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Management of craniofacial injuries typically defaults to plastic, ophthalmology, and oral maxillofacial surgeons which can challenge these surgical subspecialists' capacity to care for both trauma victims and non-trauma patients. Evaluating the need to transfer patients to a higher level of trauma care for isolated craniofacial injuries warrants investigation. Our 5-year retrospective study measured the frequency of craniofacial injuries and subsequent surgical interventions in elderly trauma patients' ≥65 years old. Eighty-one percent of patients consulted with plastic surgeons and 28% with ophthalmology. Twenty percent had craniofacial surgery with the majority of surgical interventions were in soft tissue (97%), mandible (48%), and Le Fort III (29%) injuries. A patient's ISS, GCS, head and face AIS, and presents of spinal or brain injury had no statistically significant impact on injury repair. Elderly patients with isolated craniofacial trauma may be better served by pretransfer consultation with a surgical subspecialist to determine the necessity.

When challenged by hypertonicity, dehydrated cells must recover their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless condensates, initiating a phosphorylation-dependent signal that drives net ion influx via the SLC12 cotransporters to restore cell volume. WNK1 condensate formation is driven by its intrinsically disordered C terminus, whose evolutionarily conserved signatures are necessary for efficient phase separation and volume recovery. This disorder-encoded phase behavior occurs within physiological constraints and is activated in vivo by molecular crowding rather than changes in cell size. This allows kinase activity despite an inhibitory ionic milieu and permits cell volume recovery through condensate-mediated signal amplification. Thus, WNK kinases are physiological crowding sensors that phase separate to coordinate a cell volume rescue response., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mouse models for the study of cancer immunology provide excellent systems in which to test biological mechanisms of the immune response against cancer. Historically, these models have been designed to have different strengths based on the current major research questions at the time. As such, many mouse models of immunology used today were not originally developed to study questions currently plaguing the relatively new field of cancer immunology, but instead have been adapted for such purposes. In this review, we discuss various mouse model of cancer immunology in a historical context as a means to provide a fuller perspective of each model's strengths. From this outlook, we discuss the current state of the art and strategies for tackling future modeling challenges.

CD4 T follicular helper (TFH) cells support B cells, which are critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found enrichment of TFH cell transcriptional signature correlates with GC B cell signature and with prolonged survival in individuals with lung adenocarcinoma (LUAD). We further developed a murine LUAD model in which tumor cells express B cell- and T cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells, as well as interleukin (IL)-21 primarily produced by TFH cells, are necessary for tumor control and effector CD8 T cell function. Development of TFH cells requires B cells and B cell-recognized neoantigens. Thus, tumor neoantigens can regulate the fate of tumor-specific CD4 T cells by facilitating their interactions with tumor-specific B cells, which in turn promote anti-tumor immunity by enhancing CD8 T cell effector functions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

“Stem-like” TCF1 + CD8 + T (T SL ) cells are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy, but, as tumors contain signals that should drive T cell terminal differentiation, how these cells are maintained in tumors remains unclear. In this study, we found that a small number of TCF1 + tumor-specific CD8 + T cells were present in lung tumors throughout their development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” (T cell inflamed) to “cold” (non–T cell inflamed). By contrast, most tumor-specific CD8 + T cells in tumor-draining lymph nodes (dLNs) had functions and gene expression signatures similar to T SL from chronic lymphocytic choriomeningitis virus infection, and this population was stable over time despite the changes in the TME. dLN T cells were the developmental precursors of, and were clonally related to, their more differentiated intratumoral counterparts. Our data support the hypothesis that dLN T cells are the developmental precursors of the TCF1 + T cells in tumors that are maintained by continuous migration. Last, CD8 + T cells similar to T SL were also present in LNs from patients with lung adenocarcinoma, suggesting that a similar model may be relevant in human disease. Thus, we propose that the dLN T SL reservoir has a critical function in sustaining antitumor T cells during tumor development and in protecting them from the terminal differentiation that occurs in the TME.

Kras-driven lung adenocarcinoma (LUAD) is the most common lung cancer. A significant fraction of patients with Kras-driven LUAD respond to immunotherapy, but mechanistic studies of immune responses against LUAD have been limited because of a lack of immunotherapy-responsive models. We report the development of the immunogenic KP × NINJA (inversion inducible joined neoantigen) (KP-NINJA) LUAD model. This model allows temporal uncoupling of antigen and tumor induction, which allows one to wait until after infection-induced inflammation has subsided to induce neoantigen expression by tumors. Neoantigen expression is restricted to EPCAM+ cells in the lung and expression of neoantigen was more consistent between tumors than when neoantigens were encoded on lentiviruses. Moreover, tumors were infiltrated by tumor-specific CD8 T cells. Finally, LUAD cell lines derived from KP-NINJA mice were immunogenic and responded to immune checkpoint therapy (anti-PD1 and anti-CTLA4), providing means for future studies into the immunobiology of therapeutic responses in LUAD., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Background: Chorionic villus sampling is an important invasive procedure used for early antenatal genetic testing that can be associated with anxiety and fear of pain. Pain analgesia prior to chorionic villus sampling can be offered with subdermal lidocaine; however, lidocaine injection itself is associated with pain. Our objective was to determine whether administration of topical ethyl chloride anesthetic spray is associated with decreased pain perception during transabdominal chorionic villus sampling compared to 1% lidocaine subdermal injection. Study design: Women undergoing transabdominal chorionic villus sampling from 10 to 13 weeks and 6 days in an outpatient setting were randomized with equal allocation to either 1% lidocaine injection or topical ethyl chloride anesthetic spray prior to the procedure. Women were asked about their pain on a scale of 0-100 prior to, during, and after the procedure. The primary outcome was pain perception during time of transabdominal chorionic villus sampling as measured on a 100-mm visual analog scale. The secondary outcome was pain immediately after procedure. Results: From October 2016 to June 2017, a total of 120 women were enrolled (63 in the lidocaine injection group and 57 in the topical ethyl chloride anesthetic spray group). Baseline demographic characteristics were similar between groups. During the procedure, patients in the topical ethyl chloride arm demonstrated significantly higher pain scores compared to the lidocaine injection group (median score of 50 mm (interquartile range [IQR]: 40-65) versus 50 mm (IQR: 30-60); p  = .03). There was no significant difference in pain scores before or after the procedure. Conclusion: During transabdominal chorionic villus sampling procedures, topical ethyl chloride anesthetic spray is associated with a higher distribution of pain scores as compared to 1% lidocaine subdermal injection, which suggests higher levels of pain. Clinical trial registration : This trial is registered with clinicaltrials.gov (NCT03140293). https://clinicaltrials.gov/ct2/show/NCT03140293?term=NCT03140293&rank=1.

Inducible expression of neoantigens in mice would enable the study of endogenous antigen-specific naïve T cell responses in disease and infection, but has been difficult to generate because leaky antigen expression in the thymus results in central T cell tolerance. Here we develop inversion-induced joined neoantigen (NINJA), using RNA splicing, DNA recombination and three levels of regulation to prevent leakiness and allow tight control over neoantigen expression. We apply NINJA to create tumor cell lines with inducible neoantigen expression, which could be used to study antitumor immunity. We also show that the genetic regulation in NINJA mice bypasses central and peripheral tolerance mechanisms and allows for robust endogenous CD8 and CD4 T cell responses on neoantigen induction in peripheral tissues. NINJA will enable studies of how T cells respond to defined neoantigens in the context of peripheral tolerance, transplantation, autoimmune diseases and cancer.

We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive K + intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K + -deficient, control, high-K + basic, or high-KCl diets for 10 days. Mice maintained on a K + -deficient diet exhibited no change in blood pressure, whereas K + -loaded mice developed an ~10-mmHg blood pressure increase. Following challenge with NaCl, K + -deficient mice developed a salt-sensitive 8 mmHg increase in blood pressure, whereas blood pressure was unchanged in mice fed high-K + diets. Notably, 10 days of K + depletion induced diabetes insipidus and upregulation of phosphorylated NaCl cotransporter, proximal Na + transporters, and pendrin, likely contributing to the K + -deficient NaCl sensitivity. While the anionic content with high-K + diets had distinct effects on transporter expression along the nephron, both K + basic and KCl diets had a similar increase in blood pressure. The blood pressure elevation on high-K + diets correlated with increased Na + -K + -2Cl - cotransporter and γ-epithelial Na + channel expression and increased urinary response to furosemide and amiloride. We conclude that the dietary K + maneuvers used here did not recapitulate the inverse effects of K + on blood pressure observed in human epidemiological studies. This may be due to the extreme degree of K + stress, the low-Na + -to-K + ratio, the duration of treatment, and the development of other coinciding events, such as diabetes insipidus. These factors must be taken into consideration when studying the physiological effects of dietary K + loading and depletion.

Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with local interleukin-12 (IL-12) microsphere (MS) immunotherapy results in marked tumor reduction and cures in multiple preclinical mouse models of PDA. Our findings demonstrate an increase of intratumoral interferon gamma (IFNγ) production following SBRT/IL-12 MS administration that initiates suppressor cell reprogramming and a subsequent increase in CD8 T cell activation. Furthermore, SBRT/IL-12 MS therapy results in the generation of systemic tumor immunity that is capable of eliminating established liver metastases, providing a rationale for follow-up studies in advanced metastatic disease., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate a single center's experience with adult patients who had cleft lip, cleft palate, or both. The authors aimed to identify common long-term needs in this patient population and evaluated the relationship of team-based care in meeting those needs. To do so, the authors retrospectively reviewed chart records from a single private practice and tertiary referral cleft center for all patients who were ≥15 years of age and who had a history of clefts of the lip or palate, or both, from January 1, 2013, to June 30, 2014. The authors compared the concerns of the patients who received cleft-team-based care by a single, multidisciplinary cleft team; multiple multidisciplinary cleft teams; or no formal cleft team. The authors analyzed data for 142 patients. The most common patient concerns were lip aesthetics (64%), nose aesthetics (61%), septal deviations (47%), nasal obstruction (44%), malocclusion (32%), oronasal fistulas (29%), and speech (21%). Oronasal fistulas were more commonly reported in the group of patients who had care by multiple teams (42.9%; P < .001). Malocclusion was more commonly reported in the group of patients who had care by multiple teams (50%; P = .001). The authors found that adult patients who have undergone rehabilitation for cleft lip and palate appear to have a common set of long-term needs. Multidisciplinary cleft-team-based care appears to be the most effective way to address these needs.

Objective: To quantify the degree of change in cervical length (CL) over a 3-minute transvaginal ultrasound., Study Design: We conducted a prospective observational study of nulliparous patients who underwent routine transvaginal CL screening at the time of their second-trimester ultrasound. We recorded CL at four time points (0, 1, 2, 3 minutes) and compared these values to determine the minute-to-minute change within a single patient., Results: A total of 771 patients were included. The mean gestational age was 20.8 weeks (±0.84). We used a linear mixed effect model to assess if each minute during the ultrasound is associated with a change in CL. The intraclass correlation coefficient between minute 0 to minute 3 was 0.82 (95% confidence interval: 0.80, 0.84). This indicates that there is a relatively high within-patient correlation in CL during their ultrasound. Additionally, we stratified patients based on their starting CL; the intraclass correlation coefficient remained high for all groups. We additionally compared CL at each minute. Although there is a statistically significant difference between several time points, the actual difference is small and not clinically meaningful., Conclusion: The variation in CL over a 3-minute transvaginal ultrasound examination is not clinically significant. It may be reasonable to conduct this examination over a shorter period., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose With the rise of opioid use disorder (OUD) among women of childbearing age, effective care models must address the complex needs of pregnant and postpartum women with OUD. This paper describes promising practices and implementation challenges from the Collaborative Outreach and Adaptable Care at Hallmark Health (COACHH) program, which utilizes a collaborative care team to coordinate outpatient care for pregnant and postpartum women with OUD. Description Semi-structured interviews were conducted with members of the COACHH team to discuss program logistics and takeaways. Interviews were coded to analyze themes. Assessment The COACHH team identified the need for specialized, time-intensive care coordination to address the unique needs of pregnant and postpartum women with OUD. First, the team prioritizes forming trusting relationships with patients to holistically understand patients' needs, improve patient engagement, and connect patients with resources. Second, the wide range of patient needs necessitates a team with diverse professional skills, whose members share an understanding of addiction and pregnancy. Third, finding the right quantitative outcome measurements is difficult; instead, success is measured in qualitative terms, stressing relationships and engagement as signals of change. Finally, the team encounters challenges with low referral rates, lack of provider awareness, and fragmented services. Conclusion We identified care delivery and program design considerations that may inform others who wish to coordinate care for pregnant and postpartum women with OUD. The program continues to face challenges enrolling patients and measuring outcomes, reflecting the need for tailored approaches and metrics for this population.

Objective: To assess available evidence regarding the use of oxytocin in conjunction with Foley balloon (FB) for cervical ripening., Methods: Databases from MEDLINE (U.S. National Library of Medicine, 1980-May 12, 2017), MEDLINE (Ovid, 1980-June 30, 2017), the Cochrane Library Controlled Trials Register, ClinicalTrials.gov, and Web of Science were queried for studies on FB cervical ripening with or without oxytocin in pregnant women. Search terms included: "balloon dilatation" OR "mechanical methods" OR "mechanical method" OR "mechanical dilation" OR "mechanical dilatation" OR "mechanical dilations" OR "mechanical dilatations" OR "balloon" OR "Foley" AND "Pitocin" OR "oxytocin." All relevant references were reviewed. Literature for inclusion and methodological quality were reviewed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines., Results: Out of 344 citations, six randomized clinical trials (1,133 patients) fulfilled our inclusion criteria. The pooled estimate showed that the cesarean delivery (CD) rate did not differ (relative risk [RR]: 0.91 (95% confidence interval [CI] [0.76-1.10]; p  = 0.23) between patients who underwent preinduction cervical ripening with FB alone versus those who received oxytocin in addition to FB. Heterogeneity was not significant among studies ( I 2 0.0%; p  = 0.64). Furthermore, no differences in other outcomes such as composite and maternal outcomes were detected between these two groups. Compared with simultaneous use of oxytocin with FB, the Foley alone cervical ripening group had a longer induction to delivery time, and lower deliveries within 12 and 24 hours. Subgroup analysis showed that only multiparous women in the Foley alone group had lower rate of vaginal delivery within 24 hours (RR: 0.74, 95% CI [0.61-0.89], p  = 0.002) along with a trend toward higher CD rates., Conclusion: Adding oxytocin to FB at the time of preinduction cervical ripening does not reduce cesarean rates nor improve maternal or neonatal outcomes. Multiparous women who received FB alone seem to have lower rates of vaginal deliveries within 24 hours, but these results should be interpreted with caution., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The factors that shape the distinctive tumor-immune landscapes of various types and subtypes of cancer remain poorly understood. In this issue of Immunity, Mollaoglu et al. (2018) reveal a mechanistic link between the function of lineage specifiers SOX2 and NKX2-1 and the presence of neutrophils in the tumor-immune microenvironment of lung cancer., (Copyright © 2018. Published by Elsevier Inc.)

Massachusetts' community hospitals face the challenge of achieving accountable care readiness with fewer financial and operational resources and a higher share of publicly-insured patients than their academic medical center counterparts. They are thus doubly constrained to make the investments necessary to perform in a value-based payment environment. Hallmark Health System and Lowell General Hospital are among 25 community hospital awardees engaged with the Massachusetts Health Policy Commission's Community Hospital Acceleration, Revitalization, and Transformation (CHART) investment program to implement clinical transformation programs to reduce unnecessary hospital utilization; enhance care for individuals with social, behavioral, and medical complexity; and improve post-acute community-based care, as means to advance accountable care readiness. The programs are payer-blind and designed to operate at-scale based on clinical and/or utilization criteria. Using examples from Hallmark Health System and Lowell General Hospital, we report on early lessons learned, representative of experiences from across the Phase 2 cohort: 1) locally-derived data enables hospitals to plan and implement action-oriented initiatives that are tailored to their communities; 2) investments in appropriate technologies facilitate near real-time patient engagement upon presentation to the acute care setting and/or immediately post-discharge; 3) non-medical providers are a cost-effective and high-value addition to complex care teams serving individuals with complex needs; and 4) collaboration with community partners improves care continuity and promotes stability outside the hospital-a promising approach to cost-effective population health management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Genetically engineered mouse models (GEMMs), in which autochthonous tumors develop into advanced-stage disease in the presence of a functional immune system, have contributed significantly to the understanding of most types of cancer. Using a GEMM of lung adenocarcinoma, we have found that immune cells are present in complex, highly organized, lymph node (LN)-like structures known as the tumor-associated tertiary lymphoid structures (TA-TLS). TA-TLS have been characterized in human lung cancer patients, but not in animal tumor models, and hence remain untapped targets for therapeutic interventions. We have shown that TA-TLS emerge as a result of tumor growth and that therapeutically depleting regulatory T cells (T regs ) from TA-TLS results in tumor elimination. Hence, a strong antitumor immune response exists but is suppressed in TA-TLS. Here, we describe a high-throughput immunofluorescence (IF) analysis pipeline for visualization and quantification of TA-TLS. Imaging the relatively small size of TA-TLS within tumor-bearing lung lobes using confocal microscopy is a labor-intensive process that can take up to 1 month. We have optimized this process and reduced the time required per lung lobe to 1-2 weeks using automated microscopy methods. Combining IF with multicolor fluorescence-activated cell sorting (FACS), we are able to interrogate not only the size and location of TA-TLS but also the activation status of immune cells within these structures. Using these techniques, investigation of TLS in lung adenocarcinoma combines cutting-edge technological tools in cancer biology and immunology to interrogate a fundamental, but poorly understood, tumor-associated immune structure.

Competing Interests: Conflict of Interest: None.

Although radiotherapy (RT) is widely used to control tumor growth across many cancer types, there is a relatively high incidence of RT failure exhibited by tumor recurrence, therefore a clear need exists to achieve improved effectiveness of RT. The RT-elicited immune response largely impacts the efficacy of RT and includes immune cells that kill tumor cells, but also immunosuppressive cells, which dampen anti-tumor immunity. Using murine models in which syngeneic tumor cell lines (Colon38, Glioma261, Line1) are grown intramuscularly and treated with 15 Gy local RT, we assessed the effects of RT on both the systemic and intratumoral immune response. Here we demonstrate that RT stimulates increased production of two chemokines, CCL2 and CCL5, at the tumor site. Further, that this leads to increased CCR2+ CCR5+ monocytes in circulation and subsequently alters the intratumoral immune infiltrate favoring the largely immunosuppressive CCR2+ CCR5+ monocytes. Importantly, a CCR2/CCR5 antagonist administered daily (15 mg/kg subcutaneously) starting two days prior to RT reduces both circulating and intratumoral monocytes resulting in increased efficacy of RT in radioresponsive tumors. Overall, these data have important implications for the mechanism of RT and present a means to improve RT efficacy across many cancer types.

Background: With an increasing rate of induction of labor, it is important to choose induction methods that are safe and efficient in achieving a vaginal delivery. The optimal method for inducing nulliparous women with an unfavorable cervix is not known., Objective: We sought to determine if induction of labor with simultaneous use of oxytocin and Foley balloon vs sequential use of Foley balloon followed by oxytocin decreases the time to delivery in nulliparous women., Study Design: We conducted a randomized controlled trial of nulliparous women presenting for induction at a single institution from December 2013 through March 2015. After decision for induction was made by their primary provider, women with gestational age ≥24 weeks with a nonanomalous, singleton fetus in vertex presentation with intact membranes were offered participation. Exclusion criteria included history of uterine surgery, unexplained vaginal bleeding, latex allergy, or contraindication to vaginal delivery. Participants were randomized to either simultaneous (oxytocin and Foley balloon) or sequential (oxytocin after expulsion of Foley balloon) induction group. The primary outcome was time from induction to delivery. Secondary outcomes included mode of delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, and composite neonatal outcome. Maternal and neonatal outcomes were collected via chart review. Analyses were done on an intention-to-treat basis., Results: A total of 166 patients were enrolled; 82 in the simultaneous and 84 in the sequential group. There were no differences in baseline characteristics in the 2 groups. Patients who received simultaneous oxytocin with insertion of a Foley balloon delivered significantly earlier (15.92 vs 18.87 hours, P = .004) than those in the sequential group. There was no difference in rate of cesarean delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, or composite neonatal outcome., Conclusion: Simultaneous use of oxytocin and Foley balloon for induction of labor results in a significantly shorter interval to delivery in nulliparas., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Based on anecdotal observations, there is concern that severe preeclampsia leads to greater morbidity and mortality for mothers and neonates of twin pregnancies than for mothers and neonates of singleton pregnancies. Because few studies have been done, this study compared maternal disease characteristics and maternal/neonatal clinical outcomes of twin and singleton pregnancies complicated by severe preeclampsia., Study Design: An historical cohort study of patients hospitalized at the Mount Sinai Hospital in New York City, NY, USA, from 2006 to 2010, compared 63 twin and 339 singleton pregnancies complicated by severe preeclampsia via chart review. Women were analyzed in two groups: hospitalized ≤34 weeks gestational age (GA) and hospitalized >34 weeks GA. Univariable analysis (using Chi-square test, Fisher's Exact test, Student's t-test, or Wilcoxon Rank-Sum test, as appropriate) then multivariable analysis (using multivariable linear regression or multivariable logistic regression, as appropriate) compared maternal disease characteristics and maternal/neonatal clinical outcomes in twin and singleton pregnancies., Results: Women with twins were older [mean age 34.9 years (standard deviation (SD) 7.9 years) vs. 29.4 years (SD 7.4 years), P-value<.001] and women with singletons had a higher prevalence of chronic hypertension (21% vs. 8%, P=.02) and higher prevalence of history of preeclampsia (13% vs. 2%, P=.006). Women with twins were admitted for severe preeclampsia at an earlier gestational age (GA) [median twin 34.9 weeks GA (interquartile range, IQR, 32.7, 36.1) vs. median singleton 37.1 weeks GA (IQR 35.0, 38.9), P<.001]. Among women presenting ≤34 weeks GA (27 twins; 108 singletons), women with singletons had a higher mean systolic blood pressure (BP) (181.1 vs. 163.5, P<.001), higher mean diastolic BP (108.4 vs. 100.1, P=.002), and higher prevalence of headache (56% vs. 30%, P=.02). Among women presenting >34 weeks GA (36 twins; 231 singletons), women with singletons had a higher prevalence of headache (54% vs. 28%, P=.004)., Conclusion: Mothers and neonates of twin pregnancies complicated by severe preeclampsia do not appear to have greater morbidity and mortality compared to mothers and neonates of singleton pregnancies complicated by severe preeclampsia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Education is to be provided efficiently and effectively according to guidelines in the United States by the Accreditation Council for Graduate Medical Education as core competencies and in Canada by the Royal College according to the CanMEDS framework. This article defines formative feedback, reviews the currently available validated feedback tools, and describes the future use of technology to enhance feedback in plastic surgery education.

Lithium toxicity results in a range of gastrointestinal and neurologic signs and symptoms and can ultimately be fatal. Serum lithium levels may be unreliable when evaluating patients for toxicity, since levels may not be elevated in patients on chronic lithium therapy. Serum lithium levels may also be artificially elevated if blood is collected in a tube containing lithium heparin. We present a case of a woman on chronic lithium therapy whose lithium level was artificially elevated due to blood collection in an incorrect tube., (© The Author(s) 2015.)

Background: The reliability of deep inferior epigastric artery perforator (DIEP) flap reconstruction following abdominal liposuction is controversial. The authors' early cases were technically successful; however, they experienced high partial flap loss and fat necrosis rates. The authors sought to compare DIEP flap outcomes in the setting of prior liposuction after the use of intraoperative indocyanine green angiography compared to when flaps were assessed on clinical grounds alone., Methods: A retrospective review of a consecutive series of DIEP flaps following liposuction at a single institution was performed, comparing those evaluated on clinical grounds alone and those in which indocyanine green angiography was used intraoperatively. Outcomes measured included anastomotic complications, total flap loss, partial flap loss, fat necrosis, and postoperative abdominal wounds., Results: Thirteen DIEP flaps following prior liposuction were performed on 11 patients from July of 2003 through January of 2014. All patients had preoperative imaging with duplex ultrasound or computed tomographic angiography to analyze perforator suitability before surgical exploration. Seven flaps were evaluated intraoperatively on clinical grounds alone. Six flaps were assessed and modified based on indocyanine green angiography. All flaps were successful; however, partial flap loss and fat necrosis rates dropped from 71.4 percent to 0 percent when indocyanine green angiography was used intraoperatively (p = 0.02)., Conclusions: Indocyanine green angiography is an excellent vascular imaging modality for intraoperative use to assess flap perfusion, and improves outcomes in DIEP flaps when harvested after prior abdominal suction lipectomy.

Radiation therapy (RT) continues to be a cornerstone in the treatment for many cancers. Unfortunately, not all individuals respond effectively to RT resulting clinically in two groups consisting of nonresponders (progressive disease) and responders (tumor control/cure). The mechanisms that govern the outcome of radiotherapy are poorly understood. Interestingly, a new paradigm has emerged demonstrating that the immune system mediates many of the antitumor effects of RT. Therefore, we hypothesized that the immune response following RT may dictate the efficacy of treatment. To examine this, we developed a tumor model that mirrors this clinically relevant phenomenon in which mice bearing Colon38, a colon adenocarcinoma, were treated locally with 15Gy RT resulting in both nonresponders and responders. More importantly, we were able to distinguish responders from nonresponders as early as 4 days post-RT allowing for the unique opportunity to identify critical events that ultimately determined the effectiveness of therapy. Intratumoral immune cells and interferon-gamma were increased in responsive tumors and licensed CD8 T cells to exhibit lytic activity against tumor cells, a response that was diminished in tumors refractory to RT. Combinatorial treatment with RT and the immunomodulatory cytokine IL-12 resulted in complete remission of cancer in 100% of cases compared to a cure rate of only 12% with RT alone. Similar data were obtained when IL-12 was delivered by microspheres. Therefore, the efficacy of RT may depend on the strength of the immune response induced after radiotherapy. Additionally, immunotherapy that further stimulates the immune cells may enhance the effectiveness of RT., (© 2013 UICC.)