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Thrombosis is a common complication in cancer patients, with a substantial impact on morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) and other aggressive lymphomas carry a high venous thromboembolism (VTE) risk. Extracellular vesicles (EVs) have gained attention in recent research as a new potential biomarker for VTE development. To determine the profile and association of EVs with VTE in patients with DLBCL, we conducted a prospective cohort study on 62 patients diagnosed with DLBCL. A total of 11 patients (17.7%) developed VTE. The concentrations of platelet-derived EVs (PEVs), E-selectin+ EVs, P-selectin+ EVs, tissue factor (TF)-positive/CD20+ EVs, TF−/CD19+ EVs, TF−/CD45+ EVs, and TF−/CD20+ EVs were significantly higher in DLBCL patients compared to healthy controls. In contrast, the concentration of TF− PEVs was significantly lower in DLBCL patients compared to healthy controls. No statistically significant differences were observed in the concentrations of the EV profiles among the DLBCL patients with and without VTE. Using Cox regression analysis, we found that none of the observed EV populations demonstrated an association with overall survival (OS). In conclusion, patients with DLBCL have elevated concentrations of distinct EV populations—in particular, PEVs, E-selectin EVs, P-selectin EVs, TF+/CD20+ EVs, and TF− DLBCL/B-cell EVs (CD19, CD20, CD45)—compared to healthy controls. DLBCL patients exhibit a specific EV profile, which is not significantly related to the risk of VTE and OS outcomes. Our data provide an intriguing insight into EV profiles in patients with DLBCL. Additional research is needed to elucidate these findings further.

Background Lymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma. Methods The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE. Results The majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE. Conclusion Inflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.

Venous thromboembolism (VTE) is a multifactorial disease that can possibly affect any part of venous circulation. The risk of VTE increases by about 2 fold in pregnant women and VTE is one of the major causes of maternal morbidity and mortality. For decades superficial vein thrombosis (SVT) has been considered as benign, self-limiting condition, primarily local event consequently being out of scope of well conducted epidemiological and clinical studies. Recently, the approach on SVT has significantly changed considering that prevalence of lower limb SVT is twice higher than both deep vein thrombosis (DVT) and pulmonary embolism (PE). The clinical severity of SVT largely depends on the localization of thrombosis, when it concerns the major superficial vein vessels of the lower limb and particularly the great saphenous vein. If untreated or inadequately treated, SVT can potentially cause DVT or PE. The purpose of this review is to discuss the complex interconnection between SVT and risk factors in pregnancy and to provide evidence-based considerations, suggestions, and recommendations for the diagnosis and treatment of this precarious and delicate clinical entity.

Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA and flow cytometry according to laboratory and clinical data. Interleukin-1β was elevated across lymphomas and inversely correlated with the Khorana score for venous thromboembolism, while increased tumor necrosis factor-alpha (TNF-α) was inversely associated with the International Prognostic Index (IPI) in thrombosis-associated lymphomas. Neutrophil activation was increased in DLBCL, while elevated neutrophil extracellular traps (NETs) biomarkers were inversely consistent with thrombosis and the ThroLy score. NETs were elevated in HL. Classical monocytes were increased in all lymphoma subtypes, with intermediate and tissue factor (TF)-carrying monocytes elevated in DLBCL and HL. Platelet activation was pronounced, with platelet–monocyte aggregates and platelet-associated TF elevated in DLBCL and FL but not HL. P-selectin was increased in lymphomas with thrombosis, aligned with Khorana and ThroLy scores, and reflected clinical stage while inversely correlating with IPI in non-thrombotic lymphomas. These findings highlight distinct thromboinflammatory mechanisms across lymphoma subtypes, providing insights into biomarkers for thrombosis risk and therapeutic targets in lymphoma management.

Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Thrombosis Lymphoma (ThroLy) and Khorana scores have been conceived to predict the thrombotic risk in oncohematologic patients. Currently, there is no univocal indication to perform thromboprophylaxis in classical Hodgkin lymphoma (cHL). We performed a retrospective study to validate scores and risk factors in a cohort of consecutive patients with cHL, treated from 2014 to 2022 outside clinical trials. A total of 470 cHL patients without thromboprophylaxis were included, of whom 57 (12%) experienced a thrombotic event (TE) at 3.3 months (range 1–52) from diagnosis. Neither Khorana nor ThroLy score significantly predicted the thrombotic risk. In a multivariate analysis including Throly parameters and other risk factors, an independent prognostic impact on the TE risk was found for bulky disease (3 points), ECOG PS 2–4 (2 points), presence of peripherally implanted central venous catheter (2 points), mediastinal involvement (1 point), which were combined in a new risk model (Thro‐HL). Low‐risk (score 0–1; 39%, n = 183), intermediate‐risk (score 2–3; 46%, n = 214), and high‐risk (score > 3; 15%, n = 72) patients had a significantly different TE rate, of 2.7%, 16%, and 25% (P < 0.001), respectively. Three‐year‐thrombotic event‐free survival was 97% (CI 95–100) for low‐risk and 76% (CI 66–86) for high‐risk patients (P < 0.0001, Harrel's C‐index = 0.70). Thro‐HL could be a promising tool to be validated in larger series.

Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients’ characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.

Uvod: Limfomi predstavljaju vrlo heterogenu grupu neoplazmi, čija se biološka raznolikost ogleda u različitim mehanizmima napredovanja bolesti i razvoja komplikacija. Jedna od komplikacija koja izaziva značajan morbiditet i mortalitet kod pacijenata sa malignitetima je venska tromboembolija (VTE). Pacijenti sa malignitetom imaju do 7 puta veći rizik za razvoj tromboze u odnosu na opštu populaciju. Specifična patofiziološka karakteristika limfoma je imunološka disregulacija, koja je usko povezana sa aktivacijom inflamacije. Klasični indikatori nivoa inflamacije su broj leukocita i standardizovani reaktanti akutne faze: C-reaktivni protein (CRP), brzina sedimentacije eritrocita (ESR) i fibrinogen. Međutim, danas postoji značajan broj novih markera sistemske inflamacije poput odnosa neutrofila i limfocita (neutrophil-to-lymphocyte ratio, NLR) i odnosa trombocita i limfocita (platelet-to-lymphocyte ratio, PLR). Ekstracelularne vezikule (EV) predstavljaju generički termin za formacije koje se prirodno oslobađaju iz ćelije, koje su ograničene lipidnim dvoslojem i koje se ne mogu replicirati (tj. ne sadrže funkcionalno jedro). EV imaju vrlo sofisticiranu ulogu u brojnim fiziološkim i patološkim procesima, gde se EV otpuštaju od strane različitih ćelija. Uloga EV u trombozi povezanoj sa tumorom (cancer-associated thrombosis, CAT) ispitivana je u animalnim modelima i kod ljudi. Pored toga, EV su povezane sa stanjima kako akutne tako i hronične inflamacije, a često su i „nosači“ različitih molekula od kojih pojedini imaju protrombotički potencijal. S obzirom na sve navedeno, ciljevi istraživanja bili su ispitivanje povezanosti biomarkera inflamacije i razvoja VTE kod pacijenata sa limfomom koji su lečeni (imuno)hemioterapijom, ispitivanje povezanosti VTE sa tipom terapijskog lečenja i odgovora na terapiju kod pacijenata sa limfomom. Sledeći cilj je bio karakterizacija profila EV kod pacijenata sa difuznim B- krupnoćelijskim limfomom (DBKL), ispitivanje povezanosti EV sa VTE kod pacijenata sa DBKL, ispitivanje testa ukupnog hemostaznog potencijala (overall hemostasis potential,OHP) i povezanosti sa VTE kod pacijenata sa DBKL.Metodologija: U prvom delu istraživanja sprovedena je retrospektivna kohortna studija, u koju je uključeno 706 novodijagnostikovanih i relapsirajućih pacijenata sa limfomom koji su lečeni u Klinici za hematologiju, Univerzitetskog kliničkog centra Srbije. Prikupljeni su podaci o svim VTE kod pacijenata sa novodijagnostikovanim limfomom ili relapsom bolesti. NLR i PLR su računati korišćenjem parametara kompletne krvne slike sa diferencijalnom leukocitarnom formulom. Analizirani su sledeći biohemijski parametri: ESR, CRP, laktat dehidrogenaza (LDH), fibrinogen, ukupni proteini (TP), albumin. Drugi deo istraživanja predstavlja prospektivnu kohortnu studiju, koja je uključila 62 pacijenta sa dijagnozom DBKL i sprovedeno je u kolaboraciji sa Univerzitetskom bolnicom Karolinska, Služba koagulacije i kliničke hemije, Odeljenje za molekularnu medicinu i hirurgiju, Institut Karolinska i klinička hemija, medicinska dijagnostika Karolinska. Ispitivanje EV je sprovedeno korišćenjem protočne citometrije. Korišćen je sledeći panel markera: Annexin V za fosfatidilserin (PS), CD42b/CD61 za EV porekla trombocita (platelet-derived extracellular vesicles,PEV), CD142 za tkivni faktor (TF), CD19, CD20 i CD45 za DBKL/B-ćelijsku populaciju, CD62P/CD62E za P-selektin odnosno E-selektin. Za identifikaciju EV korišćen je specifičan gejting algoritam. EV su definisane kao vezikule veličine ≤1,0 μm i pozitivne na Annexin V. Za poređenje EV kod pacijenata sa DBKL, formirana je kontrolna grupa od 5 zdravih volontera.Rezultati:U retrospektivnom delu istraživanja, od 706 pacijenata uključenih u studiju, ukupno je 69 pacijenata (9,8%) razvilo VTE. Većina pacijenata imala je simptomatsku VTE (41/69), a takođe je kod većine pacijenata došlo do razvoja VTE tokom lečenja (52,1%). Učestalost VTE bila je najveća kod pacijenata sa agresivnim non-Hočkin limfomom (NHL) (11,8%), potom kod pacijenata sa Hočkin limfomom (HL) (8,4%), a najmanja kod pacijenata sa indolentnim NHL (5,8%). U poređenju sa pacijentima bez VTE, NLR, PLR, ESR, CRP i LDH su bili statistički značajno povišeni kod pacijenata sa VTE (p=0,001, p=0,001, p=0,023, p<0,001 i p=0,035), dok su TP i albumin bili statistički značajno niži (p=0,024 i p=0,032). U univarijantnoj regresionoj analizi, NLR, PLR, TP, albumin, LDH i CRP su se pokazali prognostičkim faktorima za razvoj VTE kod pacijenata sa limfomom. B-simptomatologija, „bulky“ tumorska masa, zahvatanje medijastinuma i ECOG PS bili su značajni kliničko-patološki prognostički faktori za razvoj VTE kod pacijenata sa limfomom (p=0,001, p=0,001, p=0,005, p=0,015).Zaključak:Biomarkeri inflamacije, a pre svega NLR i CRP, povezani su sa povećanim rizikom od razvoja VTE kod pacijenata sa limfomom koji su lečeni (imuno)hemioterapijom. Disregulacija inflamacije igra značajnu ulogu u razvoju VTE u ovoj grupi pacijenata. Lako dostupni markeri inflamacije mogu adekvatno da reflektuju nivo inflamacije i stratifikuju pacijente koji su u povećanom riziku za razvoj VTE. Nezadovoljavajući terapijski odgovor na (imuno)hemioterapiju bio je povezan sa razvojem VTE kod pacijenata sa limfomom. Kompletna remisija bila je ređa kod pacijenata sa limfomom koji su razvili VTE nego kod onih koji nisu razvili VTE. U grupi pacijenata sa DBKL koja je prospektivno praćena, ukupna koncentracija Annexin V+ EV signifikantno je bila veća od koncentracije Annexin V+ EV kod zdravih kontrola. Dodatnom karakterizacijom profila EV, nađene su signifikantno veće koncentracije TF+ EV, TF+ PEV, TF+ P-selektin EV, TF+ E-selektin EV, EV porekla DBKL/B-ćelijske populacije i TF+ EV porekla DBKL/B-ćelijske populacije u grupi pacijenata sa DBKL u odnosu na koncentracije EV pomenutih obrazaca kod zdravih kontrola. U poređenju grupa pacijenata sa DBKL i VTE odnosno bez VTE nisu uočene statistički značajne razlike u koncentraciji gore pomenutih EV. Interpretacija rezultata OHP analize i nivoa D-dimera kod pacijenata sa DBKL sa odnosno bez VTE bila je značajno limitirana malim uzorkom pacijenata.

Purpose To study the initial and long-term results of angioplasty and primary stenting for the treatment of chronic total occlusion (CTO) of the subclavian artery (SA). Materials and Methods From January 1999 to February 2010, 56 patients (25 men with a mean age of 58 ± 8 years) underwent endovascular treatment for CTO of the SA. Duplex scans and arteriograms confirmed occlusion in all cases. Indications for recanalization were subclavian steal syndrome in 33 patients (58.1%), arm claudication in 13 patients (23.2%), and coronary ischemia in 7 patients (12.5%) who had a history of previous coronary artery bypass grafting that included left internal thoracic artery graft. Three patients (5.4%) were treated before the scheduled coronary artery bypass surgery, which included left internal thoracic artery graft. After successful recanalization, all arteries were stented, and all of the patients were followed-up at 1, 3, 6, and 12 months after surgery and annually thereafter. Results Successful recanalization of the SA was achieved in 46 patients (82.1%), and the complication rate was 7.1%. During follow-up (mean 40 ± 26 months; range 2 to 125), the primary patency rates after 1 and 3 years were 97.9% and 82.7%, respectively. At the end of follow-up, 76% of the arteries showed no evidence of restenosis. Univariate analysis failed to identify any variable predictive of long-term patency of successfully recanalized SA. Conclusion Percutaneous transluminal angioplasty with stenting of the complete total occlusion of the SA is a safe and effective procedure associated with low risks and good long-term results.

The study aims to determine the trust and presence of police officers in schools in Serbia, as well as the perception of the principals and secretaries, teachers and staff, parents, and students on how successful the specific police units dedicated to schools were in fulfilling their tasks. The ex-post analysis was conducted through PEST/SWAT analysis, mapping the key actors and using batteries of online questionnaires, besides interviews with the MOI representatives, surveyed with personal interviewing, computer-aided surveying, desk analysis, and content analysis. The survey was conducted from September 2021 to June 2022. The research methods were implemented in 1140 schools in Serbia, and 8,617 people were included in surveys: police officers (308); principals and secretaries (1085); the team for protection against discrimination (982); teachers and staff (2988); parents (938) and students (2316). The relationships between the covariates and perception were investigated using the t-test, one-way ANOVA, multivariate linear regression, and binary regression. The results showed that a project of school police officers was not fully recognized as one of the strategically essential instruments for safe schools; trust is low, but presence is high. Besides that, the results suggest that the entire public believes that police are needed in schools and that it positively affects school safety. Regarding school safety policy, it is necessary to undertake three measures for the sustainable development of trust and the presence of police in school: regulatory, informative-educational, and institutional-organizational.