A pilot project of expert nurses for the follow-up of complex intravenous antimicrobial treatment.

OBJECTIVE: To report a pilot project of expert nurses for outpatient parenteral antimicrobial treatment (OPAT) follow-up. METHODS: Three nurses with specific training on antibiotics started a state-funded programme including: i) consultations for OPAT follow-up; ii) hotline for satellite hospitals; iii) peer training. Patients' data were prospectively collected. A representative sample of patients and physicians was interviewed to learn about their opinion on the project. RESULTS: From December 2020 to December 2021, 118 patients (median age 66.5 years [52-75], male-to-female ratio 2.5) were enrolled, for a total of 621 consultations. Patients were mostly on OPAT for bone and joint infections (n = 76, 64 %) and cardiovascular infections (n = 16, 14 %), for a median duration of 29 days [22-57]. Eleven patients (9 %) required unplanned hospital admissions, and three experienced treatment failure. Most patients (21/22) and physicians in charge (10/10) reported a high level of satisfaction. CONCLUSIONS: Nurses may be important actors for OPAT follow-up.

Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases.

The molecular mechanisms by which tumor cells metastasize to bone are likely to involve invasion, cell adhesion to bone, and the release of soluble mediators from tumor cells that stimulate osteoclast-mediated bone resorption. Bisphosphonates (BPs) are powerful inhibitors of the osteoclast activity and are, therefore, used in the treatment of patients with osteolytic metastases. However, an added beneficial effect of BPs may be direct antitumor activity. We previously reported that BPs inhibit breast and prostate carcinoma cell adhesion to bone (Boissier et al., Cancer Res., 57: 3890-3894, 1997). Here, we provided evidence that BP pretreatment of breast and prostate carcinoma cells inhibited tumor cell invasion in a dose-dependent manner. The order of potency for four BPs in inhibiting tumor cell invasion was: zoledronate > ibandronate > NE-10244 (active pyridinium analogue of risedronate) > clodronate. In addition, NE-58051 (the inactive pyridylpropylidene analogue of risedronate) had no inhibitory effect, whereas NE-10790 (a phosphonocarboxylate analogue of risedronate in which one of the phosphonate groups is substituted by a carboxyl group) inhibited tumor cell invasion to an extent similar to that observed with NE-10244, indicating that the inhibitory activity of BPs on tumor cells involved the R2 chain of the molecule. BPs did not induce apoptosis in tumor cells, nor did they inhibit tumor cell migration at concentrations that did inhibit tumor cell invasion. However, although BPs did not interfere with the production of matrix metalloproteinases (MMPs) by tumor cells, they inhibited their proteolytic activity. The inhibitory effect of BPs on MMP activity was completely reversed in the presence of an excess of zinc. In addition, NE-10790 did not inhibit MMP activity, suggesting that phosphonate groups of BPs are responsible for the chelation of zinc and the subsequent inhibition of MMP activity. In conclusion, our results provide evidence for a direct cellular effect of BPs in preventing tumor cell invasion and an inhibitory effect of BPs on the proteolytic activity of MMPs through zinc chelation. These results suggest, therefore, that BPs may be useful agents for the prophylactic treatment of patients with cancers that are known to preferentially metastasize to bone.

Additive antitumor activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone.

A very common metastatic site for breast carcinoma is bone. Metastatic breast carcinoma cells stimulate osteoclast-mediated bone resorption leading to osteolysis. Bisphosphonates are powerful inhibitors of osteoclast activity, and are therefore used in combination with standard chemotherapy or hormonal therapy for the treatment of cancer-associated osteolytic metastases. However, there may be an added beneficial effect of the bisphosphonates, that is, additive or synergistic activities with cytotoxic agents. Here, we investigated the effects of the bisphosphonate ibandronate in combination with taxoids (taxol and taxotere) on induction of apoptosis, invasion and adhesion of breast carcinoma cells to bone. Ibandronate did not induce apoptosis of human MDA-MB-231 breast carcinoma cells, nor did it enhance the effectiveness of taxoid-induced apoptosis in MDA-MB-231 cells. In contrast, ibandronate enhanced the antitumor activity of taxoids against invasion and cell adhesion to bone. Our findings raise the interesting possibility that the combination of bisphosphonates and taxoids may be useful for the treatment of patients with cancer types that are known to metastasize preferentially to bone.

Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices.

The molecular mechanisms by which tumor cells induce osteolytic metastases are likely to involve tumor cell adhesion to bone as well as the release of soluble mediators from tumor cells that stimulate osteoclast-mediated bone resorption. Bisphosphonates (BPs) are powerful inhibitors of the osteoclast activity and are, therefore, used in the treatment of cancer-associated osteolytic metastases. Here, we investigated the effect of BPs on breast and prostate carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. BP pretreatment of tumor cells inhibited tumor cell adhesion to unmineralized and mineralized osteoblastic extracellular matrices in a dose-dependent manner. In contrast, BP did not affect adhesion of normal cells (fibroblasts) to extracellular matrices. The order of potency for four BPs in inhibiting tumor cell adhesion to extracellular matrices was found to be: ibandronate > NE-10244 (antiresorptive active pyridinium analogue of risedronate) > pamidronate > clodronate. BP did not affect [3H]thymidine incorporation by tumor cells, as assessed by a mitogenesis assay, indicating that BP did not exert any cytotoxic effect at concentrations used to inhibit tumor cell adhesion. NE-58051, the inactive pyridylpropylidene analogue of risedronate, had no inhibitory effect on tumor cell adhesion compared to that observed with its active counterpart NE-10244, suggesting that the mechanism of action of BP on tumor cells involved a stereospecific recognition step. Although integrins mediate cell-matrix interactions, BP recognition by tumor cells did not modulate cell surface integrin expression. In conclusion, our results provide evidence for a direct cellular effect of BP in preventing tumor cell adhesion to bone, suggesting that BPs may be useful agents for the prophylactic treatment of patients with cancer that is known to preferentially metastasize to bone.

Expression of oxidative phosphorylation genes in muscle cell cultures from patients with mitochondrial myopathies.

The expression of several mitochondrial and nuclear genes involved in ATP production was examined in cells cultured from muscle biopsies of patients harboring mitochondrial pathologies. The transcript patterns in muscle cells from the patients affected by carnitine palmitoyl transferase II or 2-ketoglutarate dehydrogenase deficiencies were almost similar to control patterns. In the opposite, patterns were strikingly abnormal in all the other cell cultures from patients with defects in enzymatic complexes involved in oxidative phosphorylation: mitochondrial complex II and III deficiencies, two MELAS syndromes (myopathy, encephalopathy, lactic acidosis and stroke like episodes), a case of Kearns-Sayre syndrome and a case of chronic progressive external ophthalmoplegia. In cultured muscle cells from patients with mtDNA mutations, the percentage of mutated mtDNA was low as compared with those determined in the corresponding skeletal muscle biopsy. Moreover, the complex II defect resulting of a nuclear mutation was not expressed in the cell cultures. Thus, an undetermined transcriptional event, transmitted from muscle biopsies to cultured muscle cells, should be involved to account for such abnormal transcript patterns.