Croco Eye Technique: Mucous Retention Cyst Excision with Immediate Open Sinus Lift-A Retrospective Cohort Study.

Objectives: A mucous retention cyst is a common, asymptomatic lesion that may cause complications during or after the sinus lift procedure. The goal of this study is to assess the effectiveness of the Croco Eye Technique (CET), which allows simultaneous excision of the cyst and sinus floor elevation. Methods: The technique was thoroughly described in two versions, and the group of 33 patients was analyzed. Patients who qualified for this procedure had insufficient alveolar ridge height, and their CBCT showed radiological images typical for retention cysts. Analyzed parameters included the version of CET, demographic data, anatomical parameters, intraoperative complications, recurrence of the cyst, success rate of the sinus lift and implants, and the follow-up period. Results: Out of the 33 cases, 9 were of the primary version (27.27%) and 24 of the final version (72.73%). The average height of a retention cyst was 24.05 mm, with the average alveolar ridge height of 1.86 mm. In three cases (9.09%), implants were placed immediately. The prevalence of uncontrolled Schneiderian membrane perforation was reduced from 55.56% to 4.17% between the primary and final versions. The cyst's recurrence rate was 3.13%. The implant survival rate was 100%. The mean follow-up period was 48.625 months (max 110 months). Conclusions: The Croco Eye Technique, despite the perforation of the Schneiderian membrane, enables successful sinus lift and implantation with a success rate of 100%. Excision of the retention cyst, which is the cause of perforation, allows for limiting the risk of the cyst's recurrence.

Mass Spectrometry-Based Assessment of M-protein in Peripheral Blood During Maintenance Therapy in Multiple Myeloma.

Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during post-transplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of post-transplant maintenance with either carfilzomib, lenalidomide, dexamethasone or lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in PB in the post-transplant setting, despite unavailability of pre-treatment calibration samples. There was high agreement between MRD by MS in PB and paired BM MRD results at the 10-5 threshold, assessed by either next generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which in landmark analysis reached statistical significance after 18 cycles post-transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared to MRD negativity by only one modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, post-transplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.

Mechanical and Material Analysis of 3D-Printed Temporary Materials for Implant Reconstructions-A Pilot Study.

In this study, the authors analyzed modern resin materials typically used for temporary reconstructions on implants and manufactured via 3D printing. Three broadly used resins: NextDent Denture 3D, NextDent C&B MFH Bleach, and Graphy TC-80DP were selected for analysis and compared to currently used acrylic materials and ABS-like resin. In order to achieve this, mechanical tests were conducted, starting with the static tensile test PN-EN. After the mechanical tests, analysis of the chemical composition was performed and images of the SEM microstructure were taken. Moreover, numerical simulations were conducted to create numerical models of materials and compare the accuracy with the tensile test. The parameters obtained in the computational environment enabled more than 98% correspondence between numerical and experimental charts, which constitutes an important step towards the further development of numeric methods in dentistry and prosthodontics.

Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial.

BACKGROUND: Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population. METHODS: This study is an interim analysis of ATLAS, which is an investigator-initiated, multicentre, open-label, randomised, phase 3 trial in 12 academic and clinical centres in the USA and Poland. Participants were aged 18 years or older with newly diagnosed multiple myeloma, completed any type of induction and had stable disease or better, autologous stem-cell transplantation within 100 days, initiated induction 12 months before enrolment, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) using permuted blocks of sizes 4 and 6 and a web-based system to receive up to 36 cycles of carfilzomib, lenalidomide, and dexamethasone (28-day cycles of carfilzomib 20 mg/m2 administered intravenously in cycle one on days 1 and 2 then 36 mg/m2 on days 1, 2, 8, 9, 15, and 16 in cycles one to four and 36 mg/m2 on days 1, 2, 15, and 16 from cycle five up to 36 [per protocol]; lenalidomide 25 mg administered orally on days 1-21; and dexamethasone 20 mg administered orally on days 1, 8, 15, and 22) or lenalidomide alone (10 mg administered orally for the first three cycles and then at the best tolerated dose [≤15 mg for 28 days in 28-day cycles]) until disease progression or unacceptable toxicity as maintenance therapy. After 36 cycles, patients in both treatment groups received lenalidomide maintenance. Randomisation was stratified by response to previous treatment, cytogenetic risk factors, and country. Investigators and patients were not masked to treatment allocation. Patients in the carfilzomib, lenalidomide, and dexamethasone group with no detectable minimal residual disease after cycle six (as per International Myeloma Working Group criteria) and standard-risk cytogenetics were switched to lenalidomide maintenance as of cycle nine. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all randomly assigned patients). Safety was analysed in all randomly assigned patients who received at least one dose of study treatment. This unplanned interim analysis was triggered by the occurrence of 59 (61%) of the expected 96 events for the primary analysis and the results are considered preliminary. This trial is registered with ClinicalTrials.gov, NCT02659293 (active, not recruiting) and EudraCT, 2015-002380-42. FINDINGS: Between June 10, 2016, and Oct 21, 2020, 180 patients were randomly assigned to receive either carfilzomib, lenalidomide, and dexamethasone (n=93) or lenalidomide alone (n=87; intention-to-treat population). The median age of patients was 59·0 years (IQR 49·0-63·0); 84 (47%) patients were female and 96 (53%) were male. With a median follow-up of 33·8 months (IQR 20·9-42·9), median progression-free survival was 59·1 months (95% CI 54·8-not estimable) in the carfilzomib, lenalidomide, and dexamethasone group versus 41·4 months (33·2-65·4) in the lenalidomide group (hazard ratio 0·51 [95% CI 0·31-0·86]; p=0·012). The most common grade 3 and 4 adverse events were neutropenia (44 [48%] in the carfilzomib, lenalidomide, and dexamethasone group vs 52 [60%] in the lenalidomide group), thrombocytopenia (12 [13%] vs six [7%]), and lower respiratory tract infections (seven [8%] vs one [1%]). Serious adverse events were reported in 28 (30%) patients in the carfilzomib, lenalidomide, and dexamethasone group and 19 (22%) in the lenalidomide group. One treatment-related adverse event led to death (respiratory failure due to severe pneumonia) in the carfilzomib, lenalidomide, and dexamethasone group. INTERPRETATION: This interim analysis provides support for considering carfilzomib, lenalidomide, and dexamethasone therapy in patients with newly diagnosed multiple myeloma who completed any induction regimen followed by autologous stem-cell transplantation, which requires confirmation after longer follow-up of this ongoing phase 3 trial. FUNDING: Amgen and Celgene (Bristol Myers Squibb).

Evaluation of biofilm formation on acrylic resins used to fabricate dental temporary restorations with the use of 3D printing technology.

BACKGROUND: Temporary implant-retained restorations are required to support function and esthetics of the masticatory system until the final restoration is completed and delivered. Acrylic resins are commonly used in prosthetic dentistry and lately they have been used in three-dimensional (3D) printing technology. Since this technology it is fairly new, the number of studies on their susceptibility to microbial adhesion is low. Restorations placed even for a short period of time may become the reservoir for microorganisms that may affect the peri-implant tissues and trigger inflammation endangering further procedures. The aim of the study was to test the biofilm formation on acrylamide resins used to fabricate temporary restorations in 3D printing technology and to assess if the post-processing impacts microbial adhesion. METHODS: Disk-shaped samples were manufactured using the 3D printing technique from three commercially available UV-curable resins consisting of acrylate and methacrylate oligomers with various time and inhibitors of polymerization (NextDent MFH bleach, NextDent 3D Plus, MazicD Temp). The tested samples were raw, polished and glazed. The ability to create biofilm by oral streptococci (S. mutans, S. sanguinis, S. oralis, S. mitis) was tested, as well as species with higher pathogenic potential: Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans. The roughness of the materials was measured by an atomic force microscope. Biofilm formation was assessed after 72 h of incubation by crystal violet staining with absorbance measurement, quantification of viable microorganisms, and imaging with a scanning electron microscope (SEM). RESULTS: Each tested species formed the biofilm on the samples of all three resins. Post-production processing resulted in reduced roughness parameters and biofilm abundance. Polishing and glazing reduced roughness parameters significantly in the NextDent resin group, while glazing alone caused significant surface smoothing in Mazic Temp. A thin layer of microbial biofilm covered glazed resin surfaces with a small number of microorganisms for all tested strains except S. oralis and S. epidermidis, while raw and polished surfaces were covered with a dense biofilm, rich in microorganisms. CONCLUSIONS: UV-curing acrylic resins used for fabricating temporary restorations in the 3D technology are the interim solution, but are susceptible to adhesion and biofilm formation by oral streptococci, staphylococci and Candida. Post-processing and particularly glazing process significantly reduce bacterial biofilm formation and the risk of failure of final restoration.

Electromyographic activity analysis of temporal and masseter muscles in psychoactive substance addicts. / Elektromiograficzna analiza czynnosci miesni zwaczy i skroniowych u osób uzaleznionych od substancji psychoaktywnych.

OBJECTIVES: As part of this study, a comparative analysis of the temporal and masseter muscle electrical activity at rest and during mandible excursion positions (protrusion, laterotrusion and maximal occlusion) was performed among patients aged 21 to 68 years. METHODS: Each of three groups: opioid addicts, alcohol addicts and the control group - consisted of 30 individuals (90 individuals in total, including 37 females and 53 males). Electrodes were placed on the masseter venters and mandibular movements were executed: right/left lateral, protrusion, intercuspation, rest and MVC. Then the same routine was applied to the anterior parts of temporal muscles. RESULTS: Based on EMG data in alcohol addicts, higher electrical activity of masseters and temporal muscles was observed during the mandible excursions, compared to the control group. In comparison of opiate addicts to healthy controls, no statistical significance was observed in electrical activity of masseter and temporal muscles. CONCLUSIONS: On the basis of the conducted research, a conclusion can be drawn that alcohol addiction significantly affects the function of the largest muscles of the stomatognathic system.

Evaluation of thromboelastometry parameters as predictive markers for sinusoidal obstruction syndrome in patients undergoing allogeneic stem cell transplantation for acute leukaemia.

Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied. We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence. ROTEM assays (INTEM, EXTEM, FIBTEM, APTEM) were performed on day -10, on the day of stem cell infusion (day 0) and on days +12 and +28 post-HSCT. The diagnosis of SOS/VOD was based on the Baltimore criteria. Seven patients (26%) developed SOS/VOD. On day +12, the patients with SOS/VOD had statistically significant longer INTEM-CT (clotting time, 199 ± 33.41vs166 ± 23.65s, p = 0.0033), EXTEM-CT (69.5 ± 6.39vs.52 ± 3.42s, p = 0.0139) and FIBTEM-CT (69.5 ± 22.75vs. 50.8 ± 14.31s, p = 0.0124) compared to SOS/VOD (-). ROC curve on day +12 indicated a cut-off value of 179s in INTEM-CT (AUC = 0.91), 69s in EXTEM-CT (AUC = 0.90) and 102s in FIBTEM-CT (AUC = 0.82) for the prediction of SOS/VOD. This is the first study evaluating the usefulness of ROTEM assays in the early detection of haemostasis abnormalities predictive of SOS/VOD development in patients undergoing HSCT for acute leukemia. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analysed ROTEM assays. The utility of ROTEM assays in the optimal management of patients undergoing HSCT should be clarified in further prospective studies.

Comparative proteomic profiling of sera from patients with refractory multiple myeloma reveals potential biomarkers predicting response to bortezomib-based therapy.

INTRODUCTION: In the era of implementing novel agents in multiple myeloma (MM) regimens, drug resistance has become a key factor undermining the results of treatment. Identifying biomarkers allows the prediction of therapy outcomes with specific agents and may lead to the avoidance of resistance. OBJECTIVES: This study aimed to identify biomarkers in the pretreatment sera of patients with refractory/ relapsed MM that differ from those in the sera of patients who achieved a better depth of response with bortezomib-containing therapy. PATIENTS AND METHODS: Pretreatment serum samples were obtained from 61 proteasome inhibitor-naive, transplant-eligible patients who were eligible for salvage PAD (bortezomib, doxorubicin, and dexamethasone) or VTD (bortezomib, thalidomide, and dexamethasone) chemotherapy. Based on their response to therapy, patients were classified into 3 groups: complete or very good partial response, partial response, and progressive or stable disease. A comparative proteomic analysis of the groups was performed. RESULTS: The analyzed groups significantly differed in terms of both overall survival and progression­free survival. In total, 632 proteins were identified. The proteomic signature revealed 54 proteins that differentiated each analyzed experimental group. Functional analysis revealed that the main identified pathways (17 proteins) involved the regulation of hydrolase activity and cellular response to stimuli. The identified proteins included apolipoprotein C1, complement components, and sulfhydryl oxidase 1. CONCLUSIONS: Our results demonstrated that the label-free proteomic analysis is a useful method for describing proteins differentially expressed in the sera of patients with MM. Further studies are needed to analyze the use of identified proteins as biomarkers.

Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy.

Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance.

Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma.

INTRODUCTION: Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation. OBJECTIVES: To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM. PATIENTS AND METHODS: A total of 30 patients (median age 57.5years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n=11) and those without thalidomide (B group, n=19) were analysed. RESULTS: During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5µM ADP (p=0.0285, day 1 versus 8); 3.5µM ADP (p=0.0005, day 1 versus 8 and day 1 versus 11), collagen (p=0.0014, day 4 versus 8, day 4 versus 11), 1.25mg/ml ristocetin (p=0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B. CONCLUSION: The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective--a report by Polish Myeloma Study Group.

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.

Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience.

Despite the well-defined role of autologous haematopoietic stem cell transplantation (autoHCT) in the treatment of patients with relapsed or refractory Hodgkin lymphoma (HL), relapse remains the main cause of transplant failure. We retrospectively evaluated long-term outcome and prognostic factors affecting survival of 132 patients with refractory (n = 89) or relapsed HL (n = 43) treated with autoHCT following modified BEAM. With a median follow-up of 68 months, the 10-year overall survival (OS) and progression-free survival (PFS) were 76 and 66 %, respectively. The 10-year cumulative incidence of second malignancies was 7 %. In multivariate analysis, age ≥45 years, more than one salvage regimens and disease status at transplant worse than CR were factors predictive for poor OS. In relapsed HL, age at transplant, response duration (<12 vs. ≥12 months) and the number of salvage regimens were independent predictors for PFS. In the refractory setting, disease status at autoHCT and the number of salvage regimens impacted PFS. The number of risk factors was inversely correlated with PFS in both relapsed and refractory HL (p = 0.003 and <0.001, respectively). The median PFS for patients with >1 risk factor in the relapsed and refractory setting was 5 and 11 months, respectively, in comparison with the median PFS not reached for patients with 0-1 risk factor in both settings. We conclude that high proportion of patients with relapsed/refractory HL can be cured with autoHCT. However, the presence of two or more risk factors helps to identify poor prognosis patients who may benefit from novel treatment strategies.

Treatment strategy based on gemcitabine-containing salvage chemotherapy used with intent to proceed to second stem cell transplant for patients with Hodgkin lymphoma relapsing after a prior autologous transplant.

This report is an analysis of patients with Hodgkin lymphoma who relapsed after autologous stem cell transplant (autoHCT) and who were treated with gemcitabine-based therapy as a bridge to either allogeneic or second autologous transplant. Sixteen patients were treated with gemcitabine, cisplatin and steroid and 21 with gemcitabine plus vinorelbine. The overall response rate was 68%. The grade 3-4 toxicity was myelosupression and infections. Fifteen patients proceeded to allogeneic and five to autologous transplant. Two-year overall survival (OS) and progression-free survival (PFS) for all patients were 36% and 25%, respectively. In multivariate analysis, relapse > 6 months after autoHCT and response to gemcitabine-based chemotherapy were associated with superior OS and response to gemcitabine-based chemotherapy with improved PFS. A treatment strategy based on gemcitabine-containing chemotherapy and second transplant appears to be an effective treatment option for patients relapsing > 6 months after autoHCT, providing a median survival time of 34 months.

The role of AlkB protein in repair of 1,N6-ethenoadenine in Escherichia coli cells.

Etheno (ε) DNA adducts, including 1,N(6)-ethenoadenine (εA), are formed by various bifunctional agents of exogenous and endogenous origin. The AT→TA transversion, the most frequent mutation provoked by the presence of εA in DNA, is very common in critical codons of the TP53 and RAS genes in tumours induced by exposure to carcinogenic vinyl compounds. Here, using a method that allows examination of the mutagenic potency of a metabolite of vinyl chloride, chloroacetaldehyde (CAA), but eliminates its cytotoxicity, we studied the participation of alkA, alkB and mug gene products in the repair of εA in Escherichia coli cells. The test system used comprised the pIF105 plasmid bearing the lactose operon of CC105 origin, which allowed monitoring of Lac(+) revertants that arose by AT→TA substitutions due to the modification of adenine by CAA. The plasmid was CAA-modified in vitro and replicated in E.coli of various genetic backgrounds (wt, alkA, alkB, mug, alkAalkB, alkAmug and alkBmug). To modify the levels of the AlkA and AlkB proteins, mutagenesis was studied in E.coli cells induced or not in adaptive response to alkylating agents. Considering the levels of CAA-induced Lac(+) revertants in strains harbouring the CAA-modified pIF105 plasmid and induced or not in adaptive response, we conclude that the AlkB dioxygenase plays a major role in decreasing the level of AT→TA mutations, thus in the repair of εA in E.coli cells. The observed differences of mutation frequencies in the various mutant strains assayed indicate that Mug glycosylase is also engaged in the repair of εA, whereas the role the AlkA glycosylase in this repair is negligible.

Activity of bortezomib in adult de novo and relapsed acute myeloid leukemia.

BACKGROUND: Bortezomib is an inhibitor of proteasome and NF-kappaB, with activity in various solid tumors and hematological malignancies. AIM: The aim of the study was the analysis of in vitro drug resistance to bortezomib and other anticancer drugs in de novo and relapsed adult acute myeloid leukemia (AML). PATIENTS AND METHODS: The leukemic cells of 46 adult patients with AML were tested for the in vitro drug resistance profile. The group included 20 de novo and 26 relapsed AML patients, among whom, 12 relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) and 4 after autologous HSCT. The MTT assay was performed for 21 drugs. Expression of P-glycoprotein (PGP), multidrug resistance-associated protein-1 (MRP1) and lung resistance protein (LRP) proteins was measured by flow cytometry. RESULTS: No significant differences in drug resistance were found for all tested drugs between de novo and relapsed AML samples, while expression of PGP, MRP1 and LRP was higher in relapsed patients. Patients with refractory or relapsed disease, had higher resistance of myeloblasts to cyclophosphamide (RR = 2.4, p = 0.050), and better sensitivity to busulfan (RR = 0.4, p = 0.054) and topotecan (RR = 0.4, p = 0.031). Those who have died due to refractory/relapsed disease (n = 16) had better sensitivity to bortezomib (RR = 0.6, p = 0.046) and treosulfan (RR = 0.1, p = 0.018). CONCLUSION: In vitro drug resistance in relapsed adult AML is comparable to that in de novo disease. Activity in vitro of bortezomib might be a rationale for its use in refractory/relapsed AML adult patients.

[Recurrent hemoptysis following thienopyridines and amiodarone administration. therapeutic dilemma]. / Nawracajace krwioplucie podczas leczenia tienopirydynami i amiodaronem. Dylemat terapeutyczny.

The authors describe a case of a 74-year-old man with advanced coronary heart disease in whom pulmonary hemorrhagic complications during therapy with ticlopidine and subsequently with clopidogrel and amiodarone were observed. Fever and massive hemoptysis following five days of ticlopidine treatment, before elective coronary angiography, were noticed. Transient interstitial X-ray changes of the right lung were visible. Three months later a new episode on the third day of clopidogrel administration was manifested. He was after PCI, performed because of ACS complicated with ventricular fibrillation. Two days following clopidogrel discontinuation hemoptysis remitted but after ten days occurred again (this time with bilateral X-ray changes). Amiodarone, given after VF, was stopped. Spectacular improvement with steroid treatment was observed. Indobufen (reversible COX- 1 inhibitor) as an antiplatelet therapy was availed. The authors discuss therapeutic dilemma concerning the patient with coexisting different diseases.