A side-by-side comparison of the new VITEK MS PRIME and the MALDI Biotyper sirius in the clinical microbiology laboratory.

PURPOSE: This study aims to evaluate the performance of two latest generation matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems in routine laboratory settings, focusing on turnaround time (TAT), time to results (TTR), hands-on time, and identification rate. METHODS: We conducted a time and motion study on three workflow scenarios to simulate different laboratory settings. Overall, 618 bacterial isolates from a tertiary hospital's laboratory were processed using the VITEK MS PRIME (bioMérieux) and the MALDI Biotyper sirius (Bruker Daltonics) and their corresponding databases VITEK IVD Database 3.2 and MBT reference library 12. RESULTS: The target preparation process showed no significant difference in TAT, but the Biotyper workflow had a shorter hands-on time by 3 to 6 min. In the measurement process, TTR was three to five times shorter for the Biotyper sirius while hands-on time was significantly shorter for VITEK MS PRIME (approximately 1.5 min per target). The identification rate without retesting was 97.9% for VITEK MS PRIME and 98.9% for Biotyper sirius. Both systems achieved 100% agreement at genus and 96.2% at species level. CONCLUSION: Both systems exhibited excellent identification rates for routine bacterial isolates. Due to its high speed, the Biotyper sirius is suited for laboratories with high sample throughput and a workflow designed for processing larger batches. The VITEK MS PRIME, with its "load and go" system accommodating up to 16 targets, reduces hands-on time, making it a reasonable choice for laboratories with fewer identifications overall but a higher number of targets and a workflow designed for parallel processing on different workstations.

Examining obstetric interventions and respectful maternity care in Hungary: Do informal payments for continuity of care link to quality?

BACKGROUND: In Hungary, 60% of women pay informally to secure continuity with a "chosen" provider for prenatal care and birth. It is unclear if paying informally influences quality of maternity care. This study examined associations between incentivized continuity care models and obstetric procedures and respectful care. METHODS: This is a cross-sectional survey of a representative sample of Hungarian women (N = 589) in 2014. We calculated descriptive statistics comparing experiences among women who paid informally for continuity with a chosen provider with those who received care in the public health system. After adjusting for social and clinical covariates, we used logistic regression to estimate the odds of obstetric procedures and disrespectful care and linear regression to estimate the level of autonomy (MADM scale). RESULTS: Of women in our sample, 317 (53%) saw a chosen doctor, 68 (11%) a chosen midwife, and 204 (33%) had care in the public system. Women who paid an obstetrician informally had the highest rates of cesarean (49.5%), induction of labor (31.2%), and epidural (15%), and reported lower rates of disrespectful care (41%) compared to public care (64%). Paying for continuity with an obstetrician significantly predicted cesarean (aOR 1.61 [95%CI 1.00-2.58]), episiotomy (2.64, [1.39-5.03]), and epidural (3.15 [1.07-9.34]), but not induction of labor (1.59 [0.99-2.57]). Informal payment continuity models predicted increased autonomy scores (doctor: 3.97, 95% CI 2.39-5.55; midwife: 7.37, 95% CI 5.36-9.34) and reduced odds of disrespectful care. There were no differences in the prevalence of scheduled cesareans or inductions performed without a medical indication. CONCLUSIONS: Continuity models secured with informal payments significantly increased both women's experience of respectful care and rates of obstetric procedures. Intervention rates exceed global standards, and women do not choose elective procedures to preserve continuity.

Heterologous Prime Boost Vaccination Induces Protective Melanoma-Specific CD8+ T Cell Responses.

Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8+ T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.

Evaluation of life cycle defective adenovirus mutants for production of adeno-associated virus vectors.

BACKGROUND: Adeno-associated virus-based vectors are efficient and safe drug candidates for different in vivo gene therapy applications. With increasing numbers of clinical studies based on AAV2 vectors that include not only rare, but also common diseases as a therapeutic target, there is an increased demand for the development of improved production technologies. METHODS: In the present study, we compared two life cycle defective adenovirus mutants as helper viruses for AAV2 vector production. They had deletions either in the gene coding for the preterminal protein (pTP) that is expressed early in the viral life cycle and is essential for genome replication or in the gene coding for the 100K protein, a protein with many functions, one of which is involved in virus assembly. AAV2 vector production efficiencies were evaluated by analyzing genome-containing particles using a real-time polymerase chain reaction and functional units were investigated by transduction assays. RESULTS: Somewhat contrary to our expectations, the ∆100K mutant virus showed only a moderate efficiency as a helper virus for AAV2 vector production, whereas the replication-deficient ∆pTP mutant supported AAV2 production almost as efficiently as adenovirus wild-type. We also showed that a temperature shift to 32°C together with extended incubation times improved AAV2 vector productivity. CONCLUSIONS: The present study indicates the advantages of using a ∆pTP mutant adenovirus rather than adenovirus wild-type as a helper virus for AAV2 production and also indicates that temperature shifts to lower temperatures may improve AAV2 vector production rates.

[Patient care of patients with myocardial infarction in Hungary. Analysis of National Myocardial Infarction Registry data collecting in 2015]. / A szívinfarktus miatt kezelt betegek ellátása Magyarországon. A Nemzeti Szívinfarktus Regiszter 2015. évi adatainak elemzése.

The authors summarize the most relevant data of myocardial infarction patients according to the National Myocardial Infarction Registry data base. In 2015 12,681 patients had 12,941 acute myocardial infarctions. Less than half of patients (44.4%) were treated with ST elevation myocardial infarction. National Ambulance Service was the first medical contact of more than half (51.4%) of patients with ST elevation infarction. Prehospital thrombolysis was occasionally done (0.23%), but 91.6% of the patients were treated in hospital with invasive facilities. The median of the ischaemic time (time between onset of symptoms and arrival at the invasive laboratory) was 223 minutes. Most of the patients (94%) with positive coronary arteriography were treated with percutaneous coronary intervention. The 30 day mortality of the whole group was 12.8% vs. 8.6% of patients treated with an invasive procedure. CONCLUSION: comparing the national and international registry data we conclude that we should analyse and decrease the prehospital delay time to improve the patient care in Hungary. Orv. Hetil., 2017, 158(3), 90-93.

Physicians' Reactions to Patients Taking a Position: Sequence Analysis of Admission Interviews in Orthopedic Rehabilitation.

Little is known about how patients influence health care providers' communication behavior, although this knowledge may contribute to the understanding of the reciprocal influence of patient and provider communication and the pathways between communication and health care outcomes. Therefore, the aim of this study was to explore patients' active communication behaviors and how this affects the immediate communication behavior of physicians. We coded 27 admission interviews from three German orthopedic rehabilitation centers with an adapted version of the Roter Interaction Analysis System. The data were analyzed using correlations and sequence analysis, specifically lag analysis. In this article, we report findings in relation to patients taking a position and physicians' reactions. The analysis showed that while all patients took up a position during their consultation, they very rarely contradicted the physician. Moreover, many instances of patients' expression of opinion were strongly determined by physicians' behavior. When physicians asked patients for their opinions they often used alternative questions or closed questions that limited patients' answering possibilities. While the lag analyses showed that patient communication behavior can influence physician communication, in the majority of instances patients' expression of opinions did not lead to a discussion or shared decision making.

What is competent communication behaviour of patients in physician consultations? - Chronically-ill patients answer in focus groups.

Many desirable outcomes depend on good patient-physician communication. Patient-based perspectives of what constitutes competent communication behavior with physicians are needed for patient-oriented health care. Therefore it was our main aim to identify competent patient communication skills from the patient's perspective. We also wanted to reveal any differences in opinion among various groups (chronic ischemic heart disease, chronic low back pain, breast cancer). This study examined nine guideline-supported focus groups in rehabilitation centers. The criterion for study inclusion was any one of the three diagnoses. Enrolled in the study were N = 49 patients (32 women) aged M = 60.1 (SD = 12.8). The interview recordings were transcribed and subjected to content analysis. We documented 396 commentaries in these interviews that were allocated to 82 different codes; these in turn resulted in the formation of 12 main topics. Examples are: posing questions, being an active and participatory patient, being aware of emotions and communicating them. This study represents stage two ('documentation of patient and clinician views') in the seven-stage model of communication research. Findings reveal that chronically-ill patients name behaviours that contribute to successful discussion with a physician. These enable us to develop communication trainings and design-measuring tools used for patient-based communication skills.

Patient communication competence: development of a German questionnaire and correlates of competent patient behavior.

OBJECTIVE: The aim of our study was to design and psychometrically test a patient questionnaire to capture patient communication competence in the context of patient-provider interaction (CoCo questionnaire). We also aimed to determine patient characteristics associated with competent patient behavior. METHODS: To assure content validity, we initially conducted 17 focus groups (n=97) made up of patients and providers. In the main study n=1.264 patients with chronic back pain, chronic-ischemic heart disease or breast cancer who underwent inpatient rehabilitation were surveyed at the end of rehabilitation. RESULTS: The CoCo questionnaire contains four scales (patient adherence in communication, critical and participative communication, communication about personal circumstances, active disease-related communication) and 28 items addressing competent patient behavior. We provide evidence of unidimensionality, local independence, reliability, a Rasch-Model fit, the absence of differential item functioning, and signs of construct validity. The most important correlates of communication competence are health literacy and communication self-efficacy. CONCLUSION: The CoCo questionnaire has good psychometric properties in German. Future research should examine CoCo's responsiveness and analyze criterion validity by means of observation data. PRACTICE IMPLICATIONS: The CoCo questionnaire can be recommended for use in evaluating patient communication training programs.

Predictors of communication preferences in patients with chronic low back pain.

BACKGROUND: The objective of this exploratory study was to identify patient-related predictors of communication preferences in patients with chronic low back pain for various dimensions of patient-physician communication (patient participation and orientation, effective and open communication, emotionally supportive communication, communication about personal circumstances). METHODS: Eleven rehabilitation centers from various parts of Germany participated in collection of data between 2009 and 2011. A total of 701 patients with chronic low back pain were surveyed at the start of rehabilitation. The patient questionnaire captured communication preferences, pain impact, pain intensity, and psychologic variables (fear avoidance beliefs, illness coherence, control beliefs, communication self-efficacy, and personality characteristics). The rehabilitation physicians filled out a documentation sheet containing information on diagnosis, inability to work, duration of the illness, and comorbidity at the beginning and end of rehabilitation. Hierarchical regression analyses were performed. RESULTS: On average, effective, open, and patient-centered communication was very important for patients with back pain, emotionally supportive communication was important, and communication about personal circumstances was somewhat important. The variance in communication preferences explained by the predictors studied here was 8%-19%. Older patients showed a lower preference for patient-centered and open communication, but a higher preference for communication about personal circumstances. Patients with psychologic risk factors (eg, fear avoidance beliefs), extroverted patients, and patients with high self-efficacy in patient-physician interaction generally had higher expectations of the physician's communicative behavior. CONCLUSION: Providers should take into consideration the fact that patients with back pain have a strong need for effective, open, and patient-centered communication. A flexible approach to communication needs appears to be especially important for communication about emotional and personal circumstances, because the patients differ most clearly in this respect. Personal characteristics provided only initial clues to possible preferences; for more precision, an individual assessment (by means of questionnaires or discussion) is needed.

[Quality labels and accreditation in German long-term care--a review]. / Qualitätssiegel und Zertifikate in der deutschen Langzeitpflege--ein Uberblick.

UNLABELLED: There are many quality certificates for ambulant and stationary nursing facilities obtainable in Germany. Yet there has been no systematic, topical survey in Germany since the Scientific Institute of the AOK (WldO) published "Qualitätssiegel und Zertifikate für Pflegeeinrichtungen--Ein Marktüberblick" (Gerste et al. 2004). The aim of this examination was to update the data on certification procedures and seals of quality for nursing institutions. We thus hopeto provide nursing homes, their staff, patients and their families with guidelines for assessing the various certificates. METHOD: Via literature and online searches as well as telephone interviews with the certificate providers we created an overview of the quality certificates and seals now being used by nursing facilities in Germany. RESULTS: Nine of the 17 certificates reported by Gerste and colleagues in 2004 are still being employed (as of spring 2011). We identified 11 additional certificates in use and examined a total of 20 seals of quality. Their providers claim to have certified about 3700 nursing facilities. CONCLUSIONS: The differences between the AOK WldO study by Gerste et al. in 2004 and ours seem to reveal considerable fluctuation in the quality-certification market. However, five of the six "large" certifiers (those having certified over 100 institutions) also existed in 2004. Thus the nursing-certification-market has also been somewhat stable. The market's "leaders" in 2004 were still essentially dominating the market in 2011.

The patient-physician relationship in patients with chronic low back pain as a predictor of outcomes after rehabilitation.

For patients with chronic diseases, especially those with chronic low back pain, the patient-physician relationship is significant for treatment adherence. In a sample of N = 688 low back pain patients, we examined the hypothesis that aspects of the patient-physician relationship (e.g. satisfaction with care, trust in the physician, patient participation) have a significant association with outcomes (pain, disability, quality of life, pain-related psychological impairment) after a multimodal treatment program (rehabilitation) after adjusting for a number of sociodemographic, medical, and psychological factors. Results show that the patient-physician relationship is significantly associated with the outcome. In the medium term (6 months after rehabilitation), the effect of the patient-physician relationship is clearer than in the short term (end of rehabilitation). In addition, risk factors for less improvement are female gender, higher age, low income, comorbidity, low treatment motivation, fear avoidance beliefs, and external locus of control. Future studies should examine the causal paths between the relationship variables and the outcome variables.

Taking into account patients' communication preferences: instrument development and results in chronic back pain patients.

OBJECTIVE: The objective is to develop an instrument that measures the extent of matching between patient communication preferences and physician communication behavior and takes various essential aspects of patient-provider communication into consideration. Furthermore we give a description of communication preferences and matching for chronic back pain patients. METHODS: Using an existing questionnaire for assessing patient communication preferences (named KOPRA), a questionnaire on the communication behavior of physicians (KOVA questionnaire) was developed with identical contents. Combining KOPRA and KOVA items results in preference-matching items. N=703 patients were surveyed. RESULTS: After item selection all scales of the KOVA questionnaire are unidimensional, reliable, and satisfy the requirements of an item response theory model. The preference-matching scales are also unidimensional and reliable (Cronbach's alpha .87-.91). In addition, there is evidence of the validity of both instruments. Matching between communication preferences and behavior is relatively high overall, but there are some areas with clear discrepancies. CONCLUSION AND PRACTICE IMPLICATIONS: The preference-matching scales allow areas to be identified in which physicians are not very successful in addressing the communication preferences of patients. With back pain patients, physicians should take particular consideration of the very great need for open communication and information about further treatment.

High-capacity adenoviral vectors circumvent the limitations of ΔE1 and ΔE1/ΔE3 adenovirus vectors to induce multispecific transgene product-directed CD8 T-cell responses.

BACKGROUND: The ability to induce cytotoxic T lymphocyte (CTL) responses that are multispecific is considered to comprise an essential feature for an efficacious genetic vaccine against many pathogens including HIV and hepatitis C virus. ΔE1Ad vectors are promising vectored vaccines but have been shown to induce antigen-specific CTLs with only limited multispecificity. In the present study, we investigated the applicability of gene-deleted high-capacity adenovirus (HC-Ad) vectors and focused on the induction of multispecific CTL responses. METHODS: We generated Δ E1 and HC-Ad vectors expressing hepatitis B virus small surface antigen (HBsAg). We comparatively analyzed the CTL profiles against various transgene product- and vector-derived epitopes in several mouse strains and HBsAg- and vector-directed antibody responses. RESULTS: HC-Ad vectors efficiently induced multispecific HBsAg-directed CTLs. By contrast, ΔE1Ad vectors mainly primed CTLs against one immunodominant epitope of HBsAg. This absence of multispecific CTL responses correlated with the induction of CTLs against viral epitopes generated by de novo expression of Ad genes from the ΔE1Ad vector. However, Ad-specific CTLs induced in trans did not impair HC-AdS-induced multispecific CTL responses against HBsAg. Finally, HC-Ad vectors also induced higher HBsAg antibody titers compared to ΔE1Ad vectors. CONCLUSIONS: De novo expression of viral genes from ΔE1Ad vector genomes restricts the multispecificity of transgene product-specific CTLs by immunodominance effects. HC-Ad vectors devoid of Ad genes are favorable for the induction of both multispecific CD8 T-cell responses and high antibody responses. Our results suggest the deletion of Ad genes as an important means for developing potent Ad-based vectored vaccines.

The congruence of patient communication preferences and physician communication behavior in cardiac patients.

BACKGROUND: The purpose of this study was to examine the communication preferences of patients with chronic ischemic heart disease (CIHD) and matching between the preferences and physician communication behavior. Prior to this, psychometric testing was performed on a questionnaire on the perceived communication behavior of the physician (KOVA Questionnaire). METHODS: Patients with CIHD undergoing rehabilitation (N = 342) in Germany were questioned. At the beginning of rehabilitation, patients answered questions about their communication preferences (KOPRA Questionnaire), and at the end of rehabilitation, they answered questions regarding the perceived communication behavior of the physician. Preference-matching values were determined by combining the KOPRA and KOVA items. RESULTS: The KOVA Questionnaire psychometric properties proved to be good. Patients with CIHD indicated clear and open communication and patient participation were especially important. This was followed by emotionally supportive communication and, finally, communication about personal things. Overall, the behavior of physicians corresponded quite closely with the patients' communication preferences. However, preference matching was low (the physicians demonstrated too little of the desired behavior) regarding the open communication of bad news and explanation of treatments. There was relatively high fulfillment of expectations on the part of patients in terms of seeking information from the physician, the physician's explanation of the diagnosis, and regarding aspects of shared decision making. We observed no gender differences, but did identify age-group differences. CONCLUSIONS: The instruments developed (KOPRA and KOVA questionnaires) can be used for communication studies of patients with chronic conditions. However, some patient communication needs seem to require greater consideration from physicians.

Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells.

In vivo gene transfer with adenovirus vectors would significantly benefit from a tight control of the adenovirus-inherent liver tropism. For efficient hepatocyte transduction, adenovirus vectors need to evade from Kupffer cell scavenging while delivery to peripheral tissues or tumors could be improved if both scavenging by Kupffer cells and uptake by hepatocytes were blocked. Here, we provide evidence that a single point mutation in the hexon capsomere designed to enable defined chemical capsid modifications may permit both detargeting from and targeting to hepatocytes with evasion from Kupffer cell scavenging. Vector particles modified with small polyethylene glycol (PEG) moieties specifically on hexon exhibited decreased transduction of hepatocytes by shielding from blood coagulation factor binding. Vector particles modified with transferrin or, surprisingly, 5,000 Da PEG or dextran increased hepatocyte transduction up to 18-fold independent of the presence of Kupffer cells. We further show that our strategy can be used to target high-capacity adenovirus vectors to hepatocytes emphasizing the potential for therapeutic liver-directed gene transfer. Our approach may lead to a detailed understanding of the interactions between adenovirus vectors and Kupffer cells, one of the most important barriers for adenovirus-mediated gene delivery.

The Berlin tradition in Chicago: Franz Alexander and the Chicago Institute for Psychoanalysis.

Freud considered Franz Alexander, the first graduate of the Berlin Psychoanalytic Institute and an assistant in the Berlin Polyclinic, to be "one of our strongest hopes for the future." Alexander went on to become the first director of the Chicago Institute for Psychoanalysis in 1932 and modeled some of the Chicago Institute's mission on his Berlin experiences. He was also a researcher in psychosomatic medicine, a prolific writer about psychoanalysis and prominent in psychoanalytic organizations. As he proposed modifications in psychoanalytic technique, he became a controversial figure, especially in the elaboration of his ideas about brief therapy and the corrective emotional experience. This paper puts Alexander's achievements in historical context, draws connections between the Berlin and Chicago Institutes and suggests that, despite his quarrels with traditional psychoanalysis, Alexander's legacy may be in his attitude towards psychoanalysis, characterized by a commitment to scientific study, a willingness to experiment, and a conviction about the role of psychoanalysis within the larger culture.

Recombinant complexes of antigen with stress proteins are potent CD8 T-cell-stimulating immunogens.

Heat shock proteins (Hsp) of the Hsp70/90 families facilitate cellular immune responses to antigenic peptides or proteins bound to them and have therefore been used as vaccine vehicles. We developed an expression system in which chimeric proteins with an Hsp-capturing, viral J domain fused to diverse antigen-encoding sequences form stable complexes with eukaryotic (Hsp70, Hsp73) or bacterial (DnaK) stress proteins and accumulate to high steady-state levels. J domains from different species (viruses/SV40, bacteria/Chlamydia trachomatis or plants/Arabidopsis thaliana) efficiently capture murine or human stress proteins in this system, thus making different J domains available for vaccine production. A novel expression and purification method was developed to produce native Hsp/antigen complexes in transfectants. These purified Hsp/antigen complexes efficiently elicited antigen-specific CD8 T cell responses in mice when delivered as vaccines without adjuvants. In situ complex formation of antigen with Hsp was critical for CD8 T cell priming. Because the described expression system supports the flexible design of multivalent vaccines, it is an attractive strategy to elicit CD8 T cell responses either to recombinant proteins or to selected antigenic domains of these molecules.

Combined genetic and chemical capsid modifications enable flexible and efficient de- and retargeting of adenovirus vectors.

Numerous attempts to target viral gene therapy vectors to specific cells have met with limited success. Here we describe a novel virus vector-targeting platform based on a unique combination of genetic and chemical vector particle modifications to overcome typical restrictions in virus vector targeting. We genetically introduced cysteines at solvent-exposed positions of the adenovirus capsid. The corresponding thiol groups were highly reactive, and we established procedures for controlled covalent coupling to them of protein and nonprotein ligands. After the coupling of transferrin, the particles were efficiently targeted to the transferrin receptor pathway. Depending on the chemistry used, ligands could be coupled under the formation of thioether or disulfide bonds, the latter allowing for separation of ligand and particle after cell entry in the endosome. Furthermore, this technology could be efficiently combined with vector shielding for true retargeting: after amino-PEGylation of the vector particles the genetically introduced thiols were still accessible for ligand coupling, and particles could be retargeted to the transferrin receptor. Since this platform is robust, can be scaled, is compatible with industrial standards, and can integrate chemically diverse molecules as ligands, it may be used for clinical gene therapy and, potentially, also for vaccination.

Physical properties of organic particulate UV absorbers used in sunscreens II. UV-attenuating efficiency as function of particle size.

In this study the UV-attenuating properties of microparticles consisting of a benzotriazole derivative were investigated, which are used as absorbers for UV radiation in cosmetic sunscreens. The particles were micronized in presence of a dispersing agent by means of a ball milling process. According to the energy input different particle sizes were produced in the range of 0.16 to 4 microm. In order to study even smaller particles, the sample with particle size 0.16 microm was fractionated further by centrifugation. Particle sizes were measured using fiberoptic quasi-elastic light scattering (FOQELS) and laser diffractometry. The UV-attenuating properties of the dispersions with different particle sizes were assessed using UV spectroscopy. With decreasing particle size the efficiency of the UV extinction of the dispersion increases up to a particle size of 80 nm. For particles smaller than 80 nm the UV extinction decreases again indicating an optimum at 80 nm. From reflection spectroscopic measurements it was found that scattering makes about 10%, and absorption 90%, of the UV-attenuating effect of the particles, which are obtained at the end of the milling process.

Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority.

Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl, induces major cytogenetic remission (MCR) or complete cytogenetic remission (CCR) in the majority of patients with CML in first chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome-negative (Ph-) cells. To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph- clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR.