Titanium: a review on exposure,release, penetration,allergy, epidemiology,and clinical reactivity

Exposure to titanium (Ti) from implants and from personal care products as nanoparticles (NPs) is common. This article reviews exposure sources, ion release, skin penetration, allergenic effects, and diagnostic possibilities. We conclude that human exposure to Ti mainly derives from dental and medical implants, personal care products, and foods. Despite being considered to be highly biocompatible relative to other metals, Ti is released in the presence of biological fluids and tissue, especially under certain circumstances, which seem to be more likely with regard to dental implants. Although most of the studies reviewed have important limitations, Ti seems not to penetrate a competent skin barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some indications of Ti penetration through the oral mucosa. We conclude that patch testing with the available Ti preparations for detection of type IV hypersensitivity is currently inadequate for Ti. Although several other methods for contact allergy detection have been suggested, including lymphocyte stimulation tests, none has yet been generally accepted, and the diagnosis of Ti allergy is therefore still based primarily on clinical evaluation. Reports on clinical allergy and adverse events have rarely been published. Whether this is because of unawareness of possible adverse reactions to this specific metal, difficulties in detection methods, or the metal actually being relatively safe to use, is still unresolved.     

The incidence of respiratory symptoms and diseases among pulp mill workers with peak exposures to ozone and other irritant gases

OBJECTIVES: Pulp mills in Sweden started to use ozone as a bleaching agent in the early 1990s. The goal of this study was to investigate whether the incidence of selected respiratory outcomes was associated with peak exposures to ozone or other irritant gases (ie, chlorine dioxide [ClO2] or sulfur dioxide [SO2]) used in these mills. METHODS: Bleachery workers (n = 245) from three pulp mills where ozone was used participated in surveys in the mid- to late-1990s. Comparison workers (n = 80) were from two adjacent paper mills. The person-time at risk was calculated for each participant, covering the period of employment when ozone was used. Data were collected by questionnaire, and a peak exposure was defined as a self-reported exposure to an irritant gas resulting in acute respiratory symptoms. The outcomes analyzed were self-reports of physician-diagnosed asthma, attacks of wheeze, and chronic bronchitis (ie, chronic cough with phlegm). Participants also reported when the peak exposures and outcomes occurred. RESULTS: Based on proportional hazards regression (controlling for gender, age, cigarette smoking, atopy, and peak irritant exposures that occurred before follow-up), workers who reported both ozone and ClO2/SO2 peak exposures had elevated hazard ratios (HRs) for all three outcomes. Those who reported only ozone peak exposures had elevated HRs of 6.5 (95% confidence interval [CI], 1.2 to 36.3) for asthma and 3.3 (95% CI, 1.1 to 10.2) for attacks of wheeze but no increase in risk for chronic bronchitis. Workers with only ClO2/SO2 peak exposures had elevated HRs for attacks of wheeze (HR, 7.5; 95% CI, 1.9 to 29.3) and chronic bronchitis (HR, 22.9; 95% CI, 4.5 to 118.2) but not for asthma. CONCLUSIONS: These findings suggest the need for additional efforts to prevent peak exposures in pulp-bleaching operations.     

Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR‐ABL1‐positive acute myeloid leukemia (AML). Fifty‐seven patients (median age, 48 years, range: 19‐67) with BCR‐ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR‐ABL1/ABL < 10⁴) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow‐up of 6.3 years (0.7–14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II‐IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5‐yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5‐yr: 22.7 vs. 50%), LFS (5‐yr: 61.9 vs. 31.8%), and GRFS (5‐yr: 52.4 vs. 18.2%), whereas MRD‐negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR‐ABL1‐positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.     

Levels of angiogenic factors in pregnancy and post-partum bleeding

We have studied if serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) in pregnancy could predict excess post-partum bleeding. In 392 normotensive singleton pregnancies, concentrations of sFlt-1 and PlGF in the first, second, and third trimester were compared between women with and without excess post-partum bleeding, defined as blood loss volume of at least 500 mL. Mean concentrations of sFlt-1 were consistently higher in all three trimesters among women who had excess post-partum bleeding compared to women without this, but significantly higher only in the second trimester. For PlGF, there were no significant differences between the groups. High concentrations of the anti-angiogenic factor sFlt-1 in maternal circulation during pregnancy may be associated with an increased risk of excess post-partum bleeding.