Trifluridine/tipiracil (FTD/TPI) improves the overall survival (OS) of metastatic colorectal cancer (mCRC) patients. Additionally, FTD/TPI plus bevacizumab (BEV) has demonstrated promising efficacy for mCRC patients who are refractory to standard chemotherapy. Chemotherapy-induced neutropenia (CIN) has been reported to be an indicator of efficacy for FTD/TPI. This study investigated whether CIN was an indicator of efficacy for FTD/TPI plus BEV.
 
  We reviewed chemo-refractory mCRC patients who were treated with FTD/TPI alone (monotherapy) or FTD/TPI plus BEV (combination) at our institution and compared the safety and efficacy of the two. Progression-free survival (PFS) and OS were analyzed using Kaplan-Meier curves. We also investigated correlations between CIN and outcomes.
 
  In total, 56 patients received FTD/TPI, among whom 24 and 32 were treated with monotherapy and combination therapy, respectively. The median PFS was 1.8 and 4.7months for the monotherapy and combination arms, respectively (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.15-0.51; P < 0.001). The median OS was 6.3 and 11.7months for the monotherapy and combination arms, respectively (HR 0.25; 95% CI 0.13-0.48; P < 0.001). CIN (Grade 3 or worse) developed in five (20.8%) and 17 (53.1%) patients from the monotherapy and combination arms, respectively (P = 0.030). Patients with CIN in the combination arm had improved PFS and OS compared with non-CIN patients (P = 0.033 and P = 0.045, respectively).
 
  FTD/TPI plus BEV prolonged PFS and OS and had tolerable toxicity compared with FTD/TPI alone. CIN is an indicator of patients who will benefit from FTD/TPI plus BEV.
 FTD/TPI plus BEV prolonged PFS and OS and had tolerable toxicity compared with FTD/TPI alone. CIN is an indicator of patients who will benefit from FTD/TPI plus BEV.
  Cisplatin and carboplatin are frequently used drugs in the treatment of pediatric hepatoblastoma. Dosing guidelines for these drugs in children requiring peritoneal dialysis are lacking. Here, we describe the case of a 3-year-old boy with pre-existing end-stage renal disease on peritoneal dialysis, requiring treatment with cisplatin and carboplatin for hepatoblastoma.
 
  Pharmacokinetic data were generated to support clinical dosing decisions, with the aim of adequate exposure and minimal toxicity. In the first chemotherapy cycle, 25% of the standard cisplatin dose and 75% of the carboplatin dose, calculated using the pediatric Calvert formula, were administered. Free platinum concentrations were determined in plasma ultrafiltrate and dialysate samples drawn after administration of cis- and carboplatin.
 
  Cisplatin was well tolerated and the observed AUC of cisplatin were 15.3 and 14.3mg/Lh in cycles 1 and 3, respectively. The calculated AUC of carboplatin in cycle 1 (9.8mg/mLmin) exceeded target AUC of 6.5m calculate the starting dose of carboplatin using the (pediatric) Calvert formula, assuming a dialytic clearance of zero, and to adjust the dose if required, based on therapeutic drug monitoring.The function of microRNA-27a (miR-27a) expression in cholangiocarcinoma (CCA) remains largely unclear; therefore, this study aimed to investigate the clinical significance and functional role of miR-27a in CCA. This study included 117 paired CCA tissues and adjacent normal tissues from CCA patients who received surgical resection. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-27a in CCA tissues and cell lines. A Kaplan-Meier curve and Cox regression analysis were used to determine overall prognostic performance. The effects of miR-27a on cell proliferation, migration, and invasion were measured by CCK-8 and Transwell assays. The expression levels of miR-27a in patients with CCA and cell lines were higher than those in adjacent normal tissues and normal cells, respectively. Additionally, miR-27a levels were found to be associated with lymph node metastasis and TNM stages. The overall survival time of CCA patients with high miR-27a expression was poorer than that of those with low miR-27a expression. Furthermore, miR-27a overexpression promoted CCA cell proliferation, migration, and invasion, whereas knockdown of miR-27a suppressed cell proliferation, migration, and invasion. Taken together, these results suggest the potential usefulness of miR-27a in the prognosis and progression of CCA.We provide an update on how commonly prescribed osteoporosis therapies are being initiated in older adults in Ontario. Patients newly prescribed denosumab are older, more often female, and have more comorbidities than those prescribed bisphosphonates. Their characteristics, monitoring, and persistence with prescribed therapy differ from clinical trial participants. Real-world studies on oral bisphosphonates and denosumab might be valuable.
  To provide a contemporary view on oral bisphosphonate and denosumab prescribing to older adults in routine care.
 
  Using linked healthcare databases, we conducted a population-based cohort study of adults ≥ 66years newly prescribed oral bisphosphonates or denosumab between February 2013 and March 2017 in Ontario, Canada. We captured their clinical characteristics, monitoring, and continuous use of prescribed therapies. We illustrate how "real-world" new users of bisphosphonates and denosumab differ from randomized controlled trial (RCT) participants.
 
  There were 107,847 iuct monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.
 The clinical characteristics and monitoring of new users of bisphosphonates and denosumab generally align with practice guidelines, product monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic.  https://www.selleckchem.com/products/pf-07104091.html  Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified 1 has not been evaluated due to its low content in Plantaginis Semen. In the present study, 1 was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated 1, 2, and 3 were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative 1H-NMR, using DSS-d6 as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15 mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of 1, 2, and 3.