Search

Purpose: Dose-adjusted EPOCH and rituximab (DA- EPOCH-R) is a regimen used for the treatment of high-risk diffuse large B-cell lymphoma (DLBCL) designed to overcome resistance to standard R-CHOP by combining prolonged exposure of lymphoma cells to cytotoxic agents and dose-adjustment based on toxicity. Data on outcomes of older patients are scarce. Patients and Methods: We collected data on patients with newly diagnosed high-risk DLBCL older than 60 years treated with DA-EPOCH-R. High-risk patients were defined by the age-adjusted international prognostic index score 2 or 3. Results: A total of 120 patients were included. Median age was 69 years (range 60–82). Response rate was 74% ; with 59% complete responses. Dose of DA-EPOCH-R was escalated in 50 patients (42%). Three-year progression-free survival (PFS) and overall survival (OS) was 53% and 58%, respectively, with treatment-related mortality (TRM) of 13%. In univariate analysis, favorable prognostic factors were performance status (PS) (0–2 vs. 3– 4), age (

U ovom su radu prikazane KROHEM-ove smjernice za liječenje akutne mijeloične leukemije u bolesnika koji nisu podobni za intenzivno kemoterapijsko liječenje.

Hodgkinova/Reed Sternbergova stanica je stanica porijekla B limfocita i kompleksnim interakcijama sa svojim okolišem odgovorna je za biološke i kliničke efekte bolesti. HRS stanice obično nemaju izražen B-stanični receptor (BcR). Normalne stanice germinativnog centra limfnog čvora koje nemaju izražen ovaj receptor eliminiraju se preko apoptotičkog puta ovisnog o Fas. Smatra se da je za rezistenciju HRS stanice na Fas posredovanu apoptozu odgovoran c- FLIP protein. Iako je patogeneza Hodgkinovog limfoma, a time i mehanizmi preživljavanja Reed Sternbergove stanice već dugo istraživana, postoji malo relevantnih radova o utjecaju Fas i FasL proteina na klinički tijek i prognozu bolesti. Korelacijom između imunohistokemijske ekspresije markera apoptoze i laboratorijsko-kliničkih parametara koji sačinjavaju poznate prognostičke indekse (EORTC/GHSG, IPS) u našoj kohorti bolesnika utvrdili smo po prvi puta da bolesnici s jačom ekspresijom c-FLIP proteina na HRS stanici imaju značajno češće limfopeniju te da je jaka ekspresija c-FLIP-a povezana s podtipom nodularne skleroze, koji je i najčešći histološki tip Hodgkinovog limfoma. No, c-FLIP ekspresija nije bila povezana s prognostički nepovoljnom skupinom bolesnika prema GHSG, EORTC i IPS skorovima. FasL ekspresija nije bila povezana s prognostički nepovoljnom skupinom bolesnika prema GHSG, EORTC skorovima, ali je bila povezana s prognostički povoljnom podgrupom bolesnika prema IPS skoru. Također, jača ekspresija FasL povezana je sa značajno nižom učestalošću anemije. Usporedbom ekspresije Fas, FasL i c-FLIP s ostalim kliničkim karakteristikama bolesnika i njihove bolesti nismo utvrdili statistički značajne korelacije. Nije bilo utjecaja jačine ekspresije navedenih proteina, pa ni c- FLIP-a na ukupno preživljenje ili vrijeme do progresije bolesti., Hodgkin/Reed Sternberg cell is a cell of lymphocyte B origin and due to its complex interactions with its microenvironment, is responsible for biological and clinical manifestations of Hodgkin lymphoma. HRS cells usually lack B-cell receptor (BcR). Normal lymph node cells without BcR undergo Fas (CD95)-mediated apoptosis. Mechanisms of HRS cell survival, although explored, have not been truly elucidated yet. It is believed that c-FLIP mediates resistance of HRS to Fasmediated apoptosis. Correlation between immunohistochemical expression of apoptosis markers and clinical and laboratory parameters integrated in standardized prognostic indexes (EORTC/GHSG/IPS) in our study cohort showed for the first time that patients with stronger c- FLIP expression had significantly more lymphopenias. Also, expression of c-FLIP showed strong correlation to nodular sclerosis subtype, which is the most common histologic type of Hodgkin lymphoma. C-FLIP expression did not correlate with unfavourable prognosis according to GHSG, EORTC and IPS. There were significantlly less patients with unfavourable IPS score in group of patients with stronger FasL expression. Also, patients with stronger FasL expression had significantly less anemia compared to those without it. Comparison of Fas, FasL and c-FLIP expression with other clinical and laboratory parameters did not show any statistically significant correlations. Expression of any of these proteins did not show influence on overall survival or time to disease progression in our study cohort.

AIM: A single center experience with laparoscopic splenectomy (LS) in the treatmen t of immune thrombocytopenia (ITP) is presented in this paper. In addition, we discuss the role of splenectomy in the era of thrombopoietin receptor agonists (TPO-RAs). ----- PATIENTS AND METHODS: In this retrospective study, we present our 35 patients who underwent LS in the period of 12 years. There were 26 women and nine men with a median age of 50 years (ranging from 19 to 85 years). Prior to LS, all patients were treated with glucocorticoids +/- intravenous immunoglobulins (IVIG), whereas seven patients received also rituximab. The median time to splenectomy was seven months (ranging from one to 103 months). ----- RESULTS: Four (11%) patients failed to reach response after LS, and additional six patients relapsed during the follow up. After a median follow up of 33 months, the remaining 25 (71%) patients required no further treatment. The estimated sustained response rate at fi ve years was 59%. Patients who underwent splenectomy in the fi rst year after the diagnosis had better outcome when compared to patients with delayed splenectomy (P= 0.048). Sex and age did not infl uence the treatment outcome. Four patients had early serious postoperative complications of LS: portal vein thrombosis, deep vein thrombosis of the leg, sepsis, and intraperitoneal bleeding that required surgical revision. There were no deaths, nor late serious infections. Ten (29%) patients reported fatigue after LS. ----- CONCLUSION: Long-term cure rate of about 60% is comparable to other studies. However, we observed better response in patients who underwent splenectomy earlier. In our opinion, LS may still be considered as a safe, successful, and cost-effective second-line treatment of ITP, especially in patients who are in favor of fast and highly curative treatment. Nevertheless, the introduction of TPO-RAs will inevitably decrease the role of LS in Croatia, as in the western world.

Sažetak. Cilj istraživanja: Prikazujemo vlastita iskustva s laparoskopskom splenektomijom (LS) u liječenju imunosne trombocitopenije (ITP), uz osvrt na ulogu splenektomije u kontekstu primjene agonista trombopoetinskih receptora (TPO-RA). Ispitanici i metode: U ovoj retrospektivnoj studiji prikazujemo rezultate liječenja 35 bolesnika operiranih tijekom razdoblja od 12 godina. Splenektomirano je 26 žena i 9 muškaraca s medijanom dobi od 50 godina (u rasponu između 19 i 85 godina). Svi su bolesnici prije splenektomije liječeni glukokortikoidima s dodatkom intravenskih imunoglobulina ili bez njih, a sedam bolesnika dobivalo je i rituksimab. Medijan vremena od postavljanja dijagnoze do LS-a jest sedam mjeseci (raspon od 1 do 103 mjeseca). Rezultati: U četiri (11%) bolesnika nije se povećao broj trombocita nakon LS-a, a šest ih je u kasnijem praćenju doživjelo recidiv bolesti. Tijekom praćenja (medijan 33 mjeseca) preostalih 25 bolesnika (71%) nije trebalo nikakvo daljnje liječenje. Procijenjena stopa petogodišnjeg odgovora iznosi 59%. Bolji dugotrajni odgovor imali su bolesnici splenektomirani do 12 mjeseci od postavljanja dijagnoze u odnosu prema onima kod kojih se sa splenektomijom čekalo dulje (P = 0,048). Nije bilo razlike u ishodu s obzirom na dob i spol. Četiri bolesnika imala su rane teške postoperativne komplikacije: trombozu portalne vene, duboku vensku trombozu, sepsu i krvarenje koje je nalagalo reviziju. Nije bilo letalnih ishoda ni kasnih teških infekcija. Na umor nakon operacije žalilo se deset (29%) bolesnika. Zaključci: Stopa izlječenja od oko 60% odgovara do sada objavljenim studijama, s time da je opažen bolji dugotrajni odgovor ako je splenektomija učinjena prije. Smatramo da je LS i dalje sigurna, uspješna i financijski povoljna druga linija liječenja ITP-a, posebno za bolesnike koji žele brzo i u velikom postotku trajno izlječenje. Međutim, kao i u svijetu, primjena TPO-RA zasigurno će smanjiti broj splenektomija u Hrvatskoj., Summary. Aim: A single center experience with laparoscopic splenectomy (LS) in the treatment of immune thrombocytopenia (ITP) is presented in this paper. In addition, we discuss the role of splenectomy in the era of thrombopoietin receptor agonists (TPO-RAs). Patients and methods: In this retrospective study, we present our 35 patients who underwent LS in the period of 12 years. There were 26 women and nine men with a median age of 50 years (ranging from 19 to 85 years). Prior to LS, all patients were treated with glucocorticoids +/- intravenous immunoglobulins (IVIG), whereas seven patients received also rituximab. The median time to splenectomy was seven months (ranging from one to 103 months). Results: Four (11%) patients failed to reach response after LS, and additional six patients relapsed during the follow up. After a median follow up of 33 months, the remaining 25 (71%) patients required no further treatment. The estimated sustained response rate at five years was 59%. Patients who underwent splenectomy in the first year after the diagnosis had better outcome when compared to patients with delayed splenectomy (P= 0.048). Sex and age did not influence the treatment outcome. Four patients had early serious postoperative complications of LS: portal vein thrombosis, deep vein thrombosis of the leg, sepsis, and intraperitoneal bleeding that required surgical revision. There were no deaths, nor late serious infections. Ten (29%) patients reported fatigue after LS. Conclusions: Long-term cure rate of about 60% is comparable to other studies. However, we observed better response in patients who underwent splenectomy earlier. In our opinion, LS may still be considered as a safe, successful, and cost-effective second-line treatment of ITP, especially in patients who are in favor of fast and highly curative treatment. Nevertheless, the introduction of TPO-RAs will inevitably decrease the role of LS in Croatia, as in the western world.

Ovom studijom pokazano je da određene morfološke značajke, posebno izgled megakariocita, mogu predvidjeti mutacijski status bolesnika s ET.

AIM. In this study we presented our experience with peripherally inserted central venous catheter (PICC) in patients with hematological malignancies. ----- METHODS In the period from 2009 to 2012, a total of 105 PICCs were inserted in 90 patients. Patients with Non-Hodgkin lymphoma treated with DA-EPOCH comprised almost 40% of the cohort. ----- RESULTS The total PICC in-dwell time was 14781 days with a median of 129 days (range 8-570 days). Malposition of the PICC occurred in 12 patients (11.4%) with a successful reposition or re-insertion. In 39 patients (37%) PICC was removed before the end of treatment due to suspected or proven infection (30 patients, 29%; 2.03 per 1000 PICC days), thrombosis associated with PICC in four patients (3.8%), occlusion of the PICC (two patients), misplaced catheter (two patients), and suspected thromboembolism in a single patient. ----- CONCLUSION PICC is a safe and convenient long-term venous access in patients with hematological malignancies.

Cilj: Analiza 1849G>T mutacije u JAK2 (kodira za JAK2V617F) dio je rutinske dijagnostike MPN. Kvantifikacija mutiranog alela sve se više koristi za praćenje odgovora na terapiju. Iz krvi 10 bolesnika izolirana je DNA. Metodom kvantitativnog PCR određen je postotak JAK2 V617F alela: 7 bolesnika s razvijenim PMF (29-85%), 2 prefibrotička PMF bolesnika (40-67%), 1 bolesnik sa sekundarnim PMF iz PV (49%.

Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown ; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

Bolesniku je pred 13 godina postavljena dijagnoza JAK2+ ET te je liječen hidroksiurejom. Prilikom redovite kontrole verificira se leukocitoza te se molekularno genetičkim pretragama dokazuje prisutnost Bcr/abl p210 transkripta izotipa b3a2.

Pregledani rad o patofiziologiji, kliničkim obilježjima, dijagnostici i liječenju kronične limfocitne leukemije.

In this report we presented 22 patients with high risk diffuse large B-cell lymphoma. Our results showed that DA-EPOCH-R is highly effective regimen in this group of patients. These results are conclusive with results of Garcia-Suarez and colleagues (Garcia-Suarez J et al. British journal of Haematology 2007 ; 136:276-285) who also find this regimen effective as first line treatment in DLBCL patients. Some of our patients were consolidated with autoHSCT due to high proliferation index or IPI≥3. Only 1 patient relapsed during follow up period. Of 6 patients who were transplated, all but one are still in CR. We conclude that DA-EPOCH-R is highly effective regimen as first line treatment in high risk diffuse large B-cell lymphoma.

Prikaz slučaja difuzne hiperpigmentacije kože kod bolesnika sa CD30+ limfoproliferativnom bolešću.

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted.

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted.

The aims of this study were to determine contentment of diabetic patients with mediterranean diet, and to compare expenses of mediterranean diet and standard diabetic diet. 90 adult patients (61% males and 39% females, age 33-71) with type 2 diabetes mellitus who were hospitalized due to regulation of glycaemia entered the study.50 patients were supplied with mediterranean diet and 40 patients with standard diabetic diet. Patients were controlled in the outpatient ambulance 6 months after hospitalization. After six months patients filled out poll about nutritional habits again and poll showed that 68% of patients who were supplied with mediterranean diet followed diet from hospital experience and 44% of patients who were on standard diabetic diet during the hospitalization followed the diet from hospital experience. Mediterranean diet has beneficial effect on regulation of glycemia in patients with diabetes mellitus.

Aim: To evaluate self-assessed level of clinical skills of graduating medical students at Zagreb University School of Medicine and compare them with clinical skill levels expected by their teachers and those defined by a criterion standard. Method: The study included all medical students (n = 252) graduating from the Zagreb University School of Medicine in the 2004-2005 academic year and faculty members (n = 129) involved in teaching clinical skills. The participants completed anonymous questionnaire listing 99 clinical skills divided into nine groups. Students were asked to assess their clinical skills on a 0-5 scale, and faculty members were asked to assess the minimum necessary level of clinical skills expected from graduating medical students, using the same 0-5 scale. We compared the assessment scores of faculty members with students’ self-assessment scores. Participants were grouped according to their descriptive characteristics for further comparison. Results: The response rate was 91% for students and 70% for faculty members. Students’ self-assessment scores in all nine groups of clinical skills ranged from 2.2 ± 0.8 to 3.8 ± 0.5 and were lower than those defined by the criterion standard (3.0-4.0) and those expected by teachers (from 3.1 ± 1.0 to 4.4 ± 0.5) (P