Increased risk of upstage when combinations of breast lesions of uncertain malignant potential are found on core needle biopsy: The need for surgical excision.

BACKGROUND: Management of breast lesions of uncertain malignant potential diagnosed at core needle biopsy (CNB) is controversial due to variable upstage rate (UR) with surgical excision (SE). METHODS: We performed an IRB-approved retrospective analysis of adult women who underwent CNB demonstrating atypical ductal hyperplasia (ADH), flat epithelial atypia, radial scar, or intraductal papilloma then SE between 2010 and 2022. We evaluated CNB pathology for combination diagnoses (CD), defined as multiple primary lesions or primary with lobular neoplasia (LN), and surgical pathology for upstage. RESULTS: 719 patients were included. UR was 12.2% (88/719). CD experienced higher UR than pure (17.7% (45/254) vs. 9.2% (43/465), p â€‹= â€‹0.001). ADH/LN had the highest UR of all CD (34.6% (9/26), p â€‹= â€‹0.001). Increased size (15.6 vs. 10.5 â€‹mm, p â€‹< â€‹0.001), distance from nipple (79 vs. 66 â€‹mm, p â€‹< â€‹0.001), and personal history of breast cancer (p â€‹= â€‹0.04) were associated with UR. CONCLUSIONS: CD was associated with increased UR. ADH/LN had the highest UR.

Differences in the Susceptibility of Human Tubular Epithelial Cells for Infection with Orthohantaviruses.

Diseases induced by infection with pathogenic orthohantaviruses are characterized by a pronounced organ-specific manifestation. Pathogenic Eurasian orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) with often massive proteinuria. Therefore, the use of a relevant kidney cell culture would be favorable to analyze the underlying cellular mechanisms of orthohantavirus-induced acute kidney injury (AKI). We tested different human tubular epithelial cell lines for their suitability as an in vitro infection model. Permissiveness and replication kinetics of highly pathogenic Hantaan virus (HTNV) and non-/low-pathogenic Tula virus (TULV) were analyzed in tubular epithelial cell lines and compared to human primary tubular epithelial cells. Ana-lysis of the cell line HK-2 revealed the same results for viral replication, morphological and functional effects as observed for HTNV in primary cells. In contrast, the cell lines RPTEC/TERT1 and TH1 demonstrated only poor infection rates after inoculation with HTNV and are unusable as an infection model. While pathogenic HNTV infects primary tubular and HK-2 cells, non-/low-pathogenic TULV infects neither primary tubular cells nor the cell line HK-2. Our results show that permissiveness of renal cells varies between orthohantaviruses with differences in pathogenicity and that HK-2 cells demonstrate a suitable in vitro model to study viral tropism and pathogenesis of orthohantavirus-induced AKI.

The Influence of Screening Mammography Cessation and Resumption on Breast Cancer Presentation and Treatment: A Multi-Hospital Health System Experience During the Early COVID-19 Pandemic.

Objective: To assess the impact of the coronavirus disease-2019 (COVID-19) pandemic screening restrictions on the diagnosis and treatment of breast cancer in a single health system. Materials and Methods: We performed a retrospective, cohort investigation of breast cancer patients at a multi-institution health system from March 1, 2019 to December 31, 2020 with two time periods related to the pandemic: "Early phase" (March 18 - June 7) reflecting the time of the screening mammography moratorium and "Late phase" (June 8 - December 31) to reflect the time once screening mammography resumed. 2020 was compared to 2019 to exclude potential differences from temporal or seasonal changes. Variables included demographics, COVID related-deferral, cancer specific data, method of detection, type of treatment recommended and received. Results: Fewer patients presented with a breast cancer diagnosis during Early phase 2020 when compared to any other time period. Numbers increased significantly in Late phase 2020; total numbers of patients seen in 2020 approached but did not completely reach that of 2019. When compared to other time periods, patients who presented during the moratorium on screening were younger, more likely to be black, had a higher Body Mass Index, and were more likely to have a human epidermal growth factor receptor 2 positive tumor. There was a slight increase in size of presenting tumor and node positivity, although no differences in breast or axillary surgical management were identified. Conclusion: Despite an increase in tumor size and positive nodal status seen during the screening moratorium, surgical treatment was not negatively impacted.

Framing cognitive offloading in terms of gains or losses: achieving a more optimal use of reminders.

Nowadays individuals can readily set reminders to offload intentions onto external resources, such as smartphone alerts, rather than using internal memory. Individuals tend to be biased, setting more reminders than would be optimal. We address the question whether the reminder bias depends on offloading scenarios being framed as either gains or losses, both between-participants (Experiment 1) and within-participants (Experiment 2). In both experiments, framing of reminders in terms of gains resulted in participants employing a risk-averse strategy and using more reminders than would be optimal. Importantly, however, participants used reminders more optimally and were more willing to choose the risk-seeking option of remembering internally when reminders implied a loss. Based on metacognitive measures in Experiment 2, the reminder bias increased the more underconfident participants were about their memory abilities in both framing scenarios. Framing did not alter this relationship between erroneous metacognitive underconfidence and reminder bias but provides an additional influence. We conclude that emphasizing the losses (costs) associated with external reminders helps in achieving more optimal decisions in offloading situations, and that in addition to cognitive effort and metacognitive judgments, framing needs to be considered in improving individuals' offloading behavior.

The Impact of COVID-19 on Breast Surgery Fellowships.

Purpose of Review: Across the world, medical training has been affected by the COVID-19 virus and this has changed the way physicians are educated. What is less clear is the effect of the pandemic on breast surgical oncology fellows who were in training during this time. This review discusses the experience of breast surgical oncology fellows during the pandemic and how fellowships adapted to preserve the educational experience and conserve the quality of training. Recent Findings: The challenges and changes experienced by breast surgery fellows during the COVID-19 pandemic have proved to be sudden shifts in not only fellowship training, but future patient care and research opportunities, all while confronting the global impact of a deadly pandemic. While experiences between fellowships varied, the similarities and differences encountered highlight the regional and temporal differences in how fellowships responded to the pandemic. Summary: Breast surgical oncology fellowship is one year long, with every day allocated to ensure the surgeon has a deep understanding of the multidisciplinary approach to this ever-evolving field. As the pandemic spread and affected different regions with varying severity, elective cases were canceled, resources were re-allocated, and uncertainty abounded. At the same time, novel approaches to fellowship training were rapidly implemented. It will take time and additional research to fully understand the long-term consequences for trainees affected during their breast surgery fellowship.

A Fast-Track Pathway for Emergency General Surgery at an Academic Medical Center.

BACKGROUND: Fast Track Pathways (FTP) directed at reducing length of stay (LOS) and overall costs are being increasingly implemented for emergency surgeries. The purpose of this study is to evaluate implementation of a FTP for Emergency General Surgery (EGS) at an academic medical center (AMC). METHODS: The study included 165 patients at an AMC between 2016 and 2018 who underwent laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), or laparoscopic inguinal hernia repair (LI). The FTP group enrolled 89 patients, and 76 controls prior to FTP implementation were evaluated. Time to surgery (TTS), LOS, and post-operative LOS between groups were compared. Direct costs, reimbursements, and patient reported satisfaction (satisfaction 1 = never, 4 = always) were also studied. RESULTS: The sample was 60.6% female, with a median age of 40 years. Case distribution differed slightly (56.2% versus 42.1% LA, 40.4% versus 57.9% LC, FTP versus control), but TTS was similar between groups (11h39min versus 10h02min, P = 0.633). LOS was significantly shorter in the FTP group (15h17min versus 29h09min, P < 0.001), reflected by shorter post-operative LOS (3h11min versus 20h10min, P< 0.001), fewer patients requiring a hospital bed and overnight stay (P < 0.001). Direct costs were significantly lower in the FTP group, reimbursements were similar (P < 0.001 and P = 0.999 respectively), and average patient reported satisfaction was good (3.3/4). CONCLUSION: In an era focused on decreasing cost, optimizing resources, and ensuring patient satisfaction, a FTP can play a significant role in EGS. At an AMC, an EGS FTP significantly decreased LOS, hospital bed utilization while not impacting reimbursement or patient satisfaction.

Characteristics and Long-Term Risk of Breast Angiosarcoma.

BACKGROUND: Angiosarcoma of the breast is rare and aggressive. It can occur as a de novo tumor or secondary to breast cancer treatment. The purpose of this study is to analyze differences between patients with primary and secondary angiosarcoma of the breast and investigate potential risk factors for its development. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute database was queried to identify patients with angiosarcoma of the breast, trunk, shoulder, and upper arm. The population-based incidence was analyzed. Primary and secondary angiosarcoma cases were identified and compared. Breast cancer characteristics of secondary angiosarcoma patients were compared with all breast cancer patients in the database who did not develop angiosarcoma. RESULTS: Overall, 904 patients were included, and 65.4% were secondary angiosarcomas. These patients had worse survival, were older, more likely to be White, more likely to have regionally advanced disease, and had angiosarcoma tumors of higher pathologic grade. Independent factors associated with development of secondary angiosarcoma among breast cancer patients included White race, older age, invasive tumor, lymph node removal, lumpectomy, radiation treatment, and left-sided tumor. Although the mean time to develop angiosarcoma after breast cancer diagnosis was 8.2 years, the risk continues to increase up to 30 years after breast cancer treatment. CONCLUSION: Angiosarcoma is rare but increasing in incidence. Secondary angiosarcomas are more common and exhibit more aggressive behavior. Several factors for angiosarcoma after breast cancer treatment could be identified, which may help us counsel and identify patients at risk.

A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears.

BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.

Association of Medicaid Expansion Under the Affordable Care Act With Breast Cancer Stage at Diagnosis.

Importance: The expansion of Medicaid sought to fill gaps in insurance coverage among low-income Americans. Although coverage has improved, little is known about the relationship between Medicaid expansion and breast cancer stage at diagnosis. Objective: To review the association of Medicaid expansion with breast cancer stage at diagnosis and the disparities associated with insurance status, age, and race/ethnicity. Design, Setting, and Participants: This cohort study used data from the National Cancer Database to characterize the relationship between breast cancer stage and race/ethnicity, age, and insurance status. Data from 2007 to 2016 were obtained, and breast cancer stage trends were assessed. Additionally, preexpansion years (2012-2013) were compared with postexpansion years (2015-2016) to assess Medicaid expansion in 2014. Data were analyzed from August 12, 2019, to January 19, 2020. The cohort included a total of 1 796 902 patients with primary breast cancer who had private insurance, Medicare, or Medicaid or were uninsured across 45 states. Main Outcomes and Measures: Percent change of uninsured patients with breast cancer and stage at diagnosis, stratified by insurance status, race/ethnicity, age, and state. Results: This study included a total of 1 796 902 women. Between 2012 and 2016, 71 235 (4.0%) were uninsured or had Medicaid. Among all races/ethnicities, in expansion states, there was a reduction in uninsured patients from 22.6% (4771 of 21 127) to 13.5% (2999 of 22 150) (P < .001), and in nonexpansion states, there was a reduction from 36.5% (5431 of 14 870) to 35.6% (4663 of 13 088) (P = .12). Across all races, there was a reduction in advanced-stage disease from 21.8% (4603 of 21 127) to 19.3% (4280 of 22 150) (P < .001) in expansion states compared with 24.2% (3604 of 14 870) to 23.5% (3072 of 13 088) (P = .14) in nonexpansion states. In African American patients, incidence of advanced disease decreased from 24.6% (1017 of 4136) to 21.6% (920 of 4259) (P < .001) in expansion states and remained at approximately 27% (27.4% [1220 of 4453] to 27.5% [1078 of 3924]; P = .94) in nonexpansion states. Further analysis suggested that the improvement was associated with a reduction in stage 3 diagnoses. Conclusions and Relevance: In this cohort study, expansion of Medicaid was associated with a reduced number of uninsured patients and a reduced incidence of advanced-stage breast cancer. African American patients and patients younger than 50 years experienced particular benefit. These data suggest that increasing access to health care resources may alter the distribution of breast cancer stage at diagnosis.

Prophylactic Versus Therapeutic Mastectomy: A Contemporary Analysis of the ACS-NSQIP Database.

INTRODUCTION: The objective of the study was to evaluate the morbidity, mortality, and postoperative outcomes associated with simple or subcutaneous mastectomy in the management of prophylactic versus therapeutic resection. In this study we aimed to assess if simple or subcutaneous mastectomy for prophylaxis affects perioperative outcomes compared with resection performed for biopsy proven malignancy. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for subjects who underwent simple or subcutaneous mastectomy between 2007 and 2012. Patient demographic characteristics, comorbid conditions, and postoperative complications were analyzed. RESULTS: Of the 30,803 patients, 30,644 (99.5%) underwent therapeutic mastectomy and 159 (0.5%) underwent prophylactic mastectomy. Subjects who underwent prophylactic surgery were more likely to be younger (45 vs. 58 years; P < .01) and white (134 [84%] vs. 20,647 [67%]; P < .01). Surgery time was significantly greater in the prophylactic group (265 vs. 166 minutes; P < .01). There was no significant difference in mortality between groups. There was a trend toward greater 30-day morbidity (15 [9%] vs. 1835 [6%]; P = .09) and occurrence of deep venous thrombosis (DVT; 2 [1%] vs. 74 [0.2%]; P = .06) in those who underwent prophylactic mastectomy. After age adjustment, the prophylactic group showed a nearly sixfold increase in DVT (odds ratio [OR], 5.77; 95% confidence interval [CI], 1.37-24.22), which persisted when controlling for surgery time (OR, 4.95; 95% CI, 1.18-20.86). CONCLUSION: Prophylactic simple or subcutaneous mastectomy incurs significant additional 30-day postoperative morbidity related to perioperative DVT. Risk-mitigating strategies should be considered in the perioperative care of this patient population.

Approach to the Diagnostic Workup and Management of Small Bowel Lesions at a Tertiary Care Center.

BACKGROUND: Small bowel lesions (SBL) are rare, representing diagnostic and management challenges. The purpose of this cross-sectional study was to evaluate diagnostic modalities used and management practices of patients with SBL at an advanced endoscopic referral center. METHODS: We analyzed patients undergoing surgical management for SBL from 2005 to 2015 at a single tertiary care center. Patients were stratified into gastrointestinal bleed/anemia (GIBA) or obstruction/pain (OP). RESULTS: One hundred and twelve patients underwent surgery after presenting with either GIBA (n = 67) or OP (n = 45). The mean age of our study population was 61.8 years and 45% were women. Patients with GIBA were more likely to have chronic or acute-on-chronic symptoms (100% vs 67%) and more often referred from outside hospitals (82 vs. 44%) (p < 0.01). The most common preoperative imaging modalities were video capsule endoscopy (VCE) (96%) for GIBA and computer tomography CT (78%) for OP. Findings on VCE and CT were most frequently concordant with operative findings in GIBA (67%) and OP (54%) patients, respectively. Intraoperatively, visual inspection or palpation of the bowel successfully identified lesions in 71% of patients. When performed in GIBA (n = 26), intraoperative enteroscopy (IE) confirmed or identified lesions in 69% of patients. Almost all (90%) GIBA patients underwent small bowel resections; most were laparoscopic-assisted (93%). Among patients with OP, 58% had a small bowel resection and the majority (81%) were laparoscopic-assisted. Surgical exploration failed to identify lesions in 10% of GIBA patients and 24% of OP patients. Among patients who underwent resections, 20% of GIBA patients had recurrent symptoms compared with 13% of OP patients. CONCLUSION: Management and identification of SBL is governed by presenting symptomatology. Optimal management includes VCE and IE for GIBA and CT scans for OP patients. Comprehensive evaluation may require referral to specialized centers.

Cholecystostomy Treatment in an ICU Population: Complications and Risks.

BACKGROUND: Percutaneous cholecystostomy tube placement has widely been used as an alternative treatment to cholecystectomy, especially in advanced disease or critically ill patients. Reported postprocedural complication rates have varied significantly over the last decade. The goal of this study is to evaluate the safety of percutaneous cholecystostomy tube treatment in critically ill patients. STUDY DESIGN: We performed a retrospective chart analysis of 96 critically ill patients who underwent cholecystostomy tube placement during an intensive care unit (ICU) stay between 2005 and 2010 in a tertiary care center in central Massachusetts. Complications within 72 hours of cholecystostomy tube placement and any morbidity or mortality relating to presence of cholecystostomy tube were considered. RESULTS: A total of 65 male and 31 female patients with a mean age of 67.4 years underwent percutaneous cholecystostomy tube placement during an ICU stay. Sixty-six patients experienced a total of 121 complications, resulting in an overall complication rate of 69%. Fifty-four of these complications resulted from the actual procedure or the presence of the cholecystostomy tube; the other 67 complications occurred within 72 hours of the cholecystostomy procedure. Ten patients died. Tube dislodgment was the most common complication with a total of 34 episodes. CONCLUSIONS: Cholecystostomy tube placement is associated with frequent complications, the most common of which is tube dislodgment. Severe complications may contribute to serious morbidity and death in an ICU population. Complication rates may be underreported in the medical literature. The potential impact of cholecystostomy tube placement in critically ill patients should not be underestimated.

Timing and choice of intervention influences outcome in acute cholecystitis: a prospective study.

PURPOSE: Determine which management strategy is ideal for patients with acute cholecystitis. MATERIALS AND METHODS: Prospective enrollment between August 2009 and March 2011. Large academic center. Patients with acute cholecystitis. Laparoscopic cholecystectomy, intravenous antibiotics followed by laparoscopic cholecystectomy or percutaneous cholecystostomy. Primary endpoints were postoperative complications and 30-day mortality. RESULTS: A total of 162 patients were enrolled, 53 (33%) with simple acute cholecystitis and 109 (67%) with complex acute cholecystitis. Of the 109 patients with complex cholecystitis, 77 (70.6%) underwent successful laparoscopic cholecystectomy during the same hospital admission and 6 patients (5.5%) had an unsuccessful laparoscopic cholecystectomy requiring conversion to cholecystostomy. Radiology performed cholecystostomy in 19 (11.7%) patients with complex acute cholecystitis and 4 (2.5%) patients with simple acute cholecystitis for a total 23 patients of the 162 patients in the study. Nine of the 23 patients had dislodged tubes (39.1%). Two of the 23 patients (8.7%) had significant bile leaks resulting in either sepsis or emergency surgery. One patient (4.3%) had a wound infection. Overall, patients with complex acute cholecystitis had a higher morbidity rate (31.2%) compared with patients with simple acute cholecystitis (26.4%). CONCLUSIONS AND RELEVANCE: A high complication rate seen with radiology placed percutaneous cholecystostomy tubes prompted our center to reevaluate the treatment algorithm used to treat patients with complex acute cholecystitis. Although laparoscopic cholecystectomy is considered to be the gold standard in the treatment of acute cholecystitis, if laparoscopic cholecystectomy is not felt to be safe due to gallbladder wall thickening or symptoms of >72 hours' duration, we now encourage the use of intravenous antibiotics to "cool" patients down followed by interval laparoscopic cholecystectomy approximately 6 to 8 weeks later. Patients who do not respond to antibiotics should undergo attempted laparoscopic cholecystectomy and if unable to be performed safely, a laparoscopic cholecystostomy tube can be placed under direct visualization for decompression followed by interval laparoscopic cholecystectomy at a later date.

Intraabdominal infections in the intensive care unit.

Intraabdominal infections are frequent and dangerous entity in intensive care units. Mortality and morbidity are high, causes are numerous, and treatment options are variable. The intensivist is challenged to recognize and treat intraabdominal infections in a timely fashion to prevent complications and death. Diagnosis of intraabdominal infection is often complicated by confounding underlying disease or masked by overall comorbidity. Current research describes a wide heterogeneity of patient populations, making it difficult to suggest a general treatment regimen and stressing the need of an individualized approach to decision making. Early focus-oriented intervention and antibiotic coverage tailored to the individual patient and hospital is warranted.

Modulation of visceral hyperalgesia by morphine and cholecystokinin from the rat rostroventral medial medulla.

Using a model of visceral nociception, we examined whether cholecystokinin (CCK) acts as an anti-opioid peptide in the rat rostral ventromedial medulla (RVM). Because such interaction may be affected by inflammation, rats with and without inflamed colons were studied. The visceromotor response to noxious colorectal distension (CRD), quantified electromyographically, was recorded before and after intra-RVM administration of CCK, CCK receptor antagonists, and morphine. Either 50% ethanol/saline (vehicle) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), which inflames the colon, was instilled into the colon 5 days before experiments. Intra-RVM morphine dose-dependently attenuated responses to CRD in intracolonic vehicle-treated rats. In TNBS-treated rats with inflamed colons, responses to CRD were significantly increased and 0.3, 3.0 and 6.0 microg doses of intra-RVM morphine reduced responses to control (i.e. were anti-hyperalgesic); the greatest dose tested (30 microg) further reduced responses to 40% control. In intracolonic vehicle-treated rats, intra-RVM pre-treatment with a selective CCK(B) (but not CCK(A)) receptor antagonist dose-dependently and significantly enhanced the effect of a low dose of morphine. Intra-RVM CCK-8 peptide enhanced responses to CRD in intracolonic vehicle-treated, but not TNBS-treated rats. Intra-RVM naloxone was without effect in intracolonic vehicle-or TNBS-treated rats, suggesting an absence of tonic opioid activity in RVM. These results document a CCK-opioid interaction in RVM, suggesting that colon inflammation leads to tonic activity at CCK(B) receptors in RVM.