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We evaluated long range antennae and associated solar-powered global positioning system (GPS) ear tags designed for use with domestic cattle, as a novel system for monitoring ranging behaviour of the koala (Phascolarctos cinereus). The mean location error of our GPS tags was 33.9 m (s.e. = 0.46). The tags were relatively light (30 g), reported eight locations per day when attached to koala radio-collars and had an operating life that exceeded our study period (8 months). Deployed as a stand-alone, solar powered, remote system, this technology can provide a viable option for wildlife tracking projects.

Background Objectives: We performed a randomized, double-blind, placebo-controlled trial to determine if using Secretin intra-operatively to identify leaks and subsequently target operative intervention would decrease the frequency of clinically significant post-operative pancreatic fistula formation. Methods Patients undergoing pancreaticoduodenectomy or distal pancreatectomy were randomized to receive intra-operative Secretin or placebo intra-operatively following the completed pancreaticojejunostomy or closure of the cut remnant stump. If a potential leak was identified, targeted therapy with directed suture placement was performed. Results 170 patients were randomized; 83 receiving placebo and 87 receiving Secretin. The rate of clinically significant fistula formation was 3% (3/87) in the Secretin group and 6% (5/83) in the placebo group (p = 0.489). The rate of biochemical leak was 29% (25/87) in the Secretin group and 19% (16/83) in the placebo group (p = 0.157). There were no Grade C post-operative fistula in either group. Of the 9% of patients in the Secretin group who had a targeted intra-operative intervention, none developed a clinically significant fistula. Adverse events were similar between groups. Conclusions Compared to placebo, intra-operative Secretin administration was not associated with an overall reduction in clinically significant pancreatic fistula formation. However, patients with an intra-operative leak identified by Secretin may benefit from intervention (clinicaltrials.gov: NCT02160808 ).

Aim: Image-guided surgery (IGS) allows for accurate, real-time localization of subsurface critical structures during surgery. No prior IGS systems have described a feasible method of intraoperative reregistration after manipulation of the kidney during robotic partial nephrectomy (PN). We present a method for seamless reregistration during IGS and evaluate accuracy before and after tumor resection in two validated kidney phantoms. Materials and Methods: We performed robotic PN on two validated kidney phantoms—one with an endophytic tumor and one with an exophytic tumor—with our IGS system utilizing the da Vinci Xi robot. Intraoperatively, the kidney phantoms' surfaces were digitized with the da Vinci robotic manipulator via a touch-based method and registered to a three-dimensional segmented model created from cross-sectional CT imaging of the phantoms. Fiducial points were marked with a surgical marking pen and identified after the initial registration using the robotic manipulator. Segmented images were displayed via picture-in-picture in the surgeon console as tumor resection was performed. After resection, reregistration was performed by reidentifying the fiducial points. The accuracy of the initial registration and reregistration was compared. Results: The root mean square (RMS) averages of target registration error (TRE) were 2.53 and 4.88 mm for the endophytic and exophytic phantoms, respectively. IGS enabled resection along preplanned contours. Specifically, the RMS averages of the normal TRE over the entire resection surface were 0.75 and 2.15 mm for the endophytic and exophytic phantoms, respectively. Both tumors were resected with grossly negative margins. Point-based reregistration enabled instantaneous reregistration with minimal impact on RMS TRE compared with the initial registration (from 1.34 to 1.70 mm preresection and from 1.60 to 2.10 mm postresection). Conclusions: We present a novel and accurate registration and reregistration framework for use during IGS for PN with the da Vinci Xi surgical system. The technology is easily integrated into the surgical workflow and does not require additional hardware.

Prenatal myelomeningocele (MMC) repair has been shown to provide significant benefits to the infant, decreasing the postnatal need for ventriculoperitoneal shunt and improving motor outcome. Chorioamniotic membrane separation (CAS) is a potential complication following prenatal MMC repair and may increase the risk of preterm prelabor rupture of membranes (PPROM) and preterm birth. The objectives of this study were: (1) to evaluate the incidence of CAS after prenatal MMC repair; (2) to determine risk factors associated with its occurrence; and (3) to assess its association with adverse perinatal outcomes.This was a retrospective cohort study of patients who underwent fetal MMC repair between November 2011 and December 2018. Surgery was performed using either a fetoscopic (laparotomy or exteriorized uterus) approach or an open-hysterotomy approach. Eligibility criteria were those reported in the Management of Myelomeningocele Study. If CAS was detected on ultrasound (US), its severity was graded as 'mild' if amnion detachment involved 25% of the uterine cavity, 'moderate' if it involved 25-50% and 'severe' if it involved 50%. Evolution of CAS was classified as stable, increasing or decreasing based on the difference in severity grading between the time at first diagnosis and the last US scan before delivery. Logistic regression analysis was performed to identify pre- or perisurgical factors associated with the development of CAS and to determine the risk of adverse perinatal outcome associated with CAS.In total, 91 cases were included. Fetoscopic or open-hysterotomy repair of MMC was performed in 52/91 (57.1%) and 39/91 (42.9%) cases, at a median gestational age (GA) of 25.0 weeks (range, 22.9-26.0 weeks) and 25.0 weeks (range, 21.3-25.9 weeks), respectively. CAS was diagnosed in 31/91 (34.1%) patients, at a median GA of 28.1 weeks (range, 24.4-37.6 weeks). Anterior placenta was identified as a risk factor for the postoperative development of CAS (odds ratio (OR), 3.72 (95% CI, 1.46-9.5); P 0.01). This risk was dependent on the repair technique. An anterior placenta significantly increased the risk of CAS after fetoscopic repair (OR, 3.94 (95% CI, 1.14-13.6); P = 0.03) but not after open repair (OR, 2.8 (95% CI, 0.6-12.5); P = 0.16). There was no significant difference in the rate of CAS after fetoscopic repair (21/52 (40.4%)) vs open-hysterotomy repair (10/39 (25.6%)) (P = 0.14), nor were there any differences in GA at diagnosis of CAS, interval between surgery and diagnosis, distribution of CAS severity or progression of CAS between the two groups. CAS increased the risk of PPROM (50% in those with vs 12% in those without CAS) (OR, 7.6 (95% CI, 2.5-21.9); P 0.01) and preterm delivery (70% vs 38%) (OR, 3.2 (95% CI, 1.3-8.1); P 0.01). Fetoscopically repaired cases with CAS had a higher rate of PPROM (12/20 (60.0%) vs 2/31 (6.5%); P 0.01) and preterm delivery (13/20 (65.0%) vs 5/31 (16.1%); P 0.01) than those that did not develop CAS, while the differences were not significant in cases with open-hysterotomy repair. Early detection of CAS (before 30 weeks' gestation) was a risk factor for preterm delivery (90% before 30 weeks vs 36% at or after 30 weeks) (OR, 15.7 (95% CI, 2.3-106.3); P 0.01). There was no association between PPROM or preterm delivery and the severity or progression of CAS.The presence of an anterior placenta was the only factor that increased the risk for CAS after fetoscopic MMC repair. Detection of CAS after fetoscopic MMC repair significantly increases the risk for PPROM and preterm delivery. Copyright © 2019 ISUOG. Published by John WileySons Ltd.

Introduction:We summarize the 2018 AUA (American Urological Association) Quality Improvement Summit, Opioid Stewardship in Urology, highlighting appropriate urological opioid use as well as...

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody–drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody–drug conjugates are in development. Additionally, bispecific T-cell–engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell–mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a “liquid biopsy” for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1–3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 +/− 11.81% (mean +/− SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients, and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

Wire-localized excision of non-palpable breast cancer is imprecise, resulting in positive margins 15–35% of the time. Women with a confirmed diagnosis of non-palpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) were randomized to a new technique using preoperative supine magnetic resonance imaging (MRI) with intraoperative optical scanning and tracking (MRI group) or wire-localized (WL group) partial mastectomy. The main outcome measure was the positive margin rate. In this study, 138 patients were randomly assigned. Sixty-six percent had IBC and DCIS, 22% had IBC, and 12% had DCIS. There were no differences in patient or tumor characteristics between the groups. The proportion of patients with positive margins in the MRI-guided surgery group was half that observed in the WL group (12 vs. 23%; p = 0.08). The specimen volumes in the MRI and WL groups did not differ significantly (74 ± 33.9 mL vs. 69.8 ± 25.1 mL; p = 0.45). The pathologic tumor diameters were underestimated by 2 cm or more in 4% of the cases by MRI and in 9% of the cases by mammography. Positive margins were observed in 68% and 58% of the cases underestimated by 2 cm or more using MRI and mammography, respectively, and in 15% and 14% of the cases not underestimated using MRI and mammography, respectively. A novel system using supine MRI images co-registered with intraoperative optical scanning and tracking enabled tumors to be resected with a trend toward a lower positive margin rate compared with wire-localized partial mastectomy. Margin positivity was more likely when imaging underestimated pathologic tumor size.

In patients undergoing breast-conserving surgery (BCS), the rate of re-excision procedures to remove residual tumor left behind after initial resection can be high. Projection radiography, and recently, volumetric x-ray imaging are used to assess margin adequacy, but x-ray imaging lacks contrast between healthy, abnormal benign, and malignant fibrous tissues important for surgical decision making. The purpose of this study was to compare micro-CT and optical scatter imagery of surgical breast specimens and to demonstrate enhanced contrast-to intra-tumoral morphologies and tumor boundary features revealed by optical scatter imaging. A total of 57 breast tumor slices from 57 patients were imaged ex vivo by spatially co-registered micro-CT and optical scatter scanning. Optical scatter exhibited greater similarity with micro-CT in 89% (51/57) of specimens versus diffuse white light (DWL) luminance using mutual information (mean ± standard deviation of 0.48 ± 0.21 versus 0.24 ± 0.12; p p p

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. Significance: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations. See related commentary by Bornhauser and Bourquin, p. 1322. This article is highlighted in the In This Issue feature, p. 1307

Staphylococcus aureus bacteriuria (SABU) can occur in patients with S. aureus bacteremia (SAB). However, little is known on the (molecular) pathomechanisms of the renal passage of S. aureus. This review discusses the epidemiology and pathogenesis of SABU in patients with SAB and identifies knowledge gaps. The literature search was restricted to the English language. The prevalence of SABU in patients with SAB is 7.8%–39% depending on the study design. The main risk factor for SABU is urinary tract catheterization. SABU in SAB patients is associated with increased mortality. Given present evidence, hematogenous seeding—as seen in animal models—and the development of micro-abscesses best describe the translocation of S. aureus from blood to urine. Virulence factors that might be involved are adhesion factors, sortase A, and coagulase, among others. Other potential routes of bacterial translocation (eg, transcytosis, paracytosis, translocation via “Trojan horses”) were identified as knowledge gaps.

Image-guidance during partial nephrectomy enables navigation within the operative field alongside a 3-dimensional roadmap of renal anatomy generated from patient-specific imaging. Once a process is performed by the human mind, the technology will allow standardization of the task for the benefit of all patients undergoing robot-assisted partial nephrectomy. Any surgeon will be able to visualize the kidney and key subsurface landmarks in real-time within a 3-dimensional simulation, with the goals of improving operative efficiency, decreasing surgical complications, and improving oncologic outcomes. For similar purposes, image-guidance has already been adopted as a standard of care in other surgical fields; we are now at the brink of this in urology. This review summarizes touch-based approaches to image-guidance during partial nephrectomy, as the technology begins to enter in vivo human evaluation. The processes of segmentation, localization, registration, and re-registration are all described with seamless integration into the da Vinci surgical system; this will facilitate clinical adoption sooner.

OBJECTIVE The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement. METHODS In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17), and with intracranial atherosclerosis (n = 25) served as controls. RESULTS Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p = 0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course. INTERPRETATION Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. ANN NEUROL 2021;90:118-129.

Background : Inflammatory myofibroblastic tumors (IMTs) are a rare subtype of inflammatory pseudotumor frequently associated with rearrangement of the anaplastic lymphoma kinase (ALK) gene. Their treatment has historically relied on at-times challenging and morbid surgical excision. Recent studies have shown that neo/adjuvant therapy with ALK inhibitors can significantly enhance outcomes in select patients. Methods : A systematic literature review was performed to characterize comprehensive treatment of ALK-positive IMTs in the pediatric population. This report also includes two patients from our home institutions not previously reported in the literature. Results : We identified a total of 27 patients in 12 studies in addition to 2 patients from the senior authors’ institution for a total of 29 patients (median age, 7 years; 52% male). The IMTs comprised a wide range of anatomic locations. Almost half (12, 41.3%) were treated with ALK-inhibitors alone and felt to be in remission. The remainder were treated with ALK-inhibitors either before or after surgery and had a curative response. Conclusions : ALK-positive IMTs can be successfully treated with ALK-inhibition alone or in combination with surgical resection. Further genetic characterization may be helpful in determining more precise treatment and defining needed durations thereof.

Background Infant acute myeloid leukemia is a rare but aggressive form of leukemia. Observation We report 2 children who presented with hyperleukocytosis, subsequently diagnosed with infant acute myeloid leukemia, and both developed isolated central nervous system relapse while on chemotherapy. Both infants underwent successful bone marrow transplantation with myeloablative conditioning (thiotepa, busulfan, and cyclophosphamide) without radiation, followed by 12 empiric post-transplant lumbar punctures with intrathecal cytarabine. Both patients tolerated these therapies well, and are without infections, chronic graft-versus-host disease, or any post-transplant sequelae. Conclusion Nonradiation-based conditioning followed by empiric central nervous system-directed intrathecal chemotherapy may be considered for high-risk infants with leukemia.

BACKGROUND: Current laparoscopic surgical robots are teleoperated, which requires high fidelity differential motions but does not require absolute accuracy. Emerging applications, including image guidance and automation, require absolute accuracy. The absolute accuracy of the da Vinci Xi robot has not yet been characterized or compared to the Si system, which is now being phased out. This paper compares the accuracy of the two. METHODS: We measure robot tip positions and encoder values assessing accuracy with and without robot calibration. RESULTS: The Si is accurate if the setup joints are not moved but loses accuracy otherwise. The Xi is always accurate. CONCLUSION: The Xi can achieve submillimetric average error. Calibration improves accuracy, but excellent baseline accuracy of the Xi means that calibration may not be needed for some applications. Importantly, the external tracking systems needed to account for setup joint error in the Si are no longer required with the Xi.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

Background Women of lower socioeconomic status (SES) with early‐stage breast cancer are more likely to report poorer physician‐patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices. Methods We conducted a 3‐arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon‐level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence‐based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre‐consultation) to T5 (1‐year after surgery. Results Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self‐reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety. Conclusions Paper‐based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients. Lay Summary The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices.Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text‐only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education.Conversation aids with pictures and text helped women make better breast cancer surgery choices., A paper‐based pictorial conversation aid (pictures plus text) is beneficial to all patients with early‐stage breast cancer and particularly to disadvantaged patients. Between‐surgeon variation suggests that the maximal impact of such interventions requires standardized physician training combined with these interventions.

PURPOSE: Little is known about the three-dimensional shape of breast cancer. Implicit to approaches that localize the center of the tumor for breast conserving surgery (BCS) of non-palpable cancers is the assumption that breast cancers are spherical about a central point, which may not be accurate. METHODS: Pre-operative supine breast MRI images were obtained of 83 breast cancer patients undergoing partial mastectomy using supine MRI guided resection techniques. Three-dimensional (3D) tumor models were derived after radiologists outlined tumor edges on successive MRI slices. Ideal resection volumes were determined by adding 1 cm in every dimension to the actual tumor volume. Geometrically defined parameters were used to define tumor shapes and associations between clinical variables and shapes were examined. RESULTS: Seventy five patients had invasive cancer. Breast cancers were categorized into 4 tumor shapes: 34% of tumors were discoidal, 29% segmental, 19% spherical and 18% irregular. If hypothetical spherical excisions were performed, nonspherical cases would excise 143% more tissue than the ideal resection volume. When the 3D shape of each tumor was provided to the surgeon during MR-guided BCS, the percentage of tissue overexcised in non-spherical cases was significantly less (143% vs. 66% , p < 0.001). CONCLUSIONS: Information obtained from a supine MRI can be used to generate 3D tumor models and rapidly classify breast tumor shapes. The vast majority of invasive cancers and DCIS are not spherical. Knowledge of tumor shape may allow surgeons to excise breast cancer more precisely.

Partial nephrectomy involves removing a tumor while sparing surrounding healthy kidney tissue. Compared to total kidney removal, partial nephrectomy improves outcomes for patients but is underutilized because it is challenging to accomplish minimally invasively, requiring accurate spatial awareness of unseen subsurface anatomy. Image guidance can enhance spatial awareness by displaying a 3D model of anatomical relationships derived from medical imaging information. It has been qualitatively suggested that the da Vinci robot is well suited to facilitate image guidance through touch-based registration. In this paper we validate and advance this concept toward real-world use in several important ways. First, we contribute the first quantitative accuracy evaluation of touch-based registration with the da Vinci. Next, we demonstrate real-time, touch-based registration and display of medical images for the first time. Lastly, we perform the first experiments validating use of touch-based image guidance to improve a surgeon’s ability to localize subsurface anatomical features in a geometrically realistic phantom.

Soft robotics holds enormous promise for a wide class of applications. However, system controllability, bandwidth, portability, and energy efficiency of soft robot power supplies are often inadequate. Soft robotics desperately needs improved solutions to drive soft actuators either pneumatically or hydraulically. This research paper offers a contribution to bridge this gap. It deals with small-scale power supplies for hydraulically-driven soft robots based on fluidic elastomer actuators in the power range 5-400 W. A design procedure for such power supplies is developed with an emphasis on high-bandwidth control. The performance requirements are established based on a literature survey, and design alternatives are discussed. Then, a prototype consisting of a $0.102 c^{3}$/rev positive-displacement, external gear pump directly driven by a 70 W brushless dc motor is built and experimentally characterized. Control of the targeted soft robots results possible because the proposed power supply has high-bandwidth varying between about 12 and 30 Hz (i.e., well above the actuators’ mechanical frequency). The power supply’s energy efficiency is also measured, and areas for its improvement are identified. The proposed solution is feasible, applicable to autonomous soft robots, scalable to the power levels of interest, and possibly useful for both tethered soft robots and rigid/semi-rigid robots.

BACKGROUND Our previous case series suggested that a 1-week, low-calorie and low-fat diet was associated with decreased intraoperative blood loss in patients undergoing liver surgery. OBJECTIVE The current study evaluates the effect of this diet in a randomized controlled trial. METHODS We randomly assigned 60 patients with a body mass index ≥25 kg/m(2) to no special diet or an 800-kcal, 20 g fat, and 70 g protein diet for 1 week before liver resection. Surgeons were blinded to diet assignment. Hepatic glycogen stores were evaluated using periodic acid Schiff (PAS) stains. RESULTS Ninety four percent of the patients complied with the diet. The diet group consumed fewer daily total calories (807 vs 1968 kcal, P < 0.001) and fat (21 vs 86 g, P < 0.001) than the no diet group. Intraoperative blood loss was less in the diet group: mean blood loss 452 vs 863 mL (P = 0.021). There was a trend towards decreased transfusion in the diet group (138 vs 322 mL, P = 0.06). The surgeon judged the liver to be easier to manipulate in the diet group: 1.86 versus 2.90, P = 0.004. Complication rate (20% vs 17%), length of stay (median 5 vs 4 days) and mortality did not differ between groups. There was no difference in hepatic steatosis between groups. There was less glycogen in hepatocytes in the diet group (PAS stain score 1.61 vs 2.46, P < 0.0001). CONCLUSIONS A short-course, low-fat, and low-calorie diet significantly decreases bleeding and makes the liver easier to manipulate in hepatic surgery.

The most common treatment for early-stage breast cancer involves breast-conserving surgery (BCS), which is a local resection of malignant tissue. BCS success relies on the presence of healthy tissue margins surrounding each resection. However, approximately 20% of BCS patients require follow-up surgery to remove residual tumor. Micro-computed tomography and optical structured light imaging were investigated for intraoperative margin assessment. Specimens were imaged immediately after resection and before surgical inking, and image data were compared to postoperative histopathology. The study demonstrated the feasibility of imaging during BCS and generated a baseline multimodal dataset of whole BCS resections, including positive margin signatures.

Whether you are a faculty member taking on responsibility for an existing graduate program or exploring the creation of a new program, the understanding of the differences and similarities between different types of public affairs programs is fundamental to the clear identity and focus necessary for a sustainable, effective program. The nature of your program will drive faculty and student recruitment, as well as how you brand your program to key stakeholders like employers. This chapter, providing the perspectives of both an experienced MPA director and an MPA student, provides information on two levels. First, the landscape of the array of public affairs programs nationwide is described, with a particular focus on the basic differences between programs titled MPA, MPP, MPAffairs, and MPM. Second, the chapter closes with an articulation of some fundamental issues to consider in differentiating your program, including your market and institutional setting, applied versus theoretical orientation, and a generalist versus specialist approach to the overall structure of your curriculum.

There is a paucity of data to inform appropriate opioid prescribing for patients who are discharged after a hospital admission for a surgical procedure.We studied 333 inpatients discharged to home after bariatric, benign foregut, liver, pancreas, ventral hernia, and colon surgery. Chronic opioid users or patients who had complications were excluded. Home opioid usage was quantified in 90% of the remaining patients by questionnaires and phone surveys.Eighty-five percent of patients were prescribed an opioid and 38% of prescribed opioid pills were taken. Fifteen opioid pills satisfied the opioid needs of 88% of patients discharged on postoperative day (POD) 1. For patients discharged after POD 1, in multivariate analysis, the number of opioid pills used at home was associated with the number taken the day before discharge (p0.0001) and patient age (p = 0.006), but not the type of surgery. Forty-one percent of patients took no opioids the day before discharge, 33% took 1 to 3, and 26% took more than 4 pills. Eighty-five percent of patients' home opioid requirements would be satisfied using the following guideline: if no opioid pills are taken the day before discharge, no prescription is needed; if 1 to 3 opioid pills are taken the day before discharge, then a prescription for 15 opioid pills is given at discharge; and if 4 or more pills are taken the day before discharge, then a prescription for 30 opioid pills is given at discharge. If these guidelines were used, the number of opioid pills prescribed would decrease by 40%.For patients admitted after surgical procedures, post-discharge opioid use is best predicted by usage the day before discharge. Use of this guideline could decrease opioid prescriptions substantially and effectively treat patients' pain.

// Birthe Heitkotter 1, * , Konrad Steinestel 2, * , Marcel Trautmann 1 , Inga Grunewald 1 , Peter Barth 1 , Heidrun Gevensleben 3 , Martin Bogemann 4 , Eva Wardelmann 1 , Wolfgang Hartmann 1 , Kambiz Rahbar 5 and Sebastian Huss 1 1 Gerhard Domagk Institute of Pathology, University of Munster, Munster, Germany 2 Institute of Pathology, Military Hospital Ulm, Ulm, Germany 3 Institute of Pathology, Neuss, Germany 4 Department of Urology, University Hospital Munster, University of Munster, Munster, Germany 5 Department of Nuclear Medicine, University Hospital Munster, Munster, Germany * These authors contributed equally to this work Correspondence to: Sebastian Huss, email: sebastian.huss@ukmuenster.de Keywords: PSMA; thyroid cancer; tumor neoangiogenesis; prostate cancer Received: July 26, 2017 Accepted: November 15, 2017 Published: January 04, 2018 ABSTRACT Aim: PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods: Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results: PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors ( p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions: We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.

BACKGROUND A history of proliferative breast disease with atypia (PBDA) may be indicative of an increased risk not just of breast cancer but also of a more aggressive form of breast cancer. METHODS Multifocal breast cancer (MFBC), defined as 2 or more tumors in the same breast upon a diagnosis of cancer, is associated with a poorer prognosis than unifocal (single-tumor) breast cancer. PBDA, including atypical ductal hyperplasia and atypical lobular hyperplasia, is a known risk factor for breast cancer. Using New Hampshire Mammography Network data collected for 3567 women diagnosed with incident breast cancer from 2004 to 2014, this study assessed the risk of MFBC associated with a previous diagnosis of PBDA. RESULTS Women with a history of PBDA were found to be twice as likely to be subsequently diagnosed with MFBC as women with no history of benign breast disease (BBD; odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61). Ductal carcinoma in situ on initial biopsy was associated with a 2-fold increased risk of MFBC in comparison with invasive cancer (OR, 2.13; 95% CI, 1.58-2.88). BBD and proliferative BBD without atypia were not associated with MFBC. CONCLUSIONS Women with a history of previous PBDA may be at increased risk for MFBC. Women with a history of PBDA may benefit from additional presurgical clinical workup. Cancer 2018;124:1350-7. © 2017 American Cancer Society.

In order to identify cellular pathways associated with therapy-resistant aggressive lymphoma, we generated rituximab-resistant cell lines (RRCL) and found that the acquirement of rituximab resistance was associated with a deregulation in glucose metabolism and an increase in the apoptotic threshold leading to chemotherapy resistance. Hexokinase II (HKII), the predominant isoform overexpressed in cancer cells, has dual functions of promoting glycolysis as well as inhibiting mitochondrial-mediated apoptosis. We found that RRCL demonstrated higher HKII levels. Targeting HKII resulted in decreased mitochondrial membrane potential, ATP production, cell viability; and re-sensitization to chemotherapy agents. Analyzed gene expression profiling data from diffuse large B-cell lymphoma patients, high-HKII levels were associated with a shorter progression free survival (PFS) and/or overall survival (OS). Our data suggest that over-expression of HKII is associated with resistance to rituximab and chemotherapy agents in aggressive lymphoma and identifies this enzyme isoform as a potential therapeutic target.

Magnetic resonance (MR)-guided interventional robots have recently been developed for a variety of surgeries, such as biopsy, ablation, and brachytherapy. The actuators and encoders that power and track such robots must be MR conditional. In this paper, we propose an MR-conditional pneumatic motor with an integrated and custom-built fiber-optical encoder that provides powerful and accurate actuation. The motor is coupled with a modular plastic gearbox that provides a variety of gear ratio options so that the motor can be adapted to application requirements. With a 100:1 gear reduction at 0.55 MPa, the motor achieves 460 mN⋅m stall torque and 370 r/min no-load speed, which leads to the peak output power of 6 W. The motor has the bandwidth of approximately 1.1 and 3.5 Hz when connected to 8 and 0.2 m air hoses, respectively. The motor was tested in a 3T magnetic resonance imaging (MRI) scanner. No image artifact was observed and maximum signal-to-noise ratio (SNR) variation was less than 5%. Different from most of the existing MR-conditional pneumatic actuators, the proposed motor shape is more like the traditional electric motors, which offers more flexibility in the MR-conditional robot design.

Summary Treatment with dose-adjusted EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy and rituximab (DA-EPOCH-R) has become the standard of care for primary mediastinal B-cell lymphoma (PMBCL) at many institutions despite limited data in the multi-centre setting. We report a large, multi-centre retrospective analysis of children and adults with PMBCL treated with DA-EPOCH-R to characterize outcomes and evaluate prognostic factors. We assessed 156 patients with PMBCL treated with DA-EPOCH-R across 24 academic centres, including 38 children and 118 adults. All patients received at least one cycle of DA-EPOCH-R. Radiation therapy was administered in 14·9% of patients. With median follow-up of 22·6 months, the estimated 3-year event-free survival (EFS) was 85·9% [95% confidence interval (CI) 80·3–91·5] and overall survival was 95·4% (95% CI 91·8–99·0). Outcomes were not statistically different between paediatric and adult patients. Thrombotic complications were reported in 28·2% of patients and were more common in paediatric patients (45·9% vs. 22·9%, P = 0·011). Seventy-five per cent of patients had a negative fluorodeoxyglucose positron emission tomography (FDG-PET) scan at the completion of DA-EPOCH-R, defined as Deauville score 1–3. Negative FDG-PET at end-of-therapy was associated with improved EFS (95·4% vs. 54·9%, P

Wire-localized excision of nonpalpable breast cancer is imprecise, resulting in positive margins 25-30% of the time.Patients underwent preoperative supine magnetic resonance imaging (MRI). A radiologist outlined the tumor edges on consecutive images, creating a three-dimensional (3D) view of its location. Using 3D printing, a bra-like plastic form (the Breast Cancer Locator [BCL]) was fabricated, with features that allowed a surgeon to (1) mark the edges of the tumor on the breast surface; (2) inject blue dye into the breast 1 cm from the tumor edges; and (3) place a wire in the tumor at the time of surgery.Nineteen patients with palpable cancers underwent partial mastectomy after placement of surgical cues using patient-specific BCLs. The cues were in place in5 min and no adverse events occurred. The BCL accurately localized 18/19 cancers. In the 18 accurately localized cases, all 68 blue-dye injections were outside of the tumor edges. Median distance from the blue-dye center to the pathologic tumor edge was 1.4 cm, while distance from the blue dye to the tumor edge was5 mm in 4% of injections, 0.5-2.0 cm in 72% of injections, and2 cm in 24% of injections. Median distance from the tumor center to the BCL-localized wire and to the clip placed at the time of diagnosis was similar (0.49 vs. 0.73 cm) on specimen mammograms.Information on breast cancer location and shape derived from a supine MRI can be transferred safely and accurately to patients in the operating room using a 3D-printed form.

A number of national organizations have recently expressed interest in research to develop materials and devices that achieve greater energy storage capacity, power density and increased energy efficiency on the heels of a report finding that the pneumatic sector of the fluid power industry averages only 15% efficiency. One way of improving efficiency is the use of compressed air storage and recycling devices. The pneumatic Strain Energy Accumulator is a recently developed device that recycles exhaust gas from one pneumatic component, stores it in a highly efficient process, and reuses the stored exhaust gas at a constant pressure to power another pneumatic component. This work analyzes system efficiency increases directly attributable to the implementation of a pneumatic strain energy accumulator by applying an analytical methodology for system level efficiency improvement calculations, experimental validation, and compressed air savings projections. Experimentally determined efficiency increases ranged between 32% and 78%, demonstrating that the pneumatic strain energy accumulator can be a viable part of the solution to the fluid power efficiency challenge.

There is heightened interest in research to develop materials and devices that achieve greater energy storage capacity, power density and increased energy efficiency. This work analyses the performance of a novel energy storage device, the pneumatic strain energy accumulator (pSEA), which is designed to exploit the advantageous aspects of the non-linear behaviour of elastomeric materials. An analytical method for simultaneously characterising the pneumatic energy and strain energy stored in a strain energy accumulator (SEA), and more generally for pneumatic and strain energy systems, has been employed. Component efficiency along with the expansion and contraction pressures of the pSEA are determined experimentally so that a system level efficiency calculation can be performed. Incorporating uncertainty analysis, the efficiencies of the SEA are measured to be consistently over 93% in over 800 cycles of testing. The steady-state expansion and contraction pressures of the accumulator have steady-stat...

The effect of pre-operative MRI on the in-breast tumor recurrence rate (IBTR) of patients undergoing breast-conservation treatment (BCT) remains uncertain. We began to routinely perform pre-operative MRI in 2006. Our goal was to determine the effect of pre-operative MRI on IBTR. Retrospective review of a prospective database of all patients undergoing BCT (n = 1396) from 2000 to 2010. IBTR were calculated using Kaplan–Meier estimates. 664 (47.6%) patients underwent pre-operative MRI. The use of MRI increased from 13.9% in 2000–2005 to 80.7% in 2006–2010. Ten percent of patients who underwent MRI were found to have an additional ipsilateral cancer, with a mean diameter of 1.6 cm. The IBTR for patients with and without MRI were 4% vs. 8% at 8 years (p = 0.04). In multivariate analysis, radiation therapy and endocrine therapy were associated with decreased IBTR, but MRI was not (RR 0.77 (0.45–1.28)). For 1030 patients with invasive cancer, the IBTR at 8 years with and without MRI was 4.2% vs. 7.3% (p = 0.28). For 366 DCIS patients with and without MRI, the IBTR was 3.6% vs. 10.9% (p = 0.06). In the subgroup of DCIS patients who did not receive radiation, the IBTR with and without MRI was 0% vs. 18.2% (p = 0.08). Patients with an additional cancer found by MRI had a higher IBTR at 8 years (10.1% vs. 3.3%, p = 0.02). In a study analyzing BCT patients from one time period who rarely had a pre-operative MRI and a subsequent time period where most patients had MRI, the use of MRI was associated with a decrease in the IBTR on univariate, but not multivariate analysis. Patients who had additional cancers detected had a significantly higher IBTR.

This paper investigates the effects of gamma radiation on the operation of commercially available capacitive microelectromechanical accelerometers intended for use in robotic systems deployed for nuclear disaster remediation. Radiation-induced accelerometer degradation is examined in terms of its effects on the input–output relationship of ADXL325 accelerometers (Analog Devices, Inc., Norwood, Massachusetts, USA) prior to sensor failure. Results show a moderate increase in sensor nonlinearity as well as significant, non-monotonic changes to accelerometer axis sensitivity and zero- $g$ bias. Both part-to-part variation and axis-to-axis variation within individual accelerometers are observed. The effects of the observed accelerometer degradation on the performance of a simple robotic manipulator that relies on acceleration feedback are evaluated in simulation. Additionally, using tools derived from adaptive control theory, this paper presents a real-time recalibration technique for mitigating the effects of the measured accelerometer degradation on the performance of robotic systems that can be applied in-field, without the knowledge of the degradation mechanisms. An example implementation of this technique is also evaluated. Results suggest that control-based strategies for mitigating hardware degradation may be able to extend the useful operating lifetime of non-radiation-hardened sensors in robotic systems deployed in extreme radiation environments.

This paper presents the use of the power harvesting ratio (PHR) approach for evaluating the power harvesting capabilities of an electromagnetic vibration energy harvester. This is done for different electrical loads and measured bridge vibration data displaying multiple frequency components. Bridge vibration data are collected and characterized. The modes of the bridge are determined using a model sledge hammer, and the response of the bridge to a single vehicle is measured. Analysis of the data reveals that several of the modes contribute toward a response with multiple non-negligible frequency components. Measured bridge time-series data are then replayed on an experimental setup with an electromagnetic vibration energy harvester. Six electrical loads are implemented on the experimental platform: four passive loads and two active loads. The PHR approach is used to predict the average power from each load. Experimentally measured average power is within 6% of the predicted average power. The PHR approach is also used to successfully predict harvester instability for the active load dictated by the maximum power transfer theorem and validated experimentally. This paper demonstrates the utility of the PHR approach in evaluating harvester stability and performance for multifrequency excitations and sophisticated electrical loads, including active loads.

Background: Previous studies have demonstrated excellent results with FAB/LMB86 chemotherapy alone and in combination with rituximab in children, adolescents and young adults with mature B-NHL. (Cairo et al, JCO 2012, Goldman et al, Leukemia, 2013, Goldman et al, BJH 2014) The intermediate risk FAB/LMB Group B arm consists of 180mg/m2 of doxorubicin. This was reduced to 120mg/m2 with the addition of dose-dense rituximab. Other standard NHL regimens more commonly used in young adults with advanced stage mature B-NHL, such as R-CHOP, have a total dose doxorubicin of 360mg/m2. These approaches are associated with short term morbidities and long-term health conditions, including anthracycline induced cardiac toxicities.Dose-dense rituximab containing chemoimmunotherapy in high risk mature B-NHL has shown significant improvements in outcomes. We tested the hypothesis that rituximab can be used to even further reduce the burden of anthracycline from 120mg/m2 to 50mg/m2 in patients with good risk B-NHL. Objective: To safely reduce the burden of therapy by reducing the number of IT injections and reducing the total dose of doxorubicin from 120mg/m2 to 50mg/m2 with the addition of liposomal cytarabine and dose-dense rituximab to our prior chemotherapy backbone in children with good risk mature B-NHL. Design/Methods: Multi-institutional Phase II study (NCT01859819). Patients (3-31 years) with CD20+ B-NHL with good risk (FAB Group B GR=Stage I/II, Stage III with any LDH and Stage IV {BM tumor < 25%)}) were eligible. Staging was defined per the IPNHLSS as previously described. (Roselen et al, JCO 2015) All patients received FAB backbone chemotherapy with the addition of six rituximab (375mg/m2) doses; two doses prior to each of two induction courses and one dose prior to each of two consolidation courses. Cumulative doxorubicin was reduced from 120 to 50 mg/m2 (25mg/m2 per dose) total. After systemic methotrexate clearance, patients received age-based dosing of IT liposomal cytarabine resulting in a reduction of IT injections from nine to five. The primary outcome was safety and toxic deaths with an estimated 3-year survival above 90%, monitored by an independent DSMB. Response was defined per the IPNHLRC as previously described. (Sandlund et al, JCO 2015) Results: Twenty-five FAB Group B patients were enrolled at 5 treatment centers in the United States. Histology included DLBCL in 13 patients and Burkitt in 12 patients. Table 1. All patients had at least a 20% tumor decrease after the reduction phase. Two patients were upstaged to intensified Group C therapy after residual imaging findings post first consolidation. Therefore, 23/25 patients had a cumulative doxorubicin exposure of 50 mg/m2 while the two patients who received augmented treatment had a total exposure of 170 mg/m2. There were no serious adverse events reported with rituximab administration and no reported CNS or other toxicity reported with liposomal cytarabine intrathecal prophylaxis. During the two induction cycles there were no readmissions for febrile neutropenia or other causes and no reported grade III or higher mucositis. Follow up immune globulin levels on a smaller cohort of patients revealed median IgG levels of 821 (range, 362-1172) at a median follow up of 24 months. All patients are alive and in first remission with an EFS/OS = 100% at a median follow up of 4 years (range, 2-7yr). Figure 1. Echocardiograms revealed stable left ventricular function. Rituximab CSF levels were measured as we previously described and were extremely low (< 10µg/ml) compared to peak serum levels (250-400µg/ml). Conclusions: Our results demonstrate the feasibility of careful reduction of anthracycline dose intensity with the addition of dose-dense rituximab immunotherapy in children, adolescents and young adults with good risk mature B-NHL. Our results demonstrate a 100% EFS/OS with a reduction to only 50mg/m2 total dose of anthracycline. This is consistent with published standard of care outcomes utilizing much higher doses of 120-550mg/m2 of doxorubicin. Our treatment strategy benefits good risk patients with mature B-NHL by using dose-dense rituximab to reduce the cumulative exposure of anthracycline associated short- and long-term toxicities as well as the number of required intrathecal injections. These excellent results require the investigation of this approach in a larger cohort in the future to confirm these preliminary findings. Disclosures Goldman: Jazz Pharmaceuticals, Inc.: Speakers Bureau. Harker-Murray:Regerenon Pharmaceuticals: Consultancy. Cairo:Miltenyi: Research Funding; Technology Inc/Miltenyi Biotec: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Nektar Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Museums and Art exhibition spaces are adopting Artificial Intelligence (AI) systems to engage and attract visitors in several contexts. The use of AI can boost visitors’ attention, promote informal learning through conversations in front of the exhibits, and motivate visitors to act socially. In this paper, we describe a voice-based conversational system Iris+, in which visitors are inquired to answer questions to an agent. It is a proactive agent that invites visitors to reflect and take action to improve future world. First, we will describe how this system works. Second, we will show the outcomes of evaluation studies with visitors in situ and, a survey shows how visitors engaged in social action after interacting with IRIS+ and public demographics. Based on those visitors’ studies, we propose a set of challenges to design conversational systems in public spaces and the improvements were incorporated into the redesign of IRIS++.

Background Opioid prescribing guidelines for partial mastectomy (PM) and PM with sentinel lymph node biopsy (PM-SLNB) recommend prescribing anywhere from 0 to 15 oxycodone pills for postoperative pain. We sought to eliminate opioids after breast-conserving surgery. Study Design In January 2017, we implemented a perioperative pathway in which patients received (1) preoperative acetaminophen, (2) pre-incisional bupivacaine skin infiltration, (3) post-excision bupivacaine wound deposition, (4) intraoperative ketorolac, (5) instructions to use both acetaminophen and ibuprofen for postoperative analgesia, and (6) counseling to set the expectation that opioids would not be required. We measured the percentage of patients who received, filled, and used opioid prescriptions. We compared this to historical institutional data from 2016. Results There were 226 patients (mean age: 62 ± 13 years) who underwent surgery: 50% (114 of 226) underwent PM alone and 50% (112 of 226) PM-SLNB. Twenty-four patients (11%) required opioids in the recovery unit, and 14 (6%) were discharged home with a prescription. Five of the 14 patients (36%) did not fill their prescription. Among the patients who did fill their prescription, only 1 patient used opioids. In addition, 2 (1%) patients had difficulty managing their postoperative pain and were prescribed opioids within 7 days of surgery. Ultimately, 99% (223 of 226) of patients managed their postoperative pain after discharge without opioids. This represents a significant decrease in opioid use after breast conserving surgery, from 40% in 2016 to 1% after pathway implementation, p Conclusions When a multimodal nonopioid pain pathway was implemented, 99% of patients undergoing breast-conserving surgery did not require opioids after discharge.

Passive immunotherapy with therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer, especially hematological malignancies over the last 20 years. While use of mAbs has improved outcomes, development of resistance is inevitable in most cases, hindering the long-term survival of cancer patients. This review focuses on the available data on mechanisms of resistance to rituximab and includes some additional information for other mAbs currently in use in hematological malignancies. Mechanisms of resistance have been identified that target all described mechanisms of mAb activity including altered antigen expression or binding, impaired complement-mediated cytotoxicity (CMC) or antibody-dependent cellular cytotoxicity (ADCC), altered intracellular signaling effects, and inhibition of direct induction of cell death. Numerous approaches to circumvent identified mechanisms of resistance continue to be investigated, but a thorough understanding of which resistance mechanisms are most clinically relevant is still elusive. In recent years, a deeper understanding of the tumor microenvironment and targeting the apoptotic pathway has led to promising breakthroughs. Resistance may be driven by unique patient-, disease-, and antibody-related factors. Understanding the mechanisms of resistance to mAbs will guide the development of strategies to overcome resistance and re-sensitize cancer cells to these biological agents.

Though mechanical circulatory support (MCS) devices, such as ventricular assist devices and total artificial hearts (TAH), provide heart failure patients with bridges to heart transplantation or are alternatives to transplantation, device performance, and corresponding control strategies are often difficult to evaluate. Difficulties arise due to the complex interaction of multiple domains—i.e., biological, hydraulic, hemodynamics, electromechanical, system dynamics, and controls. In an attempt to organize, integrate and clarify these interactions, a technique often used in hydraulic pump design and robotics, called “bond graph modeling,” is applied to describe the performance and functionality of MCS devices and the interaction between the cardiovascular (CV) system and the MCS device. This technical brief demonstrates the advantages of this tool in formulating a model for the systemic circulation interacting with the left side of a TAH, adopting the fundamental structure of either a hydraulic mechanism (i.e., AbioCor/Carmat) or a pneumatic mechanism (i.e., SynCardia), combined with a systemic circulation loop. The model captures the dynamics of the membrane, the hydraulic source or pneumatic source, and the systemic circulation. This multidisciplinary cross-pollination of an analytical tool from the field of dynamic systems may provide important insight to further aid and improve the design and control of future MCS systems.

Although immunohistochemistry (IHC) has improved our ability to detect melanoma metastases in sentinel lymph nodes (SLN), the American Joint Committee on Cancer (AJCC) does not provide a lower threshold for determining if a SLN is positive for metastasis. Existing literature suggests that even a small aggregate or an enlarged, abnormal cell detectable by IHC can be associated with an adverse outcome. In our experience, however, some SLNs contain small solitary cells the size of neighboring lymphocytes demonstrable only by IHC. We sought to determine their clinical significance. A total of 821 patients underwent a SLN biopsy at our institution over a 12-year period. In all, 639 (77.8%) were SLN-negative, 125 (15.2%) were SLN-positive, and 57 (6.9%) had rare IHC-positive cells of undetermined clinical significance with no disease progression over a mean 59-month follow-up. Kaplan-Meier method with pair-wise comparisons revealed no significant difference in disease-specific survival and recurrence-free survival between SLN-negative and rare IHC-positive groups. There were significant differences in survival and recurrence between patients in the rare IHC-positive group and those with melanoma metastases, including those with solitary melanoma cells and those with tumor burdens ≤0.2 mm. While the lower diagnostic threshold for metastatic melanoma on IHC-stained sections needs to be studied further, our data suggest that rare IHC-positive cells lacking cytomorphologic features of overt malignancy are equivocal for melanoma and could impart a similar prognosis as patients with no evidence of SLN involvement.