Zaburzenia krzepnięcia spowodowane przewlekłym zatruciem rodentycydami antykoagulacyjnymi — opis przypadku i przegląd piśmiennictwa

Anticoagulant rodenticides are a group of substances used in rodent poisoning. Intake of these compounds can cause severe and life-threatening poisoning in humans. This article describes the case of patient with chronic hemorrhagic manifestations and a complex deficiency of coagulation factors caused by chronic rodenticide using.Rodentycydy antykoagulacyjne to grupa substancji stosowana do zwalczania gryzoni. Spożycie tych związków może być przyczyną ciężkich i groźnych dla życia zatruć u ludzi. Przedstawiamy przypadek pacjentki z objawami przewlekłej skazy krwotocznej i złożonym niedoborem czynników krzepnięcia, które związane były z długotrwałym stosowaniem rodentycydów

Nivolumab for relapsed/refractory classical Hodgkin lymphoma after brentuximab vedotin failure – Polish Lymphoma Research Group real-life experience

AimPolish centers analyzed retrospectively the real-life experience with nivolumab in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) patients, after brentuximab vedotin (BV ) failure. BackgroundDespite the effective frontline treatment, for cHL patients relapsing after autologous stem cell transplantation, the only effective strategy remains the novel agents. Nivolumab, a checkpoint inhibitor, demonstrates the clinical benefit with an acceptable safety profile. Materials and methodsRetrospective analysis included 16 adult patients with R/R cHL after BV failure. All patients received single-agent nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. ResultsAfter six cycles of nivolumab the overall response rate was 81% (complete remission rate of 56%, partial remission rate of 25%). The median PFS was not reached after a median follow-up of 19 months. Adverse events (AEs) of any grade occurred in 12 patients (75%), including grade 3 AEs observed in 5 patients (31%). There were no AEs of grade 4 or 5. After a median of 25 nivolumab doses, 62% of responding patients proceeded to allogeneic stem cell transplantation. ConclusionNivolumab monotherapy demonstrated a high efficacy and safety in R/R cHL patients after BV failure. More patients and longer follow-up may further establish the potential benefit

Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment

Karol Ludwik Koninski "The Dreadful Thursday in Pastor's House", "The Continuing Story of Pastor Hubina" - Introduction & Authoring by Justyna Rybka

Celem pracy jest przygotowanie edycji opowiadań Karola Ludwika Konińskiego "Straszny czwartek w domu pastora", "Dalsze losy pastora Hubiny" (dwóch z trzech planowanych opowiadań cyklu). Podstawę wydania stanowią: w przypadku pierwszego opowiadania – pierwodruk, który ukazał się za życia autora w 1939 roku; w przypadku drugiego opowiadania – maszynopis autorski o charakterze brulionowym, przechowywany w Oddziale Rękopisów Biblioteki Jagiellońskiej, z 1943 roku. „Dalsze losy pastora Hubiny” nie ukazały się za życia autora. W 1955 roku po raz pierwszy drukowano je wraz z „Strasznym czwartkiem...” w „Pismach wybranych” Karola Ludwika Konińskiego. Wydanie to zawierało jednak wiele błędów i pominięć.W edycji będącej przedmiotem pracy uwspółcześniono pisownię oraz interpunkcję K.L. Konińskiego, z zachowaniem charakterystycznych właściwości stylu pisarza. Tekst opowiadań opatrzono komentarzem, na który składają się: wyjaśnienie terminów specjalistycznych, słów nienotowanych przez współczesne słowniki języka polskiego, niektórych właściwości języka epoki, metaforyki stosowanej przez autora w całości jego pisarstwa; przybliżenie realiów; lokalizacja cytatów i parafraz; objaśnienie nawiązań filozoficznych; a także tłumaczenie fragmentów obcojęzycznych. Do podstawowego korpusu tekstów dołączono aneks z podyktowanym przez autora synowi opisem opowiadania mającego kończyć cykl.Wydanie poprzedza wstęp, w którym zawarto charakterystykę postulatów literackich i prozy artystycznej K.L. Konińskiego; dokładne przedstawienie genezy opowiadań będących przedmiotem edycji; wprowadzenie w ich kompozycję i problematykę; opis stosunku biografii autorskiej oraz sytuacji społeczno-historycznej do fabuły i problematyki tekstów; ukazano także, jak dotychczas przebiegała recepcja „Strasznego czwartku...” i „Dalszych losów...”.The purpose of this work is to prepare editions of Karol Ludwik Koniński stories “The Dreadful Thursday in Pastor's House” and “Pastor Hubina's Continuing Story” (two of three planned stories of the cycle). The basis for the edition are: In the first story – first printing which appeared during author's life in 1939; in the second story – rough copy author typescript from 1943, stored in the Manuscript Department of the Jagiellonian Library. “Pastor's Hubina Continuing Story” did not appear during Koniński's life. It was printed for the first time in 1955 in “Selected Works” along with “The Dreadful Thursday...”. This edition contained many mistakes and omissions.In the edition being the purpose of this work the vocabulary and punctuation of Koniński was modernised, maintaining the characteristic features of the author's style. The text was provided with comments which consist of: explanation of specialised vocabulary, words not present in contemporary dictionaries, some features of the language of the era, metaphors used by the author in his works; introducing the realities of the times; localisation of quotations and paraphrases; explanation of philosophical allusion; and translation of fragments in foreign languages. The basic text corpus was provided with an annex with a description of the last story from the cycle, dictated by the author to his son.The edition includes an introduction which contains a profile of literary postulates and artistic prose by Koniński; a detailed depiction of the genesis of the stories; introduction to their composition and problematic aspects; a description of the ratio between author's biography and socio-historical situation to the plot and text subject matters; it was also shown how was the reception of “The Dreadful Thursday...” and “The Continuing Story of Pastor Hubina”

Treatment of Hodgkin lymphoma relapse after autologous hematopoietic cell transplantation

Despite the high response rate to first-line treatment, approximately 10% of patients with Hodgkin lymphoma (HL) develop primary resistance to chemotherapy, and 10–30% of patients experience relapse. Today, salvage chemotherapy with subsequent autologous stem cell transplantation (ASCT) remains the standard of care for those patients with relapsed/refractory HL (RRHL). Treating patients with HL who relapse following ASCT continues to be a difficult clinical challenge. For many years, allogeneic hematopoietic stem cell transplantation was the only therapeutic option in this patient population. The last decade has brought new treatment options for RRHL patients with immunotherapy, including: brentuximab vedotin anti-CD30 monoclonal antibody, or the checkpoint inhibitors nivolumab and pembrolizumab, or advanced immune therapies such as bispecific antibodies, or chimeric antigen receptor T-cell therapy

Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases

The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases