Primarni limfomi središnjeg živčanog sustava

Primary central nervous system lymphoma (PCNSL) is a distinct form of aggressive non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. PCNSL typically affects older population. Individuals with HIV infection are especially at risk of PCNSL development and their outcome is extremely poor. Due to the presence of the blood brain barrier, PCNSL is treated differently from other extranodal NHLs. The mainstay of treatment is the high-dose methotrexate (MTX). Despite the treatment, local relapses are frequent and almost inevitably fatal. Intensification of treatment is possible in patients younger than 60 years. Radiotherapy is effective but complicated with significant delayed neurotoxicity, especially in the elderly. There are no curative treatment options in older patients who represent the majority of patients. Novel less toxic agents have modest activity. Prospective multicentric trials are needed to establish the optimal treatment for PCNSL.Primarni limfom središnjeg živčanog sustava (PLSZŠ) je poseban oblik agresivnog ne-Hodgkinovog limfoma (NHL) lokaliziran u središnjem živčanom sustavu. PLSZŠ tipično zahvaća stariju populaciju. Za razvoj PLSZŠ-a posebno su rizične osobe s HIV infekcijom čija je prognoza ekstremno loša. Zbog krvno-moždane barijere, PLSZŠ se liječi drugačije od ostalih ekstranodalnih NHL. Temelj liječenja su visoke doze metotreksata. Unatoč liječenju, lokalni relapsi su česti i gotovo uvijek fatalni. Radioterapija je učinkovita, ali komplicirana značajnom kasnom neurotoksičnosti, posebno u starijih. U starijih bolesnika, koji čine većinu, nema terapijskih opcija koje bi dovele do izlječenja. Noviji, manje toksični lijekovi, skromnog su djelovanja. Potrebne su prospektivne multicentrične studije kako bi se definiralo optimalno liječenje PLSZŠ-a

Causes of thrombocytopenia in COVID-19 patients

Trombocitopenija je česta u virusnim infekcijama, prisutna je u prosječno 18 % oboljelih od bolesti COVID-19, a obično je blaga (u rasponu od 100 do 150 × 10^9/L). Zastupljenija je među teže oboljelima i predstavlja neovisan čimbenik rizika za loš ishod i mortalitet. Trombocitopenija je rezultat smanjene proizvodnje i povećane potrošnje trombocita. Smanjenje proizvodnje trombocita može nastati zbog oštećenja hematopoetskih progenitora te zbog oštećenja kapilarne mreže pluća. Povećana je potrošnja trombocita zbog njihove hiperaktivacije i trombotske mikroangiopatije kod kritično bolesnih. U bolesti COVID-19 rjeđe se može razviti i imuna trombocitopenija (ITP) te trombocitopenija uzrokovana različitim lijekovima, uključujući i trombocitopeniju uzrokovanu heparinom (HIT).Thrombocytopenia is frequent in viral infections. Approximately 18% of COVID-19 patients have thrombocytopenia that is usually mild (ranging from 100 to 150 × 10^9/L). It is more common among critically ill whereby it is an independent risk factor for poor outcome and mortality. Both decreased production and increased consumption of platelets may contribute. Decreased platelet production may occur due to a damage to hematopoietic progenitors and capillary network of the lungs. The consumption of platelets is increased due to their hyperactivation and thrombotic microangiopathy. Immune thrombocytopenia (ITP) and drug-induced thrombocytopenia including heparin-induced thrombocytopenia (HIT) can also develop during COVID-19 treatment

Metabolični sindrom i ishod u bolesnika s akutnim infarktom miokarda

The impact of the metabolic syndrome/insulin resistance syndrome (MS/IR S) on the severity and prognosis of acute ST elevation myocardial infarction (STEMI ) treated with primary percutaneous coronary intervention (PCI) was assessed using the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) definition from 2003. A total of 385 patients having suffered acute STEMI and treated with primary PCI over a two-year period were divided into two groups (with and without MS/IR S) and compared according to the parameters of severity (clinical, laboratory, echocardiography, coronary angiography parameters and complications) and prognosis using major adverse cardiovascular events (MACE) during the six-month follow-up of acute STEMI . In comparison with control group, the MS/IR S group of patients had worse or similar results of almost all study parameters of severity (hospital days 6.5 vs. 6.5, cardiogenic shock 2.9% vs. 2.6%, cardiac arrest 6.8% vs. 5.2%, reinfarction 0.5 vs. 1.6%) and prognosis (total MACE 30.7 vs. 30.7%), however, none of the differences reached statistical significance. It is concluded that the unexpected lack of such differences in MS/IR S could be due to the absence of waist-to-hip ratio in the definition and other open questions in metabolic syndrome in general.Istraživao se utjecaj metaboličnog sindroma/sindroma inzulinske rezistencije (MS/SIR ) koristeći definiciju American Association of Clinical Endocrinologists i American College of Endocrinology (AACE/ACE) iz 2003. na težinu i prognozu akutnog infarkta miokarda s elevacijom ST spojnice (STEMI ) liječenog primarnom perkutanom intervencijom (pPCI). Ukupno 395 bolesnika koji su preboljeli akutni STEMI i bili liječeni pomoću pPCI u dvogodišnjem razdoblju podijeljeno je u dvije skupine (s MS/SIR i bez njih) i uspoređeno prema parametrima težine (klinički, laboratorijski, ehokardiografski, koronarografski, komplikacije) i prognoze koristeći velike neželjene kardiovaskularne događaje (MACE) tijekom šestomjesečnog praćenja akutnog STEMI . Skupina bolesnika s MS/SIR u usporedbi s kontrolnom skupinom imala je uglavnom lošije ili jednake rezultate težine (dani u bolnici 6,5:6,5, kardiogeni šok 2,9%:2,6%, srčani zastoj 6,8%:5,2%, reinfarkt 0,5%:1,6%) i prognoze (ukupno MACE 30,7%:30,7%), no niti jedna od razlika nije dosegla statističku značajnost. Zaključuje se kako bi izostanak takvih očekivanih razlika u MS/SIR mogao biti posljedica isključenja omjera struka i kukova iz ove definicije i ostalih otvorenih pitanja u metaboličnom sindromu uopće

Biometrija sagitalnih otolita tri pridnene vrste riba istočnog Jadrana (Crna Gora)

The otolith morphology, biometry and otolith size and fish length relationship of three demersal fish species: red mullet Mullus barbatus, common pandora Pagellus erythrinus and hake Merluccius merluccius were examined. Based on otoliths relative sizes P. erythrinus and M. merluccius have Large otoliths, while M. barbatus has Small sagittal otoliths. The relationships between otolith variables and fish somatic growth were described by a linear function. All relationships were statistically highly significant (p<0.001). Otolith length (OL) was found to be the variable most strongly related to fish size, with 61.2 – 95.3 % of the variability, while otolith weight had the lowest coefficient of determination (r2). No differences were found neither between left and right otoliths, nor between male and female otoliths in these relationships. For all species studied the relationships of otolith length, height and weight against total fish length were all found to have positive allometry, indicating that the accretion of otoliths is relatively faster than increase in fish body size. The shape indices of form factor (FF), roundness (RD), aspect ratio (AR), circularity (C), rectangularity (R) and ellipticity (E) were calculated and the relationships between otolith length (OL) and shape indices were determined.Ispitana je morfologija otolita, biometrija i odnos veličine otolita i duljine tri pridnene vrste riba: trlja Mullus barbatus, arbun Pagellus erythrinus i oslić Merluccius merluccius. Na temelju relativnih veličina otolita P. erythrinus i M. merluccius imaju velike otolite, dok M. barbatus ima male sagitalne otolite. Odnosi između varijabli otolita i somatskog rasta riba opisani su linearnom funkcijom. Svi odnosi bili su statistički visoko značajni (p<0,001). Utvrđeno je da je duljina otolita (OL) pokazuje najveću povezanost s veličinom ribe, sa 61,2 – 95,3 % varijabilnosti, dok je masa otolita imala najniži koeficijent determinacije (r2). Nisu pronađene razlike ni između lijevog i desnog otolita, niti između muških i ženskih otolita u tim odnosima. Za sve proučavane vrste utvrđeno je da odnosi duljine, visine i mase otolita u odnosu na ukupnu duljinu ribe imaju pozitivnu alometriju, što ukazuje da je nakupljanje otolita relativno brže od povećanja duljine tijela ribe. Izračunati su indeksi oblika faktora forme (FF), zaobljenosti (RD), omjera stranica (AR), kružnosti (C), pravokutnosti (R) i eliptičnosti (E) te su izračunati odnosi između duljine otolita (OL) i indeksa oblika

The degree of anisocytosis predicts survival in patients with primary myelofibrosis

Introduction: Red cell distribution width (RDW) provides a quantitative measure of anisocytosis and it is associated with the presence of subclinical systemic inflammation and a poor outcome in a variety of diseases when elevated. Anisocytosis is a feature of primary myelofibrosis (PMF) but it’s prognostic role in PMF has not yet been evaluated. ----- Patients and methods: 33 newly-diagnosed patients with PMF were analyzed. Baseline RDW values were obtained in addition to CRP, LDH, complete blood count, iron metabolism parameters and JAK2 V617F mutational status. Patients were staged according to IPSS prognostic scoring system, liver and spleen size were assessed by palpation. ----- Results: Median RDW was 19.0% (15.2%-22.5%). RDW correlated significantly with hemoglobin level (p=0.005), CRP (p=0.031), spleen size (p=0.036) and IPSS score (p=0.003). Patients with more pronounced anisocytosis had an inferior overall survival (OS) – very-high RDW (≥19.0%) vs. high RDW (15.1%-18.9%) subgroup, HR 5.37, p=0.002. RDW remained significantly associated with OS (p=0.002) in a multivariate model including IPSS score, hemoglobin level and CRP. ----- Conclusion: A higher degree of anisocytosis is associated with more advanced disease features and a decreased overall survival. RDW encompasses standard prognostic score and may help in the rapid detection of patients with an unfavorable prognosis

Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome

OBJECTIVES: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS. ----- METHODS: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene. ----- RESULTS: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P = 0.039) and lower TIBC (P = 0.018). Ferritin was found to be higher for the untransfused mutated patients (P = 0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P = 0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P = 0.004 and P = 0.003, respectively). ----- DISCUSSION: The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism. ----- CONCLUSION: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options