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Abstract 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.

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.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries occurring typically in elderly patients. These patients often present with comorbidities limiting treatment options. During the last decade, the treatment paradigm has rapidly changed with the introduction of novel oral targeted agents and monoclonal antibodies., Areas Covered: The review focuses on the combination of type II antiCD20 antibody obinutuzumab in combination with chemotherapy or oral targeted agents in patients not suited for fludarabine-based therapy because of comorbidities or age. The main focus of the review is whether classical immunochemotherapy with obinutuzumab-chlorambucil is still a valid therapeutic option or whether the combination of obinutuzumab and ibrutinib or venetoclax presents novel standard of care., Expert Opinion: Both pivotal and registrational studies iLLLUMINATE study testing the combination of ibrutinib and obinutuzumab and CLL14 study testing the fixed combination of venetoclax and obinutuzumab have shown major benefit over chemoimmunotherapy approach in this population. Furthermore, they have excellent activity in high-risk subgroups of CLL paving the road toward a chemo-free immunotherapy approach in this setting. However, there are some pitfalls in these strategies warranting further research.

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

- 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.

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.

In this observational study, direct and indirect (moderator and mediator) relationships between sociodemographic (age, gender, life partner, education level, income and length of treatment) and psychological (Hospital Anxiety and Depression Scale, HADS) variables and satisfaction with hospital care (EORTC INPATSAT32) in adult (advanced cancer) patients were investigated. Study sample consisted of 75 hospitalized advanced cancer patients recruited at the Zagreb University Hospital Centre and Sestre milosrdnice University Hospital Centre in 2015. Statistically significant negative correlations were found between HADS and elementary school education level, as well as with all satisfaction variables (satisfaction with physicians, nurses and organization). Moderate to high and statistically significant positive correlations were found between elementary school level and all satisfaction variables. Gender and level of education appeared as significant moderator variables in the relationship between HADS and satisfaction with nurse care. There were no significant mediator effects of sociodemographic variables on the correlation between HADS and satisfaction with care. Male participants who were more disturbed emotionally were more satisfied with nurses. Participants with elementary and high school levels of education and lower scores on HADS were more satisfied with nurses, while participants with university level of education had higher HADS scores and lower level of satisfaction with nurses.

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.

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.

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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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.

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.

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.

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.

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.

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.

The goal of this study was to evaluate the association between self-perceived social support and chronic combat-related posttraumatic stress disorder (PTSD). The study included 262 male war veterans suffering from chronic PTSD. Their diagnosis was confirmed according to DSM-IV-TR. They were given self-reported measures Trauma Symptom Inventory-A and Multidimensional Scale of Perceived Social Support. No significant correlation was found between peer and family support and PTSD. The authors hypothesize this might be the result of secondary victimization, traumatization, and enduring personality changes during the course of PTSD. The items evaluating satisfaction with health care and state institutional support were correlated with most of the PTSD symptoms indicating the possible importance of improving institutional policies toward this population.

The aim of this study was to show how different coping mechanisms influence the prevalence of anxiety and depression in people suffering from multiple sclerosis. We also aimed at showing how different coping mechanisms contribute to subjective prosperity of the patients emphasizing general health, cognitive functions and fatigue. A questionnaire was given to attendants of the VI Symposium of Patients Suffering From Multiple Sclerosis. Scales were taken from Multiple Sclerosis Quality of Life Inventory (MSQLI), Hospital Anxiety and Depression Scale (HADS) and COPE inventory. A total of 68 anonymous questionnaires were handed in. A total of 57.9% of examinees had symptoms of depression, and 63.2% suffered from symptoms of anxiety. However, majority of the examinees suffered from the combination of these entities. Hypothesis about impact of various coping factors on depression, anxiety, fatigue was validated except an impact on physical state was not proven significant. Predictors improving these states were positive reinterpretation, social emotional support and humor, Predictors worsening these states were planning, acceptance, focus on emotional ventilation and denial. Psychiatric comorbidity has a high prevalence in people suffering from MS. Different coping mechanisms can help in improvement of everyday life.

The interrelation between chronic stress and multiple sclerosis (MS) has always been known, but the biological foundation for this phenomenon has not yet been proven. Our case-study of 5 patients, both diagnosed with multiple sclerosis and PTSD, attempts to demonstrate various dimensions of interrelation between these two diseases. We have also tried to point out the problems and possible complications doctors might encounter during the treatment of an MS patient who is suffering from chronic stress. Our findings show the need for a multidisciplinary approach in the treatment of patients with chronic PTSD and co morbid multiple sclerosis, which will optimize treatment and result in more cost-effective care. Appropriate identification and optimal pharmacological interventions for both disorders might modify further chronicity of these disorders and thus achieve better outcome.