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Objective: To determine the contribution of mammography to the comprehensive clinical evaluation of men with breast symptoms. Patients and Methods: We retrospectively reviewed the records of all men who underwent mammography between January 1, 2001, and December 31, 2004, at the Mayo Clinic In Jacksonville, Fla. Medical history, mammographic findings, and breast cancer diagnoses were assessed. Results: A total of 198 men had 212 mammograms. Nine mammograms (from 9 different men) (4%) showed suspicious findings. Eight men underwent biopsy, which yielded a breast cancer diagnosis in 2 (1%). Of the 212 mammograms, 203 (96%) showed benign findings, including gynecomastia on 132 (62%). One patient with a benign-appearing mammogram later underwent breast biopsy, and malignant disease was diagnosed. All the men with breast cancer had a dominant mass on clinical examination and other findings suggestive of breast cancer. Of the 132 mammograms showing gynecomastia, 110 (83%) were from men who had taken predisposing medications or who had predisposing medical conditions. Conclusions: Mammography added little information to the initial patient evaluation. Breast cancer may be suspected by the presence of a dominant mass. Gynecomastia can be predicted on the basis of the patient's symptoms or preexisting condition. Patients with suspicious findings on examination warrant appropriate clinical management regardless of mammographic findings. Mammography in men may be of benefit only for image guidance of percutaneous biopsy of a suspicious mass. [ABSTRACT FROM AUTHOR]

Plant species richness is an important property of ecosystems that is altered by grazing. In a semiarid environment, we tested the hypotheses that (1) small-scale herbaceous plant species richness declines linearly with increasing grazing intensity by large ungulates, (2) precipitation and percent sand interact with grazing intensity, and (3) response of herbaceous plant species richness to increasing intensity of ungulate grazing varies with patch productivity. During January-March 2012, we randomly allocated 50, 1.5-m × 1.5-m grazing exclosures within each of six 2500 ha study sites across South Texas, USA. We counted the number of herbaceous plant species and harvested vegetation in 0.25-m 2 plots within exclosures (ungrazed control plots) and in the grazed area outside the exclosures (grazed treatment plots) during October-November 2012-2019. We estimated percent use (grazing intensity) based on the difference in herbaceous plant standing crop between control plots and treatment plots. We selected the negative binomial regression model that best explained the relationship between grazing intensity and herbaceous plant species richness using the Schwarz-Bayesian information criterion. After accounting for the positive effect of precipitation and percent sand on herbaceous plant species richness, species richness/0.25 m 2 increased slightly from 0% to 30% grazing intensity and then declined with increasing grazing intensity. Linear and quadratic responses of herbaceous plant species richness to increasing grazing intensity were greater for the least productive patches (<15.7 g/0.25 m 2 ) than for productive patches (≥15.7 g/0.25 m 2 ). Our results followed the pattern predicted by the intermediate disturbance hypothesis model for the effect of grazing intensity on small-scale herbaceous plant species richness., Competing Interests: None declared., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Advances have dated the genetic testing initially offered to evaluate for hereditary breast and ovarian cancer risks. Previous research has demonstrated that many patients have not updated testing. This study reviewed the incidence of additional analysis after an uninformative BRCA1/2 result and offered updated testing with limited barriers to those who had not completed. After viewing an educational video and providing informed consent, eligible patients were mailed a saliva collection kit to complete an 84-gene hereditary cancer panel at no personal cost. A total of 704 patients had completed BRCA1/2 only testing between 2001 and 2020. Fifteen percent (N = 102) of the 671 patients with an uninformative BRCA1/2 result had already completed expanded testing. Most, 74 of 102 (73%), had been rereferred to medical genetics during a clinical visit related to cancer care. Those who had already completed additional testing were more likely to have a personal history of cancer (92% vs. 79%, p = 0.002) and live locally (p = 0.032). Invitation to complete updated testing through this study was sent to 372 people, and 116 (31%) consented to participate. For 142 of the 256 who did not proceed with testing through the study, proof of receipt of research information was available. In total, 22 pathogenic variants were reported in 21 of the 226 patients with updated testing from before and including our study: ATM (4), CHEK2 (4), LZTR1 (1), MUTYH (3), NBN (1), NF1 (1), NTHL1 (1), PALB2 (4), PMS2 (1), RAD50 (1), and SPINK1 (1). Many potential barriers of retesting were eliminated by removing personal costs or travel requirements. Still, only about 30% of patients agreed to participate, and a significant portion elected not to proceed. Future research could focus on the discovery of other factors that dissuade patients and what measures may better inform them on potential benefits., (© 2022 National Society of Genetic Counselors.)

Purpose: Examine MRI phenotypes of breast cancers arising in patients with various pathogenic variants, to assess for imaging trends and associations., Method: Multisite retrospective review evaluated 410 patients from 2001 to 2020 with breast cancer and a predisposing pathogenic variant who underwent breast MRI at time of cancer diagnosis. Dominant malignant lesion features were reported, including lesion type (mass versus non-mass enhancement), size, shape, margin, internal enhancement pattern, plus other features. Kruskal-Wallis test, Fisher's exact test, and pairwise comparisons performed comparing imaging manifestations for the most frequent genetic results., Results: BRCA1 (29.5 %) and BRCA2 (25.9 %) variants were most common, followed by CHEK2 (16.6 %), ATM (8.0 %), and PALB2 (6.3 %), with significant associated differences in race/ethnicity (p = 0.040), age at cancer diagnosis (p = 0.005), tumor shapes (p = 0.001), margins (p < 0.001), grade (p < 0.001), internal enhancement pattern (rim enhancement) (p < 0.001), kinetics (washout) (p < 0.001), and presence of necrosis (p < 0.001). CHEK2 and ATM tumors were often lower grade with spiculated margins (CHEK2: 47.1 %, ATM: 45.5 %), rarely exhibiting washout or tumor necrosis (p < 0.001), and were mostly comprised of luminal molecular subtypes (CHEK2: 88.2 %, ATM: 90.9 %). BRCA1 tumors had the highest proportions with round shape (31.4 %), circumscribed margins (24.0 %), rim enhancement (24.0 %), washout (58.7 %), and necrosis (19.8 %), with 47.9 % comprised of triple negative subtype. Bilateral mastectomy was performed in higher proportions of patients with BRCA1 (84.3 %) and BRCA2 (75.5 %) variants compared to others., Conclusions: Genetic and molecular profiles of breast cancers demonstrate reproducible MRI phenotypes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The aim of the study was to assess, characterize, and describe the prevalence and predicting factors of patient-reported severe coronavirus disease 2019 (COVID-19) infection and post-acute sequelae of COVID-19 (PASC)., Methods: We prospectively surveyed patients who received care in our outpatient clinic for COVID-19 from March 13, 2020, through August 17, 2020, and then retrospectively reviewed their electronic health records. We collected data for age, sex, and persistence of symptoms and compared data for hospitalized and nonhospitalized patients. Continuous and categorical variables were summarized, including time from COVID-19 onset, time to resuming normal activities, and length of time away from work., Results: Of those receiving the survey, 437 adult patients with different degrees of severity of COVID-19 illness responded: 77% were between 3 and 6 months from the onset of infection. In total, 34.9% had persistent symptoms, and 11.5% were hospitalized. The most common symptom was fatigue (75.9%), followed by poor sleep quality (60.3%), anosmia (56.8%), dysgeusia (55%), and dyspnea (54.6%). Predicting factors for PASC were female sex and a negative psychological impact of the disease. Age, hospitalization, persistent symptoms, psychological impact (e.g., anxiety and depression), and time missed from work were significantly associated with perception of having severe COVID-19 illness. Hospitalization was not significantly associated with PASC., Conclusions: Over one-third of patients in our study had PASC. Persistent symptoms correlated with severity of disease and were significantly more common for women, for patients who had psychological symptoms (depression and/or anxiety), and for patients reporting inability to resume normal activities., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: The current study was designed to evaluate the translation of clinical trial outcomes and clinical guidelines for the treatment of fibromyalgia (FM) into an intensive multicomponent clinical program embedded in routine care delivery. The study aimed to assess the adaptation of these recommended strategies into routine clinical care while evaluating their effectiveness and durability in improving functional status and level of distress in a large clinical sample of FM patients., Methods: Four hundred eighty-nine patients with FM completed a 2-day program that incorporated best practice recommendations for the treatment of FM. Patients completed the Fibromyalgia Impact Questionnaire-Revised, the Center for Epidemiologic Studies Depression Scale, and the Pain Catastrophizing Scale at admission to the program and at follow-up on average 5 months posttreatment., Results: Significant improvements were seen in functional status (p < 0.0001), depressive symptoms (p < 0.0001), and pain catastrophizing (p < 0.0001) after participation in the intensive multicomponent treatment program., Conclusions: The present study shows that an intensive multicomponent treatment program embedded in routine care delivery is effective in significantly improving functional status and psychological distress in a large sample of FM patients. The significant improvements were durable and maintained at follow-up., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Because most cases of coronavirus disease 2019 (COVID-19) are not severe, understanding the epidemiology of mild cases has important clinical implications. We aimed to describe the symptom profile and associated outcomes in a virtual outpatient COVID-19 clinic. We conducted a prospective cohort study from March through June 2020. We included 106 patients with positive results for SARS-CoV-2, followed up until they had 2 sequential negative tests. Exploratory regression analyses identified potential prognostic symptoms or risk factors associated with outcomes, including emergency department (ED) visits, hospitalizations, and time to resolution of viral shedding. The mean (range) patient age was 51 (18-86) years, 50% were men, and 36.5% had at least 1 risk factor, most commonly asthma (16%) and diabetes (10%). Most patients (98.1%) had symptoms-cough (80.4%), fatigue (67.6%), fever (66.0%), headache (49.0%), and ageusia (46.9%). Nine (8.5%) patients were admitted to the ED, 5 (4.7%) were hospitalized, and none died. Asthma (RR = 7.13, P = .001) and being immunocompromised (RR = 3.44, P = .03) were associated with higher risks of adverse outcomes. Asthma (HR = 0.56, P = .04) and early symptoms of ageusia (HR= 0.50, P = .01) or myalgia (HR = 0.63, P = .04) were associated with significantly longer duration of viral shedding. In contrast to reports about severe cases of COVID-19, we found a higher incidence of sinus symptoms, gastrointestinal symptoms, and myalgia and a lower incidence of fever, anosmia, and ageusia among our mild/moderate cases. Asthma and immunocompromised status were associated with adverse outcomes, and asthma and early symptoms of ageusia or myalgia with significantly longer duration of viral shedding., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest.Consent to participateAll authors have approved of this manuscript in its final form and no potential conflicts of interest exist.Consent for publicationAll authors have approved of this manuscript in its final form and no potential conflicts of interest exist., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.)

The current COVID-19 pandemic has forced the global higher education community to rapidly adapt to partially or fully online course offerings. For field- or laboratory-based courses in ecological curricula, this presents unique challenges. Fortunately, a diverse set of active learning techniques exists, and these techniques translate well to online settings. However, limited guidance and resources exist for developing, implementing, and evaluating active learning assignments that fulfill specific objectives of ecology-focused courses. To address these informational gaps, we (a) identify broad learning objectives across a variety of ecology-focused courses, (b) provide examples, based on our collective online teaching experience, of active learning activities that are relevant to the identified ecological learning objectives, and (c) provide guidelines for successful implementation of active learning assignments in online courses. Using The Wildlife Society's list of online higher education ecology-focused courses as a guide, we obtained syllabi from 45 ecology-focused courses, comprising a total of 321 course-specific learning objectives. We classified all course-specific learning objectives into at least one of five categories: (a) Identification, (b) Application of Concepts/Hypotheses/Theories, (c) Management of Natural Resources, (d) Development of Professional Skills, or (e) Evaluation of Concepts/Practices. We then provided two examples of active learning activities for each of the five categories, along with guidance on their implementation in online settings. We suggest that, when based on sound pedagogy, active learning techniques can enhance the online student's experience by activating ecological knowledge., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant., Case Presentation: The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM&#95;004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed., Conclusions: This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.

Background: Patients with DNA-damage response genes (DDR)-related pancreas cancer ( BRCA1/2 or other DNA-damage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). However, data is scarce pertaining to outcomes in this subset of patients. Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes., Methods: Pancreas cancer patients with a germline pathogenic variant in BRCA1/2 or other DDR gene were identified retrospectively through review of medical records (medical genetics/oncology) and genetic testing results at our institution. Data regarding clinical outcomes, therapy received, and survival was subsequently extracted., Results: A total of 11 patients with pancreas cancer were identified to carry a pathogenic DDR-variant: BRCA1 (3), ATM (4), BRCA2 (2), PALB2 (1) and FANCC (1). Five of these individuals had prior history of other cancers. Clinically these tumors were localized (4), locally advanced (3), and metastatic (4) at diagnosis. Four out of 11 patients were still alive at time of data review. Survival in the 7 patients who had died was 13.7, 140.0, 20.5, 22.3, 23.5, 25.8, and 111.5 months. All patients with advanced disease had exposure to platinum chemotherapy., Conclusions: Historical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Genetic testing for hereditary cancer syndromes has been revolutionized by next-generation sequencing, which allows for simultaneous review of numerous genes. Multigene panels are regularly offered to patients because of their scope and decreased cost and turnaround time. However, many genes included on larger panels have not been studied as extensively as BRCA1 and BRCA2 ( BRCA1/2 ), and their clinical effects are often not as well established., Methods: We identified patients who received positive test results for pathogenic variants of breast cancer genes from January 2012 through May 2018. We mailed a survey and conducted qualitative interviews to explore the personal and health care experiences of patients with pathogenic variants of BRCA1/2 and patients with "other" (ie, non- BRCA1/2 or PALB2; PTEN; ATM; TP53; NBM, RAD51C; MSH6 ) variants. We compared the experiences of these patients., Results: Fifty-nine out of 128 individuals responded to the survey (46%). Thirty-two patients had BRCA1/2 variants, and 27 had other variants. (49 women and 10 men; median [range] age, 63 [34-87] years). We interviewed 21 patients (17 women and 4 men; median [range] age, 59.6 [34-82] years). Of the interview participants, ten patients had BRCA1/2 variants, and 11 had non- BRCA1/2 variants. Patients reported receiving poor information about their genetic test results, and they often educated their physicians about their results. Some patients believed that they had been ignored or "brushed off" by health care professionals because non- BRCA1/2 genes are less understood outside the genetics research community. Patients with BRCA1/2 variants had similar problems with health care providers, despite increased awareness and established guidelines about BRCA1/2 ., Conclusions: Research is required to understand the clinical significance and proper management of diseases attributable to newly characterized hereditary cancer genes. Additional evaluation of patient and provider education should be at the forefront of efforts to improve patient care., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) is an ion channel permeable to Ca 2+ that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. Pathogenesis of these phenotypes is not yet completely understood, but it is known that genotype-phenotype correlations for TRPV4 pathogenic variants often are not present., Methods: Newly characterized, suspected pathogenic variant in TRPV4 was analyzed using protein informatics and personalized protein-level molecular studies, genomic exome analysis, and clinical study., Results: This statement is demonstrated in the family of our proband, a 47-year-old female having the novel c.2401A>G (p.K801E) variant of TRPV4. We discuss the common symptoms between the proband, her father, and her daughter, and compare her phenotype to known TRPV4-associated skeletal dysplasias., Conclusions: Protein informatics and molecular modeling are used to confirm the pathogenicity of the unique TRPV4 variant found in this family. Multiple data were combined in a comprehensive manner to give complete overall perspective on the patient disease and prognosis., (© 2019 Mayo Clinic. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

The CHEK2 gene and its encoded protein Chk2 have a well-known role in cancers, especially those related to breast cancer mediated through the BRCA1 gene. Additionally Chk2 has a crucial role in DNA repair, apoptosis and the cell cycle, which is why classification of variants of uncertain significance (VUS) is an area highly sought for a better elucidation of the "genomic effect" that results. Because it can often take years before enough clinical data is accumulated, and the costly and expensive functional analysis for individual variants presents a significant hurdle, it is important to identify other tools to help aid in clarifying the impact of specific variants on a protein's function and eventually the patient's health outcome. Here we describe a newly identified CHEK2 variant and analyze with an integrated approach combining genomics (whole exome analysis), clinical study, radiographic imaging, and protein informatics to identify and predict the functional impact of the VUS on the protein's behavior and predicted impact on the related pathways. The observed and analyzed defects in the protein were consistent with the expected clinical effect. Here, we support the use of personalized protein modeling and informatics and further our goal of developing a large-scale protein deposition archive for all protein-level VUS.

A growing number of physicians will interact with genetic test results as testing becomes more commonplace. While variants of uncertain significance can complicate results, it is equally important that physicians understand how to incorporate these results into clinical care. An online survey was created to assess physician self-reported comfort level with genetics and variants of uncertain significance. Physicians were asked to respond to three case examples involving genetic test results. The survey was sent to 488 physicians at Mayo Clinic FL on 8/16/2017. Physicians from all specialties were invited to participate. A total of 92 physicians responded to the survey. Only 13/84 (14.6%) responded to all three case examples with the answer deemed "most correct" by review of literature. Physicians that specialized in cancer were more likely to answer questions appropriately (P = .02). Around half (39/84) of the physicians incorrectly defined a variant of uncertain significance (VUS). Over 75% made a recommendation for genetic testing that was not warranted. Many physicians have never received formal genetics training; however, they will be expected to provide an accurate explanation of the genetic test results and subsequent evidence-based medical management recommendations. These results demonstrate that a substantial proportion of physicians lack a true understanding of the implications a VUS. Utilization of supplemental genetics training programs coupled with increase awareness of genetic services may help to improve patient care.

Women often visit their primary care physician because of breast concerns such as masses, pain, and nipple discharge. Most breast problems are benign, but it is important to know how to manage these and other breast problems and when to refer patients for further testing., (Copyright © 2019 Cleveland Clinic.)

Background: Although the process of reclassification of a variant of uncertain significance can be complex, they are commonly detected through molecular testing. It often takes years before enough clinical data are acquired, and it can be costly and time-consuming to perform functional analysis of a single variant. It is important that other tools are developed to aid in clarifying how a specific genetic variant impacts a protein's function, and ultimately the health of the patient., Methods: Two more newly characterized, suspected pathogenic variants in NBN and PTEN were analyzed through personalized protein modeling. Comparisons between the wild-type and altered protein were studied using simulations, genomic exome analysis, and clinic study., Results: Modeling of the new NBN and PTEN protein structures suggested loss of essential domains important for normal enzymatic function for these personalized genomic examples which matched the clinical findings., Conclusion: The defects detected through modeling were consistent with the expected clinical effect. Personalized protein modeling is another tool for determination of correct variant classification, which can become further useful through construction of deposition archive., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

[This corrects the article DOI: 10.1038/s41439-018-0016-8.].

Discovery of a hereditary cancer syndrome can be one of the factors that determine whether a healthy individual completes pancreas cancer screening or whether an individual with cancer receives certain chemotherapies. Retrospective review was completed to determine the likelihood of detection of a pathogenic variant causing a hereditary cancer syndrome based on personal and family history. Study was completed through the hereditary cancer clinic at Mayo Clinic Florida over a 6 year period, 1/2012 through 1/2018. All participants were referred based on suspicion for a hereditary cancer syndrome based on personal and/or family history. Patients' personal oncologic history at time of consultation was recorded, as well as, cancer diagnoses in the family history and the number of family members with a history of pancreas cancer. Test result and gene name, if variant was pathogenic or likely pathogenic, were noted as well. A total of 2,019 patients completed genetic testing during study period. Personal history of cancer included a variety of primaries, including breast ( N = 986), ovarian ( N = 119), colon ( N = 106), prostate ( N = 65), and pancreas ( N = 59). A positive result was discovered in 11% of the total group. Two hundred and eighty five reported a family history of pancreas cancer. The incidence of pathogenic variants was 13% (37/285) in those with any family history and 23% (13/56) in those with two or more relatives with pancreatic cancer. Those with multiple relatives with pancreatic cancer were significantly more likely to carry a pathogenic variant than those with a personal history of breast cancer under the age of 45 (23.2 vs. 11.9%, p = 0.02). Presence of multiple family members with a reported history of pancreatic cancer significantly increased the likelihood that a pathogenic variant would be identified in the patient even over other significant risk factors, like personal history of early onset breast cancer.

We report two female patients with focal segmental glomerulosclerosis and chronic kidney disease. The first patient was found to have a heterozygous, de novo, pathogenic variant in COL4A5 (c.141+1G>A, IVS2+1G>A), which is associated with Alport syndrome. The second patient was found to have a heterozygous, likely pathogenic variant in COL4A4 (c.2842G>T). Both these variants in COL4A5 and COL4A4 are novel, and they were detected using whole exome sequencing and gene panel testing, respectively. Additionally, we discuss the complexities of diagnosis in such cases and the benefits of using the abovementioned diagnostic approaches., Competing Interests: The authors declare that they have no conflict of interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Dense breast parenchyma obscures breast lesions on mammography and is an independent risk factor for development of breast cancer. Many states have approved laws requiring patient notification of dense breast tissue. Supplemental screening modalities are available however their utilization and efficacy are quite variable. Our aim was to survey primary care providers in an effort to gauge awareness of and familiarity with dense breast legislation and supplemental screening. A multisite survey was administered via e-mail to all Mayo Clinic staff physicians, residents and fellows, as well as nurse practitioners and physician assistants in the departments of Internal Medicine, Family Medicine, and Obstetrics and Gynecology. 362 responses were collected. 68% of respondents were aware of breast density notification laws; 32% had no knowledge of these laws. Implementation of supplemental imaging was variable. Of eligible respondents, 26% offered a supplemental examination to every patient with dense breasts, 47% offered it only to certain patients based upon unique patient or risk factors, 15% did not offer supplemental examinations, and 11% offered an examination based on other criteria. When assessing comfort level in answering questions regarding breast density, 32% were "slightly comfortable" and 18% were "not comfortable." When estimating the percentage of patients with adequate insurance coverage for supplemental imaging, 62% were unsure while 11% did not inquire. Despite public and legislative support, there is a lack of familiarity and considerable practice variation among primary care providers when managing patients with mammographically dense breast tissue. Further research and advances in patient and provider education on this topic are needed to improve management. Radiologists can assist by educating referring providers and consolidating imaging strategies to help circumvent systems-based flaws., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: This study was designed to explore whether zoledronic acid could prevent expected loss of bone mineral density (BMD) in postmenopausal women with pre-existing osteopenia or osteoporosis who were initiating adjuvant letrozole therapy for primary breast cancer., Methods: Between June 2006 and July 2007, 60 postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a BMD T-score ≤-2.0 were enrolled. Participants received letrozole 2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic acid 4 mg every 6 months for a maximum of 5 years or until disease progression. BMD at the lumbar spine and femoral neck was recorded at the start of the study and annually for 5 years. Patients were evaluated for fractures every 6 months for the duration of the trial., Results: After 5 years, mean BMD increased significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at combined sites. Femoral neck BMD increased by 4.2%, although this was not significant (p = 0.23). At the end of the trial, BMDs were consistent with osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six fractures were reported after 417 individual assessments., Conclusions: Zoledronic acid appears to prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole. These findings were maintained at 5 years and support concurrent initiation of bisphosphonate and aromatase inhibitor therapy in this high-risk population.

Objectives: Although guidelines recommend hepatitis B virus (HBV) immunization for adults with diabetes mellitus (DM), vaccination rates remain low. Our aim was to evaluate knowledge and practice regarding HBV and to assess the effectiveness of a multifaceted educational program., Methods: Primary care residents (n = 244) at three academic institutions were surveyed about various aspects of HBV. Residents at one training program were then randomly assigned to an educational intervention (E) (n = 20) and control group (C) (n = 19). The E group received a focused didactic lecture and periodic e-mail reminders with immediate feedback. We compared knowledge scores before and after the intervention. Chart audits were conducted to evaluate the residents' behavior., Results: A total of 103 (42%) residents responded to the survey. The survey indicated that residents lacked the necessary knowledge and risk assessment skills concerning HBV in patients with DM. In the controlled trial of the E intervention, both groups had similar baseline knowledge scores. The E group had a significant increase in the immediate postintervention knowledge scores from a mean of 29% at baseline to 70% (P < 0.001) that was sustained 6 months postintervention (65%; P < 0.001). In the C group, 6-month postintervention scores were not different from baseline (38% vs 29%). No significant differences were observed in documentation skills., Conclusions: A combined educational program was effective in enhancing knowledge about HBV and vaccination in DM but had limited influence on physicians' practice. Further study incorporating system changes along with educational initiatives is required to improve clinical practice.

Background: Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results., Methods: A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture., Results: The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm., Conclusions: Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms., (© 2015 American Cancer Society.)

Ductal carcinoma in situ (DCIS) of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS) and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve.

Breast cancer increases a woman's risk for bone loss. Bone loss occurs due to the skeletal fragility associated with malignancy, the occurrence of premature ovarian failure secondary to chemotherapy, and the loss of bone mineral density (BMD) associated with antiestrogen therapies. Tamoxifen has been shown to reduce BMD among premenopausal women, and aromatase inhibitors, which have become a standard therapy among postmenopausal women, increase bone loss and the risk of fracture. Bisphosphonates preserve BMD among women with breast cancer, both among postmenopausal women and those with a history of significant bone loss. The effect among premenopausal women appears modest. Despite the protective effect on bone density, a reduction in the risk of fracture has not yet been established. Therefore, other risk factors for fracture must be addressed, such as dietary intake, vitamin D, and assessment of other potentially modifiable conditions. Newer agents that target the receptor activator of nuclear factor-κB (RANK) system and RANK ligand (RANKL), such as denosumab, represent an emerging class of medications that may also preserve BMD in this population.

Background: Postmenopausal women with osteoporosis/osteopenia are at increased risk of fracture. Aromatase inhibitors further increase bone loss in these patients. This study evaluates whether zoledronic acid prevents the bone loss expected when these patients initiate letrozole., Patients and Methods: Postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a bone mineral density (BMD) T-score <-2.0 were given letrozole 2.5mg/vitamin D 400 international units daily, calcium 500mg twice daily, and 4mg zoledronic acid every 6 months. The BMD was assessed at baseline and 1 year. The primary endpoint was the mean change in lumbar spine (LS) BMD at 1 year., Results: Forty-six patients completed 1 year of treatment. LS BMD increased by 2.66% (p=0.01), femoral neck (FN) by 4.81% (p=0.01), and any measured endpoint by 4.55% (p=0.0052)., Conclusions: Zoledronic acid prevents bone loss in postmenopausal women with osteoporosis/osteopenia starting letrozole and is associated with improvements in BMD., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Recent evidence has suggested a role for vitamin D in breast cancer prevention and survival. Studies have reported an inverse relation between vitamin D intake and the risk of breast cancer, improvements in survival after a diagnosis of breast cancer in women with higher levels of vitamin D, and vitamin D insufficiency in up to 75% of women with breast cancer. Preclinical data have indicated that vitamin D affects up to 200 genes that influence cellular proliferation, apoptosis, angiogenesis, terminal differentiation of normal and cancer cells, and macrophage function. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non-cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Postmenopausal women with breast cancer (BC) are at increased risk for bone loss. Bisphosphonates improve bone mineral density (BMD) in normal postmenopausal women. The purpose of this study was to determine if immediate treatment with zoledronic acid preserves BMD in postmenopausal women with BC starting letrozole after tamoxifen. Postmenopausal women with BC completing tamoxifen were treated with daily letrozole 2.5 mg/vitamin D 400 I.U., calcium 500 mg twice daily and were randomized to upfront or delayed zoledronic acid 4 mg every 6 months. Patients in the delayed arm were only given zoledronic acid if they developed a post-baseline BMD T score <-2.0 or had a fracture. The primary endpoint was the mean percent change in lumbar spine (LS) BMD at 1 year. About 558 women enrolled; 395 provided 1 year BMD data. The upfront arm experienced a mean change of +3.66% in LS BMD versus -1.66% for the delayed group (P < 0.001). Changes at the femoral neck/total hip were also greater for the upfront versus delayed arms (P < 0.001; P < 0.001) with differences persisting at 2 years. Patients in the delayed arm were more likely to experience a clinically meaningful 5% loss of BMD at all sites versus the upfront zoledronate group. Patients in the upfront arm were slightly more likely to report limb edema, fatigue, fever, nausea and jaw osteonecrosis(1%). Upfront zoledronic acid prevents bone loss in postmenopausal women with BC starting letrozole after tamoxifen.

Background: The Lysholm score and Tegner activity scale are commonly used to document outcomes after arthroscopic knee surgery. These outcomes measurements are subjective in nature and evaluate performance and activity restrictions both before and after surgery, making them a valuable research tool when judging the effectiveness of surgical treatment., Purpose: To establish a normal knee data set for the Lysholm and Tegner rating systems, as well as to show how these scores are affected by age and gender., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A subjective questionnaire that included both the Lysholm score and Tegner activity grading scale was completed by 488 subjects in the community who considered their knee function normal. Any subject reporting a history of injury or surgery was excluded from the study. The average age was 41 years (range, 18-85), with 244 men and 244 women qualifying for statistical analysis., Results: The average Lysholm score was 94 (range, 43-100), and the average Tegner activity level was 5.7 (range, 1-10). The Lysholm score and age demonstrated no correlation. The Tegner activity level was inversely correlated with age. The average Tegner activity level for men was 6.0, and the average activity scale for women was 5.4. There was no significant difference in the Lysholm score between men and women., Conclusion: These data acquired from a normal, healthy population provide a standard point of reference for the injured or postsurgical knee. These data also serve as ideal tools when counseling patients about realistic expectations after surgery, based on age and gender.

Background: Patients with a history of knee trauma or previous surgery may exhibit pain in the infrapatellar region that is refractory to conservative care. This may be due to subtle scarring of the anterior interval., Hypothesis: Arthroscopic release of a scarred anterior interval will lead to improvement in anterior knee pain., Study Design: Case series; Level of evidence, 4., Methods: Twenty-five consecutive patients with isolated scarring of the anterior interval, confirmed with both magnetic resonance imaging (MRI) and arthroscopic examination, were included. All 25 patients had refractory anterior knee pain that was unimproved after a minimum of 6 months of physical therapy and nonsteroidal anti-inflammatory medications and pain during knee extension. All patients had a minimum of 2 previous surgical procedures, and 11 (44%) of the patients had a previous anterior cruciate ligament (ACL) reconstruction. All 25 (100%) patients had an apparent decrease in the cranial excursion of the patella and had a positive Hoffa test result. Fourteen (56%) patients had a preoperative flexion contracture of at least 5 degrees . All patients underwent an isolated arthroscopic anterior interval release., Results: All patients were evaluated by physical examination and standardized scoring instruments with an average follow-up of 4.0 years (range, 2.0-7.2). Twenty-one patients had full range of motion of the patella in all directions and a negative Hoffa test finding at final follow-up. All 14 (100%) patients with preoperative flexion contractures (>5 degrees ) experienced a full return of extension. The average Lysholm score improved from 59 preoperatively to 81 postoperatively (P < .0001). The average International Knee Documentation Committee (IKDC) score improved from 49 to 70 (P < .001). There were no complications. Four patients (16%) had failed results and required a second surgical release. Patients with failures had significantly lower preoperative Lysholm scores (score = 40) than those who did not (score = 58) (P = .022). Three of the failures were workers' compensation cases., Conclusion: Scarring of the anterior interval changes the mechanics of the anterior structures of the knee and may lead to refractory anterior knee pain. Arthroscopic anterior interval release successfully provides pain relief in this patient population.

Background: Women with triple-negative (TN) breast cancer are at increased risk of distant metastases and have reduced survival versus other breast cancer patients. Relative survival of women with TN breast cancer who develop brain metastases is unknown., Methods: Patients with breast cancer who developed brain metastases at our institution from 1993 to 2006 were reviewed. Four survival time intervals were compared in patients with TN disease and those with non-TN disease: initial diagnosis to distant metastases, distant metastases to brain metastases, brain metastases to death, and overall diagnosis to death., Results: One hundred and eighteen patients were identified. Fifty-one (50%) of 103 were estrogen receptor positive, 26 (39%) of 67 were human epidermal growth factor receptor 2 positive, and 20 (22%) of 91 were TN. Survival times were shorter for TN patients, with overall survival of 26 months in TN patients versus 49 months for non-TN patients. In TN patients, time to development of distant metastases, brain metastases, and death after brain metastases was shorter than in non-TN patients., Conclusion: Patients with TN disease were more likely to develop distant metastases earlier than non-TN patients, developed brain metastases sooner, and had shorter overall survival.

Breast cancer must be considered in the evaluation of breast masses in men, although various benign causes are more common, including gynecomastia and conditions of the skin and subcutaneous tissue. A patient's history may identify key features suspicious for malignancy or reassuring for benign disease. Physical examination has been documented to be as effective as mammography in distinguishing benign from malignant lesions, and both have been reported as highly accurate for the identification of malignancy. Mammography is therefore best used when the physical examination findings are indeterminate. Ultrasonography may be used as an adjunct to mammography; no evidence supports the use of magnetic resonance imaging in male breast patients. If clinical or mammographic features are suspicious or indeterminate for malignancy, tissue diagnosis is warranted and may be achieved surgically or via core-needle biopsy or fine-needle aspiration cytology. Given the lack of uniformity in the clinical recommendations for the evaluation of breast masses in men, a practical approach is proposed.

In March 1981, a 32-year-old male naturalist involved with collecting mammals for study was found to have an unexpected eosinophilia. Serum parasitic screening done at the Centers for Disease Control showed filarial titer by indirect hemagglutination of 1:1,024 and of 1:40 by bentonite flocculation. His travel history disclosed 3 months spent in Cameroon in 1978. He also gave a history of intermittent arm swelling for at least a year. Peripheral blood, collected repeatedly at mid-day and midnight and tested for microfilariae by the Knott technique, was negative. He was begun empirically on diethylcarbamazine, and on day 11 of treatment he removed a worm, identified as a male Loa loa, from his leg. He completed treatment without difficulty and has done well.