Feasibility of Measuring Physical Activity Using Accelerometry in Hospitalized and Community-Living Older People with Cognitive Impairment

Letters to the EditorWetensch. publicati

Minimally invasive complete response assessment of the breast after neoadjuvant systemic therapy for early breast cancer (micra trial) : interim analysis of a multicenter observational cohort study

Background The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI. Methods We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1-4(N0 or N +) breast cancer with MRI rPR and enhancement <= 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR). Results Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45-61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27-49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72-55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95-21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87-1.00; p = 0.051). Conclusion The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients

A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats

Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT6) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT6 receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT6 receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control

Immediate or delayed oncoplastic surgery after breast conserving surgery at the Netherlands Cancer Institute:a cohort study of 251 cases

Purpose: Oncoplastic surgery (OPS) after breast conserving surgery is preferably performed during the same operation. Offering delayed OPS instead of mastectomy to patients with a high risk of tumor-positive margins allows breast conservation with the option of margin re-excision during OPS, without having to dismantle the reconstruction. We aimed to evaluate surgical outcomes after immediate and delayed OPS. Methods: We included early-stage breast cancer patients who underwent OPS at the Netherlands Cancer Institute between 2016 and 2019. Patients were selected for delayed OPS after multidisciplinary consultation if the risk of tumor-positive margins with immediate OPS was considered significant (&gt; 30%). Groups were compared on baseline characteristics and short-term surgical outcomes. Results: Of 242 patients with 251 OPS, 130 (52%) OPS had neoadjuvant chemotherapy. Immediate OPS was performed in 176 (70%) cases and delayed OPS in 76 (30%). Selection for delayed OPS was associated with tumor size (OR 1.03, 95% CI 1.01–1.04), ILC (OR 2.61, 95% CI 1.10–6.20), DCIS (OR 3.45, 95% CI 1.42–8.34) and bra size (OR 0.76, 95% CI 0.62–0.94). Delayed and immediate OPS differed in tissue weight (54 vs. 67 g, p = 0.034), tissue replacement (51% vs. 26%, p &lt;.001) and tumor-positive margins (66% vs. 18%, p &lt;.001). Re-excision was performed in 48 (63%) delayed OPS and in 11 (6%) immediate OPS. Groups did not differ in complications (21% vs. 18%, p = 0.333). Breast conservation after immediate and delayed OPS was 98% and 93%, respectively. Conclusion: Performing delayed OPS in selected cases facilitated simultaneous margin re-excision without increasing complications, and resulted in an excellent breast conservation rate.</p