Pharmacist-Urologist Collaborative Management for Patients with Renal Cell Carcinoma Receiving Pazopanib Monotherapy.

Pazopanib is one of recommended treatment for metastatic renal cell carcinoma (RCC). Despite its effectiveness, patients often difficult to continue pazopanib treatment due to adverse events (AEs). We established an ambulatory care pharmacy practice that enables pharmacist-urologist collaboration to manage patients with RCC. This study evaluated the usefulness of this collaborative management. We retrospectively reviewed the medical records of 51 consecutive patients with metastatic RCC receiving pazopanib at the Kobe City Medical Center General Hospital between April 2014 and December 2020. Our collaborative management was implemented in October 2016. The time to pazopanib discontinuation was compared between patients who started pazopanib before (n = 30) and after (n = 21) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with pazopanib discontinuation. In the collaborative management, the oncology pharmacists had a total of 245 face-to-face patient consultations, and provided 286 suggestions [according to supportive care in pazopanib treatment (214 suggestions) were most frequent], and 236 (82.5%) were accepted by urologists. The median time to discontinuation (6.1 months vs. 2.4 months, p = 0.024) was significantly longer in the after group. Multivariate analysis showed that collaborative management (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.26-0.88, p = 0.017), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at pazopanib initiation (HR 3.87, 95% CI 1.47-9.13, p = 0.008) were significantly associated with pazopanib discontinuation. These results suggested that, compared to conventional management, collaborative management is effective at prolonging the time to pazopanib discontinuation.

Risk evaluation of denosumab and zoledronic acid for medication-related osteonecrosis of the jaw in patients with bone metastases: a propensity score-matched analysis.

PURPOSE: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis. METHODS: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups. RESULTS: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65-5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38-7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17-5.01; p = 0.016). CONCLUSION: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases.

PURPOSE: Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases. METHODS: The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ. RESULTS: Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37-4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63-10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75-8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06-2.96; p = 0.030) were significant risk factors for MRONJ. CONCLUSION: Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.

Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii.

The MacA-MacB-TolC tripartite complex is a transmembrane machine that spans both plasma membrane and outer membrane and actively extrudes substrates, including macrolide antibiotics, virulence factors, peptides and cell envelope precursors. These transport activities are driven by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. Here, we present the crystal structure of MacB at 3.4-Å resolution. MacB forms a dimer in which each protomer contains a nucleotide-binding domain and four transmembrane helices that protrude in the periplasm into a binding domain for interaction with the membrane fusion protein MacA. MacB represents an ABC transporter in pathogenic microorganisms with unique structural features.

Revolver is a new class of transposon-like gene composing the triticeae genome.

Revolver discovered in the Triticeae plant is a novel class of transposon-like gene and a major component of the large cereal genome. An 89 bp segment of Revolver that is enriched in the genome of rye was isolated by deleting the DNA sequences common to rye and wheat. The entire structure of Revolver was determined by using rye genomic clones, which were screened by the 89 bp probe. Revolver consists of 2929-3041 bp with an inverted repeated sequence on each end and is dispersed through all seven chromosomes of the rye genome. Revolver is transcriptionally active, and the isolated full-length cDNA (726 bp) reveals that Revolver harbors a single gene consisting of three exons (342, 88, and 296 bp) and two introns (750 and 1237 bp), and encodes 139 amino acid residues of protein, which shows similarity to some transcriptional regulators. Revolver variants ranging from 2665 to 4269 bp, in which 5' regions were destructed, indicate structural diversities around the first exon. Revolver does not share identity with any known class I or class II autonomous transposable elements of any living species. DNA blot analysis of Triticeae plants shows that Revolver has existed since the diploid progenitor of wheat, and has been amplified or lost in several species during the evolution of the Triticeae.