Immediate occlusal loading of extrasinus zygomatic implants: A prospective cohort study with a follow-up period of 8 years

The aim of this study was to evaluate the long-term success rate of immediate occlusal loading of extrasinus zygomatic implants after an 8-year follow-up. From 62 patients who needed implant treatment in 2003, 25 patients who presented with maxillary atrophy met the inclusion criteria and agreed to participate in the study. All patients received fixed dentures under immediate occlusal loading supported by extrasinus zygomatic implants associated with anterior standard implants. No bone grafting procedures were performed. During the 8-year follow-up period, 21 patients underwent clinical evaluation and radiographic examinations every 6 months. This study conforms to the STROBE guidelines regarding prospective cohort studies. 40 extrasinus zygomatic and 74 anterior standard implants were evaluated. All patients were clinically free of signs and symptoms of sinus disturbance at all follow-up appointments. After 8 years, the success rates of extrasinus zygomatic implants, standard anterior implants and definitive prostheses were 97.5%, 95.9% and 95.2%, respectively. Within the limits of this study, immediate occlusal loading of extrasinus zygomatic implants presents a predictable treatment option for the atrophic maxilla.     

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy.     

Severe Asthma in Adults : An Orphan Disease?

Severe asthma affects fewer than 10% of patients with asthma, is associated with a severe risk of death and disability, has a great impact on health and quality of life, and represents a huge cost to patients and society. Given the poor response to treatment and the side effects associated with medications for severe asthma, more efficient, cost-effective, and phenotype-specific medications are needed. Considering severe asthma as an orphan disease could encourage the pharmaceutical industry to stratify studies based on a more detailed characterization of study subjects at baseline, resulting in the development of novel therapeutic approaches.     

The novel combination of sirolimus and bortezomib prevents graft-versus-host disease but maintains the graft-versus-leukemia effect after allogeneic transplantation

Background We have previously shown that bortezomib induces a depletion of alloreactive T cells and allows the expansion of T cells with suppressive properties. In the current study, we analyzed the potential synergistic effect of bortezomib in conjunction with sirolimus in order to reduce-graft-versus-host disease without hampering graft-versus-leukemia effect in the allogeneic transplant setting. DESIGN AND METHODS: We evaluated the effect of sirolimus, bortezomib or the combination of both in the proliferation and activation of in vitro stimulated T lymphocytes. Pathways involved in this synergy were also analyzed using Western blot assays. Finally, BALB/c mice receiving C57BL/6 allogeneic donor bone marrow with splenocytes were used to measure in vivo the effect of this novel combination on the risk of graft-versus-host disease. RESULTS: The combination of both drugs synergistically inhibited both activation and proliferation of stimulated T cells. Also, the production of Th1 cytokines (IFN γ, IL-2 and TNF) was significantly inhibited. This effect was due, at least in part, to the inhibition of Erk and Akt phosphorylation. In vivo, the combination reduced the risk of graft-versus-host disease without hampering graft-versus-leukemia effect, as shown in mice receiving graft-versus-host disease prophylaxis with sirolimus plus bortezomib being infused with tumor WEHI cells plus C57BL/6 donor BM and splenocytes. Conclusions The current study reveals a synergistic effect of the combination sirolimus and bortezomib to prevent graft-versus-host disease while maintaining the graft-versus-leukemia effect.     

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.