Influence of Nutritional Status on a Family-Centered Care Intervention for Older Adults with Cognitive Impairment following Hip-Fracture Surgery: Secondary Data Analysis of a Randomized Controlled Trial.

OBJECTIVES: In Taiwan, older adults with cognitive impairment who undergo hip-fracture surgery are routinely cared for by family members. This study aimed to determine if nutritional status influenced the effects of a family-centered intervention for older adults with cognitive impairment recovering from hip-fracture surgery. DESIGN: Secondary data analysis of data from a randomized controlled trial was conducted to examine the influences of nutritional status 1 month after hospital discharge on the effects of a family-centered care intervention model, which was designed for older adults with hip fracture and cognitive impairment. Outcomes were compared among participants according to nutrition status (well-nourished/poorly-nourished) and treatment approach (control/intervention). SETTING: The original study was conducted at a 3000-bed medical center from July 2015 to October 2019. PARTICIPANTS: Participants were older adults with cognitive impairment who had undergone hip-fracture surgery. Participants were assessed as poorly-nourished or well-nourished with the Mini-Nutritional Assessment (MNA) 1-month post-discharge and were then randomly assigned to either the intervention group or control group. INTERVENTION: A family-centered intervention model for family caregivers of older adults with cognitive impairment recovering from hip-fracture surgery was implemented. The intervention was delivered by geriatric nurses, which included instructions for family caregivers in overseeing exercises for strengthening the hip, understanding dietary requirements, and managing behavioral problems associated with cognitive impairment. MEASUREMENTS: Outcome measures included activities of daily living (ADLs), instrumental ADLs, hip range of motion, hip muscle strength, depression, measured with the Geriatric Depressive Scale, and physical and mental health related quality of life, measured with the Short Form Survey (SF-36), Taiwanese version. Participants were assessed at 1-, 3-, 6-, and 12-months post-discharge. RESULTS: Most of the 134 participants were assessed as poorly nourished (n = 122); 57 were the control group and 65 received the intervention. For the well-nourished participants (n = 12), four were in the intervention group and eight were controls. There were no significant differences in any outcome variables for poorly nourished participants who received the intervention compared with controls. For the sample of well-nourished participants, those who received the intervention performed significantly better in outcomes of IADLs (b = 1.74, p < .05), hip muscle strength (b = 9.64, p < .01), and physical health related quality of life (b = 10.47, p < .01). CONCLUSION: The family-centered care intervention was only effective for older adults with cognitive impairment recovering from hip-fracture surgery who were well-nourished at 1 month following hospital discharge, but not for those at risk of malnutrition. Interventions should focus on enhancing nutritional status following hip surgery which could allow the family-centered in-home intervention to be beneficial for more older adults with cognitive impairment recovering from hip-fracture surgery.

Fostering School Belonging and Students' Well-Being Through a Positive School Interethnic Climate in Diverse High Schools.

BACKGROUND: School belonging has been linked to students' health and well-being. As US schools become more ethnically diverse, it is important to understand how schools can contribute to a sense of belonging for students from all ethnic groups. METHODS: The present study examines the association between school interethnic climate, school belonging, and 3 well-being indicators (psychological, physical, and academic) among 657 10th graders across 2 states. RESULTS: Positive school interethnic climate was associated with stronger feelings of school belonging, and was indirectly associated with better psychological adjustment, fewer physical symptoms, and better grades via school belonging. There were no differences between White and non-White students in the findings. CONCLUSIONS: Focusing on fostering a positive interethnic atmosphere may be a useful target for schools to support students' health and well-being as well as academic performance.

In the Aftermath of School Victimization: Links Between Authoritative School Climate and Adolescents' Perceptions of the Negative Effects of Bullying Victimization.

Although authoritative school climate-strict, yet fair enforcement of rules alongside strong adult support-is associated with lower rates of bullying victimization, less is known about whether it influences how negatively adolescents feel after being victimized at school. Further, it is unclear whether boys and girls respond differently to an authoritative climate. Identifying ways that schools can reduce negative feelings after being bullied is important given the long term psychological ramifications of bullying that, if left unaddressed, can extend into adulthood. To address these gaps, this study examined whether authoritative school climate related to how negatively adolescents felt about their schoolwork, relationships, physical health and self-perception after being bullied. Differences between boys and girls were also investigated. Analyses were conducting using national data from the 2017 School Crime Supplement on a sample of 1,331 adolescents aged 12 to 18 years (Mage = 14.3 years; 59% girls). Findings from a set of ordinal regression models with a robust set of student, parent and school controls demonstrated that adolescents in more supportive schools were less likely to report that bullying victimization negatively impacted their schoolwork and feelings about themselves. Similar results were found for girls but not boys. By investing in supportive school climates, schools can be potentially transformative places where adolescents, especially girls, can feel more positively about themselves despite being bullied.

Maintaining breast cancer care in the face of COVID-19.

The battle of COVID-19 is currently at different levels of intensity in each country and even each city. The authors have prepared succinct recommendations regarding the care of patients with breast cancer, divided into phases that can easily be adapted to each units' needs and resources, and stepped up or stepped down according to escalating and de-escalating circumstances. The structure can also be transposed easily to different cancer types, enabling continued provision of best standards of care despite unprecedented stressors. Surgery must go on.

Cubital Tunnel Decompression: Equivalent Outcome Scores when Procedure Performed with Local versus General Anesthetic.

Background Ulnar nerve compression at the cubital tunnel is the second commonest upper limb neuropathy. Unlike carpal tunnel surgery, most of decompression procedures for this condition are undertaken using general anesthesia (GA). This has inherent economic and patient safety implications. We aimed to assess if there is a difference in early and medium-term outcome scores in patients who have cubital tunnel decompression under general versus local anesthesia (LA). Materials and Methods We undertook a patient outcome evaluation of patients who were under the care of two upper limb surgeons. Patients were evaluated postoperatively using the patient-related ulnar nerve evaluation (PRUNE) questionnaire. Patients were contacted by phone, mail, and face to face in clinics. Results A total of 34 patients were identified in the study. Eleven were excluded from the study. Thirteen patients underwent surgery under LA. The LA group had their procedures performed using local infiltration of the surgical site with 20 mL of 0.5% bupivacaine with adrenaline. Ten patients had their procedures using standard GA and tourniquet. The average PRUNE score in the LA group was 33.8, and that in the GA group was 34.1. This difference in PRUNE score was not statistically significant p > 0.05. Discussion Our data suggest that there is no significant difference in early and midterm outcomes between patients who undergo cubital tunnel decompression using either GA or LA. We advocate the use of LA as it does lead to decreased anesthetic risk and has obvious economic benefits such as lowering the demands on theater and anesthetic resources.

Species interactions mediate thermal evolution.

Understanding whether populations and communities can evolve fast enough to keep up with ongoing climate change is one of the most pressing issues in biology today. A growing number of studies have documented rapid evolutionary responses to warming, suggesting that populations may be able to persist despite temperature increases. The challenge now is to better understand how species interactions, which are ubiquitous in nature, mediate these population responses to warming. Here, we use laboratory natural selection experiments in a freshwater community to test hypotheses related to how thermal evolution of Daphnia pulex to two selection temperatures (12 and 18°C) is mediated by rapid thermal evolution of its algal resource (Scenedesmus obliquus) or by the presence of the zooplankton predator Chaoborus americanus. We found that cold-evolved algae (a high-quality resource) facilitated the evolution of increased thermal plasticity in Daphnia populations selected at 12°C, for both body size and per capita growth rates (r). Conversely, warm-evolved algae facilitated the evolution of increased r thermal plasticity for Daphnia selected at 18°C. Lastly, we found that the effect of selection temperature on evolved Daphnia body size was more pronounced when Daphnia were also reared with predators. These data demonstrate that trait evolution of a focal population to the thermal environment can be affected by both bottom-up and top-down species interactions and that rapid temperature evolution of a resource can have cascading effects on consumer thermal evolution. Our study highlights the importance of incorporating species interactions when estimating ecological and evolutionary responses of populations and communities to ongoing temperature warming.

Physiological and pathological characterization of capsaicin-induced reversible nerve degeneration and hyperalgesia.

BACKGROUND: The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. METHODS: We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration-regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. RESULTS: After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. CONCLUSIONS: There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP-IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. SIGNIFICANCE: These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia.

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.

Genetic alterations and their clinical implications in older patients with acute myeloid leukemia.

A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.

Liver Transplantation in a Patient With CD40 Ligand Deficiency and Hyper-IgM Syndrome: Clinical and Immunological Assessments.

Monoclonal antibodies that disrupt CD40-CD40 ligand (CD40L) interactions are likely to have use in human transplantation. However, the extent of the immunosuppressive effects of CD40-CD40L blockade in humans is unknown. Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency syndrome characterized by defects in the CD40-CD40L pathway, severe immune deficiency (IgG), and high or normal IgM levels. However, the effects of CD40L deficiency on T- and natural killer (NK)-cell function is not established. Here, we present a patient with HIGM syndrome who underwent liver transplantation for hepatitis C virus infection. Posttransplantation, NK-cell antibody-dependent cytokine release (γ-interferon) to alloantigens and T cell responses to viral antigens and mitogens were assessed and showed normal CD4+ , CD8+ , and NK-cell responses. We also examined antibody-dependent cellular cytotoxicity against a CD40+ and HLA-expressing cell line. These experiments confirmed that the patient's NK cells were equivalent to those of normal subjects in mediating antibody-dependent cellular cytotoxicity despite the absence of CD40-CD40L interactions. Mitogenic stimulation of the patient's peripheral blood mononuclear cells showed no expression of CD40L on T and NK cells compared with increased expression in normal subjects. Taken together, these data suggest that absence of CD40L expression is responsible for aberrant B cell immunity but had little impact on NK- and T cell immune responses in vitro.

Increasing incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) in Michigan and association with clinical illness.

Infection with Shiga toxin-producing Escherichia coli (STEC) by serotypes other than O157 (non-O157) have been increasingly reported in the United States. This increase in reporting is primarily due to the improvements in diagnostic tests. We analysed 1497 STEC cases reported in Michigan from 2001 to 2012. A significant increase in the number of non-O157 STEC cases was observed over time, and similar incidence rates were observed for O157 and non-O157 STEC cases in certain time periods. The odds of hospitalization was two times higher in O157 STEC cases relative to non-O157 STEC cases when adjusted for age and gender, suggesting that O157 STEC causes more severe clinical outcomes in all age groups. The use of population-based surveillance to better define trends and associations with disease severity are critical to enhance our understanding of STEC infections and improve upon current prevention and control efforts.

Predators modify the evolutionary response of prey to temperature change.

As climate regimes shift in many ecosystems worldwide, evolution may be a critical process allowing persistence in rapidly changing environments. Organisms regularly interact with other species, yet whether climate-mediated evolution can occur in the context of species interactions is not well understood. We tested whether a species interaction could modify evolutionary responses to temperature. We demonstrate that predation pressure by Dipteran larvae (Chaoborus americanus) modified the evolutionary response of a freshwater crustacean (Daphnia pulex) to its thermal environment over approximately seven generations in laboratory conditions. Daphnia kept at 21°C evolved higher population growth rates than those kept at 18°C, but only in those populations that were also reared with predators. Furthermore, predator-mediated selection resulted in the evolution of elevated Daphnia thermal plasticity. This laboratory natural selection experiment demonstrates that biotic interactions can modify evolutionary adaptation to temperature. Understanding the interplay between multiple selective forces can improve predictions of ecological and evolutionary responses of organisms to rapid environmental change.

Cost-effective identification of Mycobacterium tuberculosis complex using microscopic morphology and rapid tests.

BACKGROUND: The rapid diagnosis of tuberculosis (TB) by detecting and identifying Mycobacterium tuberculosis complex (MTC) in clinical culture isolates can be achieved by a combination of rapid tests. OBJECTIVE: To propose a cost-effective laboratory protocol for MTC identification. DESIGN: MTC (n = 278) was identified using microscopic morphology, two immunochromatographic assays (ICAs) (Tibilia™ and MeDiPro(®) M. tuberculosis Antigen Rapid Test) and the strand displacement amplification (SDA) method (ProbeTec), and the results were compared. RESULTS: Microscopic morphology (cord-like) had a sensitivity of 99.3%, a specificity of 84.3%, a positive predictive value (PPV) of 88.2% and a negative predictive value (NPV) of 99.1%. The overall sensitivity/specificity of the Tibilia, MeDiPro and ProbeTec assays were respectively 98.7%/98.4%, 88.0%/85.2% and 97.4%/98.4%. The PPV/NPV for Tibilia, MeDiPro and ProbeTec were respectively 98.7%/98.4%, 87.4%/85.8% and 98.7%/96.8%. Cord-like microscopy was the least expensive method and could be used for the identification of MTC. ICA offers cost-effective screening compared to the SDA method. Tibilia performed better than MeDiPro, while its diagnostic value was similar to the SDA method. CONCLUSION: We recommend a combination of microscopic morphology and Tibilia to further improve the sensitivity and PPV of MTC identification at lower cost.

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

Does food store access modify associations between intrapersonal factors and fruit and vegetable consumption?

BACKGROUND/OBJECTIVES: Existing theoretical frameworks suggest that healthy eating is facilitated by an individual's ability, motivation and environmental opportunities. It is plausible, although largely untested, that the importance of factors related to ability and motivation differ under varied environmental conditions. This study aimed to determine whether the magnitude of associations between fruit and vegetable consumption and intrapersonal factors (ability and motivation) were modified by differences in access to stores selling these items (environmental opportunities). SUBJECTS/METHODS: Cross-sectional analysis of 4335 women from socioeconomically disadvantaged neighbourhoods in the state of Victoria, Australia. Self-reported fruit and vegetable consumption was assessed against a number of ability- and motivation-related factors. To examine whether associations were modified by store access, interactions with access to supermarkets and greengrocers within 2 km of participants' households were tested. RESULTS: Of the two factors related to ability and seven factors related to motivation, almost all were associated with fruit and vegetable consumption. In general, associations were not modified by store access suggesting that these factors were not tempered by environmental opportunities. CONCLUSIONS: This study provides little support for the hypothesis that the importance of intra-personal factors to fruit and vegetable consumption is modified by food store access. Further research on this topic is required to inform behaviour change interventions.

Shiga toxin-producing E. coli (STEC) in swine: prevalence over the finishing period and characteristics of the STEC isolates.

This descriptive longitudinal study was conducted to investigate the faecal shedding of Shiga toxin-producing E. coli (STEC) in finishing swine and to characterize the swine STEC isolates that were recovered. Three cohorts of finishing swine (n = 50/cohort; total 150 pigs) were included in the longitudinal study. Individual faecal samples were collected every 2 weeks (8 collections/pig) from the beginning (pig age 10 weeks) to the end (pig age 24 weeks) of the finishing period. STEC isolates were recovered in at least one sample from 65·3% (98/150) of the pigs, and the frequency distribution of first-time STEC detection during the finishing period resembled a point-source outbreak curve. Nineteen O:H serotypes were identified among the STEC isolates. Most STEC isolates (n = 148) belonged to serotype O59:H21 and carried the stx 2e gene. One O49:H21 STEC isolate carried the stx 2e and eae genes. High prevalence rates of STEC during the finishing period were observed, and STEC isolates in various non-O157 serogroups were recovered. These data enhance understanding of swine STEC epidemiology, and future research is needed to confirm whether or not swine STEC are of public health concern.

Agronomically important thrips: development of species-specific primers in multiplex PCR and microarray assay using internal transcribed spacer 1 (ITS1) sequences for identification.

Thrips, the sole vector of plant Tospovirus, are major pests of many agricultural crops throughout the world. Molecular approaches have been applied in recent decades to identify these minute and morphologically difficult to distinguish insects. In this study, sequences of internal transcribed spacer 1 (ITS1) region of 15 agronomically important thrips, including several virus transmission species, have been analyzed in order to design species-specific primers for multiplex PCR and probes for microarray assay. That the ITS1 sequence distances within species were smaller than those among species suggests that the ITS1 fragment can be used for thrips species identification. The specificity and stability of these primers, combined with universal paired primers, were tested and verified in multiplex PCR. Using these specific primers as probes, microarray assay showed that PCR products of all thrips species hybridized consistently to their corresponding probes, though some signals were weak. We have demonstrated that multiplex PCR using specific primers based on ITS1 sequences is a simple, reliable, and cost-effective diagnostic tool for thrips species identification. Moreover, the DNA microarray assay is expected to extend into a reliable high-throughput screening tool for the vast numbers of thrips.

Vesico-cutaneous fistula: a simple method for continent urinary diversion.

INTRODUCTION: Patients with lower urinary tract anomalies or neurogenic disorders often suffer from voiding difficulties. Clean intermittent catheterization (CIC) is effective for bladder drainage; however, this is often painful. Transurethral catheterization is also impossible in patients with urethral stricture. A Mitrofanoff conduit may solve some of these problems, but a few disadvantages have been reported, including: difficult surgical techniques and frequent operative complications. A vesicostomy is easy to perform but persistent urine leak over the abdomen and diaper rash can be annoying. A better way to achieve continent urinary diversion is indicated. METHOD: Between December 01 1998 and December 31 2013, six patients underwent a vesico-cutaneous fistula for CIC. The etiologies included urethral stricture (n=2) and neurogenic bladder (n=4). The fistula was created at the bladder dome with only the muscle layer of the bladder sutured to the skin. A Foley catheter was left in place for at least two weeks to prevent stoma stricture. After removing the Foley catheter, regular CIC from the fistula was performed every 2 h during the daytime with a Fr. 10-12 feeding tube, depending on the patient's age. Further stenting during the night in the first six months was necessary to prevent early closure of the fistula. Patients were followed with periodic renal ultrasonography, blood tests and urinalysis in the outpatient department. RESULTS: Follow-up ranged from 6 months to 16 years. All patients showed improvements in hydronephrosis. Decreased UTI frequency was seen in five patients. Renal function was normal in five patients, whilst the other suffered from chronic renal failure preoperatively. Only one patient had occasional mild urine leakage from the stoma at night, which was once in two weeks. No patient experienced painful or difficult catheterization and CIC becomes easy, even by young children. CONCLUSIONS: The vesico-cutaneous fistula is a simple, effective and tolerable method for CIC. It may be a substitute for or a transition to a Mitrofanoff conduit in some patients.

Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome.

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.

Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia.

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.