Does a Positive Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screen Predict the Risk for MRSA Skin and Soft Tissue Infection?

BACKGROUND: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited. OBJECTIVE: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs. METHODS: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel. RESULTS: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%. CONCLUSIONS: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis.

BACKGROUND: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban. OBJECTIVE: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban. METHODS: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration. RESULTS: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159). CONCLUSION AND RELEVANCE: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed.

Prophylactic Enoxaparin in Critically Ill Trauma Patients: Evaluation of the Initial Dose.

Background: Trauma patients are at increased risk of developing venous thromboembolism given alterations in the coagulation cascade. Chemoprophylaxis with standard dosing of enoxaparin 30 mg subcutaneously twice daily has evolved to incorporate the use of anti-factor Xa (AFXa) trough level monitoring given concerns for decreased enoxaparin bioavailability in this patient population. Current available evidence suggests low rates of goal AFXa trough level achievement with standard enoxaparin dosing. Our study aims to identify the incidence of critically ill trauma patients that did not achieve goal AFXa trough levels and attempts to identify predictors that may influence the lack of achievement of goal levels. Methods: This was a retrospective, cohort analysis performed at a single academic medical center. Adult patients 18 years or older admitted to the surgical intensive care unit secondary to trauma who were initiated on standard prophylactic enoxaparin and had at least 1 AFXa trough level representative of steady state were included. Patient demographics and clinical data were collected, and descriptive statistics were utilized. All statistical tests were 2-tailed and a P < .05 was considered significant. Variables with a P < .10 on univariable analysis were included in a multivariable logistic regression analysis. Results: A majority of our patient population did not achieve goal AFXa trough levels while receiving standard doses of prophylactic enoxaparin (82.4% [108/131]). Sub-target AFXa levels were associated with higher creatinine clearance values. Positive predictors of obtaining target AFXa levels included automobile versus pedestrian mechanism of injury and requiring an enoxaparin dose escalation to at least 40 mg twice daily. Conclusions: Our study found low rates of achievement of goal AFXa trough levels in critically ill trauma patients receiving standard prophylactic enoxaparin dosing. Certain variables were identified as negative and positive predictors for achievement of goal AFXa trough levels, although the biologic plausibility of these predictors is questionable and requires further investigation.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Performance and Practice Guideline for the Use of Neoadjuvant Systemic Therapy in the Management of Breast Cancer.

PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide an evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the management of clinical stage II and III invasive breast cancer. METHODS: A comprehensive nonsystematic review was performed of selected peer-reviewed literature published since 2000. The Education Committee of the ASBrS convened to develop guideline recommendations. RESULTS: A performance and practice guideline was prepared to outline the baseline assessment and perioperative management of patients with clinical stage II-III breast cancer under consideration for NST. RECOMMENDATIONS: Preoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon's perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.

Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck.

BACKGROUND: The objective of this trial was to determine how a mucoadhesive hydrogel (MuGard), a marketed medical device, would fare when tested with the strictness of a conventional multi-institutional, double-blind, randomized, placebo-controlled study format. METHODS: A total of 120 subjects planned to receive chemoradiation therapy (CRT) for treatment of head and neck cancers were randomized to receive either MuGard or sham control rinse (SC) during CRT. Subjects completed the validated Oral Mucositis Daily Questionnaire. Weight, opiate use, and World Health Organization (WHO) oral mucositis (OM) scores were recorded. Subjects who dosed at least once daily during the first 2.5 weeks of CRT were included in the efficacy analysis. RESULTS: Of 120 subjects enrolled, 78 (SC, N=41; MuGard, N=37) were eligible for efficacy analysis. Both cohorts were similar in demographics, baseline characteristics, primary tumor type, and planned CRT regimen. MuGard effectively mitigated OM symptoms as reflected by area under the curve of daily patient-reported oral soreness (P=.034) and WHO scores on the last day of radiation therapy (P=.038). MuGard was also associated with nonsignificant trends related to therapeutic benefit including opioid use duration, and OM scores (WHO criteria) at CRT week 4. Rinse compliance was identical between cohorts. No significant adverse events were reported, and the adverse event incidence was similar between cohorts. CONCLUSIONS: Testing MuGard, a rinse marketed as a device, in a standard clinical trial format demonstrated its superiority to SC in mitigating OM symptoms, delaying OM progression, and its safety and tolerability.

Intentions for bilateral mastectomy among newly diagnosed breast cancer patients.

BACKGROUND: Recent trends suggest that bilateral mastectomy (BM) is on the rise among women diagnosed with unilateral breast cancer. Few studies have investigated the factors associated with the decision to have more aggressive surgery among young, high risk patients. METHODS: As part of a larger study, 284 women aged 50 and under completed an initial survey within 6 weeks of a breast cancer diagnosis. We assessed sociodemographics, medical and family history variables, treatment recommendations, preferences and concerns, distress, perceived risk, knowledge, and neuroticism. We used multiple regression with backward entry to assess the relationship between these variables and our outcomes of decisional conflict and intentions for BM. RESULTS: Higher decisional conflict was associated with being less educated, unmarried, more anxious and less likely to have received a surgical recommendation. Preference for BM was associated with higher neuroticism, perceived risk for contralateral breast cancer, pre-testing risk of carrying a BRCA1/2 mutation, having received either a surgical recommendation (vs. no recommendation), and lower preference for lumpectomy. CONCLUSIONS: For younger women, a surgical recommendation is associated with lower decisional conflict and stronger intention for BM. Results highlight the importance of effective risk communication and decision support between a woman and her surgeon.

Correlation between severity of obesity and mortality in cardiogenic shock.

INTRODUCTION: Cardiogenic shock (CS) is associated with high mortality despite the development of risk stratification tools and new treatment strategies. Obesity, although a risk factor for cardiovascular disease, is not included in current risk stratification tools for CS. A relationship between mortality and obesity has only been shown in subsets populations of CS; there is not yet a clear relationship between severity of obesity and all-cause CS. OBJECTIVES: In this study we evaluate the relationship between rising body mass index (BMI) and mortality in all-cause CS. METHODS: All patients with BMI measurements and hospitalizations complicated by CS from 2014 to 2019 at a single quaternary care institution were identified. Patients were grouped by obesity classification. Multivariate logistic regression was performed to determine a relationship between higher obesity classifications with 30-day mortality in patients with CS. RESULTS: Seventy-two patients were available for analysis. Mean BMI for those who survived compared to those who did not was 29.7 ± 8 kg/m2 vs 33.7 ± 7.6 kg/m2 (p = 0.04). The odds ratio for mortality with incremental increase in obesity classification was 1.6 (95% CI 1.1 - 2.6, p = 0.03) after adjusting for etiology of CS and other common associations with CS mortality. CONCLUSION: This study suggests that the higher mortality risk with incremental increases in BMI should be taken into account when risk stratifying these patients.

Breast cancer screening: clinical, radiologic, and biochemical.

Breast cancer screening is a highly complex and more recently a controversial topic. Conventional screening includes breast self-examination, clinical breast examination, and screening mammography. Several newer imaging modalities have been introduced into the screening armamentarium including breast magnetic resonance imaging and whole-breast automated ultrasound. Novel imaging techniques like positron emission mammography are currently under clinical investigation in the hopes of improving the sensitivity of breast cancer screening. In addition, the development of biochemical assays, which employ minimally invasive sampling are also promising.

Use of an argatroban systemic infusion and purge solution in a patient with a percutaneous ventricular assist device with suspected heparin-induced thrombocytopenia.

PURPOSE: Thrombocytopenia can occur when using an Impella percutaneous ventricular assist device (pVAD), and heparin-induced thrombocytopenia (HIT) is often suspected. Data on heparin- and anticoagulant-free purge solutions in these devices are limited. Previous case reports have described argatroban-based purge solutions, both with and without systemic argatroban, at varying concentrations in patients with known or suspected HIT. SUMMARY: A 33-year-old male was transferred to our institution and emergently initiated on life support with venoarterial extracorporeal membrane oxygenation (ECMO), an Impella pVAD, and continuous venovenous hemofiltration to receive an urgent aortic valve replacement. Over the next several days, the patient's platelet count declined with a nadir of 17 × 103/µL on hospital day 13. The patient's 4T score for probability of HIT was calculated as 4. All heparin products were discontinued on hospital day 15, and the patient was initiated on systemic infusion with argatroban 1,000 µg/mL at a rate of 0.2 µg/kg/min with a purge solution of argatroban 0.05 mg/mL. The systemic infusion remained at a rate of 0.2 µg/kg/min, and the total argatroban dose was, on average, less than 0.25 µg/kg/min. On hospital day 21, the patient was transferred to another institution. CONCLUSION: Systemic infusion and a purge solution with argatroban were used in a patient with an Impella pVAD with multisystem organ dysfunction and suspected HIT. The patient achieved therapeutic activated partial thromboplastin times without adjustment of the systemic argatroban infusion and did not experience bleeding or thrombosis. Further studies concerning the safety and effectiveness of argatroban-based purge solutions in patients with pVADs are needed.

Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3.

BACKGROUND: Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial. METHODS AND RESULTS: The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A(1)-adenosine receptor (A(1)-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A(1)-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P < .001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P < .05) between levels of caveolin-3 protein and Ca(2+)-adenosine triphosphatase, a marker of the heart failure phenotype. CONCLUSIONS: These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy.

Presentation and outcomes of sepsis in the cardiac intensive care unit.

The prevalence of sepsis is increasing in subspecialty intensive care units, including the cardiac intensive care unit (CICU). The clinical characteristics and outcomes of CICU patients with sepsis are not well understood. We conducted a retrospective cohort study of sepsis patients in the CICU compared to other ICUs using the PROGRESS registry. CICU-sepsis patients were older with fewer acute organ failures (median 2 v. 3, p < 0.001), lower SOFA scores (median 7 v. 9, p < 0.001), and more comorbidities. The use of fluid resuscitation, mechanical ventilation, and renal replacement were similar. Mortality was 47.3% for CICU-sepsis patients compared to 43.6% for sepsis patients in other ICU (P = 0.37). We conclude that, in a prior cohort of septic patients, sepsis in CICU patients had outcomes that are comparably poor to sepsis in other ICUs. Septic CICU patients presented with fewer acute organ failures, but more chronic comorbidities. Contemporary data as well as novel interventions and investigations targeted specifically to cardiac patients with sepsis should be prioritized.

Trust your gut: Effect of a pharmacist-driven pilot project to decrease alvimopan use past gastrointestinal recovery in postsurgical patients.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Alvimopan is a peripherally acting opioid receptor antagonist indicated to accelerate gastrointestinal (GI) recovery following surgery, but its benefits past GI recovery are unknown and evidence suggests that it may increase risk for myocardial infarction. The purpose of this study was to evaluate the efficacy of a pilot alvimopan stewardship program aimed at intervening to discontinue alvimopan use following GI recovery. METHODS: This was a retrospective, observational study examining the first 5 months of the alvimopan stewardship pilot program. During this initial period, a pharmacy resident assessed whether each patient met criteria for GI recovery, defined as solid food toleration and first bowel movement or flatus. If a patient met the criteria for GI recovery, the resident intervened and recommended that the primary team discontinue alvimopan. Primary outcomes were the percentage of patients with alvimopan continued past GI recovery and the percentage of patients for whom alvimopan ordered past GI recovery was discontinued following intervention by stewardship. Secondary outcomes included the percentage of accepted recommendations to discontinue alvimopan following GI recovery and the number of alvimopan doses ordered following GI recovery. RESULTS: In total, 73 patients were included in the study analysis, all of whom underwent abdominal and/or urologic surgery. Alvimopan was ordered to be administered in 35.6% (26/73) of patients after GI recovery. The stewardship program intervened and recommended discontinuation on 50% (13/26) of the alvimopan doses ordered past GI recovery. Recommendations were accepted by the primary team for 92.3% (12/13) of the patients. A total of 51 doses of alvimopan were ordered for administration past GI recovery, with an average of 2 doses per patient. CONCLUSION: A pilot pharmacy-driven alvimopan stewardship program was able to identify and intervene on alvimopan orders continued past GI recovery. Interventions decreasing alvimopan use past GI recovery could be of benefit by minimizing potential risk and decreasing potential costs without a negative impact on patient outcomes.

Complete denture prosthodontics in children with ectodermal dysplasia: review of principles and techniques.

Ectodermal dysplasia (ED) is a hereditary condition in which a minimum of two ectodermal structures fail to develop. Anodontia, or hypodontia, is one of the most common manifestations of this condition. As a result, it is critical that prosthodontic habilitation or rehabilitation is started early. Complete dentures are a simple, inexpensive, and reversible option. Several case reports have demonstrated the successful use of complete dentures in children with ED. However, few articles have exclusively addressed the principles of complete denture prosthodontics in these individuals. This report critically analyzes the literature with respect to complete denture principles and techniques in children. Evidence to date is insufficient for advocating any one technique; therefore, the authors recommend a simplified yet scientific approach in fabricating complete dentures for children. This can aid the practicing dentist in using this simple therapeutic option to provide esthetic, functional, and psychological benefits for children with ED and other congenital anomalies related to missing teeth.

Targeted Medication Deprescribing in the Elderly: Results of a Pharmacist-Driven Procedure in a Transitional Care Unit.

OBJECTIVE: Assess the impact of a pharmacist-driven deprescribing procedure on reduction of target medications at discharge among geriatric patients receiving care in a hospital-based transitional care unit.
DESIGN: Retrospective, single-center chart review.
SETTING: Transitional care unit located within a hospital.
PARTICIPANTS: Patients 65 years of age and older were included if they were admitted to the transitional care unit between June 1, 2017, and December 15, 2017, on one or more of the following target medication classes: antihistamines, benzodiazepines, hypnotic sleep aids, proton-pump inhibitors, and skeletal muscle relaxants.
INTERVENTIONS: Pharmacists performed a structured review of patient's medications upon admission and utilized the deprescribing procedure developed by our institution to identify and deprescribe target medications in an attempt to optimize the patient's medication regimen prior to discharge.
RESULTS: Overall, 129 patients on 198 target medications were included in the study. Patients were on an average of 1.5 ± 0.78 target medications at admission, which was reduced to 0.78 ± 0.73 at discharge (P < 0.001). Overall, a 50% reduction of target medications was achieved.
CONCLUSION: A pharmacist-driven deprescribing procedure significantly reduced the quantity of target medications that older patients were discharged on.

Significant Hyperbilirubinemia and Acute Hepatocellular Jaundice in a Pediatric Patient Receiving Deferasirox: A Case Report.

Despite a boxed warning, postmarketing reports of deferasirox-associated hepatic injury in patients with chronic transfusions are not well described. Hepatic impairment, including failure, has been reported to occur more frequently in patients older than 55 years and in those with significant comorbidities, including liver cirrhosis and multiorgan failure. In this case report, we describe significant hyperbilirubinemia and acute hepatocellular jaundice related to deferasirox in a 7-year-old female being treated for iron overload secondary to chronic transfusions. This report outlines a unique case without preexisting risk factors in which other causes of liver injury are excluded as defined by the Roussel Uclaf Causality Assessment Method, which indicates a probable score of deferasirox causing the injury.

Contraceptive needs among newly incarcerated women in a county jail in the United States.

PURPOSE: The purpose of this paper is to examine the risk of unintended pregnancy among women during Cook County Jail intake by assessing basic contraceptive history, the need for emergency contraception (EC) at intake, and contraception at release. DESIGN/METHODOLOGY/APPROACH: This is a cross-sectional study of women 18-50 years old at Cook County Jail in Chicago, Illinois from June 2011 through August 2012. The authors administered the survey at the time of intake on 33 convenient evenings. Surveys consisted of multiple-choice close-ended questions administered via interview. Topics included contraceptive use, pregnancy risk and pregnancy desire. The authors computed frequencies to describe the distribution of question responses and used logistic regression modeling to identify factors significantly related to the use of contraception at intake and to the acceptance of contraception at release. FINDINGS: Overall, 194 women participated. Excluding women not at risk for pregnancy (4.6 percent currently pregnant, 17.5 percent surgically sterilized/postmenopausal and 4.6 percent using long-acting reversible contraceptives), 73.2 percent of women were at risk for pregnancy ( n = 142) and, therefore, had a potential need for contraception. Among these women at risk for unintended pregnancy, 68 (47.9 percent) had unprotected intercourse within five days prior to survey administration. When asked about EC, most women (81.4 percent) would be interested if available. Additionally, 141 (72.7 percent) of women would be interested in contraceptive supplies if provided free at release. ORIGINALITY/VALUE: Newly incarcerated women are at high risk for unintended pregnancy. Knowledge about EC and ability to access birth control services are both significantly limited. These conclusions support providing an intake screening in jails to identify women at risk for unintended pregnancy.

Breast Cancer following Augmentation Mammaplasty: A Case-Control Study.

BACKGROUND: The purpose of this study was to determine whether augmentation mammaplasty, implant type, and implant location affect breast cancer detection, stage, and treatment. METHODS: An institutional case-control study was performed of patients with prior breast augmentation undergoing breast cancer treatment from 2000 to 2013. Controls were propensity matched and randomized, and data were retrospectively reviewed. RESULTS: Forty-eight cases and 302 controls were analyzed. Palpable lesions were detected at a smaller size in augmentation patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients were detected by screening mammography (77.8 percent of cases versus 90.7 percent of controls; p = 0.010). Patients with implants were more likely to undergo an excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001), rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p < 0.001). Earlier staging in augmented patients approached but did not reach statistical significance (p = 0.073). Augmented patients had higher mastectomy rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type nor anatomic location affected method of diagnosis, stage, or treatment. CONCLUSIONS: Palpable detection of breast cancer is more likely at a smaller size in augmented patients, yet it is less likely on screening mammography than in controls. Augmentation breast cancer patients have a comparable disease stage and are more likely to undergo mastectomy rather than lumpectomy. Both silicone and saline implants, whether placed submuscularly or subglandularly, have comparable effects on breast imaging, biopsy modality, and surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The role of interleukin 1 in growth and metastasis of human cancer xenografts.

BACKGROUND: Interleukin 1 (IL-1) is a pluripotent cytokine that promotes angiogenesis, tumor growth, and metastasis in experimental models; its presence in some human cancers is associated with aggressive tumor biology. The purpose of these studies was to characterize the role of IL-1 in human cancers and determine if inhibition of IL-1 via its receptor antagonist, IL-1Ra, alters tumor growth and metastatic potential. METHODS: IL-1 mRNA or protein levels were determined in clinical tumor samples, cancer cell lines, and xenografts using quantitative reverse transcription-PCR or ELISA. Biological activity of tumor-derived IL-1 protein was shown via induction of permeability across endothelial cell monolayers. The effects of recombinant IL-1Ra on tumor lines in culture (cell proliferation and IL-8 secretion) and in xenograft models (tumor growth, metastatic potential, and intratumoral levels of IL-8 and VEGF) were characterized. The effects of IL-1Ra-mediated regression of xenograft growth on angiogenic proteins (IL-8 and VEGF) were evaluated in an IL-1-producing melanoma (SMEL) xenograft model. RESULTS: IL-1 mRNA was highly expressed in more than half of all tested metastatic human tumor specimens including non-small-cell lung carcinoma, colorectal adenocarcinoma, and melanoma tumor samples. Constitutive IL-1 mRNA expression was identified in several cancer cell lines; tumor supernatant from these cell lines produced a significant increase in endothelial cell monolayer permeability, a hallmark event in early angiogenesis, in an IL-1-dependent manner. Moreover, systemic recombinant IL-1Ra resulted in significant inhibition of xenograft growth and neovessel density of IL-1-producing, but not non-IL-1-producing, tumor cell lines. Subsequent analysis of SMEL, a melanoma cell line with constitutive IL-1 production, showed that neither exogenous IL-1 nor IL-1Ra altered tumor cell proliferation rates in vitro. Gene expression analyses of IL-1Ra-treated SMEL xenografts showed a >3-fold down-regulation of 100 genes compared with control including a marked down-regulation of IL-8 and VEGF. CONCLUSIONS: These data show that the IL-1 gene is frequently expressed in metastases from patients with several types of human cancers. IL-1Ra inhibits xenograft growth in IL-1-producing tumors but has no direct antiproliferative effects in vitro; decreased tumor levels of IL-8 and VEGF may be an early surrogate of IL-1Ra-mediated antitumor activity. IL-1Ra may have a role alone or with other agents in the treatment of human cancers.