Hind feet position score: A novel trait to genetically reduce lameness incidence.

Lameness is an important health and welfare issue that causes considerable economic losses in dairy herds. The objective of this study was to investigate whether the hind feet position score (HFPS) can be used as an auxiliary trait for genetic evaluation of lameness. The HFPS is evaluated by visual scoring of the position of both the hind-digits to the mid-line of the cow's body. The higher the heel height of the lateral claw, the higher is the HFPS, and the higher is the risk for development of lameness. In total, 3,478 records from 1,064 Fleckvieh cows from 35 farms were obtained between September 1, 2021, and March 5, 2022. Data collection was carried out by the regional milk recording organizations. Hind feet position was scored visually by trained personnel during routine milk performance testing in the milking parlor using a 3-class scoring system: score 1 = 0° to <17° indicating a balanced heel height of both the medial and the lateral claw; score 2 = angle of 17° to 24°; score 3 = angle of >24°. After all cows had been milked, locomotion scoring was performed for each animal using a 5-class scoring system with locomotion scores ranging between 1 (normal) and 5 (severely lame). Using HFPS, sensitivity and specificity were 69.5% and 66.8%, respectively, for detecting lameness defined by locomotion score ≥2. For genetic analyses, a bivariate linear animal model was fitted with fixed effects of herd, parity, lactation stage, and classifier, and random effects of animal and permanent environment. Heritabilities for HFPS and locomotion score were 0.07 and 0.10, respectively, and the genetic correlation between the 2 traits studied was 0.80. These results suggest that the HFPS could be used for genetic evaluations to reduce lameness incidence in dairy cattle.

Food craving in daily life: comparison of overweight and normal-weight participants with ecological momentary assessment.

BACKGROUND: The present study examined food cravings in daily life by comparing overweight and normal-weight participants right before eating events and at non-eating moments. It was hypothesised that overweight participants would have (i) more frequent, (ii) stronger and (iii) a greater variety of high-caloric palatable food cravings, and also would (iv) consume more high-caloric palatable foods, than normal-weight participants. METHODS: Ecological momentary assessment (EMA) was used to assess food craving strength and frequency, variety of specific food cravings, and food intake. Fifty-seven overweight and 43 normal-weight adult participants were assessed at eating events and at an average of eight random non-eating moments per day for 2 weeks. Foods were categorised as: high-caloric high palatable foods (HCHP), fruits and salads, staple food dishes and sandwiches, and soups and yoghurts. RESULTS: Overweight participants reported more frequent HCHP food cravings specifically at non-eating moments than did normal-weight participants. Normal-weight participants reported more food cravings for staple foods, specifically at eating events. Moreover, overweight participants craved a greater variety of HCHP foods than normal-weight participants at both eating events and random non-eating moments. No other significant between-group differences were found. CONCLUSIONS: The results highlight the importance for obesity interventions (i) to specifically target high-caloric palatable food cravings that are experienced during the day and are not tied to eating moments and (ii) to aim for a reduction in the variety of high-caloric palatable food cravings. It might be fruitful to deliver treatment aimed at reducing cravings via mobile devices because this allows for easy individual tailoring and timing of interventions.

[Cognitive therapy and interpersonal psychotherapy for major depressive disorder: how do they work, how long, and for whom?] / Cognitieve therapie en interpersoonlijke psychotherapie voor depressie: hoe werken ze, hoe lang en voor wie?

BACKGROUND: Although the effectiveness of cognitive therapy (ct) and interpersonal psychotherapy (ipt) for depression has been well established, little is known about how, how long and for whom they work.
AIM: To summarize findings from a large rct to the (differential) effects and mechanisms of change of ct/ipt for depression.
METHOD: 182 adult depressed outpatients were randomized to ct (n = 76), ipt (n = 75), or a two-month wait-list-control condition (n = 31). Primary outcome was depression severity (bdi-ii). Other outcomes were quality of life, social and general psychological functioning and various potential process measures. Interventions were compared at the end of treatment, and up to 17 months follow-up.
RESULTS: Overall, ct and ipt were both superior to the wait-list, but did not differ significantly from one another. However, the pathway through which therapeutic change occurred appeared to be different for ct and ipt, and many patients were predicted to have a clinically meaningful advantage in one of the two interventions. We did not find empirical support for the theoretical models of change.
CONCLUSION: (Long-term) outcomes of ct and ipt appear to not differ significantly. The field would benefit from further refinement of research methods to disentangle mechanisms of change, and from advances in the field of personalized medicine.

Optimization of laboratory procedures for intrauterine insemination: survey of methods in relation to clinical outcome.

BACKGROUND: There is a wide practice variation of used methods and outcomes in IUI in fertility laboratories. Standardization of the IUI procedure is important for reducing inconsistency among laboratories in counseling infertile couples and in pregnancy results. The aim of the study was to evaluate the currently used laboratory procedures of IUI in Dutch fertility laboratories and their effect on IUI pregnancy results. Additionally, the methods for semen analysis (SA) were evaluated, as SA is related to IUI in terms of inseminated sperm number and IUI counseling. MATERIAL AND METHODS: This questionnaire survey study was sent to laboratories participating in the Dutch external quality control program for semen analysis (SKML) and consisted of 46 questions concerning laboratory management, methods for semen analysis and IUI, and clinical results. The results were analyzed using univariable and multivariable logistic regression models. RESULTS: A total of 52 laboratories (out of 99) provided information on used methodologies for SA or laboratory procedures of IUI and the organization of the laboratory. A wide variability was confirmed in used methods for both SA and IUI. Evaluation of pregnancy results obtained during 3 years (2013-2015) showed that specific used laboratory methods have a significant effect on the probability of becoming pregnant. DISCUSSION AND CONCLUSION: Important to remark is that in this survey study cycle-specific data, including variables of the individual couples (age, stimulation protocol, etc), were not included and may have effects on the results. The reported results provide an overview of the current practice performance; however, the organization of fertility laboratories is changing rapidly. The use of standardized methods in IUI is important for optimizing the performance of care and improving pregnancy results. The knowledge on used procedures, however, is limited, and further research on factors involving SA and the IUI procedure is necessary.

Techniques used for IUI: is it time for a change?

STUDY QUESTION: Are the guidelines for the technical aspects of IUI (WHO, 2010) still in accordance with the current literature? SUMMARY ANSWER: In general, the laboratory guidelines of the World Health Organization (WHO) are a suitable protocol, although the evidence is not always conclusive and some changes are advisable. WHAT IS KNOWN ALREADY: Lack of standardization of the technical procedures required for IUI might result in inter-laboratory variation in pregnancy rates. Most centers still use their own materials and methods even though some guidelines are available. STUDY DESIGN, SIZE, DURATION: A structural review focusing on the association between pregnancy rates and the procedures of semen collection (e.g. ejaculatory abstinence, collection place), semen processing (e.g. preparation method, temperature during centrifugation/storage), insemination (e.g. timing of IUI, bed rest after IUI) and the equipment used. PARTICIPANTS/MATERIALS, SETTING, METHODS: A literature search was performed in Medline and the Cochrane library. When no adequate studies of the impact of a parameter on pregnancy results were found, its association with sperm parameters was reviewed. MAIN RESULTS AND THE ROLE OF CHANCE: For most variables, the literature review revealed a low level of evidence, a limited number of studies and/or an inadequate outcome measure. Moreover, the comparison of procedures (i.e. semen preparation technique, time interval between semen, collection, processing and IUI) revealed no consensus about their results. It was not possible to develop an evidence-based, optimal IUI treatment protocol. LIMITATIONS, REASONS FOR CAUTION: The included studies exhibited a lack of standardization in inclusion criteria and methods used. WIDER IMPLICATIONS OF THE FINDINGS: This review emphasizes the need for more knowledge about and standardization of assisted reproduction technologies. Our literature search indicates that some of the recommendations in the laboratory guidelines could be adapted to improve standardization, comfort, quality control and to cut costs. STUDY FUNDING/COMPETING INTEREST(S): The Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands. S.K. and W.N. have no conflicts of interest to disclose. C.B. and A.W. are members of the board of the SKML. With a grant from SKML, L.L. was paid for her time to perform the research and write the publication. D.B. received grants from Merck Serono, Ferring and MSD, outside the submitted work. REGISTRATION NUMBER: N/A.

[A population-targeted approach to connect prevention, care and welfare: visualising the trend]. / Populatiegerichte aanpak voor verbinding van preventie, zorg en welzijn.

OBJECTIVE: To map initiatives in the Netherlands using a population-targeted approach to link prevention, care and welfare. DESIGN: Descriptive investigation, based on conversations and structured interviews. METHOD: We searched for initiatives in which providers in the areas of prevention, care and welfare together with health insurers and/or local authorities attempted to provide the 'triple aim': improving the health of the population and the quality of care, and managing costs. We found potential initiatives on the basis of interviews with key figures, project databases and congress programmes. We looked for additional information on websites and via contact persons to gather additional information to determine whether the initiative met the inclusion criteria. An initiative should link prevention, care and welfare with a minimum of three players actively pursuing a population-targeted goal through multiple interventions for a non-disease specific and district-transcending population. We described the goal, organisational structure, parties involved, activities and funding on the basis of interviews conducted in the period August-December 2015 with the managers of the initiatives included. RESULTS: We found 19 initiatives which met the criteria where there was experimentation with organisational forms, levels of participation, interventions and funding. It was noticeable that the interventions mostly concerned medical care. There was a lack of insight into the 'triple aim', mostly because data exchange between parties is generally difficult. CONCLUSION: There is an increasing number of initiatives that follow a population-targeted approach. Although the different parties strive to connect the three domains, they are still searching for an optimal collaboration, organisational form, data exchange and financing.

Clinical effectiveness of cognitive therapy v. interpersonal psychotherapy for depression: results of a randomized controlled trial.

BACKGROUND: Although both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have been shown to be effective treatments for major depressive disorder (MDD), it is not clear yet whether one therapy outperforms the other with regard to severity and course of the disorder. This study examined the clinical effectiveness of CT v. IPT in a large sample of depressed patients seeking treatment in a Dutch outpatient mental health clinic. We tested whether one of the treatments was superior to the other at post-treatment and at 5 months follow-up. Furthermore, we tested whether active treatment was superior to no treatment. We also assessed whether initial depression severity moderated the effect of time and condition and tested for therapist differences. METHOD: Depressed adults (n = 182) were randomized to either CT (n = 76), IPT (n = 75) or a 2-month waiting list control (WLC) condition (n = 31). Main outcome was depression severity, measured with the Beck Depression Inventory - II (BDI-II), assessed at baseline, 2, 3, and 7 months (treatment phase) and monthly up to 5 months follow-up (8-12 months). RESULTS: No differential effects between CT and IPT were found. Both treatments exceeded response in the WLC condition, and led to considerable improvement in depression severity that was sustained up to 1 year. Baseline depression severity did not moderate the effect of time and condition. CONCLUSIONS: Within our power and time ranges, CT and IPT appeared not to differ in the treatment of depression in the acute phase and beyond.

Revealing the dynamic network structure of the Beck Depression Inventory-II.

BACKGROUND: Structured interviews and questionnaires are important tools to screen for major depressive disorder. Recent research suggests that, in addition to studying the mean level of total scores, researchers should focus on the dynamic relations among depressive symptoms as they unfold over time. Using network analysis, this paper is the first to investigate these patterns of short-term (i.e. session to session) dynamics for a widely used psychological questionnaire for depression - the Beck Depression Inventory (BDI-II). METHOD: With the newly developed vector autoregressive (VAR) multilevel method we estimated the network of symptom dynamics that characterizes the BDI-II, based on repeated administrations of the questionnaire to a group of depressed individuals who participated in a treatment study of an average of 14 weekly assessments. Also the centrality of symptoms and the community structure of the network were examined. RESULTS: The analysis showed that all BDI-II symptoms are directly or indirectly connected through patterns of temporal influence. In addition, these influences are mutually reinforcing, 'loss of pleasure' being the most central item in the network. Community analyses indicated that the dynamic structure of the BDI-II involves two clusters, which is consistent with earlier psychometric analyses. CONCLUSION: The network approach expands the range of depression research, making it possible to investigate the dynamic architecture of depression and opening up a whole new range of questions and analyses. Regarding clinical practice, network analyses may be used to indicate which symptoms should be targeted, and in this sense may help in setting up treatment strategies.

Management of dermatologic toxicities related to epidermal growth factor receptor inhibitor therapy across Europe: can we get a consensus?

To date, there are no phase III trial data that can guide healthcare professionals in managing toxicities of epidermal growth factor receptor inhibitors (EGFRIs). This exploratory survey assessed the similarities and differences in nursing management of EGFRI-related toxicities across 10 European countries. A questionnaire that was sent to ten nurses who specialize in the treatment of patients with EGFRI asked about the prevention and treatment of acneiform rash, dry skin/eczema, fissures, paronychia, and pyogenic granuloma. Responses from seven nurses showed that overall (with the exception of rash), treatment differed markedly between countries in the management of dermatologic toxicities. These substantial differences across the European hospitals surveyed suggest that it might be worthwhile to develop treatment algorithms by conducting a consensus conference or a follow-up survey with several assessments and a larger sample.

Clinical and organizational content of clinical pathways for digestive surgery: a systematic review.

BACKGROUND/AIMS: Oncology surgery of the gastrointestinal tract is complex and infamous for its high complication rates. One of the methods for implementing interventions to optimize the patients' condition and to enhance postoperative outcome is the development and implementation of a clinical pathway. The aim of this study was to analyze the content, i.e. the interventions of clinical pathways for digestive surgery and their effects on postoperative outcome measures. METHODS: We performed a systematic review to study clinical pathways in hospital care for adult patients undergoing elective surgery of the stomach, esophagus, pancreas, liver, colon or rectum. The MEDLINE, EMBASE and CINAHL literature databases were searched. RESULTS: The most common interventions in the clinical pathways in this review were defined in the pre- and postoperative phase and included: nutritional management, pain management, mobilization, education and discharge planning. The primary aim of these interventions was to enhance postoperative recovery. CONCLUSION: Clinical pathways for digestive surgery contain specific interventions to improve postoperative outcome. Most of these interventions are in accordance with the Enhanced Recovery After Surgery (ERAS) protocol, which is an evidence-based protocol for care after colon resections. They result in reduced length of stay without compromising other postoperative outcome measures.

Implementation of outpatient preoperative evaluation clinics: facilitating and limiting factors.

BACKGROUND: Several studies have shown that outpatient preoperative evaluation by anaesthetists increases quality of care and is cost-effective. The aim of this study was to gain insight into the factors that positively or negatively influence the implementation of outpatient preoperative evaluation clinics (OPE clinics). METHODS: After an extensive literature study and pilot interviews, we constructed written questionnaires that were sent to all Dutch hospitals. The respondents were members of the board of directors, members of the medical staff, anaesthetists, internists, and surgeons. RESULTS: Cooperation of anaesthetists was most frequently mentioned as facilitating factor for implementation of an OPE clinic across all medical specialists interviewed. Lack of finance was most frequently reported as limiting factor in all categories of hospitals (with a complete, partial, or no OPE clinic), but it was significantly more often reported in hospitals without OPE clinic (P<0.01). Perceived benefits and disadvantages, financial rewarding system, and organizational structure played a clear role in the implementation of OPE clinics. CONCLUSIONS: A variety of factors play a role in the implementation of an OPE clinic. Besides the more obvious ones, such as financing and cooperation of the professional groups involved, underlying factors, such as perceptions of the professionals involved, were found to be related to implementation of an OPE clinic. These underlying factors explain differences between different kinds of hospitals and between professional groups, regarding their resources and motivation to implement an OPE clinic.

The effect of national guidelines on the implementation of outpatient preoperative evaluation clinics in Dutch hospitals.

BACKGROUND AND OBJECTIVES: Preoperative evaluation performed by anaesthesiologists primarily aims to estimate the risk of perioperative complications and to create opportunities to optimize the patients' condition before surgery. In this study an inventory was made of the current practice of preoperative evaluation in Dutch hospitals. It was estimated how many hospitals had implemented an outpatient preoperative evaluation clinic in 2004. Subsequently, current practice was compared with the results of a previous inventory (2000). It was also evaluated to what extent the guidelines of the Dutch Health Council and the Netherlands Society of Anaesthesiology were followed. METHODS: The study consisted of two phases. First, a literature research was performed and pilot interviews were constructed. The interviews were conducted face-to-face with anaesthesiologists in a sample of Dutch hospitals. Based on the results, written questionnaires were constructed. In the second phase these questionnaires were sent to all general and academic hospitals in the Netherlands. RESULTS: In 2004, 74% of the hospitals had an outpatient preoperative evaluation clinic, compared with 50% in 2000. The percentage of hospitals with an outpatient preoperative evaluation clinic available for all elective patients increased from 20% to 52%. CONCLUSIONS: The Dutch guidelines on preoperative evaluation seem to have influenced current practice. An increase in the number of outpatient preoperative evaluation clinics was seen after the guidelines were published. The implementation of an outpatient preoperative clinic seems to warrant that anaesthesiologists are carrying out the activities prescribed by the guidelines. Most hospitals without a clinic aim to implement one in the future.

Blocking temperature in magnetic nanoclusters.

A recent study of non-extensive phase transitions in nuclei and nuclear clusters needs a probability model compatible with the appropriate Hamiltonian. For magnetic molecules a representation of the evolution by a Markov process achieves the required probability model that is used to study the probability density function (PDF) of the order parameter, i.e., the magnetization. The existence of one or more modes in this PDF is an indication for the super-paramagnetic transition of the cluster. This allows us to determine the factors that influence the blocking temperature, i.e., the temperature related to the change of the number of modes in the density. It turns out that for our model, rather than the evolution of the system implied by the Hamiltonian, the high temperature density of the magnetization is the important factor for the temperature of the transition. We find that an initial probability density function with a high entropy leads to a magnetic cluster with a high blocking temperature.

Giant diverticulum of the colon: report of two new cases and review of the literature.

Diverticulosis coli affects more than one in three individuals older than 65 in the Western world. Giant diverticulum of the colon is an extremely rare complication of diverticular disease; only 113 cases, mostly situated in the colon sigmoideum, have been reported in the world literature. Two new cases of giant diverticulum of the colon sigmoideum, with totally different clinical presentation, diagnosis, and management, are reported-one being the cause of chronic anemia and the other presenting as an acute abdomen. Based on a review of the literature, an update on symptomatology, diagnosis, pathogenesis, and therapeutical options of this rare disorder is provided.

Treatment of active Crohn's disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study.

BACKGROUND: Monoclonal antibodies to the pro-inflammatory cytokine tumour necrosis factor-alpha have shown efficacy in treating Crohn's disease, but can be immunogenic. Soluble tumour necrosis factor-binding proteins are being studied as potential alternative anti-tumour necrosis factor agents in Crohn's disease. AIM: To investigate the safety and efficacy of onercept, a recombinant form of the natural human soluble p55 tumour necrosis factor receptor, in the treatment of patients with active Crohn's disease. METHODS: In a pilot study, 12 patients with active Crohn's disease were randomized to receive onercept at either 11.7 or 50 mg three times weekly for 2 weeks. Patients were followed up for 6 months after the end of treatment. RESULTS: The Crohn's disease activity index decreased rapidly during treatment in both groups. Seven responses (Crohn's disease activity index decrease of 100 points) were observed over the first 6 weeks of the study, including five remissions (Crohn's disease activity index decrease of 150 points). Improvement was sustained for 2-4 months after stopping treatment. Treatment was well tolerated. No patients developed antibodies to onercept. CONCLUSIONS: Neutralizing the activity of tumour necrosis factor-alpha with its soluble p55 receptor may be valuable in the treatment of patients with Crohn's disease. Larger placebo-controlled trials are indicated.

Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial.

OBJECTIVES: Etanercept, an injectable tumor necrosis factor (TNF) receptor fusion protein, binds and inactivates human TNF and is used in active rheumatoid arthritis. Blocking TNF with monoclonal antibodies has also been beneficial in Crohn's disease. We attempted to determine the efficacy and safety of etanercept for induction of clinical, endoscopic, and histological improvement in patients with moderate to severe Crohn's disease despite standard treatment. METHODS: Ten patients with active Crohn's disease were treated with etanercept (25 mg s.c.) twice per week for 12 wk. Background therapy was kept stable during the trial. Crohn's disease activity index (CDAI), Inflammatory Bowel Disease Questionnaire, and C-reactive protein levels were measured at weeks 0, 2, 4, 8, and 12. Colonoscopies were performed before and after therapy in responders; endoscopic biopsies were scored for inflammation. RESULTS: At week 2 after the start, a clinical response (deltaCDAI > or = 70) was observed in 6/10 patients (median = 305 [294-418] to 166 [107-392]), with reduction in serum C-reactive protein levels (median = 17.2 [6.8-67.2] to 9.1 [0.9-17.2] mg/dl). Colonoscopies showed a reduction in inflammatory lesions in the four patients who attained remission (CDAI < 150), whereas the inflammatory score of the biopsies did not decrease significantly. No moderate or severe adverse events were observed. CONCLUSIONS: Etanercept may be effective in Crohn's disease refractory to standard therapy.

Density of a gas of spin-polarized fermions in a magnetic field.

For a fermion gas with equally spaced energy levels that is subjected to a magnetic field, the particle density is calculated. The derivation is based on the path integral approach for identical particles, in combination with the inversion techniques for the generating function of the static response functions. Explicit results are presented for the ground state density as a function of the magnetic field with a number of particles ranging from 1 to 45.

Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis.

BACKGROUND & AIMS: Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids. METHODS: Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy. RESULTS: Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed. CONCLUSIONS: Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC.

Chondrosarcoma of the hyoid bone.

The CT and MRI findings in a case of chondrosarcoma of the hyoid bone are reported. Although chondrosarcoma is the second most common primary malignant bone tumor, only 10 % of chondrosarcomas occur in the head and neck region. The hyoid bone is a rare site of involvement with only seven cases reported previously.

[Leukemia and pre-leukemic conditions occurring after treatment of breast cancer]. / Leucémies et états préleucémiques survenus après traitement d'un cancer du sein.

OBJECTIVE: The purpose of this study was to determine the clinical and prognostic features of leukemias and preleukemic states, whatever the mode of development, observed in patients after treatment of breast cancer. PATIENTS AND METHODS: A retrospective multicentric analysis was made of 121 patients treated for breast cancer and who later developed leukemia or a preleukemic state. Initially, 44 patients had undergone mastectomy, 72 had conservative surgery and 119 had locoregional irradiation. At least one chemotherapy session was performed in 90 patients and 48 had received tamoxifen. The risk of relapse of breast cancer was high, moderate or low for 44, 46 and 24 patients respectively (data not available for 7 patients). RESULTS: By class, the hematology diseases found were: myelodysplasia (n = 9), refractory anemia with blast excess (n = 7), acute lymphoblastic leukemia (n = 6), acute myoblastic leukemia (n = 93 including a majority of type 2 and type 4). For acute myeloblastic leukemia, mean delay to onset was 65 and 37 months respectively without and after chemotherapy. The prognosis of these cases of leukemia and preleukemic states was poor with an overall death rate of 86%. CONCLUSION: In light of the recent development of indications for adjuvant chemotherapy even for subgroups of patients at moderate risk, it is important to more precisely assess the absolute benefit in terms of survival compared with the risk of severe complications, particular secondary leukemia. In the future, a systematic registry and a case-control study are required.