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.

BCR::ABL1 negative myeloproliferative neoplasms: A review focused on essential thrombocythemia and polycythemia vera.

The classical myeloproliferative neoplasms are divided into chronic myeloid leukemia, and the Philadelphia negative polycythemia vera, essential thrombocythemia and primary myelofibrosis. These are heterogenous diseases, originating from the clonal proliferation of myeloid stem cells, resulting in increased mature cell numbers in one or more myeloid lineages. The most commonly seen mutations in the Philadelphia negative myeloproliferative neoplasms include those in Janus kinase, myeloproliferative leukemia protein and the calreticulin genes. Philadelphia negative myeloproliferative neoplasms occur infrequently, with a combined annual incidence of 2.58 per 100,000. There are many overlapping symptoms of Philadelphia negative MPNs, such as fatigue, night sweats, hepatosplenomegaly and circulatory symptoms due to increased cell numbers. Total Symptom Score of the MPN Symptom Assessment Form is used to assess symptom burden on patients. The most worrisome complications are thrombo-hemorrhagic events, and risk stratification is especially important as treatment of disease is based on their category. Phlebotomy and aspirin are the mainstay of treatment in low-risk polycythemia vera and essential thrombocythemia patients, whereas high-risk disease calls for additional cytoreduction, usually with hydroxyurea.

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.

[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.

[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.

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.