Scurvy

Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to perios-teal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socio-economic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Here-in, we present an illustrative case of scurvy in order to raise the awareness of this disorder

Scurvy

Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to perios-teal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socio-economic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Here-in, we present an illustrative case of scurvy in order to raise the awareness of this disorder

NUTRITIVNI ZBROJ (CONTROLLING NUTRITIONAL STATUS - CONUT) MOŽE PREDVIDJETI PREŽIVLJENJE BOLESNIKA NA HEMODIJALIZI

Malnutrition causes substantial morbidity in maintenance hemodialysis (HD) patients. The Controlling Nutritional Status (CONUT) has emerged as a simple and an easily obtainable tool to comprehensively assess nutrition as it consists of serum albumin levels, absolute lymphocyte counts, and total cholesterol levels. The CONUT has been shown to predict overall survival (OS) in peritoneal dialysis patients. This study investigated whether CONUT might also predict OS in maintenance HD patients. Clinical and laboratory data were retrospectively collected. Survival time was calculated from the fi rst HD until death or last follow-up; survival analyses were performed using the methods of Kaplan-Meier and Cox regression analysis. Eighty-nine patients were included; mean age was 65.76 years (±14), 35 (39.3%) were female, and the mean CONUT was 3. Higher CONUT score correlated with lower low-density liproprotein, higher serum creatinine, higher serum C-reactive protein and higher neutrophil-to-lymphocyte ratio, as well as with a higher incidence of nephrotic proteinuria (p<0.050 for all analyses). Univariately, patients with higher CONUT (≥5) had an inferior OS (median 54 vs. 112 months, HR 2.27; p=0.013). In the Cox regression analysis, higher CONUT remained independently associated with inferior OS (HR 9.50; p=0.002) when adjusted to age, sex, diabetes mellitus and nephrotic proteinuria. Therefore, the CONUT score might identify HD patients at an increased risk of death; however, future studies are needed to elucidate whether CONUT score might be able to guide nutritional support in HD patients.Pothranjenost uzrokuje značajan pobol i smrtnost bolesnika na hemodijalizi (HD). Controlling Nutritional Status (CONUT) je jednostavan nutritivni zbroj koji cjelovito procjenjuje uhranjenost, a sastoji se od serumske koncentracije albumina, apsolutnog broja limfocita i koncentracije serumskog kolesterola. Ova unicentrična retrospektivna studija analizirala je prediktivnu sposobnost zbroja CONUT da procijeni preživljenje bolesnika na HD. Ukupno preživljenje mjereno je kao vrijeme od prve HD do smrti ili posljednjeg pregleda bolesnika, a krivulje preživljenja uspoređene su Kaplan-Meirovom metodom, dok je Coxova regresijska metoda primijenjena u multivarijatnim analizama. Uključeno je 89 bolesnika, od toga 35 (39,3 %) žena; srednja dob bila je 65,76 godina (±14). Srednji zbroj CONUT bio je 3. Viši zbroj CONUT korelirao je s nižim koncentracijama serumskog lipoproteina niske gustoće, višim serumskim kreatininom, višim serumskim C-reaktivnim proteinom i višim omjerom neutrofi la/limfocita, kao i s većom učestalošću nefrotske proteinurije (p<0,050 za sve analize). U univarijatnoj analizi je viši zbroj CONUT (≥5) bio povezan s lošijim preživljenjem (medijan 54 prema 112 mjeseci, HR 2,27; p=0,013). U multivarijatnoj Coxovoj regresijskoj analizi je viši CONUT ostao nezavisno povezan s lošijim preživljenjem (HR 9,50; p=0,002) kada je bio ispravljen za dob, spol, šećernu bolest i nefrotsku proteinuriju. Zaključno, zbroj CONUT može identifi cirati bolesnike na HD s povišenim rizikom od smrti. Potrebne su dodatna istraživanja kako bi se analizirala sposobnost zbroja CONUT da usmjeri nutritivnu potporu u bolesnika na HD

Serum chitotriosidase: a circulating biomarker in polycythemia vera

Objectives: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs). ----- Methods: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls. ----- Results: CHIT1 was significantly higher in PV (p < .001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p = .020), but not in ET (p = .080), post-ET MF transformation (p = .086), and PMF patients (p = .287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p = .026), hematocrit (p = .012), absolute basophil count (p = .030) and the presence of reticulin fibrosis in the bone marrow (p = .023). ----- Discussion: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression. ----- Conclusion: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV

Glycoprotein YKL-40: a novel biomarker of chronic graftvs- host disease activity and severity?

Aim To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. Methods This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician’s Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. Results YKL-40 levels were significantly higher in cGVHD patients than in controls (P = 0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P = 0.017). YKL-40 level significantly positively correlated with disease severity (P < 0.001; correlation coefficient 0.455), and activity estimated using Clinician’s Impression of Activity (P = 0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P = 0.085; correlation coefficient 0.296). Conclusion YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD

FLUDARABINE, CYCLOPHOSPHAMIDE AND RITUXIMAB (FCR) IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): UNIVERSITY HOSPITAL CENTRE ZAGREB EXPERIENCE

U kliničkim je studijama kombinacija fludarabina, ciklofosfamida i rituksimaba (FCR) pokazala odlične rezultate u liječenju bolesnika s kroničnom limfocitnom leukemijom (KLL) i postala zlatni standard u prvoj liniji liječenja takvih bolesnika bez znatnijih komorbiditeta. Cilj rada bio je ispitati terapijsku djelotvornost, toksičnost i provedivost ovog protokola u svakodnevnoj kliničkoj praksi. Retrospektivno su analizirani tijek i ishodi liječenja 43-oje bolesnika s KLL-om sa Zavoda za hematologiju Klinike za unutarnje bolesti Kliničkoga bolničkog centra Zagreb. Shema primjene rituksimaba razlikovala se od one u kliničkim studijama; primjenjivan je infuzijski u dozi od 375 mg/m2 u svim ciklusima, u ukupno osam doza u prvoj, odnosno šest u kasnijim linijama liječenja. Na liječenje je odgovorilo 95% bolesnika, a 83% postignulo je kompletnu remisiju. Trogodišnje preživljenje i preživljenje bez progresije bolesti u prvoj liniji liječenja (29 bolesnika) bilo je 90 i 80%, a u kasnijim linijama 86 i 62%. Teške neutropenije zabilježene su u 46% bolesnika, a teške infekcije u 9% bolesnika. Ishodi liječenja i toksični profil u svakodnevnome kliničkom radu usporedivi su s onima iz kliničkih studijaIn clinical trials the combination of fludarabine, cyclophosphamide and rituximab (FCR) demonstrated superior results and became the gold standard for first-line treatment of fit patients with chronic lymphocytic leukemia (CLL). The aim of this study was to evaluate the efficacy, toxicity and feasibility of this protocol in everyday clinical practice. We ­retrospectively analyzed the outcomes of 43 CLL patients treated at the Division of Haematology, Department of Internal Medicine, University Hospital Centre Zagreb. The dosing of rituximab differed from that in clinical trials, we administered 375mg/m2 of rituximab per cycle, in previously untreated patients for eight and in relapsed/refractory patients for six cycles. The response rate was 95% with 83% of complete remissions. Twenty–nine patients received FCR as a front–line therapy; three-year overall and progression–free survival were 90% and 80%, respectively. In relapsed/refractory disease three–year overall and progression–free survival were 86% and 62%, respectively. Severe neutropenias occurred in 46% and serious infections in 9% of patients. According to these results, the toxicity profile and treatment outcomes in everyday routine clinical practice are similar to those reported in clinical trials

Fludarabin, ciklofosfamid i rituksimab (FCR) u liječenju bolesnika s kroničnom limfocitnom leukemijom (KLL): iskustvo Kliničkoga bolničkog centra Zagreb [Fludarabine, cyclophosphamide and rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL): University Hospital Centre Zagreb experience]

In clinical trials the combination of fludarabine, cyclophosphamide and rituximab (FCR) demonstrated superior results and became the gold standard for first-line treatment of fit patients with chronic lymphocytic leukemia (CLL). The aim of this study was to evaluate the efficacy, toxicity and feasibility of this protocol in everyday clinical practice. We ­retrospectively analyzed the outcomes of 43 CLL patients treated at the Division of Haematology, Department of Internal Medicine, University Hospital Centre Zagreb. The dosing of rituximab differed from that in clinical trials, we administered 375mg/m2 of rituximab per cycle, in previously untreated patients for eight and in relapsed/refractory patients for six cycles. The response rate was 95% with 83% of complete remissions. Twenty–nine patients received FCR as a front–line therapy; three-year overall and progression–free survival were 90% and 80%, respectively. In relapsed/refractory disease three–year overall and progression–free survival were 86% and 62%, respectively. Severe neutropenias occurred in 46% and serious infections in 9% of patients. According to these results, the toxicity profile and treatment outcomes in everyday routine clinical practice are similar to those reported in clinical trials

FLUDARABINE, CYCLOPHOSPHAMIDE AND RITUXIMAB (FCR) IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): UNIVERSITY HOSPITAL CENTRE ZAGREB EXPERIENCE

U kliničkim je studijama kombinacija fludarabina, ciklofosfamida i rituksimaba (FCR) pokazala odlične rezultate u liječenju bolesnika s kroničnom limfocitnom leukemijom (KLL) i postala zlatni standard u prvoj liniji liječenja takvih bolesnika bez znatnijih komorbiditeta. Cilj rada bio je ispitati terapijsku djelotvornost, toksičnost i provedivost ovog protokola u svakodnevnoj kliničkoj praksi. Retrospektivno su analizirani tijek i ishodi liječenja 43-oje bolesnika s KLL-om sa Zavoda za hematologiju Klinike za unutarnje bolesti Kliničkoga bolničkog centra Zagreb. Shema primjene rituksimaba razlikovala se od one u kliničkim studijama; primjenjivan je infuzijski u dozi od 375 mg/m2 u svim ciklusima, u ukupno osam doza u prvoj, odnosno šest u kasnijim linijama liječenja. Na liječenje je odgovorilo 95% bolesnika, a 83% postignulo je kompletnu remisiju. Trogodišnje preživljenje i preživljenje bez progresije bolesti u prvoj liniji liječenja (29 bolesnika) bilo je 90 i 80%, a u kasnijim linijama 86 i 62%. Teške neutropenije zabilježene su u 46% bolesnika, a teške infekcije u 9% bolesnika. Ishodi liječenja i toksični profil u svakodnevnome kliničkom radu usporedivi su s onima iz kliničkih studijaIn clinical trials the combination of fludarabine, cyclophosphamide and rituximab (FCR) demonstrated superior results and became the gold standard for first-line treatment of fit patients with chronic lymphocytic leukemia (CLL). The aim of this study was to evaluate the efficacy, toxicity and feasibility of this protocol in everyday clinical practice. We ­retrospectively analyzed the outcomes of 43 CLL patients treated at the Division of Haematology, Department of Internal Medicine, University Hospital Centre Zagreb. The dosing of rituximab differed from that in clinical trials, we administered 375mg/m2 of rituximab per cycle, in previously untreated patients for eight and in relapsed/refractory patients for six cycles. The response rate was 95% with 83% of complete remissions. Twenty–nine patients received FCR as a front–line therapy; three-year overall and progression–free survival were 90% and 80%, respectively. In relapsed/refractory disease three–year overall and progression–free survival were 86% and 62%, respectively. Severe neutropenias occurred in 46% and serious infections in 9% of patients. According to these results, the toxicity profile and treatment outcomes in everyday routine clinical practice are similar to those reported in clinical trials