Autologous peripheral blood progenitor cells cryopreserved with 5 and 10 percent dimethyl sulfoxide alone give comparable hematopoietic reconstitution after transplantation

BACKGROUND: Previous in vitro studies have demonstrated decreased apoptosis and necrosis in peripheral blood progenitor cells (PBPCs) cryopreserved with 5 percent instead of 10 percent dimethyl sulfoxide (DMSO). This study was carried out to investigate whether these in vitro findings were supported by clinical data concerning hematopoietic engraftment after autologous stem cell transplantations with PBPCs cryopreserved with 5 and 10 percent DMSO. STUDY DESIGN AND METHODS: During a 6-year period, 103 consecutive patients with newly diagnosed multiple myeloma (MM; n = 58) and lymphoma (n = 45) were transplanted with autologous PBPCs. Throughout the first part of the period cells were cryopreserved with 10 percent DMSO and later with 5 percent. A retrospective comparison was carried out of the clinical results for these two groups. RESULTS: No significant difference in median time to neutrophil and platelet (PLT) engraftment was demonstrated for MM and lymphoma patients transplanted with PBPCs cryopreserved with 5 or 10 percent DMSO. Time until neutrophil counts of more than 0.5 x 10(9) per L was 10 days both for the 5 and 10 percent MM groups and 12 days for both the 5 and the 10 percent lymphoma patients. Median time until stable PLT counts of more than 20 x 10(9) per L was 11 days in all four groups. In addition, transfusion requirements and duration of days admitted to hospital did not differ between the groups. CONCLUSION: The routines for cryopreservation of autografts vary considerably between transplantation centers, and this makes it difficult to compare different clinical studies. Our results suggest that cryopreservation with 5 percent DMSO alone followed by storage in nitrogen is a simple, highly standardized, and safe procedure for cryopreservation of autologous stem cell graft.     

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.     

Intra-operative correction of brain-shift

Background

Brain-shift is a major source of error in neuronavigation systems based on pre-operative images. In this paper, we present intra-operative correction of brain-shift using 3D ultrasound.

Methods

The method is based on image registration of vessels extracted from pre-operative MRA and intra-operative power Doppler-based ultrasound and is fully integrated in the neuronavigation software.

Results

We have performed correction of brain-shift in the operating room during surgery and provided the surgeon with updated information. Here, we present data from seven clinical cases with qualitative and quantitative error measures.

Conclusion

The registration algorithm is fast enough to provide the surgeon with updated information within minutes and accounts for large portions of the experienced shift. Correction of brain-shift can make pre-operative data like fMRI and DTI reliable for a longer period of time and increase the usefulness of the MR data as a supplement to intra-operative 3D ultrasound in terms of overview and interpretation.     

Cellular immune responses in multiple myeloma patients with treatment-induced cytopenia early after high-dose chemotherapy and autologous peripheral blood stem cell transplantation

Proliferative T cell responses were compared for two patient groups with severe treatment-induced leukopenia (white blood cell counts < 0.5 x 10(9)/l): (i). multiple myeloma patients receiving high-dose melphalan and autologous peripheral blood stem cell transplantation; (ii). patients receiving conventional intensive chemotherapy for acute leukemia or myelodysplasia. Although the majority of circulating leukocytes were CD2(+)TCRalphabeta(+) in both groups, the myeloma patients showed significantly lower T cell proliferation in responses to several activation signals (anti-CD3, anti-CD3 + IL2, anti-CD3 + anti-CD28, anti-CD3 + anti-CD28+IL2. Our results suggest that myeloma patients with post-transplant cytopenia have a more severe cellular immune defect than patients with other hematological malignancies and severe cytopenia due to conventional intensive chemotherapy.     

Does oral magnesium substitution relieve pregnancy-induced leg cramps?

Objective

Our aim was to assess the effect of 360 mg magnesium oral substitution daily among pregnant women suffering from leg cramps in pregnancy, defined as painful cramps different from restless legs symptoms.

Study design

In a double blind randomised controlled trial healthy pregnant women between 18 and 36 weeks of pregnancy suffering from painful leg cramps, at least twice a week, were invited to participate. Forty-five women were enrolled initially, 38 completed the treatment and were treated during 2 weeks with either magnesium (360 mg = 15 mmol magnesium lactate and magnesium citrate, Nycoplus Magnesium^®), or placebo tablets. Serum magnesium and calcium were investigated together with urine magnesium and magnesium–creatinin ratio on day 1 and day 15. Frequency and intensity of leg cramps were recorded. The study was powered to detect a 50% reduction in leg cramps.

Results

Registration of pain frequency and intensity during the two study weeks demonstrated no significant differences between the two groups. Mean number and intensity of cramps were 9.5 (S.D. 5.1) and 13.2 (S.D. 6.5) in the magnesium group, compared to 7.7 (S.D. 4.7) and 11.4 (S.D. 8.5) in the placebo group. Baseline magnesium levels were 0.77 and 0.74 mmol/L in the magnesium group and the placebo group, respectively No significant differences between the two groups, or within the groups, were found when comparing serum values of serum magnesium and total calcium at inclusion time and at the end of the treatment. There was a statistically significant increase in magnesium excretion in the magnesium treatment group (p < 0.01). The number of dropouts was two in the treatment group and five in the control group.

Conclusions

No significant effect on frequency or intensity of leg cramps in pregnant women of magnesium treatment with 360 mg daily could be detected in this trial.     

EFFECT OF VESTIBULAR REHABILITATION ON CHANGE IN HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH DIZZINESS AND BALANCE PROBLEMS AFTER TRAUMATIC BRAIN INJURY: A RANDOMIZED CONTROLLED TRIAL

ObjectiveSecondary analysis, testing the effect on change in health-related quality of life of group-based vestibular rehabilitation in patients with mild-moderate traumatic brain injury, dizziness and balance problems.DesignA single-blind randomized controlled trial.SubjectsA total of 65 patients aged 16–60 years with a Rivermead Post-concussion Symptoms Questionnaire dizziness score ≥2, and DizzinessHandicap Inventory score >15 points. Data collection was performed at baseline 3.5 (standard deviation (SD) 2.1) months post-injury, end of intervention, and 4.4 (SD 1.0) months after baseline.MethodsQuality of Life after Brain Injury was the main outcome. Independent variables were demographic and injury variables, Hospital Anxiety and Depression Scale, changes on the Rivermead Post-concussion Symptoms Questionnaire (RPQ3 physical and RPQ13 psychological/cognitive), and Vertigo Symptom Scale-Short Form.ResultsMean age of participants was 39.4 years (SD 13.0); 70.3% women. Predictors of change inthe Quality of Life after Brain Injury were receiving the vestibular rehabilitation (p =0.049), baseline psychological distress (p =0.020), and changein RPQ3 physical (p =0.047) and RPQ13 psychological/cognitive (p =0.047). Adjusted R2 was 0.399,F=6.13, p < 0.001.ConclusionThere was an effect in favour of the intervention group in improvement in health-related quality of life. Changes on the Rivermead Post-concussion Symptoms Questionnaire were also associated with change on the Quality of Life after Brain Injury.LAY ABSTRACTThis paper is the first to present results of a vestibular rehabilitation intervention study on changes in health-related quality of life in patients with dizziness and balance problems after mild-to-moderate traumatic brain injury. The intervention group received exercises and guidance aimed at self-efficacy and how to cope with their dizziness and balance problems. In addition, both the intervention and control groups received treatment as usual, comprising multidisciplinary rehabilitation at a university hospital. The main result was measured as change on the Quality of Life after Brain Injury questionnaire. Post-concussion symptoms, vertigo and psychological distress were also measured. The study showed that the group receiving the vestibular rehabilitation intervention underwent more improvement in health-related quality of life than the group receiving usual treatment alone. Other factors that influenced the improvement in quality of life were psychological distress at the start of the study and fewer post-concussion symptoms.Key words: quality of life, traumatic brain injury, dizziness, randomized controlled trial, psychological distress, patientreported outcome measure

Sustaining a traumatic brain injury (TBI) affects patients’ functioning and health-related quality of life (HRQL) (1). TBI is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force (2). Research shows that HRQL is often reduced after a TBI, independent of the severity of the injury (3). Problems in cognitive, emotional, or physical functioning are associated with HRQL after TBI (4). Systematic reviews emphasize the multifactorial aetiology of post-concussion syndrome/symptoms (PCS), and that pre- and post-injury mental health are predictors of post-injury functioning after mild TBI (5, 6). Furthermore, both psychological and physical post-concussion symptoms, including dizziness, show significant correlation with the physical and mental aspects of HRQL (7).Dizziness is a subjective experience that is often described as vertigo and balance problems, or lightheadedness and disorientation (8). The aetiology of dizziness after a TBI can be caused by injuries in the vestibular system (9, 10), or have a non-vestibular origin (10). Zeldovich et al. found that 46% of patients with mild or moderate TBI and persistent PCS experienced dizziness post-injury and, at 6 months post-injury, dizziness was reported by approximately 30% of patients with complicated mild TBI (4). After 1 year, dizziness was reported in 25% of patients (11). Challenges caused by dizziness may hamper return to physical activities and work and increase the patients’ perception of post-concussion symptom pressure (12). There is, however, a lack of intervention studies on dizziness and balance problems after TBI (13). We have shown previously that self-reported dizzinessrelated disability, measured by the Dizziness Handicap Inventory (DHI), is associated with vertigo symptoms, balance problems, and psychological distress (14). These findings showed that a group-based adjusted programme for vestibular rehabilitation (VR) had an immediate, but not long-term, effect on dizzinessrelated disability (15). However, to our knowledge, there are no studies into how HRQL is affected in the subgroup of the TBI population having dizziness and balance problems.The current study reports results for HRQL from a randomized controlled trial (RCT) that tested the efficacy of an individually modified, group-based VR intervention designed specifically for reducing dizziness and balance problems after TBI (15, 16). It is not known how HRQL change was in this subgroup of patients with TBI, and whether injury-related factors and changes in post-injury functioning had an effect on change in HRQL reported on a TBI-specific outcome measure. Hence, the main objectives of this secondary analysis of a RCT was to test the effect on changes in HRQL of a group-based VR programme in addition to routine multidisciplinary rehabilitation on patients with mild-to-moderate TBI and dizziness and balance problems. Secondarily, the current study aimed to describe the HRQL over time. It was hypothesized that mental health at baseline, improved persistent PCS and functioning, and reduced dizziness would have significant positive effects on changes in HRQL, and that the intervention group would show significantly more improvement in HRQL than the control group.     

Sleeve gastrectomy,but not duodenojejunostomy,preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography

Background

In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.

Methods

Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.

Results

Body weight did not differ between groups (P _g = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (P _g = 0.037); HbA1c levels in SG were lower compared to DJ only (p < 0.05). GLP-1 levels were elevated for DJ compared to SG and sham (P _g = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (P _g = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).

Conclusion

Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.

     

Gastrin Secretion After Bariatric Surgery—Response to a Protein-Rich Mixed Meal Following Roux-En-Y Gastric Bypass and Sleeve Gastrectomy: a Pilot Study in Normoglycemic Women

Background

Recent investigations have linked elevated gastrin levels to the improvement of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective treatments for T2DM, but it is not known if this is related to postoperative alterations of gastrin secretion.

Methods

Twenty women previously operated with RYGB or SG and 13 female controls were enrolled and evaluated for body mass index, lipids, C-peptide, HbA1c, and anti-H. pylori IgG. Glucose, gastrin, insulin, and glucagon-like peptide 1 (GLP-1) concentrations were measured before and 30, 60, 90, and 120 min after ingestion of a protein-rich mixed meal.

Results

Six participants primarily selected were excluded due to usage of proton pump inhibitors, positive H.pylori IgG, or history of T2DM, yielding the following groups: RYGB (n?=?9), SG (n?=?8), and controls (n?=?10). There were no differences in age, body mass index, HbA1c, or C-peptide levels between groups. RYGB had significantly lower area under the curve (AUC) for glucose during the test compared to controls (p?=?0.013). RYGB showed lower serum gastrin levels compared to SG and controls (p?<?0.05 for all). There was a non-significant increased gastrin release in SG compared to controls (p?=?0.091). For SG and controls, there was a negative correlation between glucose and gastrin response (p?=?0.0043).

Conclusion

Gastrin secretion is diminished after RYGB. Hypergastrinemia was not present after SG, but a tendency of enhanced gastrin secretion was observed. These findings require further investigation in prospective studies.