Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

Background

Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease.

Design and Methods

In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria.

Results

There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively).

Conclusions

Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:{"type":"clinical-trial","attrs":{"text":"NCT00560053","term_id":"NCT00560053"}}NCT00560053)     

The experience of caregiving: the influence of coping strategies on behavioral and psychological symptoms in patients with Alzheimer's disease

Objectives: To determine whether caregiver coping strategies are independently associated with behavioral and psychological symptoms (BPS) in Alzheimer's disease (AD) after accounting for patient characteristics.

Methods: Cross-sectional data analysis of 80 patients with AD and their primary caregivers. The presence of BPS was recorded using the Neuropsychiatric Inventory (NPI). The relationship between caregiver characteristics and BPS was assessed through one-way analysis of variance, two-tailed student t-tests or correlation coefficients. Multivariate linear regression was used to determine the combined effect of all caregiver factors that were significant on bivariate analysis regarding coping and BPS controlling for patient characteristics.

Results: Caregivers were on average 62 years old, 77% female, and most were the children or the spouse of the patient. Over 50% had significant depression or anxiety. Patients were on average 77 years old and 62% were female, and most had moderate to severe dementia. After adjusting for patient characteristics, patients cared for by more depressed, more burdened, or those using more disengagement coping strategies showed higher NPI mean composite scores.

Conclusion: Coping strategies are associated with BPS regardeless of patient characteristics. Interventions to reduce BPS should focus on which psychological coping strategies caregivers use. Understanding how coping strategies influence BPS may help tailor specific interventions for caregivers.     

Characteristics of Asthma Patients Admitted to an Intermediate Respiratory Care Unit

IntroductionIntermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICUs). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated.MethodsClinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis.ResultsA total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58 ± 20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO₂. Ten patients admitted to the IRCU required non-invasive mechanical ventilation (NIMV). There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge.ConclusionsPatients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.     

l-dopa-induced dyskinesias in unilateral 6-hydroxydopamine-lesioned rats are not modified by excitotoxic lesion of the entopeduncular nucleus and substantia nigra pars reticulata

l -Dopa-induced dyskinesias (LIDs) are a troublesome complication in Parkinson's disease after long-term therapy and a major reason for surgical treatment. LIDs are effectively eliminated by surgery. We aimed to reproduce such effect in the 6-hydroxydopamine (6-OHDA)-lesioned rat model. Single or combined lesions with quinolinic acid were caused in the entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) on 6-hydroxydopamine (6-OHDA)-lesioned rats treated for 3 weeks with l -Dopa (6 mg/kg plus 15 mg/kg benserazide, i.p.). l -Dopa administration was continued for a further week following the lesion and abnormal involuntary movements (AIMs) scored at the end of treatment. Neither the individual lesions of the EP and SNr nor the combined lesions had any antidyskinetic effect nor decreased the total number of rotations. These results suggest that excitotoxic lesions of neurons bodies of the output nuclei of the basal ganglia, which destroy cell bodies and spare fibers of passage, do not induce a beneficial reduction of dyskinesias in contrast to thermolytic lesions in humans (which provokes a complete tissue destruction), thus supporting the possibility that other nuclei or systems might be involved in the antidyskinetic effect of pallidotomy. Synapse 67:407–414, 2013. © 2013 Wiley Periodicals, Inc.     

Doxycycline restrains glia and confers neuroprotection in a 6‐OHDA Parkinson model

Neuron–glia interactions play a key role in maintaining and regulating the central nervous system. Glial cells are implicated in the function of dopamine neurons and regulate their survival and resistance to injury. Parkinson's disease is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, decreased striatal dopamine levels and consequent onset of extrapyramidal motor dysfunction. Parkinson's disease is a common chronic, neurodegenerative disorder with no effective protective treatment. In the 6‐OHDA mouse model of Parkinson's disease, doxycycline administered at a dose that both induces/represses conditional transgene expression in the tetracycline system, mitigates the loss of dopaminergic neurons in the substantia nigra compacta and nerve terminals in the striatum. This protective effect was associated with: (1) a reduction of microglia in normal mice as a result of doxycycline administration per se; (2) a decrease in the astrocyte and microglia response to the neurotoxin 6‐OHDA in the globus pallidus and substantia nigra compacta, and (3) the astrocyte reaction in the striatum. Our results suggest that doxycycline blocks 6‐OHDA neurotoxicity in vivo by inhibiting microglial and astrocyte expression. This action of doxycycline in nigrostriatal dopaminergic neuron protection is consistent with a role of glial cells in Parkinson's disease neurodegeneration. The neuroprotective effect of doxycycline may be useful in preventing or slowing the progression of Parkinson's disease and other neurodegenerative diseases linked to glia function.     

Cerebral and somatic NIRS-determined oxygenation in IUGR preterm infants during transition

Background: Fetal growth restriction (intra-uterine growth restriction [IUGR]) has a considerable impact on perinatal morbidity. Preterm IUGR infants are prone to impaired intestine function. Near-infrared spectroscopy (NIRS) has been used to monitor oxygenation status of the brain and of the intestine.

Patients and methods: We conducted a prospective case–control study at our NICU in 20 preterm infants of whom 10 infants complicated by compared with 10 non-IUGR preterm infants. Splanchnic and cerebral regional oximetry values were measured with NIRS. Three hours of consecutive recordings were performed in the first 24?h of life, T0, and during the transitional period, T1. The cerebral/splanchnic oxygenation ratio, CSOR, (cerebral regional saturations [rScO_2]/splanchnic regional saturations [rSsO₂]) was also calculated.

Results: Both in the IUGR and the non-IUGR infants, at T0 and T1 monitoring time-points, the rSO₂ values were higher in the cerebral district when compared to those of the splanchnic area. Comparison of the NIRS parameters between the IUGR and non-IUGR infants at T0 showed no difference in rScO₂, while rSsO₂ was significantly lower in the IUGR group. At T1, rScO₂ was significantly lower and rSsO₂ higher in the IUGR group.

Conclusions: Cerebral/splanchnic vascular adaptation of IUGR infants to the extra-uterine environment is characterized by a postnatal persistence of the brain sparing effect with reperfusion in the transitional period.