are facilitated by the activation of the hemostatic system. Thromboembolic events are associated with a worse prognosis in case of patients with malignant diseases. Thromboembolism is the second most frequent cause of death in patients with malignant tumors. Mortality is twice as high in patients with thromboembolism compared to those without it. The incidence of thromboembolism shows an increasing tendency. There has been a 28% increase among hospitalized cancer patients between 1995 and 2003. One reason is that the new anti-tumor agents have more pronounced prothrombotic activity than those of traditional chemotherapeutic drugs. Assessment of the thrombotic risk of cancer patients becomes more important. Several guidelines have been published concerning the prevention and treatment of thromboembolism in patients with malignancy. The risk of thrombosis is influenced not only by the type of malignancy but there are also large individual differences. Furthermore, the risk of thrombosis changes during the disease process in the same patient. Perioperative thromboprophylaxis is a very important issue considering oncologic surgery. Thromboprophylaxis of oncologic patients has a high significance in respect of morbidity and mortality. However, thromboprophylaxis may also cause serious complications thus the correct risk assessment of cancer patients is very important.

[AL amyloidosis]. / AL-amyloidosis.

AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis - such as in case of other types of amyloidosis - is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flared in the past few decades, several drugs with new mechanisms of action are available (thalidomide, lenalidomide, bortezomib). The standard treatment is high dose chemotherapy followed by autologous stem cell transplantation in case of eligible patients. Transplantation uneligible patients can be treated with a low dose alkylating agent with or without dexamethasone, or with the new agents. The therapeutical decision must be preceded by very thorough risk assessment. Early diagnosis and the prompt beginning of the treatment has great significance because the evolving functional abnormalities of parenchymal organs (mainly cardiac failure) prevents the effectivity of the treatment. Amyloidosis is an orphan disease, special centers play a significant role in the field of clinical trials.

[Contribution of microbiology to an effective control of healthcare-associated infections]. / Mikrobiológiai értéktöbblet az infekciókontroll-centrum kialakításához.

An effective control of healthcare-associated infections is not realized without an intensive participation of microbiologic activities. Authors present the model of a centre for healthcare-associated infection control established in 2008 at Semmelweis University. The new model of the surveillance system is based on diagnostic and experimental microbiologic data. Clinical and epidemiological microbiologic examinations are performed in the same laboratory using identical methods, and the results are continually compared. Reports consist of two functional parts; namely list of pathogens isolated and antibiotic sensitivity patterns for clinicians and messages especially for epidemiologists including abbreviated information on bacteria of nosocomial importance. Rapid detection of the most important pathogens both from clinical samples and from those obtained for detecting nasal carriage is carried out by a sensitive and specific method of an automated real time PCR. Biotyping of isolates by detailed biochemical substrate spectrum, genotyping by ready-to-use kits depending on polymorphism of repetitive DNA sequences, and cluster analysis of data are used for up-to-date survey of nosocomial situation. Statistical analysis of reports is performed by the multifactorial software OSIRIS Epidemiology.

Detection of four lymphotropic herpesviruses in Hungarian patients with multiple myeloma and lymphoma.

It has been suggested that human herpesvirus 8 (HHV-8), also known as KSHV (Kaposi's sarcoma-associated human herpesvirus), might possess a promoting effect in the development and progression of monoclonal gammopathies. In this study, the presence of Epstein-Barr virus (EBV), human cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and human herpesvirus 8 (HHV-8) were tested in patients with multiple myeloma (MM) using both serologic and nucleic acid amplification techniques. The transient reactivation or continuous presence of EBV, CMV, HHV-6 and HHV-8 could be detected in, respectively, 36, eight, 13 and 29 of 69 MM patients; nine, one, four and six of 16 monoclonal gammopathy of unknown significance patients; and seven, four, zero and five of 10 Waldenström's macroglobulinemia patients. The total number of MM patients was 95. HHV-8 PCR-positivity was significantly more frequent in the MM group than in the control group of patients with non-Hodgkin's lymphoma (NHL). However, serologic testing did not reveal significant differences between the two patient groups. The number of MM patients with concomitant herpesvirus infections as detected by PCR was as follows: 15 double, seven triple and two quadruple virus nucleic acid positive. In 13/95 MM patients, the simultaneous presence of acute EBV infection and HHV-8 PCR-positivity was detected compared with none of the control group (P=0.009). These results indicate that in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.

[Soluble syndecan-1 levels in different plasma cell dyscrasias]. / Szolúbilis syndecan-1-(CD 138)-koncentráció plazmasejt-dyscrasiákban.

INTRODUCTION: Syndecans are a family of cell surface proteoglycans. In the bone marrow of multiple myeloma patients syndecan-1 is expressed only on the surface of malignant plasma cells. The aim of the study was to determine the soluble syndecan-1 levels in different plasma cell dyscrasias. METHODS: The serum concentration of soluble syndecan-1 was measured using human syndecan-1 enzyme-linked immunosorbent assay kit. RESULTS: Patients with multiple myeloma showed a significantly higher median serum syndecan-1 level than patients with plasmocytoma or monoclonal gammopathy of undetermined significance. Statistically significant differences were also observed among Salmon-Durie subgroups of 50 patients suffering from multiple myeloma. In addition to these findings a statistical correlation with other independent prognostic factors such as serum beta2-microglobulin level, monoclonal immunoglobulin concentration, and bone marrow plasma cell count could also be noted. A significant decrease in median serum syndecan level was observed in patients who responded to chemotherapy, whereas no change in the median syndecan-1 level could be observed in nonresponders. CONCLUSION: These findings confirm the observation that high serum soluble syndecan-1 level is associated with a more advanced disease stage and is a strong independent indicator of poor prognosis. A diminished serum syndecan-1 reading as a result of chemotherapy may be a good indicator of favorable response to antitumor treatment.

Prolactin influences proliferation and apoptosis of a human IgE secreting myeloma cell line, U266.

In certain types of solid tumours and lymphomas prolactin (PRL) potentiates tumour cell proliferation and exerts anti-apoptotic effect. Tumour cells themselves can produce PRL and express PRL-receptors. Hyperprolactinemia is associated with different tumours, also. Multiple myeloma (MM) is a haematological malignancy caused by the clonal expansion of terminally differentiated plasma cells in the bone marrow. Recently, we demonstrated PRL immunostaining in bone marrow cells of MM patients and an elevated level of serum PRL of MM patients with advanced disease. In the present study, we tested the effect of PRL on a U266 human myeloma cell line and demonstrated constitutive and melphalan-stimulated intracytoplasmic PRL in U266 cells. Exogeneous PRL inhibited the proliferation and immunoglobulin (Ig) production of U266 myeloma cells. Concerning etoposide-induced apoptosis, PRL had a double-faceted effect depending on the applied dose: high, pharmacological doses (corresponding to hyperprolactinemia), inhibited apoptosis, whereas near physiological doses exerted a pro-apoptotic effect. These data indicate a definite effect of PRL on a human myeloma cell line. We demonstrated a direct inhibition of PRL on tumour cell growth, while its reciprocal effect on apoptosis refers to an important regulatory role of PRL.

Functional significance of genetic abnormalities in multiple myeloma.

Multiple myeloma (MM) is a B-cell neoplasm characterized by infiltration of the bone marrow with malignant plasma cells, synthesizing and secreting monoclonal immunoglobulin fragments. The malignant transformation of this terminally differentiated plasma cell is the result of a multistep transformation process. In spite of recent advances in this field, the cause and the exact molecular genetic basis of MM remain obscure. In this review, an attempt has been made to summarize the genetic alterations having functional significance in the generation and progression of MM, and also the existing relationship between genetic abnormalities and chemosensitivity, as well as the typical genetic alterations in various MM subgroups. Factors known to have a role in the conversion of monoclonal gammopathy of unknown significance (MGUS) to MM are also reviewed.