No association between subnormal serum vitamin B12 and anemia in older nursing home patients.

PURPOSE: Since evidence of an association between vitamin B12 (B12) deficiency and anemia in older people is limited and inconclusive, we wanted to investigate this association in old, frail nursing home patients. METHODS: The study includes patients admitted to short-term, post-acute care (n = 765) and residents in long-term care (LTC) (n = 1665), in the municipality of Bergen. Anemia was defined according to the WHO criteria: Hb < 13 g/dL in men and < 12 g/dL in women, and as Hb < 11 g/dL, in both sex (moderate/severe anemia). The presence of anemia was analyzed in patients with subnormal (< 250 pmol/L), normal (250-650 pmol/L) and high (> 650 pmol/L) B12, and the association between anemia and clinical parameters, and including B12, was analyzed using logistic regression models. The use of B12 supplementation was investigated in the LTC patients. RESULTS: Mean age of the 2430 patients was 86 ± 7 years. WHO-defined anemia was seen in 1023 (42%), and moderate/severe anemia in 384 (16%) of the patients. In multiple logistic regression analyses, we found no statistically significant associations of subnormal B12 with WHO-defined anemia or moderate/severe anemia. Renal insufficiency, iron deficiency and CRP > 10 mg/L were significantly associated with both types of anemia, (p < 0.001). Among the LTC residents, 405 (24%) received B12 supplements, 112 (7%) of them had elevated B12 > 650 pmol/L. CONCLUSION: In older nursing home patients, no association was observed between subnormal B12 and anemia. Older patients in Western societies with mild/moderate anemia should not be treated with B12 supplements without further investigation.

Assessment of recovery in older patients hospitalized with different diagnoses and functional levels, evaluated with and without geriatric assessment.

BACKGROUND: The objective of the present study was to investigate 1) the role of different admission diagnoses and 2) the degree of functional loss, on the rate of recovery of older patients after acute hospitalization. Furthermore, to compare the predictive value of simple assessments that can be carried out in a hospital lacking geriatric service, with assessments including geriatric screening tests. METHODS: Prospective, observational cohort study, including 961community dwelling patients aged ≥ 70 years, transferred from medical, cardiac, pulmonary and orthopedic acute hospital departments to intermediate care in nursing home. Functional assessment with Barthel index (BI) was performed at admission to the nursing home and further geriatric assessment tests was performed during the first week. Logistic regression models with and without geriatric assessment were compared concerning the patients having 1) slow recovery (nursing home stay up to 2 months before return home) or, 2) poor recovery (dead or still in nursing home at 2 months). RESULTS: Slow recovery was independently associated with a diagnosis of non-vertebral fracture, BI subgroups 50-79 and <50, and, in the model including geriatric assessment, also with cognitive impairment. Poor recovery was more complex, and independently associated both with BI < 50, receiving home care before admission, higher age, admission with a non-vertebral fracture, and in the geriatric assessment model, cognitive impairment. CONCLUSIONS: Geriatric assessment is optimal for determining the recovery potential of older patients after acute hospitalization. As some hospitals lack geriatric services and ability to perform geriatric screening tests, a simpler assessment based on admission diagnoses and ADL function (BI), gives good information regarding the possible rehabilitation time and possibility to return home.

Readmission and mortality one year after acute hospitalization in older patients with explained and unexplained anemia - a prospective observational cohort study.

BACKGROUND: Few studies have examined whether specific subtypes of anemia in older persons are more related to adverse outcomes such as hospital readmissions and death after acute hospitalization and post-acute care. METHODS: An observational prospective cohort study was conducted between 2011 and 2014. A total of 884 community-dwelling patients, ≥70 years of age were transferred from acute medical and orthopaedic hospital departments to a skilled nursing home where they were examined by comprehensive geriatric assessment and had laboratory tests taken for the investigation of anemia. They were divided into three major groups and compared; 1) no anemia (reference group), 2) explained anemia (renal insufficiency, iron deficiency, vitaminB12/folate deficiency or multifactorial anemia) and 3) unexplained anemia. The groups were compared, and association of anemia with hospital readmission and death was estimated by logistic regression analyses. RESULTS: Compared to the patients with unexplained anemia (n=135), patients with explained anemia (n=275) had more often died (22 % vs. 14 %, p=0.05) and had more frequenlty been readmitted to hospital (39 % vs. 27 %, p=0.03). Compared to the patients without anemia (n=474), the patients with explained anemia had increased odds of hospital readmissions (OR = 1.54 (95 % CI: 1.05-2.25), p=0.03), while patients with unexplained anemia, (n=135), had neither increased odds of hospital readmissions, (OR=0.83, 95 % CI: 0.51-1.34, p=0.44) nor death (OR = 0.74, 95 % CI: 0.41-1.31, p=0.30), in adjusted regression analysis. CONCLUSION: Since no increased risk of hospital readmissions or death was seen in older patients with unexplained anemia in the first year after acute hospitalization, no further invasive investigations might be necessary to investigate the cause of anemia in these patients. A close clinical follow up might be the best way to care for older patients with a mild and unexplained anemia.

Long-term cryopreservation of autologous stem cell grafts: a clinical and experimental study of hematopoietic and immunocompetent cells.

BACKGROUND: Autologous stem cell transplantation(ASCT) is used in the treatment of several malignancies.Harvesting sufficient peripheral blood progenitor cells (PBPCs) for a potential second autotransplantation at the time of relapse several years after diagnosis is becoming an increasingly common practice. STUDY DESIGN AND METHODS: Cryopreserved PBPCs were prepared with different concentrations of dimethyl sulfoxide (DMSO; 2, 4, 5, and 10%) and stored for at least 5 years before the recovery of CD34+ cells and various T- and natural killer (NK)-cell subsets were analyzed by flow cytometry. Furthermore,clinical variables for myeloma patients having a second autotransplantation with long-term-stored autografts were evaluated. RESULTS: The number of viable CD34+ cells in longterm-stored grafts was higher when autografts were cryopreserved with 4 or 5% than with 2 and 10%DMSO. The number of viable CD34+ cells was reduced by 13.9% after 5 years of cryostorage in 5% DMSO.Lymphocyte viability was also higher with 4 or 5%DMSO. However, the frequencies of several T-cell subsets showed DMSO-dependent differences,whereas NK-cell subsets did not. Furthermore, after a second autotransplantation with long-term-stored PBPC grafts at the time of myeloma relapse (median storage time, 42 months) all 17 patients reached neutrophil counts exceeding 0.5 x 109/L and platelet counts exceeding 20 x 109/L within 15 days. There was no difference in engraftment between patients receiving autografts preserved with 5 and 10% DMSO. CONCLUSION: PBPC autografts can safely be stored for at least 5 years in 5% DMSO and used for ASCT.

Circadian variations in clock gene expression of human bone marrow CD34+ cells.

Time-dependent variations in clock gene expression have recently been observed in mouse hematopoietic cells, but the activity of these genes in human bone marrow (BM) has so far not been investigated. Since such data can be of considerable clinical interest for monitoring the dynamics in stem/progenitor cells, the authors have studied mRNA expression of the clock genes hPer1 , hPer2, hCry1, hCry2, hBmal1, hRev-erb alpha, and hClock in human hematopoietic CD34-positive (CD34( +)) cells. CD34(+) cells were isolated from the BM samples obtained from 10 healthy men at 6 times over 24 h. In addition, clock gene mRNA expression was analyzed in the whole BM in 3 subjects. Rhythms in serum cortisol, growth hormone, testosterone, and leukocyte counts documented that subjects exhibited standardized circadian patterns. All 7 clock genes were expressed both in CD34(+) cells and the whole BM, with some differences in magnitude between the 2 cell populations. A clear circadian rhythm was shown for hPer1, hPer2, and hCry2 expression in CD34(+) cells and for hPer1 in the whole BM, with maxima from early morning to midday. Similar to mouse hematopoietic cells, h Bmal1 was not oscillating rhythmically. The study demonstrates that clock gene expression in human BM stem/progenitor cells may be developmentally regulated, with strong or weaker circadian profiles as compared to those reported in other mature tissues.

[Survival after high-dose therapy with autologous stem cell support]. / Overlevelse etter høydosebehandling med autolog stamcellestøtte.

BACKGROUND: High-dose therapy with autologous stem cell support has been carried out in our hospital since 1996. We have recently collected survival data on patients who have undergone this procedure. MATERIAL AND METHODS: The study population comprised 111 patients, 58 of whom had been diagnosed with multiple myeloma, 38 with various forms of malignant lymphoma, 11 with sarcoma and 4 with testicular cancer. RESULTS: Median survival from reinfusion of stem cells was 74.8 months for patients with myeloma, 47.8 months for patients with malignant lymphoma and 11.7 months for patients with sarcoma. Three-year survival was 72.2 % for myeloma patients and 54.8 % for lymphoma patients. While the survival slope decreased steadily throughout the study period for patients with multiple myeloma, it seemed to level out after approximately 18 months for patients with malignant lymphomas. INTERPRETATION: Our data on myeloma patients show survival comparable to previously published data. For malignant lymphoma patients, our data support the assumption that high-dose therapy has the potential for cure.

Better preservation of early hematopoietic progenitor cells when human peripheral blood progenitor cells are cryopreserved with 5 percent dimethylsulfoxide instead of 10 percent dimethylsulfoxide.

BACKGROUND: Previous studies have demonstrated that cryopreservation of PBPCs in 5 percent DMSO is superior to 10 percent DMSO with regard to CD34+ cell viability and preservation of mature clonogenic cells. Nevertheless, preservation with 5 percent DMSO of primitive progenitors responsible for long-term post-transplant reconstitution must be characterized before this decreased concentration is further evaluated in clinical studies of autotransplantation in cancer patients. STUDY DESIGN AND METHODS: PBPCs from 15 patients with malignant diseases were cryopreserved in 5 and 10 percent DMSO and stored in liquid nitrogen for at least 14 months before the preservation of long-term culture-initiating cells (LTC-ICs) was evaluated. RESULTS: LTC-IC survival was significantly better after PBPC cryopreservation with 5 percent DMSO instead of 10 percent DMSO (median, 43 colonies vs. 7 colonies, p = 0.003) The frequency of 5-week LTC colony-forming cells showed a significant correlation with the percent-age and number of viable CD34+ cells but not to the number of mature colony-forming cells in cryopreserved PBPCs. CONCLUSION: Primitive progenitor cells in PBPC autografts from patients with malignant disorders can be cryopreserved with 5 percent DMSO, and the number of viable CD34+ cells can be used as a marker for the number of primitive progenitors in the graft.

Cryopreserving human peripheral blood progenitor cells with 5-percent rather than 10-percent DMSO results in less apoptosis and necrosis in CD34+ cells.

BACKGROUND: The grade of toxicity experienced by patients when cryopreserved peripheral blood progenitor cells (PBPCs) are reinfused is related to the amount of DMSO present in the PBPC concentrate. This study was initiated to investigate whether cell viability, apoptosis, and necrosis would be altered in CD34+ cells if PBPCs were cryopreserved with 5-percent as opposed to the conventional 10-percent DMSO. STUDY DESIGN AND METHODS: Samples of PBPCs from consecutive patients were mixed in parallel with 5- and 10-percent DMSO, frozen at a controlled rate, and stored in liquid nitrogen for periods of 3 to 22 months. Two different flow cytometric methods were used to measure both the absolute count of total and viable CD34+ cells as well as the fraction of apoptotic and necrotic cells in the post-thaw samples frozen with 5- and 10-percent DMSO. RESULTS: Both the number of total and viable CD34+ cells were higher (n = 18) or equal (n = 1) in all the samples cryopreserved with 5-percent as opposed to 10-percent DMSO. The percentage of viable CD34+ cells in the PBPC sample was significantly higher, and the fraction of apoptotic and necrotic CD34+ cells was significantly lower in the samples frozen with 5-percent as compared to 10-percent DMSO. CONCLUSION: Cryopreserving PBPC with 5-percent rather than 10-percent DMSO results in improved CD34+ cell viability and possibly a higher potential for in vivo engraftment and ex vivo manipulations of HPCs.

Rhythms in human bone marrow and blood cells.

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.