How I Follow Hodgkin Lymphoma in First Complete (Metabolic) Remission?

Hodgkin lymphoma is characterized by a high cure rate in the modern era of medicine regardless of stage, but patients suffer from a high risk of comorbidity associated with the administered therapy. The main aim of this review article is to assess and analyze the various comorbidities associated with Hodgkin lymphoma and address the survivorship of patients, including fertility, secondary cancers due to cardiovascular toxicity, and quality of life. Furthermore, this review explores the optimal strategy for detecting relapse. The treatment paradigm of Hodgkin lymphoma has shifted, with a paradigm shift toward achieving a high cure rate and low toxicity as a standard of care in this patient population. Checkpoint inhibitors, especially nivolumab, in combination with chemotherapy are increasingly being studied in the first line of therapy. However, their long-term toxicity remains to be assessed in longer follow-up. In conclusion, Hodgkin lymphoma survivors, regardless of their treatment, should be followed up individually by a multidisciplinary survivorship team in order to detect and properly treat the long-term side effects of therapy.

First-Line Therapy for Nodal T-cell Non-Hodgkin Lymphomas: an Unmet Need in Hematology.

PURPOSEOF REVIEW: The main aim of this review is to summarize first-line therapy of nodal T-cell non-Hodgkin lymphoma. RECENT FINDINGS: Current treatment with CHOP chemotherapy results in poor outcomes in the majority of patients. However, there are advances within the field. First breakthrough is the ECHELON-2 trial which showed that the addition of brentuximab vedotin improves outcomes in anaplastic large cell lymphoma. However, other types of peripheral T-cell non-Hodgkin lymphoma were underrepresented with optimal treatment not known. Second breakthrough is an increase of autologous stem cell transplantation usage in the first complete metabolic remission, except in ALK + anaplastic large cell lymphoma, offering better disease control. Despite advances in the field, CHOP remains the standard treatment for the majority of these lymphomas, but multiple trials are underway with the aim to improve this unmet need in hematology and, hopefully, leading us to a new era in the treatment of peripheral T-cell lymphomas.

FDA's and EMA's approval of brentuximab vedotin for advanced Hodgkin lymphoma: Another player in the town?

ECHELON-1 study is a randomized open-labeled controlled trial investigating whether addition of brentuximab vedotin to chemotherapy offers benefit over the standard chemotherapy regimen in advanced Hodgkin lymphoma. After a median follow-up of 24.6 months, it has met its primary endpoint the reduction of modified progression-free survival being 23 percent. However, the beneficial effects have not been seen across all subgroups leading to further questions. The main aim of this review is to tackle these questions to provide the reader with in-depth insight of pros and cons of this novel, promising but ultimately controversial regimen.

Hematogenous extramedullary relapse in multiple myeloma - a multicenter retrospective study in 127 patients.

The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010-2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high-risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM (P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM (P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non-secretory disease and 43% had light-chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02-4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8-7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 - 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.

BENDAMUSTINE: AN OLD DRUG IN THE NEW ERA FOR PATIENTS WITH NON-HODGKIN LYMPHOMAS AND CHRONIC LYMPHOCYTIC LEUKEMIA.

- The aim of this review is to present data on bendamustine, a non-cross resistant alkylating agent, alone or in combination for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bendamustine is currently approved for rituximab-resistant indolent NHL and CLL in patients not fit for conventional chemotherapy. Recent studies have shown superiority of bendamustine combination with rituximab (B-R) in first line treatment of indolent NHLs and mantle cell lymphoma, suggesting a shift of the standard of care in this setting. B-R regimen has also shown efficacy in relapsed setting suggesting the possible treatment option for patients failing conventional chemotherapy. In rituximab-resistant NHL, the recent GADOLIN study exploring the addition of obinutuzumab to bendamustine has yielded impressive result changing the standard of care in this hard-to-treat population. Concerning CLL, despite inferiority to the standard of care in young fit patients, as defined in CLL10 study, B-R has yielded a more beneficial toxicity profile and its use in first line treatment should be decided individually. In relapsed setting, the addition of ibrutinib to B-R has shown superior results compared to B-R alone, possibly changing the paradigm of treatment of relapsed CLL. In conclusion, bendamustine as a single agent or in combinations has shown activity with acceptable toxic profile in the treatment of patients with indolent NHLs or CLL without del(17p) mutation.

Factor structure and cut-off scores of the Hospital Anxiety and Depression scale (HADS) in a Croatian sample of adult patients suffering from advanced cancer.

BACKGROUND: Patients with cancer should be systematically screened for psychological problems at key points in their pathway. Usage of self-report scales for measuring anxiety and depression (such as Hospital Anxiety and Depression scale (HADS)) is a very practical methodfor detecting anxiety and depression. The aim of this research was to determine latent structure, reliability and cut-off scores of HADSin a Croatian sample of adult patients suffering from advanced metastatic cancer. SUBJECTS AND METHODS: According to inclusion and exclusion criteria, participant were recruited at University Hospital Centre Zagreb (N=46; January 2015) and Clinical Hospital Centre 'Sisters of Mercy' (N=29; April 2015). All participants underwent short structured psychodiagnostic interview, cognitive evaluation (usingMontreal Cognitive Assessment (MoCA) test) and were given HADS. RESULTS: When using PCA separately for the items of each original scale of HADS, only four items for the component Depression satisfactorily saturate principal component and when using PCA for all the items, only seven items from the original scale satisfactorily saturate unique principal component. Maximum Likelihood extraction method showed that only four items from the original scale satisfactorily saturated the theoretical scales. CONCLUSIONS: The results show that the best solution to use HADS, in defined Croatian population, is as one-dimensional screening instrument (Cronbach's alpha coefficient of internal consistency=0.774) with cut-off score 11/12.

Rituximab Maintenance Strategy in Advanced Follicular Lymphoma: Facts and Controversies

Rituximab is a chimeric monoclonal CD20 antibody used in the treatment of CD20 positive non-Hodgkin lymphomas and has revolutionized treatment approach to these hematologic malignancies in the last decade. The main aim of this review is to present data on the use of rituximab in the treatment of follicular lymphoma (FL). We will focus on rituximab maintenance strategies in the first and second line treatment. This approach has improved the outcome in FL patients with better progression-free survival in all patients and better overall survival in relapsed setting. Regardless of good results, this strategy has generated controversies in medical community in the range from the lack of overall survival benefit in first line setting, adverse effects of possible overtreatment and toxicities to its unknown role in the era of novel agents. The existing data suggest that rituximab maintenance should be a rational therapeutic option for all patients with FL responding to fi rst line therapy and transplant-ineligible patients responding to reinduction.

The role of microRNA in myelodysplastic syndromes: beyond DNA methylation and histone modification.

Myelodysplastic syndromes (MDS) are heterogeneous group of hematologic disorders of mostly elderly and based on distinct clinical phenotypes. Current paradigm of their pathogenesis relies on somatic gene mutations combined with the predisposing defective osteohematopoietic niche, but due to the breakout in epigenetic research scientific focus has steered toward two most common epigenetic modifications: methylation mechanisms and histone modification. At the same time, relatively few studies have been undertaken regarding the third epigenetic pathway - microRNAs - in MDS. The main aim of this review is to provide the basics of microRNA biology and function in oncogenesis, showing the complexity of mechanisms behind this single-stranded 22 nucleotides long RNA molecule, with further focus on its implication in MDS pathology and clinical context. By extensive literature search, we have shown enough evidence for their deregulation in MDS. However, few studies have addressed the issue on pathogenic events in MDS and its association with specific microRNAs. Preliminary research in clinical setting has shown the possible utility of microRNAs in terms of prognosis and therapy, although we are only beginning to understand various implications of microRNAs in MDS and further extensive research is warranted to answer multiple questions arising from interconnection of this epigenetic mechanism in MDS.

[FOLLOW-UP OF PATIENTS WITH CLASSICAL HODGIN LYMPHOMA AFTER TREATMENT--NOVEL EVIDENCE AND DILEMMAS. LITERATURE REVIEW]. / PRACENJE BOLESNIKA S KLASICNIM HODGKINOVIM LIMFOMOM NAKON LIJECENJA--SUVREMENA SAZNANJA I NEDOUMICE. PREGLED LITERATURE.

In this review we present current evidence for the follow-up of patients treated for classical Hodgkin lymphoma (HL). Nowadays introduction of novel therapies enabled successful treatment in most patients with classical HL in first remission with 5-year overall survival rate estimation of 80%. We have performed extensive literature search on the methodological approach to detection of relapse. Evidence regarding imaging clinical methods in detecting relapse on serial computed tomography and/or positron emission tomography scans is scarce. These imaging modalities are associated with considerable economic cost, unnecessary exposure to radiation and patients' stress. Furthermore, the detection of asymptomatic relapse does not seem to be associated with improved outcome in this patient group. Available data on this subject indicate that standard imaging methods, such as ultrasound, and judicious clinical examination in detecting of relapse should be the basis of HL patient follow-up. Late toxicity due to various modalities of treatment represents serious morbidity in HL. They vary from secondary solid cancers and hematologic neoplasms, associated with poor outcome, to benign disorders (fertility issues, thyroid dysfunction, cardiovascular and lung disorders). Current data on the incidence, prevalence and etiological factors do not yet provide evidence on appropriate screening methods. Most recommendations in various guidelines are associated with low level of evidence (grade IV). We, therefore, propose individually-tailored screening methods for each patient based on the modality of treatment received.

[CURRENT APPROACH TO NON-HODGKIN MANTLE CELL LYMPHOMA: LITERATURE REVIEW].

Mantle cell lymphoma (MCL) represents the fourth most common type of non-Hodgkin lymphomas. It is characterized by aggressive course and frequent relapses. The main aim of this review is to evaluate current treatment approach towards this type of lymphoma. In younger patients the chemotherapy including high doses of cytarabine is the gold standard. In case of complete or partial remission, the consolidation with autologous stem cell transplantation is indicated as consolidation approach. In older patients CHOP-R regimen is not the treatment of choice. These patients should be treated with bendamustine in combination with rituximab. In case of complete or partial remission, further therapy with rituximab maintenance as consolidation represents an option. The vast majority of patients with MCL will ultimately relapse which poses a challenge in treatment approach. The approach in relapsed MCL can be divided in two types: chemotherapy or biologic therapy. In young fit patients chemotherapy based on bendamustine and cytarabine is a reasonable option. In patients with comorbidities or poor performance status biologic agents are reasonable options. Ibrutinib, Bruton kinase inhibitor, is characterized by highest overall response rate and the longest duration of response and should be offered to these patients. With the development of novel potent inhibitor of B cell receptor signaling pathway, these agents may become the gold standard in future and introduce the treatment of MCL in "chemo-free"era.

[AUTOLOGOUS STEM CELL TRANSPLANTATION IN REFRACTORY OR RELAPSED DIFFUSE LARGE B CELL LYMPHOMA - A SINGLE CENTRE EXPERIENCE]. / AUTOLOGNA TRANSPLANTACIJA PERIFERNIH MATICNIH STANICA U REFRAKTORNOM ILI RELAPSNOM NE-HODGKINOVU LIMFOMU DIFUZNOGA B-VELIKOSTANICNOG TIPA - ISKUSTVO JEDNOG CENTRA.

Autologous stem cell transplantation represents the gold standard in chemosensitive diffuse B large cell lymphoma in relapse or in refractory setting. The aim of this study was to present the outcome of peripheral autologous stem cell transplantation in patients with refractory or relapsed diffuse large B cell lymphoma. We retrospectively analysed the data of 62 patients, who underwent this procedure for the period 2000-2013. The majority of patients (71%) were treated with miniBEAM salvage chemotherapy and all received BEAM myeloablative protocol followed by the stem cell reinfusion. The overall response rate for autologous transplantation was 75.8%. Median overall survival was 37.2 months. Median event-free survival was 16.9 months. Factors associated with overall survival were state of disease prior to salvage chemotherapy, chemosensitivity of disease, International prognostic index, disease activity at the relapse, response to autologous transplantation and post-transplantation radiotherapy. The use of rituximab was not significantly correlated to the outcome. In this patient group autologous stem cell transplantation was found to be effective in achieving remission and survival showing the adequate role of this procedure in this clinical setting. We stress out that autologous stem cell transplantation was effective in 32.5% patients with chemorefractory disease after salvage therapy.

[Diagnostic approach and treatment of immune thrombocytopenia in adults]. / Dijagnosticki pristup i lijecenje imune trombocitopenije u odrasloj dobi.

The aim of this review is to provide the Croatian medical public with novel insights into the definition, pathogenesis, diagnostic algorithms and treatment approaches to immune thrombocytopenia (ITP) in adults. Recently, primary ITP has been uniformly defined as an autoimmune disorder characterized by an isolated platelet count lower than 100 x 10(9)/L without preexisting disease or conditions, which could lead to thrombocytopenia. The recognition of primary and secondary ITP is important because they require different treatment strategies. In secondary ITP, therapeutic approach oriented towards the underlying disorder. Unlike childhood onset ITP, which is a self-limited condition with high rates of spontaneous remissions, adulthood onset ITP usually has chronic course. Previously, the pathogenesis of ITP was considered to be immune mediated destruction of platelets in liver and spleen, while recent findings have shown a novel pathophysiological pathway based on the inhibition of thrombopoiesis, leading to novel treatment approaches. The diagnosis of ITP is based on exclusion of the possible underlying causes of thrombocytopenia and consists of simple diagnostic procedures. The decision to treat ITP should be based individually: platelets count (lower than 30 x 10(9)/L), various bleeding risk factors and patient's preference. The use of corticosteroids is the mainstay of first line therapy. Two most commonly used corticosteroids are prednisone and dexamethasone. Prednisone is administered continuously, while dexamethasone is applied in cycles. Due to the lack of randomized clinical trials, it is not possible to recommend certain class of corticosteroid therapy. Another two agents used as first line therapy in case of corticosteroid refractoriness or the need of rapid platelet elevation, are intravenous immunoglobulins and anti-D immunoglobulin (anti-D is not approved in Europe). They are characterized by rapid onset of platelet recovery and low long-term remission rates. Until recently, splenectomy, with adequate infectious and thromboprophylaxis, was the therapy of choice in patients who did not respond to corticosteroids due to high long-term remission rates and low relapse rates. This procedure can be offered to a younger patient without significant comorbidities after the first year of ITP duration. With advances in the understanding of ITP pathogenesis, a new class of drug has been established: thrombopoietin agonists (TPO). Eltrombopag and romiplostim, the TPO agonists currently approved for the management of ITP in patients who failed the first line therapy and are not suitable for splenectomy, are only two agents that have shown benefits in large clinical randomized trials. They are characterized by a high response rate and appropriate safety profile, but the need for continuous use, a high relapse rate after therapy withdrawal, and price limit their use in everyday practice. TPO agonists represent an appropriate treatment choice in patients who have relapse after splenectomy. Another agent, often used in everyday clinical practice, is rituximab with high response and relapse rates. Its use is based on small studies, and due to the lack of clinical randomized controlled trials, rituximab is not approved by the leading medical agencies for this indication. As shown in this review article, our understanding and therapy for ITP has improved, but further research is needed to implement evidence-based therapy in clinical practice.

Outcome of Second Primary Malignancies Developing in Multiple Myeloma Patients.

BACKGROUND: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. RESULTS: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS. CONCLUSIONS: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

Psychiatrists' empathy, beliefs and attitudes towards veterans suffering from combat-related posttraumatic stress disorder.

BACKGROUND: Empathy is a powerful and necessary skill for understanding another person's subjective experience. In this study we wanted to explore psychiatrists' attitudes towards PTSD, general empathy, possible differences related to age, sex and regional location in Croatia. SUBJECTS AND METHODS: 205 psychiatrists from different Croatian regions participated in this study. To define psychiatrists' attitudes towards PTSD patients a questionnaire was devised. It contained 14 items related to psychiatrists' ability to live through emotional and social conditions of PTSD patients. BarOn Emotional Quotient-Inventory Empathy Subscale was used to measure the empathy among the subjects. RESULTS: This study has found statistically significant differences regarding gender in measured variables of the designed questionnaire. Male participants believed they were able to understand war veterans' feeling's and relate to traumatic experience while female participants stated that they had the ability to understand the trivial triggers for suicidal intentions. Regional differences were found in the understanding of war traumatic experience and social deviations occurring in PTSD. Older psychiatrists stated their incomprehension of the social difficulties the PTSD patients were facing. The years of experience in the psychiatric field were associated with inability to understand the patients' feelings'. Differences in empathy among the subjects were not found. CONCLUSION: The understanding of the empathic process in the therapeutic approach towards PTSD explored in this study was associated with basic variables such as gender and age but the construct of empathy itself is more complex and related with variables not assessed in this study, so our findings are preliminary and further research is needed.

Efficacy and Safety of Obinutuzumab-chemotherapy Combinations in Front-line Treatment of Follicular Non-Hodgkin Lymphoma During the COVID-19 Pandemic: A Study of KROHEM, the Croatian Cooperative Group for Hematologic Diseases.

Obinutuzumab (G) has become part of front-line treatment of follicular lymphoma (FL) based on results of a large randomized study. Data on patients treated outside of clinical trials are lacking. We have retrospectively investigated efficacy and safety of G-based immunochemotherapy regimens in 114 patients treated in a real-life setting during a period of 2 years, largely coinciding with the COVID-19 pandemic. The response rate was 93.8%; 18-months overall (OS) and progression-free survival (PFS) were 88% and 84%, respectively. Patients treated with G-cyclophosphamide, vincristine and glucocorticoid + doxorubicine (CHOP) had statistically significantly superior OS and PFS compared to patients treated with G-bendamustine (G-B) (P = 0.002 and P = 0.006, respectively) due to an increase in lethal infections, most notably COVID-19, in the latter group. A total of 12 patients died during follow-up; 9 of 61 treated with G-B, 1 of 49 treated with G-CHOP and 2 of 4 treated with G-cyclophosphamide, vincristine and glucocorticoid (CVP). SARS-CoV-2 infection was diagnosed in 20 (17.5%) patients. All of the 7 treated with G-CHOP recovered, while 4 of 12 treated with G-B died. Immunoglobulin levels and severity of neutropenia were similar between the groups. In multivariate analysis, G-B in comparison to G-CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front-line treatment for FL in real-life setting, but during the COVID-19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.

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.

Quality of life in Croatian Homeland war (1991-1995) veterans who suffer from post-traumatic stress disorder and chronic pain.

BACKGROUND: The aim of this study was to investigate the quality of life in Croatian homeland war veterans who suffer from post-traumatic stress disorder and chronic low back pain (LBP). METHODS: A total of 369 participants were included, classified in four study groups: those with post-traumatic stress disorder (PTSD; N = 59), those with both PTSD and lower back pain (PTSD+LBP; N = 80), those with isolated LBP (N = 95) and controls (N = 135). WHOQOL-BREF survey was used in the estimation of quality of life. The data were analysed using statistical methods and hierarchical clustering. RESULTS: The results indicated a general pattern of lowering quality of life in participants with both psychological (PTSD) and physical (LBP) burden. The average overall quality of life was 2.82 ± 1.14 for the PTSD+LBP group, 3.29 ± 1.28 for the PTSD group, 4.04 ± 1.25 for the LBP group and 4.48 ± 0.80 for the controls (notably, all the pair-wise comparisons were significantly different at the level of P < 0.001, except for the pair LBP-controls, which was insignificant). This result indicated that quality of life was reduced for 9.9% in patients with LBP, 26.6% in patients with PTSD and 37.1% in PTSD+LBP, suggesting strong synergistic effect of PTSD and LBP. The analysis also identified several clusters of participants with different pattern of quality of life related outcomes, reflecting the complex nature of this indicator. CONCLUSIONS: The results of this study reiterate strong impact of PTSD on quality of life, which is additionally reduced if the patient also suffers from LBP. PTSD remains a substantial problem in Croatia, nearly two decades after the beginning of the 1991-1996 Homeland war.

A quality of life in chronic combat related posttraumatic stress disorder--a study on Croatian War veterans.

The main objective of this study was to examine an association of various symptoms in chronic combat-related post traumatic stress disorder (PTSD) and the quality of life in this population. 248 Croatian male war veterans all diagnosed with chronic PTSD were consecutively enrolled in this study as they showed up at the routine check-up. They were given self report questionnaires Trauma Symptom Inventory (TSI-A) evaluating different PTSD symptoms and WHO Quality of Life-BREF assessing four different domains of the quality of life. After independent sample t- test was performed, the presence of each symptom defined by Trauma Symptom Inventory indicated the impairment of all four quality of life domains in a group of subject suffering from it, except of intrusive experience not being associated with the lesser quality in social domain. All quality of life domains were significantly correlated with various PTSD symptoms; however Pearson correlation factors ranged from small to medium value. As expected, PTSD symptoms are associated with lesser quality of life in the affected population. The further research is needed to show possible causal relationship between PTSD and, especially, physical health of these patients.

[Multiple myeloma in a patient with chronic lymphocytic leukemia--case report and literature review]. / Multipli mijelom u bolesnika s dugogodisnjom kronicnom limfocitnom leukemijom--prikaz bolesnika i pregled literature.

The occurrence of B-cell chronic lymphocytic leukemia (B-CLL) and another B-cell neoplasm in the same patient is a rare event and is mostly described in the literature as single case reports. In most cases reported in the literature, CLL was diagnosed several years before multiple myeloma. Some patients were only observed for CLL without therapy, whereas others had already been treated for CLL when the diagnosis of myeloma was established. Some authors came to a conclusion that therapy used for treating CLL can induce some secondary neoplasms, like multiple myeloma. We present a male patient who was diagnosed with multiple myeloma 11 years after B-CLL had been diagnosed. Two hematologic neoplasms in one patient could be a diagnostic problem, but also a therapeutic challenge.

Person-centered medicine versus personalized medicine: is it just a sophism? A view from chronic pain management.

The main aim of this brief overview is to explore the concepts of person-centered medicine and personalized medicine in the areas of chronic pain research and management. Through several definitions and paradigms of pain, the authors introduce the complexity of pain phenomenology in order to establish the challenge of person-centered and personalized medicine in everyday practice. By providing deeper insight into fibromyalgia, its presentation, biology and treatment, several questions are addressed, ranging from person-centered diagnosis to personalizing the various processes of the fibromyalgia spectrum complex. By reviewing current treatment options and evaluating treatment pitfalls derived from methodological flaws in current research, the authors discuss various possibilities of personalizing treatment and, therefore, propose how the use of these two paradigms could enhance outcomes in chronic pain management. If we wish to make comments about enhanced outcomes we need to talk about outcomes of pain treatments, we need to discuss what successful treatment is from the patient's point of view as well as in the reviewed models.