Injection Molding of Encapsulated Diffractive Optical Elements.

Microstructuring techniques, such as laser direct writing, enable the integration of microstructures into conventional polymer lens systems and may be used to generate advanced functionality. Hybrid polymer lenses combining multiple functions such as diffraction and refraction in a single component become possible. In this paper, a process chain to enable encapsulated and aligned optical systems with advanced functionality in a cost-efficient way is presented. Within a surface diameter of 30 mm, diffractive optical microstructures are integrated in an optical system based on two conventional polymer lenses. To ensure precise alignment between the lens surfaces and the microstructure, resist-coated ultra-precision-turned brass substrates are structured via laser direct writing, and the resulting master structures with a height of less than 0.002 mm are replicated into metallic nickel plates via electroforming. The functionality of the lens system is demonstrated through the production of a zero refractive element. This approach provides a cost-efficient and highly accurate method for producing complicated optical systems with integrated alignment and advanced functionality.

Adhesion-Induced Demolding Forces of Hard Coated Microstructures Measured with a Novel Injection Molding Tool.

The demolding of plastic parts remains a challenging aspect of injection molding. Despite various experimental studies and known solutions to reduce demolding forces, there is still not a complete understanding of the effects that occur. For this reason, laboratory devices and in-process measurement injection molding tools have been developed to measure demolding forces. However, these tools are mostly used to measure either frictional forces or demolding forces for a specific part geometry. Tools that can be used to measure the adhesion components are still the exception. In this study, a novel injection molding tool based on the principle of measuring adhesion-induced tensile forces is presented. With this tool, the measurement of the demolding force is separated from the actual ejection step of the molded part. The functionality of the tool was verified by molding PET specimens at different mold temperatures, mold insert conditions and geometries. It was demonstrated that once a stable thermal state of the molding tool was achieved, the demolding force could be accurately measured with a comparatively low force variance. A built-in camera was found to be an efficient tool for monitoring the contact surface between the specimen and the mold insert. By comparing the adhesion forces of PET molded on polished uncoated, diamond-like carbon and chromium nitride (CrN) coated mold inserts, it was found that a CrN coating reduced the demolding force by 98.5% and could therefore be an efficient solution to significantly improve demolding by reducing adhesive bond strength under tensile loading.

Direct Processing of PVD Hard Coatings via Focused Ion Beam Milling for Microinjection Molding.

Hard coatings can be applied onto microstructured molds to influence wear, form filling and demolding behaviors in microinjection molding. As an alternative to this conventional manufacturing procedure, "direct processing" of physical-vapor-deposited (PVD) hard coatings was investigated in this study, by fabricating submicron features directly into the coatings for a subsequent replication via molding. Different diamondlike carbon (DLC) and chromium nitride (CrN) PVD coatings were investigated regarding their suitability for focused ion beam (FIB) milling and microinjection molding using microscope imaging and areal roughness measurements. Each coating type was deposited onto high-gloss polished mold inserts. A specific test pattern containing different submicron features was then FIB-milled into the coatings using varied FIB parameters. The milling results were found to be influenced by the coating morphology and grain microstructure. Using injection-compression molding, the submicron structures were molded onto polycarbonate (PC) and cyclic olefin polymer (COP). The molding results revealed contrasting molding performances for the studied coatings and polymers. For CrN and PC, a sufficient replication fidelity based on AFM measurements was achieved. In contrast, only an insufficient molding result could be obtained for the DLC. No abrasive wear or coating delamination could be found after molding.

Use of PtC Nanotips for Low-Voltage Quantum Tunneling Applications.

The use of focused ion and focused electron beam (FIB/FEB) technology permits the fabrication of micro- and nanometer scale geometries. Therefore, FIB/FEB technology is a favorable technique for preparing TEM lamellae, nanocontacts, or nanowires and repairing electronic circuits. This work investigates FIB/FEB technology as a tool for nanotip fabrication and quantum mechanical tunneling applications at a low tunneling voltage. Using a gas injection system (GIS), the Ga-FIB and FEB technology allows both additive and subtractive fabrication of arbitrary structures. Using energy dispersive X-ray spectroscopy (EDX), resistance measurement (RM), and scanning tunneling microscope (STM)/spectroscopy (STS) methods, the tunneling suitability of the utilized metal-organic material-platinum carbon (PtC) is investigated. Thus, to create electrode tips with radii down to 15 nm, a stable and reproducible process has to be developed. The metal-organic microstructure analysis shows suitable FIB parameters for the tunneling effect at high aperture currents (260 pA, 30 kV). These are required to ensure the suitability of the electrodes for the tunneling effect by an increased platinum content (EDX), a low resistivity (RM), and a small band gap (STM). The STM application allows the imaging of highly oriented pyrolytic graphite (HOPG) layers and demonstrates the tunneling suitability of PtC electrodes based on high FIB aperture currents and a low tunneling voltage.

Material flow cost accounting (MFCA) for the circular economy: An empirical study of the triadic relationship between MFCA, environmental performance, and the economic performance of Japanese companies.

The purpose of this study is to address the question of whether material flow cost accounting (MFCA) can contribute to the circular economy. Because MFCA is an environmental management accounting tool that simultaneously assesses company material and financial flows, it is expected to contribute to the circular economy by assisting companies to achieve both environmental and economic goals through resource efficiency. In short, the expected linkages between MFCA, company environmental and economic goals, and the circular economy are inputs, outputs, and outcomes. However, there is a lack of consensus regarding its potential, perhaps because of the scarcity of studies, with most being models and case studies without readily generalizable results. To address this gap, we analyze the triadic relationship between MFCA, environmental performance, and economic performance using a two-stage regression of data from Japanese listed companies. The main findings are as follows. Companies that implement MFCA more proactively are more likely to improve their environmental performance in terms of energy consumption, CO2 emissions, and waste produced. In turn, those that improve their environmental performance are also more likely to improve their productivity, while those that specifically improve environmental performance in terms of waste produced are also more likely to increase in profitability. Consequently, because MFCA can improve several aspects of environmental performance by saving resources, it can improve productivity by improving a range of environmental performance indicators. In particular, MFCA can improve company productivity and thereby profit, at least by reducing the amount of waste produced. This supports the view that MFCA is an effective tool to contribute to the circular economy.

Characterization and Benchmark of a Novel Capacitive and Fluidic Inclination Sensor.

In this paper, a fluidic capacitive inclination sensor is presented and compared to three types of silicon-based microelectromechanical system (MEMS) accelerometers. MEMS accelerometers are commonly used for tilt measurement. They can only be manufactured by large companies with clean-room technology due to the high requirements during assembly. In contrast, the fluidic sensor can be produced by small- and medium-sized enterprises (SMEs) as well, since only surface mount technologies (SMT) are required. Three different variants of the fluidic sensor were investigated. Two variants using stacked printed circuit boards (PCBs) and one variant with 3D-molded interconnect devices (MIDs) to form the sensor element are presented. Allan deviation, non-repeatability, hysteresis, and offset temperature stability were measured to compare the sensors. Within the fluidic sensors, the PCB variant with two sensor cavities performed best regarding all the measurement results except non-repeatability. Regarding bias stability, white noise, which was determined from the Allan deviation, and hysteresis, the fluidic sensors outperformed the MEMS-based sensors. The accelerometer Analog Devices ADXL355 offers slightly better results regarding offset temperature stability and non-repeatability. The MEMS sensors Bosch BMA280 and TDK InvenSense MPU6500 do not match the performance of fluidic sensors in any category. Their advantages are the favorable price and the smaller package. From the investigations, it can be concluded that the fluidic sensor is competitive in the targeted price range, especially for applications with extended requirements regarding bias stability, noise, and hysteresis.

Results after Repair of Functional Tricuspid Regurgitation with a Three-Dimensional Annuloplasty Ring.

BACKGROUND: Tricuspid valve (TV) repair is the recommended treatment for severe functional tricuspid regurgitation (fTR) in patients undergoing left-sided surgery. For this purpose, a wide range of annuloplasty devices differing in form and flexibility are available. This study reports the results using a three-dimensional annuloplasty ring (Medtronic, Contour 3D Ring) for TV repair and analysis of risk factors. METHODS: A cohort of 468 patients who underwent TV repair (TVr) with a concomitant cardiac procedure from December 2010 to January 2017 was retrospectively analyzed. RESULTS: At follow-up, 96.1% of patients had no/trivial or mild TR. The 30-day mortality was 4.7%; it significantly differed between electively performed operations (2.7%) and urgent/emergent operations (11.7%). Risk factors for recurrent moderate and severe TR were LVEF < 50%, TAPSE < 16 mm, and moderate mitral valve (MV) regurgitation at follow-up. Preoperatively reduced renal function lead to a higher 30-day and overall mortality. Reoperation of the TV was required in six patients (1.6%). Risk factors for TV related reoperations were preoperative TV annulus over 50 mm and an implanted permanent pacemaker. CONCLUSIONS: TVr with the Contour 3D annuloplasty ring shows low TR recurrence and reoperation rates. Risk-factor analysis for the recurrence of TR revealed the importance of left- and right-ventricular function.

Expression of Surface-associated 82 kDa proMMP-9 in Lymphatic Leukemia Blast Cells Differentially Correlates With Prognosis.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) degrade extracellular matrix and process regulatory proteins. Recently, a membrane-bound 82kDa variant of proMMP-9 identified on myeloid blasts was shown to be associated with prognosis. PATIENTS AND METHODS: To investigate the role of 82kDa proMMP-9 with acute lymphoblastic leukemia (ALL) and chronic lymphoid leukemia (CLL), we performed flow-cytometry analysis of expression on ALL blasts (n=18) and CLL lymphocytes (n=21) from blood and correlated data with clinical parameters. RESULTS: In ALL, mature B-linear blasts expressed higher levels of 82kDa proMMP-9 compared to T-linear blasts. Elevated levels of 82kDa proMMP-9 were found in elderly patients and at patients with relapse. No correlation was observed on blood cells and extramedullary disease. In CLL, the 82kDa proMMP-9 expression did not correlate with any of the clinical parameters. CONCLUSION: Our findings suggest that higher levels of 82kDa proMMP-9 expression on blast cells may correlate with a more unfavorable ALL-subtype. Further studies are required to clarify the prognostic role of the 82kDa pro-MMP-9 expression.

Development and Proof of Concept of a Miniaturized MEMS Quantum Tunneling Accelerometer Based on PtC Tips by Focused Ion Beam 3D Nano-Patterning.

Most accelerometers today are based on the capacitive principle. However, further miniaturization for micro integration of those sensors leads to a poorer signal-to-noise ratio due to a small total area of the capacitor plates. Thus, other transducer principles should be taken into account to develop smaller sensors. This paper presents the development and realization of a miniaturized accelerometer based on the tunneling effect, whereas its highly sensitive effect regarding the tunneling distance is used to detect small deflections in the range of sub-nm. The spring-mass-system is manufactured by a surface micro-machining foundry process. The area of the shown polysilicon (PolySi) sensor structures has a size smaller than 100 µm × 50 µm (L × W). The tunneling electrodes are placed and patterned by a focused ion beam (FIB) and gas injection system (GIS) with MeCpPtMe3 as a precursor. A dual-beam system enables maximum flexibility for post-processing of the spring-mass-system and patterning of sharp tips with radii in the range of a few nm and initial distances between the electrodes of about 30-300 nm. The use of metal-organic precursor material platinum carbon (PtC) limits the tunneling currents to about 150 pA due to the high inherent resistance. The measuring range is set to 20 g. The sensitivity of the sensor signal, which depends exponentially on the electrode distance due to the tunneling effect, ranges from 0.4 pA/g at 0 g in the sensor operational point up to 20.9 pA/g at 20 g. The acceleration-equivalent thermal noise amplitude is calculated to be 2.4-3.4 mg/Hz. Electrostatic actuators are used to lead the electrodes in distances where direct quantum tunneling occurs.

Expression profiles of HMGB1 on B-CLL related leukocytes contribute to prediction of relapse.

BACKGROUND: The High Mobility Group Box 1 (HMGB1) is a nuclear protein that is frequently overexpressed in hematologic diseases and might be of relevance in immunogenic cancer control thus correlating with patients' (pts.) prognosis in diseases such as acute myeloid, acute lymphatic and chronic lymphocytic leukemia. MATERIALS AND METHODS: Expression profiles of blasts from AML (n = 21), ALL (n = 16) and of B-lymphocytes of CLL (n = 9) pts. were analyzed for surface expression of HMGB1 using flow cytometry. Expression was quantified and correlated with clinically and prognostically relevant markers. RESULTS: Expression profiling of HMGB1 in blasts of AML and ALL subtypes did not show differences between primary vs. secondary disease development and gender related differences. In ALL pts. however, age groups at initial diagnosis between ≥20 vs. <20 years were compared and showed significant differences (≥20 vs. <20 years; 89% vs. 49%, p  <0.05) with higher expression in higher age. In AML and CLL these differences were not visible. To evaluate the prognostic significance of HMGB1 expression, expression quantity was correlated with established and prognostic classification systems (in AML ELN, in ALL GMALL) and probability to relapse. No significant correlation was seen in these entities. However, when AML pts. were analyzed for remission rates after first anthracycline based induction therapy, in those who did not experience a complete remission significantly enhanced HMGB1 surface expression was seen (98 vs. 94%; p < 0.05; n = 20). Furthermore, for CLL it was shown that higher HMGB1 expression was found in pretreated patients with relapsed or/and refractory disease (1 vs. more relapses; 94 vs. 98%; p  <0.05; n = 9). CONCLUSION: HMGB1 is frequently expressed in hematologic malignancies. In this study it was shown that HMGB1 surface expression on AML blasts can be used as predictors for treatment response. In CLL it may be a marker for advanced disease. In order to implement this marker in FACS routine it could be a useful and practical tool for prognostic assessment and treatment planning.

Mass-producible micro-optical elements by injection compression molding and focused ion beam structured titanium molding tools.

We demonstrate mass production compatible fabrication of polymer-based micro Fresnel lenses by injection compression molding. The extremely robust titanium-molding tool is structured with high precision by focused ion beam milling. In order to achieve optimal shape accuracy in the titanium we use an iterative design optimization. The inverse Fresnel lens structured into the titanium is transferred to polymers by injection compression molding, enabling rapid mass replication. We show that the optical performance of the molded diffractive Fresnel lenses is in good agreement with simulations, rendering our approach suitable for applications that require compact and high-quality optical elements in large numbers.

Functional and Degenerative Mitral Regurgitation: One Ring Fits All?

BACKGROUND: Three-dimensional saddle-shaped annuloplasty rings have been shown to create a larger surface of leaflet coaptation in mitral valve repair (MVR) for functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) which may increase repair durability. For the first time, this study reports mid-term results after MVR for DMR and FMR using a rigid three-dimensional ring (Profile 3D, Medtronic). METHODS: Between June 2009 and June 2012, 369 patients with DMR (n = 326) or FMR (n = 43) underwent MVR (mean age 62.3 ± 12.6 years). A total of 205 patients (55.6%) underwent isolated MVR and 164 patients (44.4%) a combined procedure. Follow-up examinations were performed in 94.9% (mean 4.9 ± 0.9 years). Echocardiographic assessment was complete in 93.2% (mean 4.3 ± 1.2 years). RESULTS: The 30-day mortality was 1.5% (5/326) for DMR (1.5% for isolated and 1.6% for combined procedures) and 9.3% (4/43) for FMR (0% for isolated and 10.5% for combined procedures). Survival at 6 years was 92.1 ± 1.9% for DMR (92.9 ± 2.6% for isolated and 90.7 ± 2.7% for combined procedures) and 66.4 ± 7.9% for FMR (80.0 ± 17.9% for isolated and 63.7 ± 8.9% for combined procedures). Cumulative risk for mitral valve-related reoperation at 6 years was 0% for FMR and 7.1 ± 1.5% for DMR. At echocardiographic follow-up, one patient presented with mitral regurgitation (MR) more than moderate. The only predictor of recurrent MR after MVR for DMR was residual mild MR at discharge. CONCLUSION: Repair of FMR with the three-dimensional Profile 3D annuloplasty ring shows excellent mid-term results with regard to recurrence of MR. In cases of DMR, the results are conforming to the current literature.

Review on Fabrication Technologies for Optical Mold Inserts.

Polymer optics have gained increasing importance in recent years. With advancing requirements for the optical components, the fabrication process remains a challenge. In particular, the fabrication of the mold inserts for the replication process is crucial for obtaining high-quality optical components. This review focuses on fabrication technologies for optical mold inserts. Thereby, two main types of technologies can be distinguished: fabrication methods to create mold inserts with optical surface quality and methods to create optical microstructures. Since optical mold inserts usually require outstanding form accuracies and surface qualities, a focus is placed on these factors. This review aims to give an overview of available methods as well as support the selection process when a fabrication technology is needed for a defined application. Furthermore, references are given to detailed descriptions of each technology if a deeper understanding of the processes is required.

Injection Compression Molded Microlens Arrays for Hyperspectral Imaging.

In this work, a polymer microlens array (MLA) for a hyperspectral imaging (HSI) system is produced by means of ultraprecision milling (UP-milling) and injection compression molding. Due to the large number of over 12,000 microlenses on less than 2 cm², the fabrication process is challenging and requires full process control. The study evaluates the process chain and optimizes the single process steps to achieve high quality polymer MLAs. Furthermore, design elements like mounting features are included to facilitate the integration into the final HSI system. The mold insert was produced using ultraprecision milling with a diamond cutting tool. The machining time was optimized to avoid temperature drifts and enable high accuracy. Therefore, single immersions of the diamond tool at a defined angle was used to fabricate each microlens. The MLAs were replicated using injection compression molding. For this process, an injection compression molding tool with moveable frame plate was designed and fabricated. The structured mold insert was used to generate the compression movement, resulting in a homogeneous pressure distribution. The characterization of the MLAs showed high form accuracy of the microlenses and the mounting features. The functionality of the molded optical part could be demonstrated in an HIS system by focusing light spectrums onto a CCD image sensor.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Significance of Frequencies, Compositions, and/or Antileukemic Activity of (DC-stimulated) Invariant NKT, NK and CIK Cells on the Outcome of Patients With AML, ALL and CLL.

Invariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the Vα24-Jα18-invariant T-cell receptor) with CD4/CD8/CD1d/Vα24 for iNKT subset detection and "T/NK cell-like"-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11/6B11CD3/6B11CD161), NK cells (CD3CD56/CD3CD161), and CIK cells (CD3CD56/CD3CD161) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)/chronic lymphoid leukemia (CLL) patients in acute disease stages. Subtyping of iNKT cells revealed (significantly) higher proportions of CD3 T cells and CD161 NK cells in AML/ALL/CLL expressing 6B11 compared with healthy MNC. Prognostic evaluations showed higher proportions of iNKT/NK/CIK cells in favorable AML subgroups (younger age, primary, no extramedullary disease, achievement/maintenance of complete remission) or adult ALL and CLL patients. (II) iNKT/NK/CIK cell frequencies increased after (vs. before) mixed lymphocyte cultures of T-cell-enriched immune reactive cells stimulated with MNC/whole blood with or without pretreatment with "cocktails" (dendritic cells generating methods/kits inducing blasts' conversion to leukemia-derived dendritic cells from AML patients). Individual "cocktails" leading to "highest" iNKT cell frequencies could be defined. Antileukemic blast lytic activity correlated significantly with frequencies of iNKT/NK/CIK cells. In summary healthy MNC show significantly more iNKT/NK/CIK cells compared with AML/ALL/CLL MNC, a shift in the iNKT cell composition is seen in healthy versus leukemic samples and iNKT/NK/CIK cell-proportions in AML/ALL/CLL MNC samples correlate with prognosis. "Cocktail"-treated AML blasts lead to higher iNKT/NK/CIK cell frequencies and samples with antileukemic activity show significantly higher frequencies of iNKT/NK/CIK cells. Proportions of iNKT/NK/CIK cells should regularly be evaluated in AML/ALL/CLL diagnosis panels for quantitative/prognostic estimation of individual patients' antileukemic potential and their role in dendritic cells/leukemia-derived dendritic cells triggered immune surveillance.

Inactivation of JNK2 as carcinogenic factor in colitis-associated and sporadic colorectal carcinogenesis.

We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis. We investigated expression of p-JNK2, p-JNK1-3, p21WAF1, γ-H2AX and Ki67 by immunohistochemistry in cases of quiescent UC (QUC), active UC (AUC), UC-dysplasia and UC-related colorectal carcinoma (UC-CRC). Comparison was made to normal healthy colorectal mucosa, sporadic adenoma and colorectal carcinoma (CRC), diverticulitis and Crohns disease (CD). We found p-JNK2 up-regulation in AUC and its early down-regulation in UC-CRC and CRC carcinogenesis. With down-regulated p-JNK2, p21WAF1 was also decreased. Ki67 was inversely expressed, showing increased proliferation early in UC-CRC and CRC carcinogenesis. p-JNK1-3 was increased in AUC and QUC. Less increased γ-H2AX in UC-CRC compared to CRC gave evidence that colitis-triggered inflammation masks DNA damage, thus contributing to neoplastic transformation. We hypothesize that JNK-dependent cell cycle arrest is important in AUC, while chronic inflammation causes dysregulated JNK activity in quiescent phase that may contribute to checkpoint override, promoting UC carcinogenesis. We suggest restoring p-JNK2 expression as a novel therapeutic strategy to early prevent the development of UC-related cancer.

Expression of surface-associated 82kDa-proMMP-9 in primary acute leukemia blast cells inversely correlates with patients' risk.

With its ability to degrade extracellular matrix proteins and activate growth factors and cytokines, matrix metalloproteinase (MMP)-9 is an important regulator of cell function. Previously, we reported that myeloid leukemic cells express a unique 82kDa-proMMP-9 variant on their cell surface that is not affected by its natural inhibitor. In this study, we generated monoclonal antibodies that specifically recognize 82kDa-proMMP-9. Flow cytometry analysis using these antibodies revealed significant surface expression of 82kDa-proMMP-9 in monocytes, but minimal amounts in T and B cells isolated from peripheral blood of nine healthy donors and 22 patients with acute myeloid leukemia (AML). In all AML patients, blasts expressed 82kDa-proMMP-9 at levels of 4%-46%, with significantly higher levels in patients with a better risk defined according to National Comprehensive Cancer Network (NCCN) guidelines (ρ = -0.748, p < 0.001) and favorable phenotype according to the French-American-British classification (p = 0.02) compared with patients with adverse prognoses. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy of 82kDa-proMMP-9 measurement in AML blasts (area under the curve: 0.893 [0.739-1.000], p = 0.019). It led us to define a cutoff value of 11.5% for identifying patients with lower NCCN risk (p = 0.005) and with a tendency toward a higher probability of response to anthracycline-based therapy (p = 0.109) and increased event-free survival (p = 0.24). Thus, 82kDa-proMMP-9 expression on blasts may represent a novel independent marker of prognosis in patients with AML.