Search

Simple Summary: Patients with HER2-positive metastatic breast cancer develop brain metastases in up to 30% of cases. The aim of this systematic review and meta-analysis was to determine the effect of different systemic therapies in patients with HER2-positive metastatic breast cancer and brain metastases, acknowledging the heterogeneity and sometimes low quality of 51 included studies. Tucatinib (combined with trastuzumab and capecitabine) and trastuzumab-deruxtecan appear to constitute the most effective systemic therapy, while pyrotinib might be an option in Asian patients. Preferably, future research will comprise of randomized controlled trials, including patients with active and/or inactive brain metastases. Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM. Methods: A systematic search was performed in the databases PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and the Wiley/Cochrane Library. Eligible articles included prospective or retrospective studies reporting on the effect of systemic therapy on objective response rate (ORR) and/or median progression free survival (mPFS) in patients with HER2+ mBC and BM. The timeframe within the databases was from inception to 19 January 2022. Fixed-effects meta-analyses were used. Quality appraisal was performed using the ROBINS-I tool. Results: Fifty-one studies were included, involving 3118 patients. Most studies, which contained the largest patient numbers, but also often carried a moderate-serious risk of bias, investigated lapatinib and capecitabine (LC), trastuzumab-emtansine (T-DM1) or pyrotinib. The best quality data and/or highest ORR were described with tucatinib (combined with trastuzumab and capecitabine, TTC) and trastuzumab-deruxtecan (T-DXd). TTC demonstrated an ORR of 47.3% in patients with asymptomatic and/or active BM. T-DXd achieved a pooled ORR of 64% (95% CI 43–85%, I2 0%) in a heavily pretreated population with asymptomatic BM (3 studies, n = 96). Conclusions: Though our meta-analysis should be interpreted with caution due to the heterogeneity of included studies and a related serious risk of bias, this review provides a comprehensive overview of all currently available systemic treatment options. T-Dxd and TTC that appear to constitute the most effective systemic therapy in patients with HER2+ mBC and BM, while pyrotinib might be an option in Asian patients. [ABSTRACT FROM AUTHOR]

Background: Joint replacement surgery of the lower extremities are common procedures in elderly persons who are at increased risk of postoperative falls. The use of mental state altering medications, such as opioids, antidepressants or benzodiazepines, can further contribute to impaired balance and risk of falls. The objective of the current systematic review was to evaluate the risk of the use of mental state altering medications on postoperative falls in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: A comprehensive search of Medline, Embase and Cochrane Controlled Trials Register was conducted from 1 October 1975 to 1 September 2021. The search was repeated in may 2023 and conducted from 1 October 1975 to 1 June 2023. Clinical trials that evaluated the risk of medication on postoperative THA and TKA falls were eligible for inclusion. Articles were evaluated independently by two researchers for risk of bias using the Newcastle-Ottawa Scale. A meta-analysis was performed to determine the potential effect of postoperative use of mental state altering medications on the risk of falls. Lastly, a qualitative synthesis was conducted for preoperative mental state altering medications use. Results: Seven cohort studies were included, of which five studies focussed on the postoperative use of mental state altering medications and two investigated the preoperative use. Meta-analysis was performed for the postoperative mental state altering medications use. The postoperative use of mental state altering medications was associated with fall incidents (OR: 1.81; 95% CI: 1.04; 3.17) (p < 0.01) after THA and TKA. The preoperative use of opioids > 6 months was associated with a higher risk of fall incidents, whereas a preoperative opioid prescription up to 3 months before a major arthroplasty had a similar risk as opioid-naïve patients. Conclusions: The postoperative use of mental state altering medications increases the risk of postoperative falls after THA and TKA. Prior to surgery, orthopaedic surgeons and anaesthesiologists should be aware of the associated risks in order to prevent postoperative falls and associated injuries. [ABSTRACT FROM AUTHOR]