Development of an Automated Ultrasound Signal Indicator of Lung Interstitial Syndrome.

OBJECTIVES: The number and distribution of lung ultrasound (LUS) imaging artifacts termed B-lines correlate with the presence of acute lung disease such as infection, acute respiratory distress syndrome (ARDS), and pulmonary edema. Detection and interpretation of B-lines require dedicated training and is machine and operator-dependent. The goal of this study was to identify radio frequency (RF) signal features associated with B-lines in a cohort of patients with cardiogenic pulmonary edema. A quantitative signal indicator could then be used in a single-element, non-imaging, wearable, automated lung ultrasound sensor (LUSS) for continuous hands-free monitoring of lung fluid. METHODS: In this prospective study a 10-zone LUS exam was performed in 16 participants, including 12 patients admitted with acute cardiogenic pulmonary edema (mean age 60 ± 12 years) and 4 healthy controls (mean age 44 ± 21). Overall,160 individual LUS video clips were recorded. The LUS exams were performed with a phased array probe driven by an open-platform ultrasound system with simultaneous RF signal collection. RF data were analyzed offline for candidate B-line indicators based on signal amplitude, temporal variability, and frequency spectrum; blinded independent review of LUS images for the presence or absence of B-lines served as ground truth. Predictive performance of the signal indicators was determined with receiving operator characteristic (ROC) analysis with k-fold cross-validation. RESULTS: Two RF signal features-temporal variability of signal amplitude at large depths and at the pleural line-were strongly associated with B-line presence. The sensitivity and specificity of a combinatorial indicator were 93.2 and 58.5%, respectively, with cross-validated area under the ROC curve (AUC) of 0.91 (95% CI = 0.80-0.94). CONCLUSION: A combinatorial signal indicator for use with single-element non-imaging LUSS was developed to facilitate continuous monitoring of lung fluid in patients with respiratory illness.

First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones.

PURPOSE: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. MATERIALS AND METHODS: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. RESULTS: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. CONCLUSIONS: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

Nipple Sparing Mastectomy in Patients With Prior Breast Scars: Is It Safe?

BACKGROUND: Nipple-sparing mastectomy (NSM) preserves the native skin envelope, including the nipple-areolar skin, and has significant benefits including improved aesthetic outcome and psychosocial well-being. Patients with prior breast scars undergoing NSM are thought to be at increased risk for postoperative complications, such as skin and/or nipple necrosis. This study describes our experience performing NSM in patients who have had prior breast surgery and aims to identify potential risk factors in this subset of patients. METHODS: A retrospective review of all patients undergoing nipple sparing mastectomy at The University of Utah from 2005 to 2011 was performed. Fifty-two patients had prior breast scars, for a total of 65 breasts. Scars were categorized into 4 groups depending on scar location: inframammary fold, outer quadrant, periareolar, and circumareolar. Information regarding patient demographics, social and medical history, treatment intent, and postoperative complications were collected and analyzed. RESULTS: Eight of the 65 breasts (12%) developed a postoperative infection requiring antibiotic treatment. Tobacco use was associated with an increased risk of infection in patients with prior breast scars (odds ratio [OR], 7.95; 95% confidence interval [CI], 1.37-46.00; P = 0.0206). There was a 13.8% rate of combined nipple and skin flap necrosis and receipt of chemotherapy (OR, 5.00; CI, 1.11-22.46; P = 0.0357) and prior BCT (OR, 12.5; CI, 2.2-71.0; P = 0.004) were found to be associated with skin flap or NAC necrosis. CONCLUSIONS: Nipple-sparing mastectomy is a safe and viable option for patients with a prior breast scar. Our results are comparable to the published data in patients without a prior scar. Caution should be exercised with patients who have a history of tobacco use or those requiring chemotherapy because these patients are at increased risk for infection and NAC/skin flap necrosis, respectively, when undergoing NSM in the setting of a prior breast scar.

Correlates of elevated distress thermometer scores in breast cancer patients.

PURPOSE: Distress is prevalent in breast cancer patients and can be detrimental to quality of life, performance status, treatment adherence, and satisfaction with medical care. The National Comprehensive Cancer Network developed the distress thermometer (DT) as a self-assessment tool for screening distress in cancer patients. Given time and financial constraints, it is important to refine screening criteria to identify patients with elevated risk for distress. In this study, we identify clinical and epidemiological factors that are associated with an increased likelihood of elevated DT scores (≥ 4 and ≥ 7). METHODS: We assessed 229 female patients with the DT at their initial consultation for breast cancer at the Huntsman Cancer Hospital between September 2007 and December 2008. Descriptive statistics and logistic regression models were used to analyze DT and patient data. RESULTS: Patients undergoing their initial distress thermometer screening within 30 days of receiving a diagnosis of breast cancer had the highest likelihood of scoring ≥ 4 and ≥ 7 on the DT screening tool. Emotional and physical concerns were associated with scores ≥ 4 and scores ≥ 7. Spiritual concerns became significant in patients reporting scores ≥ 7. Patients who were non-Caucasian, unemployed, had a prior history of depression, presented for recurrent disease, or who had been recently diagnosed had a higher likelihood of scores ≥ 4 and scores ≥ 7. CONCLUSIONS: Four groups of patients should be targeted for aggressive screening; patients with a prior diagnosis of depression, patients presenting with recurrent disease, unemployed patients, and non-Caucasian patients. Interventions should address physical, emotional, and spiritual concerns.

Implementation Fidelity of Chatbot Screening for Social Needs: Acceptability, Feasibility, Appropriateness.

OBJECTIVES: Patient and provider-facing screening tools for social determinants of health have been explored in a variety of contexts; however, effective screening and resource referral remain challenging, and less is known about how patients perceive chatbots as potential social needs screening tools. We investigated patient perceptions of a chatbot for social needs screening using three implementation outcome measures: acceptability, feasibility, and appropriateness. METHODS: We implemented a chatbot for social needs screening at one large public hospital emergency department (ED) and used concurrent triangulation to assess perceptions of the chatbot use for screening. A total of 350 ED visitors completed the social needs screening and rated the chatbot on implementation outcome measures, and 22 participants engaged in follow-up phone interviews. RESULTS: The screened participants ranged in age from 18 to 90 years old and were diverse in race/ethnicity, education, and insurance status. Participants (n = 350) rated the chatbot as an acceptable, feasible, and appropriate way of screening. Through interviews (n = 22), participants explained that the chatbot was a responsive, private, easy to use, efficient, and comfortable channel to report social needs in the ED, but wanted more information on data use and more support in accessing resources. CONCLUSION: In this study, we deployed a chatbot for social needs screening in a real-world context and found patients perceived the chatbot to be an acceptable, feasible, and appropriate modality for social needs screening. Findings suggest that chatbots are a promising modality for social needs screening and can successfully engage a large, diverse patient population in the ED. This is significant, as it suggests that chatbots could facilitate a screening process that ultimately connects patients to care for social needs, improving health and well-being for members of vulnerable patient populations.

Impact of Chemotherapy and Radiation Therapy on Inflammatory Response, Neovascularization, and Capsule Formation of Acellular Dermal Matrix in Breast Reconstruction: Analysis of the BREASTrial Biopsy Specimens.

BACKGROUND: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a single-center, blinded, prospective, randomized, controlled trial established to compare outcomes using two popular types of acellular dermal matrices, AlloDerm and DermaMatrix, in tissue expander breast reconstruction. This study used the acellular dermal matrix biopsy specimens from the trial to evaluate how adjuvant therapy influences inflammation, neovascularization, and capsule formation of the acellular dermal matrix. METHODS: Punch biopsy specimens were taken at the time of expander exchange and were analyzed by a blinded pathologist. The inflammatory response was quantified by the number of fibroblasts, giant cells, and lymphocytes. Neovascularization and capsule formation were similarly quantified by the number of new capillaries and capsule presence and thickness, respectively. RESULTS: Histology specimens were collected from 109 patients (170 breasts). In the absence of adjuvant therapy, there was no significant difference between AlloDerm and DermaMatrix in terms of inflammation, neovascularization, or capsule thickness. Both acellular dermal matrices showed a significant decrease in inflammation and neovascularization with adjuvant therapy. When chemotherapy and radiation therapy were used, the decrease in inflammation was greatest for the group reconstructed with DermaMatrix (p < 0.039). CONCLUSIONS: Adjuvant therapy influences the inflammatory response, neovascularization, and capsule formation in both acellular dermal matrices. Adjuvant therapy has a protective effect on the inflammatory response toward both acellular dermal matrices in breast reconstruction. In the setting of chemotherapy and radiation therapy, DermaMatrix produced the greatest reduction in inflammation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Publisher Correction: Combating subclonal evolution of resistant cancer phenotypes.

The originally published version of this Article contained an error in Figure 4. In panel a, grey boxes surrounding the subclones associated with patients #2 and #4 obscured adjacent portions of the heatmap. This error has now been corrected in both the PDF and HTML versions of the Article.

Breast Cancer Risk Reduction Decisions of the BRCA-Positive Patient: An Observational Study at a Single Institution.

BACKGROUND: BRCA1 and BRCA2 gene mutations carry with them a 50%-80% risk of developing breast cancer. The best choice for managing breast cancer risk in patients with a BRCA1/2 mutation is a highly personal decision. Options for risk management include surveillance with multiple modalities or prophylactic surgical intervention. The goal of this study was to gain a better understanding of contributing factors affecting the decision for managing breast cancer risk made by patients who are BRCA mutation positive and cancer free. METHODS: A retrospective chart review of patients, who tested positive for BRCA1/2 gene mutation between 2003 and 2013 without history of breast cancer, was performed. A logistic regression model was used to assess the association between preselected risk factors and the decision of the patient to undergo prophylactic mastectomy versus surveillance. RESULTS: Of the 106 patients who were cancer free and BRCA positive, seventy (66%) opted for surveillance, whereas 36 (34%) chose prophylactic mastectomy. Three preselected risk factors were found to significantly affect a patient's likelihood of choosing surgery: having a family member with breast cancer before the age of 50 (OR: 4.67 [95% CI: 1.86-11.68]), p = 0.001), cancer-related death of a relative younger than 50 years old (OR: 2.26 [95% CI: 0.92-5.55], p = 0.07), and prophylactic oophorectomy before planned mastectomy (OR: 3.72 [95% CI: 1.49-9.31], p = 0.005). Patient age less than 30 was found to be significantly associated with the decision to proceed with surveillance (OR: 0.2 [95% CI: 0.05-0.75], p = 0.02). CONCLUSION: Risk-reducing strategy is a very personal decision for the patient with positive BRCA mutation, and many factors go into choosing which options are best for each individual. We found that age of patient, relative with breast cancer or death of a relative before age 50, and prophylactic oophorectomy all play significant roles in which risk reduction strategy is chosen.

The BREASTrial Stage II: ADM Breast Reconstruction Outcomes from Definitive Reconstruction to 3 Months Postoperative.

BACKGROUND: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a prospective randomized trial comparing outcomes of tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The trial was divided into 3 outcome stages; this study reports stage II outcomes, which are those from the time of definitive reconstruction to 3 months postoperative. METHODS: A randomized trial was conducted to compare complication rates between AlloDerm and DermaMatrix groups. The impact of matrix type, age, obesity, radiation therapy, chemotherapy, and reconstruction type on complications was analyzed with regression models. RESULTS: Of the 128 patients (199 breasts) who were randomly assigned into the trial, 111 patients (173 breasts) were available for analysis in stage II. There was no difference in overall rates of complications (15.4% vs 18.3%, P = 0.8) or implant loss (2.2% vs 3.7%, P = 0.5) between the AlloDerm and DermaMatrix groups, respectively. Obesity was the only significant predictor of complications on regression analysis (odds ratio, 4.31, P = 0.007). Matrix type, age, radiation therapy, chemotherapy, or reconstruction type had no impact on the incidence/severity of complications. CONCLUSIONS: Acellular dermal matrix (ADM) will likely continue to have a role in breast reconstructive surgery; however, caution should be taken when using ADM because of relatively high complication rates, especially in obese patients. The particular ADM product should be selected based on individual surgeon preference, experience, and success rates. These data and forthcoming long-term outcomes from the Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial will enable surgeons to carefully weigh the risks and benefits of ADM use in breast reconstruction.

Combating subclonal evolution of resistant cancer phenotypes.

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves.

The Effect of Previsit Education in Breast Cancer Patients: A Study of a Shared-decision-making Tool.

To enhance shared decision-making for patients with breast cancer, we developed an evidence-based educational breast cancer video (BCV) providing an overview of breast cancer biology, prognostic indicators, and surgical treatment options while introducing health care choice. By providing patients access to a BCV with information necessary to make informed surgical decisions before seeing a surgeon, we aimed to increase patient participation in the decision-making process, while decreasing distress. Patients with a new diagnosis of breast cancer were provided a link to the BCV. Group 1 participated in online pre- and postvideo questionnaires, with the BCV embedded in between. The questionnaires evaluated self-reported baseline knowledge of breast cancer and perceived distress related to the diagnosis. Changes in self-reported responses were analyzed using the Wilcoxon matched pairs test. Group 2 received a survey collecting demographics, decision-making information, and perceptions of the BCV at the time of clinic visit before meeting the surgeon. Group 1 included 69 subjects with 62 per cent reporting improved knowledge and 30 per cent reporting reduced distress in regard to their breast cancer diagnosis. Group 2 included 87 subjects; 94 to 98 per cent felt the BCV provided information and stimulated thoughts and questions to assist in breast cancer treatment decision-making. The BCV was positively received by participants and feasible to implement into clinical practice. Evidence-based media tools improve knowledge and reduce distress in patients with a new diagnosis of breast cancer as well as contributing to the shared decision-making process.

The breast reconstruction evaluation of acellular dermal matrix as a sling trial (BREASTrial): design and methods of a prospective randomized trial.

BACKGROUND: Recent literature has focused on the advantages and disadvantages of using acellular dermal matrix in breast reconstruction. Many of the reported data are from low level-of-evidence studies, leaving many questions incompletely answered. The present randomized trial provides high-level data on the incidence and severity of complications in acellular dermal matrix breast reconstruction between two commonly used types of acellular dermal matrix. METHODS: A prospective randomized trial was conducted to compare outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of body mass index, smoking, diabetes, mastectomy type, radiation therapy, and chemotherapy on outcomes was analyzed. Acellular dermal matrix biointegration was analyzed clinically and histologically. Patient satisfaction was assessed by means of preoperative and postoperative surveys. Logistic regression models were used to identify predictors of complications. RESULTS: This article reports on the study design, surgical technique, patient characteristics, and preoperative survey results, with outcomes data in a separate report. After 2.5 years, we successfully enrolled and randomized 128 patients (199 breasts). The majority of patients were healthy nonsmokers, with 41 percent of patients receiving radiation therapy and 49 percent receiving chemotherapy. Half of the mastectomies were prophylactic, with nipple-sparing mastectomy common in both cancer and prophylactic cases. Preoperative survey results indicate that patients were satisfied with their premastectomy breast reconstruction education. CONCLUSION: Results from the Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial will assist plastic surgeons in making evidence-based decisions regarding acellular dermal matrix-assisted tissue expander breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The BREASTrial: stage I. Outcomes from the time of tissue expander and acellular dermal matrix placement to definitive reconstruction.

BACKGROUND: Use of acellular dermal matrix in tissue expander breast reconstruction has become a popular adjunct to the total submuscular technique. The question remains as to which matrix, if any, is ideal for breast reconstruction. METHODS: A randomized trial was conducted to analyze outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of obesity, radiation, and chemotherapy on complications and biointegration of matrix was investigated. The trial was divided into three stages, with stage I results reported here. RESULTS: One hundred twenty-eight patients (199 breasts) were randomized equally over 2.5 years. Most patients were white, healthy nonsmokers. The overall complication rate was 36.2 percent; half of the complications were minor. The AlloDerm and DermaMatrix groups had similar rates of complications (33.6 percent versus 38.8 percent; p = 0.52), consisting mostly of skin necrosis (17.8 percent versus 21.4 percent; p = 0.66) and infections (13.9 percent versus 16.3 percent; p = 0.29), both of which led to tissue expander losses (5 percent versus 11.2 percent; p = 0.11). The AlloDerm group required less time for completion of expansion (42 days versus 70 days; p < 0.001). Obesity was associated with poor matrix biointegration and a longer drain time, both of which were associated with higher complication rates. CONCLUSION: The Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial is the largest randomized trial to date in matrix breast reconstruction and emphasizes the importance of careful patient and allograft selection to minimize complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.