A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

A Comprehensive Review on the Supraclavicular Flap for Head and Neck Reconstruction.

ABSTRACT: The supraclavicular artery flap (SCF) is a highly vascularized fasciocutaneous flap overlying the shoulder. The flap was first described in 1979 by Lamberty but did not gain popularity until much later due to lack of a reliable technique. The main advantages of using the SCF include avoiding microsurgical techniques, requiring only a single-stage operation, shorter operative time compared with alternative options, and a wider patient population including those with comorbidities who may be excluded from more extensive operations including free flaps surgeries. The SCF has been successfully performed on individuals with advanced age, poor nutrition, cachexia, obesity, diabetes, tobacco use, severe chronic obstructive pulmonary disease, hypertension, coronary artery disease, peripheral vascular disease, supraventricular tachycardia, atrial fibrillation, heart failure, asthma, and steroid use. The largest disadvantages of the SCF include the possibility of distal tip necrosis, size limitation without pre-expansion, and a moderately visible donor site scar. The following review and meta-analysis of the SCF details its use historically as both an island and a pedicle flap, and its application in head and neck reconstruction.

Direct Neurotization: Past, Present, and Future Considerations.

ABSTRACT: Direct neurotization is a method that involves direct implantation of nerve fascicles into a target tissue, that is, muscle fibers, skin, cornea, and so on, with the goal of restoring aesthetic, sensation and or functional capacity. This technique has been implemented since the early 1900s, with numerous experimental and clinical reports of success. Applications have included both sensory and motor neurotization of muscle, as well as protective sensory provision for other organs. These techniques have been used to restore corneal sensation, repair brachial plexus injuries, reestablish tongue movement and function through direct tongue neurotization, and reinnervate multiple facial muscles in patients with facial paralysis. Most recently, these methods have even been used in conjunction with acellular cadaveric nerve grafts to directly neurotize skin. Indications for direct neurotization remain limited, including those in which neural coaptation is not feasible (ie, surgical or traumatic damage to neuromuscular junction, severe avulsion injuries of the distal nerve); however, the success and wide-range application of direct neurotization shows its potential to be implemented as an adjunct treatment in contrast to views that it should solely be used as a salvage therapy. The purpose of the following review is to detail the historic and current applications of direct neurotization and describe the future areas of investigation and development of this technique.

Long-term Effects of Repeated Botulinum Toxin Injection in Cosmetic Therapeutics.

BACKGROUND: Botulinum toxin (BT), a potent neurotoxin, has been used in clinical medicine since the 1970s for cosmetic and therapeutic purposes. Studies have consistently shown positive outcomes with a very limited adverse effect profile and a conventional understanding that results dissipate after 3 to 5 months. However, more recent evidence suggests that changes in muscle composition, function, and appearance persist for much longer, even years. To examine the potential implications of these findings on cosmetic use of BT injections in reduction of skin lines and wrinkles, we first needed to further our understanding of the current literature on long-term outcomes after repeated BT injections. METHODS: A comprehensive review of the literature on long-term outcomes after repeated BT injections for cosmetic indications was performed. We evaluated the study designs, and results were compared. RESULTS: A total of 22 publications met our inclusion criteria, of which 14 were clinical trials. Few studies extended outcome measurement past 6 months postinjection, and many were funded or supported by industry. However, the studies that extended follow-up saw persistent changes after BT injection, in some cases as far as 4 years postinjection. CONCLUSION: The current body of knowledge on the long-term results after repeated cosmetic BT injections is very limited, and the available literature provides insufficient evidence on how prolonged effects could alter clinical use of BT. Further clinical studies with extended follow-up periods with inclusion of both subjective and objective measured outcomes of appearance and muscle function are required to better understand the long-term impacts of repeated BT injections.