[Translated article] Immobilisation with compression bandage vs. antebraquial splint in distal radius fractures operated by open reduction and locking plate. Randomised clinical trial.

INTRODUCTION: Currently, there is a lack of prospective studies to unify criteria about type and time for postoperative immobilisation in surgical distal radius fractures. The aim of this study is to compare functional and radiological results in two groups of distal radius fractures treated with internal fixation with locking plate, and immobilised with antebrachial splint or compression bandage for 3 weeks. MATERIAL AND METHOD: A randomised clinical trial was carried out with two parallel groups with 3, 6, and 12 weeks of follow-up. Main and secondary functional variables were measured, such as pain on VAS scale, values on PRWE, DASH and MRS scale, range of motion in flexion-extension, complications, etc. In addition, some radiological variables were measured at preoperative period and one week after surgery, such as union time, dorsal displacement, shortening, ulnar variance, etc. RESULTS: A total of 62 patients were evaluated: 27 immobilised with bandage and 35 with splint. Analysis of the results obtained showed significant differences in both groups for almost all radiological variables from pre to postoperative period, and for all functional variables from 3 to 12 weeks after surgery. No significant differences were found between the two groups for any of the radiological and functional variables evaluated (VAS 3-12 weeks: p=.584; PWRE 3-12 weeks: p=.248; flexion range of motion 3-12 weeks: p=.959; extension range of motion: p=.50; union time: p=.89). CONCLUSIONS: We do not find clinical or radiological differences between immobilisation with antebrachial splint or compression bandage for distal radius fractures operated with locking plate. A greater number of patients and follow-up are necessary to extrapolate the results to the general population and to establish criteria for good postoperative management of these fractures.

Immobilization with compression bandage vs antebraquial splint in distal radius fractures operated by open reduction and locking plate. Randomized clinical trial. / Inmovilización con vendaje compresivo vs férula antebraquial en fracturas de radio distal intervenidas mediante reducción abierta y placa bloqueada. Ensayo clínico aleatorizado.

INTRODUCTION: Currently, there is a lack of prospective studies to unify criteria about type and time for postoperative immobilization in surgical distal radius fractures. The aim of this study is to compare functional and radiological results in two groups of distal radius fractures treated with internal fixation with locking plate, and immobilized with antebrachial splint or compression bandage for 3weeks. MATERIAL AND METHOD: A randomized clinical trial was carried out with two parallel groups with 3, 6, and 12weeks of follow-up. Main and secondary functional variables were measured, such as pain on VAS scale, values on PRWE, DASH and MRS scale, range of motion in flexion-extension, complications, etc. In addition, some radiological variables were measured at preoperative period and one week after surgery, such as union time, dorsal displacement, shortening, ulnar variance, etc. RESULTS: A total of 62 patients were evaluated: 27 immobilized with bandage and 35 with splint. Analysis of the results obtained showed significant differences in both groups for almost all radiological variables from pre to postoperative period, and for all functional variables from 3 to 12weeks after surgery. No significant differences were found between the two groups for any of the radiological and functional variables evaluated (VAS 3-12weeks: P=.584; PWRE 3-12weeks: P=.248; flexion range of motion 3-12weeks: P=.959; extension range of motion: P=.50; union time: P=.89). CONCLUSIONS: We do not find clinical or radiological differences between immobilization with antebrachial splint or compression bandage for distal radius fractures operated with locking plate. A greater number of patients and follow-up are necessary to extrapolate the results to the general population and to establish criteria for good postoperative management of these fractures.

Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults.

BACKGROUND: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available. AIMS: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy. METHODS: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE). RESULTS: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings. CONCLUSION: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

Drug prescriptions in nursing home residents: an Italian multicenter observational study.

PURPOSE: Pharmacoepidemiological studies aimed to distinguish drug use in nursing home (NH) residents with and without dementia could be useful to target specific interventions to improve prescribing. This multicenter retrospective study aimed (i) to describe drug therapy in a large sample of NH residents according to the diagnosis of dementia, and (ii) to record the most frequent potentially severe drug-drug interactions. METHODS: This study was conducted in a sample of Italian long-term care NHs. Drug prescription information, diseases, and socio-demographic characteristics of NH residents were collected at three different times during 2018. RESULTS: The mean number of drugs was significantly higher in NH residents without dementia than in those with (p = 0.05). Antipsychotics, laxatives, benzodiazepines, antiplatelets, and proton pump inhibitors (PPIs) were most commonly prescribed in patients with dementia, and PPIs, benzodiazepines, and laxatives in those without. The prevalence of patients with potentially severe drug-drug interactions was higher among those without dementia, 1216 (64.7%) and 518 (74.2%, p < 0.0001). There were significant differences between the mean numbers of drugs prescribed in individual NH after adjusting the analysis for age, sex, and mean Charlson index, the estimated mean number of drugs prescribed (± standard error) ranging from 5.1 (± 0.3) to 9.3 (± 0.3) in patients with dementia (p < 0.0001) and from 6.0 (± 0.7) to 10.9 (± 0.50) in those without dementia (p < 0.0001). Chronic use of psychotropic drugs was common in NH residents with and without dementia. CONCLUSIONS: The wide variability between NHs in drug prescriptions and potentially inappropriate prescribing suggests the need to recommend a standardized approach to medication review of psychotropic drugs, antiulcer, laxatives, and antiplatelets in this complex and vulnerable population.

New method of synthesis and in vitro studies of a porous biomaterial.

Biomaterials for bone reconstruction represent a widely studied area. In this paper, a new method of synthesis of a porous glass-ceramic obtained by thermal treatment is presented. The prepared biomaterial was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and induced couple plasma-optical emission spectroscopy (ICP-OES), mercury porosimetry and by the Archimedes method. In vitro evaluations in a simulated body fluid (SBF) and in contact with SaOS2 human osteoblasts were also carried out. The porous glass-ceramic is composed of a total porous network of 60% suitable for body fluid and cell infiltration, with pore sizes varying from 60 nm to 143 µm. The presence of two crystalline phases decreases the kinetic of bioactivity compared to an amorphous biomaterial (bioactive glass). A hydroxyapatite layer appears from 15 days of immersion on the surface and inside the pores, showing a biodegradation and a bioactivity in four steps. Cytotoxicity assessments present an increase of the cellular viability after 72 h proving the non-cytotoxic effect of the glass-ceramic. Thus, the results of these different studies indicate that the porous biomaterial may have a potential application for the bone regeneration. This paper also presents the novelty of this method. It is a rapid synthesis which combines simplicity and low cost. This represents an advantage for an eventual industrialization.

Characterization of a programmed necrosis process in 3-dimensional cultures of dental pulp fibroblasts.

AIM: To analyse and compare the expression of necrosis markers in human lung and dental pulp fibroblasts and to determine whether this process differs by the type of mesenchymal cell. METHODS: Human dental pulp fibroblasts were obtained from unerupted third molars. Sound lung and pulpal fibroblasts were cultured in vitro as spheroids to determine the expression of the necrosis hallmark cyclooxygenase-2 (COX-2) mRNA using RT-PCR and the concentrations of vascular endothelial growth factor (VEGF) and hepatocyte growth factor/scatter factor (HGF/SF) proteins using an ELISA test. Cell viability within spheroids was also compared with spheroid diameters over time. RESULTS: Increased expression of COX-2 and VEGF was found in all spheroids compared with corresponding monolayers. Although HGF/SF was highly expressed in MRC5 cells, dental pulp fibroblasts aggregates maintained only a basal level compared with monolayer cultures. Further, the observed progressive loss of viable cells explained the decreased diameters of spheroids over time. The results demonstrate that necrosis occurs in sound lung and pulpal fibroblasts. This cell death also displays differences between these two different cell types, as they do not produce the same growth factors quantity release. CONCLUSIONS: The necrosis process occurred in human dental pulp fibroblasts and is different between the two cell types studied. This in vitro experimental necrosis model could become an interesting inflammatory tool. More investigations are needed to compare necrosis process in dental pulp fibroblast and inflammation during pulpitis.

Unbalanced X-chromosome inactivation in haemopoietic cells from normal women.

We studied X-chromosome inactivation patterns in blood cells from normal females in three age groups: neonates (umbilical cord blood), 25-32 years old (young women group) and >75 years old (elderly women). Using PCR, the differential allele methylation status was evaluated on active and inactive X chromosomes at the human androgen receptor (HUMARA) and phosphoglycerate kinase (PGK) loci. A cleavage ratio (CR) > or = 3.0 was adopted as a cut-off to discriminate between balanced and unbalanced X-chromosome inactivation. In adult women this analysis was also performed on hair bulbs. The frequency of skewed X-inactivation in polymorphonuclear (PMN) cells increased with age: CR > or = 3.0 was found in 3/36 cord blood samples, 5/30 young women and 14/31 elderly women. Mathematical analysis of patterns found in neonates indicated that X-chromosome inactivation probably occurs when the total number of haemopoietic stem cell precursors is 14-16. The inactivation patterns found in T lymphocytes were significantly related to those observed in PMNs in both young (P < 0.001) and elderly women (P < 0.01). However, the use of T lymphocytes as a control tissue for distinguishing between skewed inactivation and clonal proliferation proved to be reliable in young females, but not in elderly women, where overestimation of the frequency of clonal myelopoiesis may appear.

Expression of adhesion molecules and functional stimulation in human neutrophils: modulation by GM-CSF and role of the Bcr gene.

Although devoid of proliferative capacity, polymorphonuclear neutrophils (PMN) express receptors for haemopoietic growth factors and need growth factors for survival and functional stimulation. This study showed that in vitro treatment of human PMN with GM-CSF for up to 48 h increases cell surface expression of the beta 2-integrin molecules CD11b/CD18 and CD11c/CD18 and of the receptor for the chemotactic peptide fMLP. Such modifications are usually expression of PMN activation. PMN treated with GM-CSF also displayed increased phagocytosis of latex particles and enhanced oxidative burst and superoxide anion release. Since integrins mediate PMN adhesion to endothelium, homotypic adhesion, chemotaxis/phagocytosis and the triggering of respiratory burst, our results suggested that functional stimulation of PMN persisted following prolonged exposure of PMN to growth factors and that it was not a temporary phenomenon which lasted only for the first 12-24 h of treatment. We also used oligonucleotides antisense to the Bcr gene mRNA to inhibit expression of the gene and evaluate its function in PMN, following the recent observation that PMN from Bcr-null mutant mice produced increased amounts of reactive oxygen metabolites upon activation. The antisense oligonucleotides had no effect on the parameters investigated. This may indicate that increased production of O2 by neutrophils in which the Bcr gene is not expressed requires either that gene expression is absent in the earlier stages of myeloid differentiation/maturation, so that when inhibition occurs in the terminally differentiated neutrophils their functional status is no longer influenced, or that the residual low-level expression of the gene which may be present in the antisense-treated cells is sufficient to provide a normal response to stimulation.

Prediction of response to recombinant human erythropoietin (rHuEpo) in anemia of malignancy.

BACKGROUND: Since only a portion of anemic patients outside the uremia setting benefit from erythropoietin treatment, a reliable means of predicting potential responders and nonresponders would be very useful. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 58 patients with refractory anemia associated with various malignant disorders who had been treated with subcutaneous rHuEpo. The starting rHuEpo dose was 375 U/kg/week for 4 weeks, and was increased to 750 U/kg/week for another 4 weeks if no response was observed. Response was defined as a Hb increase > or = 2 g/dL with no need for blood transfusion. We examined the value of various laboratory parameters (baseline levels, 2-week and 4-week changes) as predictors of response. Endogenous erythropoietin production was evaluated by its serum level and erythroid activity was assessed through reticulocyte count and circulating transferrin receptor. RESULTS: Forty-eight individuals were evaluable, 58% of whom responded to rHuEpo within 8 weeks. Multiple regression analysis showed that 53% of the variation in the 8-week Hb concentration was explained by variations in baseline serum erythropoietin and the 2-week change in serum transferrin receptor (p < 0.001). Based on these two parameters, response prediction in individual patients would have resulted in a sensitivity of 96%, a specificity of 79% and an overall accuracy of 88%. In addition, 58% of the variation in the 8-week Hb was explained by variations in the 4-week changes in Hb and reticulocyte count (p < 0.001). Utilizing these latter parameters and baseline serum erythropoietin, response prediction in individual patients would have resulted in a sensitivity of 92%, a specificity of 82% and an overall accuracy of 88%. CONCLUSIONS: This retrospective analysis suggests that response to rHuEpo can be reasonably predicted by pretreatment serum erythropoietin together with early changes in simple laboratory parameters.

Saporin, a ribosome-inactivating protein used to prepare immunotoxins, induces cell death via apoptosis.

The plant toxin saporin is a ribosome-inactivating protein which inhibits protein synthesis and growth of both normal and tumour cells. Its cytotoxic activity can be increased by coupling with antibodies recognizing cell surface antigens. In this work we performed experiments to test the hypothesis that saporin induces cell death via apoptosis. Exposure to saporin induced apoptosis in different cellular models, such as human peripheral blood B lymphocytes and neutrophils, in the Daudi B-cell line, and in the haemopoietic cell lines HL-60 and TF-1. This was indicated by: (a) the appearance of typical morphological features such as chromatin condensation, nuclear fragmentation and blebbing of plasma membranes: (b) DNA degradation into oligonucleosomal fragments: (c) the appearance of apoptotic cells on DNA flow cytometry as a cell population with reduced DNA content (A0 region). The fraction of cells showing features of apoptosis ranged from 19 +/- 5% for TF-1 cells to 35 +/- 8% for neutrophils. In experiments with normal peripheral blood B lymphocytes or with Daudi cells, we compared the activity of native saporin with that of an immunotoxin hybrid molecule obtained by binding the toxin to two bispecific antibodies recognizing both saporin and the B lymphocyte-specific antigen CD22 (Sap/BsAb complexes). Saporin bound to the antibodies was 2-3 logs more effective than native saporin in inducing apoptosis, with maximal inhibitions being observed at concentrations of 10(-6) M for native saporin and 10(-9)-10(-8) M for the hybrid molecules. These findings indicate that treatment with saporin results in apoptosis of target cells and suggest that this may be relevant to the therapeutic use of saporin-containing immunotoxins. In fact, if used in vivo as an immunotoxin, its cytotoxic activity could be devoid of more extensive and non-specific tissue damaging effects as would be the case if saporin induced necrosis of target cells.

Effect of recombinant human erythropoietin on hematopoietic and non-hematopoietic malignant cell growth in vitro.

BACKGROUND: Several clinical studies have shown that recombinant human erythropoietin (rHuEpo) can ameliorate the anemia associated with hematologic malignancies and solid tumors. On the other hand, only a few studies have been performed to investigate whether rHuEpo can affect or modulate the growth of malignant cells. MATERIALS AND METHODS: We studied the effects of rHuEpo (0.5 to 10 IU/mL) on clonogenic growth and cell kinetics in ten cell lines derived from both hematologic malignancies and solid tumors. Clonogenic assays were performed by plating 5 x 10(3) cells in agar, while the percentage of cells in S phase was assessed by DNA flow cytometry. RESULTS: rHuEpo did not affect either in vitro colony formation or S phase percentage in the human erythroid cell lines K-562 and HEL expressing erythropoietin receptors (< 40 receptors per cell). No effect of rHuEpo was observed in the remaining hematopoietic cell lines or in five solid tumor cell lines. CONCLUSIONS: These findings indicate that rHuEpo, even at very high concentrations, does not affect either clonogenic growth or DNA synthesis in the cell lines tested. Available evidence suggests that rHuEpo can be safely employed in all malignancies except acute myeloid leukemia.

Treatment of perennial allergic rhinitis with cetirizine.

A study was made of 30 patients with perennial extrinsic rhinitis sensitized only to dust mites who were treated with cetirizine for 15 days, at a dose of 10 mg/24 hours. The following parameters were evaluated in each patient on day -1 before initiating treatment and on day 15: histamine 1/100 prick-test, Dermatohophagoides pteronyssinus prick-test, physical examination, assessment of nasal edema and rhinorrhea by anterior rhinoscopy, and of the degree of nasal obstruction by active anterior rhinomanometry. Each patient was given a form for daily clinical self-evaluation of the following subjective symptoms: sneezing, rhinorrhea, nasal obstruction, and nasal itchiness. The occurrence of side effects was evaluated. Cetirizine reduced significantly the area of the histamine and D. pteronyssinus papules elicited by prick-test. Clinical symptoms decreased significantly, with sneezing, nasal itchiness and rhinorrhea being greatly relieved, and nasal obstruction, evaluated by means of active anterior rhinomanometry performed before and after 15 days of treatment, being less alleviated. There was scant incidence of side effects in patients treated with cetirizine.