Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis.

We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, complete remission (CR) and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal hematopoiesis of indeterminate potential years before AML, older age, secondary AML and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2). In 82% of AML patients with LM-CH, the preleukemic clone was refractory to chemotherapy and was the founding clone for relapse. Both LM-CH and non-LM-CH MRD-positive AML patients who achieved CR had a high risk of relapse after 10 years (75% and 75%, respectively) compared with patients without clonal hematopoiesis in CR with negative MRD (27% relapse rate). Long-term survival of patients with LM-CH was only seen after allogeneic hematopoietic stem cell transplantation (HSCT). We define AML patients with LM-CH as a distinct high-risk group of AML patients that can be identified at diagnosis through mutation analysis in T cells and should be considered for HSCT.

Backward walking measures are sensitive to age-related changes in mobility and balance.

Many falls occur from backward perturbations or during transitional movements that require a person to turn and step backwards, suggesting that deficits in backward stepping may negatively impact mobility. Previous studies found significant declines in backward walking (BW) spatiotemporal measures in healthy elderly compared to young adults. No studies to date have examined BW performance in middle-aged adults and in elderly with impaired mobility. This study compared spatiotemporal measures of BW and forward walking (FW) in young, middle-aged, and elderly and in elderly fallers and non-fallers; and compared the strength of the relationship between age and BW and FW spatiotemporal measures to determine the utility of BW performance as a clinical tool for examining safety and mobility. BW measures were significantly more impaired in the elderly (n=62) compared to young (n=37) and middle-aged (n=31) adults and age effects were greater in BW than FW. No significant differences were found between young and middle-aged except for base of support in BW. Stronger correlations were found between age and BW measures than between age and FW measures, particularly correlations between age and BW velocity and stride length. Elderly fallers had greater deficits in BW performance than non-fallers. All elderly fallers had BW velocities<.6m/s. Clinicians are encouraged to assess BW, particularly BW velocity, as part of mobility examinations.

A randomized controlled trial of resistance exercise in individuals with ALS.

OBJECTIVE: To determine the effects of resistance exercise on function, fatigue, and quality of life in individuals with ALS. METHODS: Subjects with a diagnosis of clinically definite, probable, or laboratory-supported ALS, forced vital capacity (FVC) of 90% predicted or greater, and an ALS Functional Rating Scale (ALSFRS) score of 30 or greater were randomly assigned to a resistance exercise group that received a home exercise program consisting of daily stretching and resistance exercises three times weekly or to a usual care group, who performed only the daily stretching exercises. ALSFRS, the Fatigue Severity Scale (FSS), and Short Form-36 (SF-36) were completed at baseline and monthly for 6 months. FVC and maximum voluntary isometric contraction (MVIC) were monitored monthly throughout the study. RESULTS: Of 33 subjects screened, 27 were randomly assigned (resistance = 13; usual care = 14). Eight resistance exercise subjects and 10 usual care subjects completed the trial. At 6 months, the resistance exercise group had significantly higher ALSFRS and SF-36 physical function subscale scores. No adverse events related to the intervention occurred, MVIC and FVC indicated no negative effects, and less decline in leg strength measured by MVIC was found in the resistance exercise group. CONCLUSION: Our study, although small, showed that the resistance exercise group had significantly better function, as measured by total ALS Functional Rating Scale and upper and lower extremity subscale scores, and quality of life without adverse effects as compared with subjects receiving usual care.

Development, analysis, refinement, and utility of an interdisciplinary amyotrophic lateral sclerosis database.

The current status of evaluation and management provided by individual healthcare professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics needs to be analyzed. This paper describes one ALS center's experiences with the development, analysis, refinement, and utility of an interdisciplinary, HCP-driven ALS database. The purpose and conceptual framework of the database, the general data that needed to be collected, and the types of reports that needed to be generated were determined, and, in collaboration with a computer programmer, data entry and database management systems were developed. Data were collected on 234 patients between September 1996 and August 1998, and were analyzed by a biostatistician. Based on review of the biostatistician's report and discussion of problems encountered with the systems, the database was then refined. Benefits of the database system included: systematization of data collection and reporting, reduction of redundant data collection by individuals, decreased variability of evaluation methods and management decisions from patient to patient, and increased availability of a variety of uniform patient information to assist team members in making care decisions. Ongoing refinement will ensure that this HCP-driven ALS database continues to be informative, practical and effective for decision-making and enhancing delivery of care.

Physical therapy for a patient through six stages of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: This case report describes the use of Sinaki and Mulder's approach to staging amyotrophic lateral sclerosis (ALS) and functional outcome measures in designing a treatment program for a 59-year-old woman with ALS. CASE DESCRIPTION AND OUTCOMES: As the patient progressed from stage I through stage VI, over 12 months, the physical therapy goals changed from optimizing remaining function, to maintaining functional mobility, and finally to maximizing quality of life. DISCUSSION: Disease staging and the use of functional outcome measures provide a framework for physical therapy evaluation and treatment of patients with ALS throughout the disease process. Physical therapists can assist patients with ALS through the provision of education, psychological support, rehabilitation programs, and recommendations for appropriate equipment and community resources.

Trait anxiety, negative emotions, and the mothers' adaptation to an infant born subsequent to late pregnancy loss: a case-control study.

Women with (n = 27) a history of late pregnancy loss (> or = 20 weeks) due to congenital anomalies who had completed the subsequent pregnancy with a live-birth were compared with a group of mothers with newborns without such a history (n = 29) at 4 and 16 weeks post-partum. The following aspects were assessed; depression, anxiety, psychological distress, and mother-infant adaptation. The women with a previous pregnancy loss showed significantly more negative emotions than the women without such a history. In addition, they considered that their healthy baby experienced more problems with sleeping, crying, eating, and acquiring a regular pattern of this behaviour than the average baby. They also perceived their baby as being less ideal than the women without a previous pregnancy loss. These problems were particularly present 4 weeks post-partum and were significantly positively related to trait anxiety. The implications of this study are that in women with a history of late pregnancy loss, family physicians and welfare officers should be made aware of possible problems in the mother and in mother-infant adaptation shortly after a normal live-birth, particularly in those with high trait anxiety. They will then be able to arrange psychological support at an early stage.