Clinical Dilemmas in the Treatment of Elderly Patients Suffering from Hodgkin Lymphoma: A Review.

Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasibility and toxicity in phase II trials. The introduction of brentuximab vedotin-based regimens led to a paradigm shift in first- and further-line treatment of elderly Hodgkin lymphoma patients, providing adequate disease control within a broader patient population. As far as checkpoint inhibitors are concerned, we are only just beginning to understand the role in the treatment of this population. In relapsed/refractory settings there are few options, ranging from autologous stem cell transplantation in selected patients to pembrolizumab, but unfortunately, palliative care is the most common modality. Importantly, published studies are frequently burdened with numerous biases (such as low numbers of patients, selection bias and lack of geriatric assessment), leading to low level of evidence. Furthermore, there are few ongoing studies on this topic. Thus, elderly Hodgkin lymphoma patients are hard to treat and represent an unmet need in hematologic oncology. In conclusion, treatment needs to be personalized and tailored on a case-by-case basis. In this article, we outline treatment options for elderly Hodgkin lymphoma patients.

ASSOCIATION BETWEEN PERIODONTITIS AND LIVER DISEASE.

Recent clinical and scientific evidence confirms the negative impact of long-term periodontitis on the clinical course and progression of various liver diseases. Periodontitis is a chronic, slow-progressing infectious disease of the tooth supporting tissues caused mainly by the gram-negative bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola and Tannerella forsythia. These specific pathogens can be easily translocated from oral cavity to the intestine. Disruption of the intestine microbiota composition by orally derived periodontal pathogenic bacteria has recently been suggested to be a causal mechanism between periodontitis and liver disease. Furthermore, both diseases have the ability to induce an inflammatory response and lead to the creation of inflammatory mediators through which they may influence each other. Recent epidemiologic studies have demonstrated that individuals with liver cirrhosis have considerably poorer periodontal clinical parameters than those without cirrhosis. Periodontal therapy in cirrhosis patients favorably modulates oral and gut microbiome, the course of systemic inflammation, cirrhosis prognostic factors, and cognitive function. Therefore, future clinical researches should be focused on detailed examination of the biological mechanisms, strength and direction of the association between advanced liver disease and periodontitis.

IDIOPHATIC ASYNCHRONOUS BILATERAL SEGMENTAL TESTICULAR INFARCTION AND ANTICOAGULANT THERAPY: A CASE REPORT.

We present an unusual case of sudden onset of pain in the left testis in a patient with a previous medical history of right orchiectomy due to hemorrhagic infarction. A partial orchiectomy was performed with complete removal of the lesion and reconstruction of the testicular parenchyma. Histopathological assessment confirmed segmental testicular infarction without the presence of malignancy. The patient subsequently received anticoagulant therapy.

EFFECTS OF OCCUPATIONAL STRESS ON THE ACTIVATION OF HEMOSTATIC AND INFLAMMATORY SYSTEM.

A 24-hour shift is one of the major stressors for physicians because, apart from causing fatigue and circadian rhythm disorders, it often requires making vital decisions for patients within a short time frame. It is known that workplace stress leads to the activation of the coagulation system, which can result in imbalance of the coagulation and fibrinolysis system. The state of stress can also generate proinflammatory mediators. The aim of this study was to examine the effect of 24-hour shift on global coagulation tests of D-dimers and fibrinolysis, and on C-reactive protein (CRP) as an acute inflammatory agent and proatherosclerotic factor. Sixty physicians (residents) aged 25-35 participated in this study (30 participants in the experimental group and 30 participants in the control group). In experimental group, blood samples were collected on three occasions: shortly before 24-hour shift, twelve hours after the shift had begun, and at the end of the shift. Blood samples were collected from control group participants at the same time points. The results showed that there was no statistically significant difference in the values of D-dimer and fibrinolysis between the experimental and control groups. CRP values were statistically significantly higher in the experimental (1.57, 1.49 and 1.50) than in the control group (0.79, 0.75 and 0.84) on all three measurements (p=0.024, p=0.020 and p=0.030, respectively). These results confirmed the existence of proinflammatory changes in the endothelium of blood vessels, which is a factor associated with accelerated atherosclerosis.

T-Cell Large Granular Lymphocytic Leukemia - Case Reports.

T-cell large granular lymphocytic leukemia (T-LGLL) is an uncommon but probably underdiagnosed disease caused by clonal proliferation of large granular lymphocytes. Diagnosis is typically based on the high number of morphologically characteristic lymphoid cells and finding of an abnormal immunophenotype by flow cytometry. Because of its relatively indolent clinical behavior, observation is often an appropriate therapy. Here we present a case of a 53-year-old male admitted to the hospital because of abdominal pain. Blood examination revealed mild mycrocitic anemia and multiplied lactate dehydrogenase level. Abdominal ultrasound showed splenomegaly of 16 cm, with no lymphadenopathy. Fine needle aspiration of bone marrow revealed hypocellular marrow with 50% of atypical lymphoid cells. There were 81% of atypical medium sized granular lymphocytes with irregularly shaped nuclei in peripheral blood, so the cytologic diagnosis was lymphoproliferative process. Bone marrow biopsy showed nodular and interstitial proliferation of small, partially atypical T lymphocytic cells positive for CD2, CD3, CD5, CD8, granzyme and TIA, and negative for hairy cell markers, CD10, MUM 1, bcl 1, CD4 and CD56. The finding was consistent with T-LGLL. Due to splenomegaly, the patient was treated with cyclosporine and gradually reduced dose of corticosteroids, leading to regression of splenomegaly and normalization of lactate dehydrogenase level.

Evaluation of Periodontal Parameters in Patients with Early Stage Chronic Lymphocytic Leukemia.

OBJECTIVE: To assess periodontal conditions in patients with early stage CLL and to compare it with the periodontal status of age matched healthy controls and to analyze the relationship between periodontal and hematological parameters in CLL patients. MATERIALS AND METHODS: 60 subjects were examined: 30 patients with CLL Rai 0 (test group) and 30 age-matching healthy individuals (control group). The exclusion criteria were: presence of other systemic disease or condition (e.g. diabetes), history of treatment for periodontitis, use of antibiotics during the last 3 months, use of medications. Socio-demographic data were obtained by means of a questionnaire. Participants with at least 8 teeth underwent a full mouth examination assessing API, PBI, PPD, REC and CAL. Medical data for CLL patients were collected from the patients' records, while hematological data were obtained from the hemogram. RESULTS: Difference between groups was statistically significant for age, number of teeth and frequency of dental checkups (p<0.05). Patients with CLL had significantly higher average values of periodontal indices (API 0.81±0.18; PBI 2.72±0.68; PPD 3.40±0.53; REC 1.95±0.87, CAL 4.37±0.80) compared to the control group (API 0.69±0.15; PBI 1.91±0.45; PPD 2.51±0.40; REC 0.99±0.54; CAL 3.00±0.58). The correlation coefficients between age and periodontal indices showed statistically significance between age and REC (r=0.357; p<0.01), and age and CAL (r=0.295; p<0.05). Age was not statistically significant covariate for CAL (F=2.205; p>0.05), only for REC (F=4.601; p<0.05). After the removal of the statistical effect of age, the difference in REC between CLL and control group remained statistically significant (F=19.732; p<0.01; eta(2)=0.287). Statistically significant association between periodontal and hematological parameters in CLL patients was not found (p>0.05). CONCLUSION: The results of this study showed that patients with CLL had worse periodontal status compared to healthy subjects. Causal relationship between periodontal and hematological parameters was not proved.

Nontraumatic bilateral subdural hematoma caused by antiaggregation therapy: case report and review of the literature.

A 64-year-old female receiving clopidogrel and aspirin antiaggregation therapy after percutaneous coronary intervention for non-STEMI myocardial infarction developed nontraumatic bilateral subdural hematoma with dizziness, vertigo and headache. Craniotomy had to be postponed because of reduced ADP platelet aggregability. Four days after clopidogrel withdrawal and transfusion of 12 platelet concentrate units, ADP aggregation transiently normalized and bilateral trepanation with hematoma evacuation was performed. The procedure was followed by excellent neurologic and clinical recovery; however, decreased platelet aggregability was recorded by postoperative day 12 despite strict clopidogrel and other platelet inhibitor withdrawal. Suspicion of Glanzmann thrombastenia was excluded by flow cytometry. Two weeks after neurosurgery, the right femoral vein thrombosis was detected by color doppler ultrasonography and therapy with fractionated heparin was initiated, followed by warfarin. The risk and incidence of hemorrhagic complications of antiaggregation and anticoagulation therapy are discussed. Caution is warranted on prescribing this potentially harmful therapy to older patients, generally burdened with other chronic comorbidities.

Recurrent venous thrombosis despite 'optimal anticoagulation therapy' for antiphospholipid syndrome--could new oral anticoagulants solve the problem?

The aim was to determine the validity of the international normalized ratio (INR) and prothrombin time (PT) as a monitor for warfarin therapy in patients with lupus anticoagulants and recurrent thrombosis, and to investigate alternative approaches to monitoring warfarin therapy and new treatment options in these patients. A case is described of a 63-year-old female with antiphospholipid syndrome and recurrent venous thrombosis despite optimal adjusted warfarin therapy. In patients with lupus anticoagulants, the INRs obtained while receiving warfarin vary and often overestimate the extent of anticoagulation, while PT without receiving warfarin is often prolonged. In conclusion, lupus anticoagulants can influence PT and lead to INR that does not accurately reflect the true level of anticoagulation. Optimizing of (warfarin) oral anticoagulation therapy could be achieved by individual monitoring of anticoagulation effect with a test thatis insensitive to lupus anticoagulants (chromogenic factor X assay). Emerging oral anticoagulants, direct thrombin inhibitors and direct factor Xa inhibitors, such as dabigatran and rivaroxaban, with a predictable anticoagulant response and little potential for food or drug interactions, have been designed to be administered in fixed doses without coagulation monitoring and could be the treatment choice for these patients.

Combined megaloblastic and immunohemolytic anemia associated--a case report.

A 55-year-old female with a history of psychosis and rheumatoid arthritis was admitted to the hospital for fatigue and dizziness. At admission, macrocytic anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations, decreased serum vitamin B12 concentration, with macroovalocytes and poikilocytes in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B12 and folic acid administered for two weeks was ineffective and followed by transitory worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the presence of autoimmune hemolytic anemia, could be explained by change in the macroblastic erythrocyte population, i.e. emerging red cells with completely exposed membrane antigens due to vitamin B12 treatment and/or higher degree of dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We proposed the coexistence of pernicious and autoimmune hemolytic anemia; therefore, methylprednisolone was added to vitamin B12 treatment. This therapy successfully improved hemoglobin and erythrocyte concentration. Although megaloblastic-pernicious anemia is a common disease, association of pernicious and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective erythropoiesis and immune mechanism) is a rare condition, with only several dozens of cases described so far.