Citations

Abstract Purpose: HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor–positive (ER+) breast cancer. Patients and Methods: In this single-arm multi-cohort phase II trial, we evaluated the efficacy of neratinib plus fulvestrant in patients with ER+/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n = 24) or fulvestrant-naïve cohort (n = 11). Patients with ER-negative (ER−)/HER2mut MBC received neratinib monotherapy in an exploratory ER− cohort (n = 5). Results: The clinical benefit rate [CBR (95% confidence interval)] was 38% (18%–62%), 30% (7%–65%), and 25% (1%–81%) in the fulvestrant-treated, fulvestrant-naïve, and ER− cohorts, respectively. Adding trastuzumab at progression in 5 patients resulted in three partial responses and one stable disease ≥24 weeks. CBR appeared positively associated with lobular histology and negatively associated with HER2 L755 alterations. Acquired HER2mut were detected in 5 of 23 patients at progression. Conclusions: Neratinib and fulvestrant are active for ER+/HER2mut MBC. Our data support further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.

Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P < .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms.

Context: Athletes are a unique group of patients whose activities, particularly in high-contact sports such as wrestling and football, place them at high risk of developing skin conditions. The correct diagnosis of sports dermatoses requires familiarity with their clinical characteristics. It is critical that primary care physicians recognize the most common skin disorders to provide prompt treatment and prevent transmission. Evidence Acquisition: The Mayo Clinic library obtained articles from 2012 onward related to dermatologic conditions in athletes. Study Design: Review article. Level of Evidence: Level 3. Results: Dermatologic diseases in athletes are often infectious and contagious due to close-contact sports environments. Sports-related dermatoses include bacterial infections, such as impetigo, ecthyma, folliculitis, abscesses, furuncles, carbuncles, erysipelas, and cellulitis; fungal infections, such as tinea and intertrigo; viral infections, such as herpes, verrucae, and molluscum contagiosum; and noninfectious conditions, such as acne, blisters, and contact dermatitis. Conclusion: This article aims to address the manifestations of the most common cutaneous diseases in athletes on the first primary care visit. It discusses the appropriate tests and most recent evidence-based treatments for each ailment. It also addresses return-to-play recommendations related to the guidelines and regulations of selected sports organizations in the United States. Strength of Recommendation Taxonomy (SORT): C.

Research quantifying the unique workload demands of starters and reserves in training and match settings throughout a season in collegiate soccer is limited. Purpose: The purpose of the current study is to compare accumulated workloads between starters and reserves in collegiate soccer. Methods: Twenty-two NCAA Division III female soccer athletes (height: 1.67 ± 0.05 m; body mass: 65.42 ± 6.33 kg; fat-free mass: 48.99 ± 3.81 kg; body fat %: 25.22 ± 4.78%) were equipped with wearable global positioning systems with on-board inertial sensors, which assessed a proprietary training load metric and distance covered for each practice and 22 matches throughout an entire season. Nine players were classified as starters (S), defined as those playing >50% of playing time throughout the entire season. The remaining 17 were reserves (R). Goalkeepers were excluded. A one-way ANOVA was used to determine the extent of differences in accumulated training load throughout the season by player status. Results: Accumulated training load and total distance covered for starters were greater than reserves ((S: 9431 ± 1471 vs. R: 6310 ± 2263 AU; p < 0.001) and (S: 401.7 ± 31.9 vs. R: 272.9 ± 51.4 km; p < 0.001), respectively) throughout the season. Conclusions: Starters covered a much greater distance throughout the season, resulting in almost double the training load compared to reserves. It is unknown if the high workloads experienced by starters or the low workloads of the reserves is more problematic. Managing player workloads in soccer may require attention to address potential imbalances that emerge between starters and reserves throughout a season.

Abstract Background Tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. Objectives The aim of this study was to investigate the value and safety profile of both intravenous and topically administered TXA in the setting of bilateral reduction mammaplasty. Methods A retrospective review was performed to identify consecutive patients who underwent bilateral reduction mammaplasty for symptomatic macromastia (January 2016-July 2021). Pertinent preoperative, intraoperative, and postoperative details were collected/reviewed. Primary outcome measures included hematoma requiring surgical evacuation and clinically significant/symptomatic seroma formation mandating percutaneous aspiration. Patients taking anticoagulation/antiplatelet medication or those with a history of thromboembolic diseases were excluded. Patients who had received TXA were compared to a historical control group who did not receive TXA within the same consecutive cohort. Results A total of 385 consecutive patients (770 breasts) were included. TXA was used in 514 (66.8%) cases (topical, 318 [61.9%]; intravenous, 170 [33.1%]; intravenous and topical, 26 [5.1%]). Neither seroma nor hematoma were impacted/reduced with TXA (P &gt; 0.05). Increased age (hazards ratio, 1.06 per 1-year increase; 95% CI, 1.004-1.118) significantly increased the risk of hematoma (P = 0.032). The use of drains significantly decreased the risk of seroma (P &lt; 0.0001). Increased BMI increased the risk of seroma (hazards ratio, 1.16 per 1-kg/m2 increase; 95% CI, 1.06-1.26; P = 0.0013). The use of TXA did not impact drain duration. Conclusions This study, the largest to date on the use of IV and topical TXA, did not find any reduction in risk when using TXA in breast reduction surgery. Level of Evidence: 3

Cholangiocarcinoma (CCA) is a heterogenous group of malignancies originating in the biliary tree, and associated with poor prognosis. Until recently, treatment options have been limited to surgical resection, liver-directed therapies, and chemotherapy. Identification of actionable genomic alterations with biomarker testing has revolutionized the treatment paradigm for these patients. However, several challenges exist to the seamless adoption of precision medicine in patients with CCA, relating to a lack of awareness of the importance of biomarker testing, hurdles in tissue acquisition, and ineffective collaboration among the multidisciplinary team (MDT). To identify gaps in standard practices and define best practices, multidisciplinary hepatobiliary teams from the University of California (UC) Davis and UC Irvine were convened; discussions of the meeting, including optimal approaches to tissue acquisition for diagnosis and biomarker testing, communication among academic and community healthcare teams, and physician education regarding biomarker testing, are summarized in this review.

Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy for which no prevention or cure exists. Cancer and cancer treatments can adversely affect nutritional status. Nutrition may play a role in development of CIPN, yet the relationship between nutrition and CIPN is not well understood. Common laboratory values measuring various aspects of nutrition (hemoglobin/hematocrit, vitamin B12, calcium, and magnesium) may be associated with CIPN. The aim of this systematic review is to evaluate the empirical evidence surrounding the relationship between laboratory measures of nutrition and CIPN among persons with cancer who received neurotoxic chemotherapy drugs. We conducted an extensive review of the literature to identify articles that evaluated relationships between laboratory measures of nutrition and CIPN. A total of eleven articles satisfied the inclusion/exclusion criteria. Participants in the studies had breast or colorectal cancer, lymphoma or multiple myeloma and were receiving a variety of neurotoxic drugs. Hemoglobin/hematocrit, vitamin D, albumin, and magnesium were associated with CIPN. The quality of the studies ranges from fair to good. Evidence suggests that low levels of the above-mentioned tests could be associated with CIPN but additional research is needed.