ObJEctIVE: the unique pharmacokinetics of bisphosphonates (bPs) in conjunction with their use by an increasing number of women at reproductive age has raised serious concerns about their safety during pregnancy and lactation. bisphosphonates cross the placenta. Animal studies have shown adverse effects on both the fetus and the mother, mostly at doses much higher than those commonly used in humans. Protracted parturition, maternal mortality, embryolethality, severe general underdevelopment and marked skeletal retardation of the fetuses (increased amount of diaphyseal bone trabeculae, decreased diaphyseal length), small fetal weight and abnormal tooth growth have been observed. DEsIGN: We conducted a thorough research of the literature in order to identify human studies concerning this issue. rEsULts: We identified a total of 78 cases involving fetuses whose mothers had been exposed to bPs before conception or during pregnancy, along with 7 cases of bPs exposure prior to or during lactation. the vast majority of mothers and infants did not demonstrate serious adverse effects. However, there were cases of shortened gestational age, low neonatal birth weight and transient hypocalcaemia of the newborns, while the very few reported cases of spontaneous abortions and congenital anomalies probably resulted from maternal underlying diseases and concomitant medication. cONcLUsION: the administration of bisphosphonates in pregnancy should be assessed in view of their potential hazardous effects on both mother and fetus. In cases of absolute or relative indications of bPs prior to pregnancy, close observation of the mother and the infant, especially during the first two weeks of life, is imperative for the successful outcome of pregnancy.

Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutralization in a preclinical mouse model of lung carcinogenesis. For this, Balb/c mice (n = 42) received four weekly intraperitoneal urethane injections (1 g/kg) and twice-weekly intraperitoneal soluble TNF receptor (etanercept; 10 mg/kg) administered during tumor initiation/promotion, tumor progression, or continuously (months 1, 6, and 1-8 after urethane start, respectively). Lung oncogenesis was assessed after 8 months. In separate short-term studies, Balb/c mice (n = 21) received a single control or urethane injection followed by twice-weekly intraperitoneal control or sTNFR:Fc injections. Lung inflammation was assessed after 1 week. We found that sTNFR:Fc treatment during tumor initiation/promotion resulted in a significant reduction of tumor number but not dimensions. However, sTNFR:Fc administered during tumor progression did not impact tumor multiplicity but significantly decreased tumor diameter. Continued sTNFR:Fc administration was effective in halting both respiratory tumor formation and progression in response to urethane. This favorable impact was associated with impaired cellular proliferation and new vessel formation in lung tumors. In addition, TNF neutralization altered the lung inflammatory response to urethane, evidenced by reductions in TNF and macrophage and increases in interferon γ and interleukin 10 content of the air spaces. sTNFR:Fc treatment of RAW264.7 macrophages downregulated TNF and enhanced interferon γ and interleukin 10 expression. In conclusion, TNF neutralization is effective against urethane-induced lung oncogenesis in mice and could present a lung chemoprevention strategy worth testing clinically.

Background. Periprosthetic joint infection (PJI) is the most severe complication, following joint arthroplasty. Identification of the causal microbial factor is of paramount importance for the successful treatment. Purpose. The aim of this study is to compare the sonication fluid cultures derived from joint prosthetic components with the respective periprosthetic tissue cultures. Methods. Explanted prosthesis components for suspected infection were placed into a tank containing sterile Ringer's solution and sonicated for 1 minute at 40 kHz. Sonication fluid cultures were examined for 10 days, and the number and identity of any colony morphology was recorded. In addition, periprosthetic tissue specimens (>5) were collected and cultured according to standard practice. The duration of antimicrobial interruption interval before culture sampling was recorded. Results. Thirty-four patients composed the study group. Sonication fluid cultures were positive in 24 patients (70.5%). Sixteen of thirty four periprosthetic tissue cultures (47.1%) were considered positive, all revealing the same microbial species with the respective sonication fluid cultures: 3 tissue samples showed polymicrobial infection. All tissue cultures were also found positive by the sonication fluid culture. Conclusions. Sonication fluid cultures represent a cheap, easy, accurate, and sensitive diagnostic modality demonstrating increased sensitivity compared to periprosthetic tissue cultures (70.5 versus 47.1%).