Evaluating the Margins of Breast Cancer Tumors by Using Digital Breast Tomosynthesis with Deep Learning: A Preliminary Assessment.

BACKGROUND: The assessment information of tumor margins is extremely important for the success of the breast cancer surgery and whether the patient undergoes a second operation. However, conducting surgical margin assessments is a time-consuming task that requires pathology-related skills and equipment, and often cannot be provided in a timely manner. To address this challenge, digital breast tomosynthesis technology was utilized to generate detailed cross-sectional images of the breast tissue and integrate deep learning algorithms for image segmentation, achieving an assessment of tumor margins during surgery. METHODS: this study utilized post-operative tissue samples from 46 patients who underwent breast-conserving treatment, and generated image sets using digital breast tomosynthesis for the training and evaluation of deep learning models. RESULTS: Deep learning algorithms effectively identifying the tumor area. They achieved a Mean Intersection over Union (MIoU) of 0.91, global accuracy of 99%, weighted IoU of 44%, precision of 98%, recall of 83%, F1 score of 89%, and dice coefficient of 93% on the training dataset; for the testing dataset, MIoU was at 83%, global accuracy at 97%, weighted IoU at 38%, precision at 87%, recall rate at 69%, F1 score at 76%, dice coefficient at 86%. CONCLUSIONS: The initial evaluation suggests that the deep learning-based image segmentation method is highly accurate in measuring breast tumor margins. This helps provide information related to tumor margins during surgery, and by using different datasets, this research method can also be applied to the surgical margin assessment of various types of tumors.

Identifying Novel Inhibitors of Workplace Support and the Importance of Value Congruence and Feeling Valued in General Surgery Residency Training.

OBJECTIVE: To explore residents' perceptions of workplace support inhibitors and their relationship to resident wellbeing. We aim to provide evidence-based targets to inform future work operationalizing support in surgical training. DESIGN: This is a 2-part mixed-methods cross-sectional study. Part 1 analyzed qualitative data from focus groups (April 2021-May 2022). Part 2 comprised an online survey (informed by findings in Part 1, May 2022) to assess the association between perceived workplace support (e.g. feeling valued and value congruence) and poor individual global wellbeing (e.g. languishing). SETTING: National multi-center study including 16 ACGME-accredited academic programs. PARTICIPANTS: General surgery residents at all training levels, both clinical and research years. RESULTS: 28 residents participated in the focus groups which revealed three major themes around perceived inhibitors of workplace support: lack of trust in residency program (e.g. ulterior motives), poor communication from leadership (e.g. lack of transparency, ineffective dialogue), and unfair systems in residency training (e.g. exploitation of residents, paternal leave policies). These themes emphasized the importance of feeling valued and value congruence, with the latter reflected in the form of trust and communication with leadership, a key element of worker-workplace alignment. 251 residents responded to the survey (response rate 31%, 50.6% women) which revealed that a lower sense of feeling valued and lower perceived value congruence were significantly associated with languishing. CONCLUSIONS: Our findings suggest feeling valued and value congruence (specifically, having trust and communication with leadership) are important targets for increasing workplace support in surgical training, offering evidence-based targets for future work to operationalize support in surgical training.

LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD+ depletion.

Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD+) depletion in macrophages. Cholesterol-mediated NAD+ depletion induces macrophage senescence, promoting key features of age-related macular degeneration (AMD), including subretinal lipid deposition and neurodegeneration. NAD+ augmentation reverses cellular senescence and macrophage dysfunction, preventing the development of AMD phenotype. Genetic and pharmacological senolysis protect against the development of AMD and neurodegeneration. Subretinal administration of healthy macrophages promotes the clearance of senescent macrophages, reversing the AMD disease burden. Thus, NAD+ deficit induced by excess intracellular cholesterol is the converging mechanism of macrophage senescence and a causal process underlying age-related neurodegeneration.

Aqueous Macrophages Contribute to Conserved CCL2 and CXCL10 Gradients in Uveitis.

Purpose: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies. Design: Experimental study. Subjects: Biospecimens from patients with active or inactive uveitis and healthy controls. Methods: Protein concentration and single cell gene expression were assessed in aqueous fluid biopsies and plasma samples from deidentified patients with uveitis or healthy controls. Main Outcome Measures: The concentration of 31 inflammatory proteins was measured in all aqueous samples, as well as plasma samples from patients with active uveitis. Chemokine and cytokine ligand and receptor expression were assessed in individual cell types from aqueous biopsies obtained from patients with active uveitis. Results: We identified 6 chemokines that were both elevated in active uveitis compared with controls and enriched in aqueous compared with plasma during active uveitis (C-C motif chemokine ligand [CCL]2, C-X-C motif chemokine ligand [CXCL]10, CXCL9, CXCL8, CCL3, and CCL14), forming potential gradients for migration of immune cells from the blood to the eye. Of these, CCL2 and CXCL10 were consistently enriched in the aqueous of all patients in our cohort, as well as in a larger cohort of patients from a previously published study. These data suggest that CCL2 and CXCL10 are key mediators in immune cell migration to the eye during uveitis. Next, single cell RNA sequencing suggested that macrophages contribute to aqueous enrichment of CCL2 and CXCL10 during human uveitis. Finally, using chemokine ligand and receptor expression mapping, we identified a broad signaling network for macrophage-derived CCL2 and CXCL10 in human uveitis. Conclusions: These data suggest that ocular macrophages may play a central role, via CCL2 and CXCL10 production, in recruiting inflammatory cells to the eye in patients with uveitis. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular Degeneration.

Purpose: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined. The purpose of this study was to identify transcriptional signatures of circulating immune cells that are associated with high anti-VEGF treatment burden. Design: Experimental pilot study. Participants: Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System. Methods: We profiled by single cell RNA sequencing the peripheral blood mononuclear cells of 27 treatment-experienced patients with wet AMD. We stratified this cohort into 2 groups with low and high treatment burden (≤ 5 or ≥ 6 injections in the past 12 months, respectively). Main Outcome Measures: Identification of immune cells associated with high treatment burden. Results: Gene expression signature of CD16+ monocytes may be associated with high treatment burden. Conclusions: These studies delineate potential signatures of circulating immune cells that may be associated with high treatment burden in neovascular AMD, potentially informing the development of diagnostic predictors of anti-VEGF response and new precision medicine-based approaches to complement anti-VEGF therapies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

"It Gives Me Peace of Mind So I Can Focus on Healing": Views on Advance Care Planning for Older Surgical Patients.

Introduction: The period of time before an elective operation may be an opportune time to engage older adults in advance care planning (ACP). Past interventions have not been readily incorporated into surgical workflows leaving a need for ACP tools that are generalizable, easy to implement, and effective. Design: This is a qualitative study. Setting and Subjects: Older adults with a history of cancer and a recent major operation were recruited through their surgical oncologist at a tertiary medical center in the United States. Interviews were conducted to determine how to adapt the validated PrepareForYourCare.org ACP program with electronic health record prompts for the perioperative setting and openness to introducing ACP during a presurgical visit. We used qualitative content analysis to determine themes. Results: Eight themes were identified: (1) ACP as static and private, (2) people expected a prompt, (3) family trusted to do the "right" thing, (4) lack of relationship or comfort with providers, (5) a team-based approach can be helpful, (6) surgeon's expertise (e.g., prognosis and surgical risk), (7) ACP belongs on the surgical checklist, and (8) patients would welcome a conversation starter. Discussion: Older surgical patients are interested in engaging with ACP, particularly if prompted, and believe it has a place on the preoperative "checklist." Conclusions: To effectively engage patients with ACP, a combination of routine prompts by the health care team and patient-centered follow-up may be required.

Investigating Workplace Support and the Importance of Psychological Safety in General Surgery Residency Training.

OBJECTIVE: Workplace interventions that increase support can mitigate burnout, improve workplace satisfaction, and increase well-being. Our aim is to provide evidence-based targets to inform future work for operationalizing support in general surgery residency. DESIGN: This is a 2-part mixed-methods cross-sectional study. Part 1 analyzed qualitative data from focus groups (April 2021-May 2022). Part 2 comprised an online survey (informed by findings in Part 1) in May 2022 to assess the association between perceived psychological safety (PS) and flourishing, as well as PS and languishing. SETTING: National multi-center study including 16 ACGME-accredited academic programs. PARTICIPANTS: General surgery residents at various training levels, in both clinical and research. RESULTS: A total of 28 residents participated in the focus groups which revealed both enhancers and inhibitors of support pertaining to PS in the workplace. Enhancers of support included those currently implemented (i.e., allyship of mentors) and those proposed by residents (i.e., nonpunitive analysis of mistakes). Inhibitors of support included both systems (i.e., wellness initiatives as a 'band-aid' for systems issues) and culture (i.e., indefatigability, stoicism). About 251 residents (31%) responded to the survey which revealed higher perception of PS was significantly associated with flourishing at the level of residency program and departmental leadership. Lower perception of PS was significantly associated with languishing at the level of residency program leadership only. CONCLUSION: Our findings highlight the promotion of PS, such as expansion of mentorship to include advocacy (advocating on a resident's behalf, recognition when mistreated) and affirmation (i.e., soliciting opinions on controversial social matters/events, recognizing different life experiences), cultural acceptance of asking for help (without being perceived as weak), formal help navigating interpersonal dynamics (i.e., guidance from senior residents), and leadership presentations and modeling to destigmatize asking for help, as a means of operationalizing workplace support to increase flourishing and decrease languishing.

Targeting cell-type-specific, choroid-peripheral immune signaling to treat age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization of the choroidal vasculature (CNV). Although systemic immunity plays a role in AMD, the ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear cells from 65 individuals including AMD and controls, which we integrate with existing choroid data. We generate a network of choroid-peripheral immune interactions dysregulated in AMD, including known AMD-relevant gene vascular endothelial growth factor (VEGF) receptor 2. Additionally, we find CYR61 is upregulated in choroidal veins and may signal to circulating monocytes. In mice, we validate that CYR61 is abundant in endothelial cells within CNV lesions neighboring monocyte-derived macrophages. Mechanistically, CYR61 activates macrophage anti-angiogenic gene expression, and ocular Cyr61 knockdown increases murine CNV size, indicating CYR61 inhibits CNV. This study highlights the potential of multi-tissue human datasets to identify disease-relevant and potentially therapeutically modifiable targets.

Catalytic isoforms of AMP-activated protein kinase differentially regulate IMPDH activity and photoreceptor neuron function.

AMP-activated protein kinase (AMPK) plays a crucial role in maintaining ATP homeostasis in photoreceptor neurons. AMPK is a heterotrimeric protein consisting of α, ß, and γ subunits. The independent functions of the 2 isoforms of the catalytic α subunit, PRKAA1 and PRKAA2, are uncharacterized in specialized neurons, such as photoreceptors. Here, we demonstrate in mice that rod photoreceptors lacking PRKAA2, but not PRKAA1, showed altered levels of cGMP, GTP, and ATP, suggesting isoform-specific regulation of photoreceptor metabolism. Furthermore, PRKAA2-deficient mice displayed visual functional deficits on electroretinography and photoreceptor outer segment structural abnormalities on transmission electron microscopy consistent with neuronal dysfunction, but not neurodegeneration. Phosphoproteomics identified inosine monophosphate dehydrogenase (IMPDH) as a molecular driver of PRKAA2-specific photoreceptor dysfunction, and inhibition of IMPDH improved visual function in Prkaa2 rod photoreceptor-knockout mice. These findings highlight a therapeutically targetable PRKAA2 isoform-specific function of AMPK in regulating photoreceptor metabolism and function through a potentially previously uncharacterized mechanism affecting IMPDH activity.

Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.

Use of Magnetic Resonance Imaging for Evaluating Residual Breast Tissue After Robotic-Assisted Nipple-Sparing Mastectomy in Women With Early Breast Cancer.

OBJECTIVE: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer. MATERIALS AND METHODS: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence. RESULTS: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free. CONCLUSION: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT.

Loss of stearoyl-CoA desaturase 2 disrupts inflammatory response in macrophages.

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of Scd2 from macrophages dysregulated basal and bacterial lipopolysaccharide (LPS)-stimulated transcription of numerous inflammation-associated genes. Specifically, deletion of Scd2 from macrophages decreased basal and LPS-induced expression of Il1b transcript that corresponded to decreased production of precursor IL1B protein and release of mature IL1B. Furthermore, we identified disruptions in autophagy and depletion of unsaturated cardiolipins in SCD2-deficient macrophages. To assess the functional relevance of SCD2 in the macrophage response to infection, we challenged SCD2-deficient macrophages with uropathogenic Escherichia coli and found that there was impaired clearance of intracellular bacteria. This increased burden of intracellular bacteria was accompanied by increased release of pro-inflammatory cytokines IL6 and TNF but decreased IL1B. Taken together, these results indicate that macrophage expression of Scd2 is necessary for maintaining the macrophage response to inflammatory stimuli. This link between fatty acid metabolism and fundamental macrophage effector functions may potentially be relevant to diverse age-related pathologies. IMPORTANCE Macrophages are immune cells that respond to infection, but their dysfunction is implicated in many age-related diseases. Recent evidence showed that macrophage expression of a fatty acid enzyme, stearoyl-CoA desaturase 2, declines in aged organisms. In this work, we characterize the effects when stearoyl-CoA desaturase 2 is deficient in macrophages. We identify aspects of the macrophage inflammatory response to infection that may be affected when expression of a key fatty acid enzyme is decreased, and these findings may provide cellular insight into how macrophages contribute to age-related diseases.

Time is Short: Tools to Integrate Palliative Care and Communication Skills Education into Your Surgical Residency.

The need to integrate palliative care (PC) training into surgical education has been increasingly recognized. Our aim is to describe a set of PC educational strategies, with a range of requisite resources, time, and prior expertise, to provide options that surgical educators can tailor for different programs. Each of these strategies has been successfully employed individually or in some combination at our institutions, and components can be generalized to other training programs. Asynchronous and individually paced PC training can be provided using existing resources published by the American College of Surgeons and upcoming SCORE curriculum modules. A multiyear PC curriculum, with didactic components of increasing complexity for more advanced residents, can be applied based on available time in the didactic schedule and local expertise. Simulation-based training in PC skills can be developed to provide objective competency-based training. Finally, a dedicated rotation on a surgical palliative care service can provide the most immersive experience with steps toward clinical entrustment of PC skills for trainees.

Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.

BACKGROUND: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma. OBJECTIVE: We aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations. METHODS: Total IgE and HRF-reactive IgE/IgG as well as HRF in sera from patients with mild/moderate asthma or severe asthma (SA) and healthy controls (HCs) were quantified by ELISA. HRF secretion in culture media from RV-infected adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by Western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified. RESULTS: HRF-reactive IgE and total IgE levels were higher in patients with SA than in HCs, whereas HRF-reactive IgG (and IgG1) level was lower in asthmatic patients versus HCs. In comparison with HRF-reactive IgElow asthmatic patients, HRF-reactive IgEhigh asthmatic patients had a tendency to release more tryptase and prostaglandin D2 on anti-IgE stimulation of bronchoalveolar lavage cells. RV infection induced HRF secretion from adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections. CONCLUSIONS: HRF-reactive IgE is higher in patients with SA. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.

Experiences with targeting inpatient advance care planning for emergency general surgery patients: A resident-led quality improvement project.

BACKGROUND: For patients who may permanently or temporarily lose their ability to communicate preferences, advance care planning is a critical mechanism to guide medical decision-making but is currently underused among surgical patients. METHODS: A resident-led quality improvement project, including education and performance measurement, was conducted on an emergency general surgery service to increase the completion of inpatient advance care planning notes using a specialized template in the electronic health record. Advance care planning documentation was defined as either preadmission advance care planning documentation (eg, advance directive) or inpatient advance care planning (use of the electronic health record template). Data from patients admitted to the emergency general surgery service for 12+ hours were analyzed, and baseline data (July 2020 to June 2021) were compared with data from the intervention period (July 2021 to June 2022). The chart review evaluated the content of the inpatient advance care planning documentation from the intervention period. RESULTS: The frequency of inpatient advance care planning documentation increased (9.3%, n = 56 to 16.6%, n = 92, P < .001) with a greater contribution of inpatient advance care planning notes by the surgery team (16.7% to 55.4%) in the intervention period. Content analysis indicated that 79.0% of inpatient advance care planning notes listed preferences for life-sustaining therapy, 78.3% listed surrogacy, 57.3% listed overall health goals, and 50.3% listed treatment goals specific to the surgical encounter. CONCLUSION: Although a resident-led quality improvement project contributed to greater adoption of standardized inpatient advance care planning documentation on an emergency general surgery service, progress was slow, and integration into standard work was not achieved. Future efforts are needed to better understand the integration of essential advance care planning elements into workflows and to establish inclusive educational programming to prepare all team members for conducting and documenting advance care planning conversations.

Disparities in advance care planning rates persist among emergency general surgery patients: Current state and recommendations for improvement.

BACKGROUND: Unanticipated changes in health status and worsening of chronic conditions often prompt the need to consider emergency general surgery (EGS). Although discussions about goals of care may promote goal-concordant care and reduce patient and caregiver depression and anxiety, these conversations, as well as standardized documentation, remain infrequent for EGS patients. METHODS: We conducted a retrospective cohort study using electronic health record data from patients admitted to an EGS service at a tertiary academic center to determine the prevalence of clinically meaningful advance care planning (ACP) documentation (conversations and legal ACP forms) during the EGS hospitalization. Multivariable regression was performed to identify patient, clinician, and procedural factors associated with the lack of ACP. RESULTS: Among 681 patients admitted to the EGS service in 2019, only 20.1% had ACP documentation in the electronic health record at any time point during their hospitalization (of those, 75.5% completed before and 24.5% completed during admission). Two thirds (65.8%) of the total cohort had surgery during their admission, but none of them had a documented ACP conversation with the surgical team preoperatively. Patients with ACP documentation tended to have Medicare insurance (adjusted odds ratio, 5.06; 95% confidence interval, 2.09-12.23; p < 0.001) and had greater burden of comorbid conditions (adjusted odds ratio, 4.19; 95% confidence interval, 2.55-6.88; p < 0.001). CONCLUSION: Adults experiencing a significant, often abrupt change in health status leading to an EGS admission are infrequently engaged in ACP conducted by the surgical team. This is a critical missed opportunity to promote patient-centered care and to communicate patients' care preferences to the surgical and other inpatient medical teams. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Oncoplastic and reconstructive breast surgeon performance and impact on breast reconstructions: Clinical outcomes, learning curve, and patients' satisfaction.

BACKGROUND: Compared to mastectomy alone, the addition of breast reconstruction could improve quality of life and it is usually performed by two-team approach, which consisted of both breast surgeons and plastic surgeons. This study aims to illustrate the positive impacts of the dual-trained oncoplastic reconstructive breast surgeon (ORBS) and reveal the factors influencing reconstruction rates. METHODS: This retrospective study enrolled 542 breast cancer patients who undergone mastectomy with reconstruction performed by a particular ORBS between January 2011 and December 2021 at a single institution. Clinical and oncological outcomes, impact of case accumulation on performance and patient-reported aesthetic satisfactions were analyzed and reported. Furthermore, in this study 1851 breast cancer patients treated with mastectomy combined with or without breast reconstructions, which included 542 performed by ORBS, were reviewed to identify factors affecting breast reconstructions. RESULTS: Among the 524 breast reconstructions performed by the ORBS, 73.6% were gel implant reconstructions, 2.7% were tissue expanders, 19.5% were transverse rectus abdominal myocutaneous (TRAM) flaps, 2.7% were latissimus dorsi (LD) flaps, 0.8% were omentum flaps, and 0.8% involved LD flaps and implants. There was no total flap loss in the 124 autologous reconstructions, and the implant loss rate was 1.2% (5/403). Patient-reported aesthetic evaluations showed that 95% of the patients were satisfied. As the ORBS's accumulated case experiences, the implant loss rate decreased, and the overall satisfaction rate increased. According to the cumulative sum plot learning curve analysis, it took 58 procedures for the ORBS to shorten the operative time. In multivariate analysis, younger age, MRI, nipple sparing mastectomy, ORBS, and high-volume surgeon were factors related to breast reconstruction. CONCLUSION: The current study demonstrated that a breast surgeon after adequate training could become an ORBS and perform mastectomies with various types of breast reconstruction with acceptable clinical and oncological outcomes for breast cancer patients. ORBSs could increase breast reconstruction rates, which remain low worldwide.

Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis.

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with <15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise "adaptive regeneration." We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease.

Saline irrigation versus gauze wiping and suction only for peritoneal decontamination during laparoscopic repair for perforated peptic ulcer disease.

The aim of current single-center study was to compare the short-term outcome of suction and gauze wiping alone versus the irrigation and suction technique for peritoneal decontamination among patients who underwent laparoscopic repair of PPU. Using data from our institution's prospectively maintained database, 105 patients who underwent laparoscopic repair were enrolled in this study. The participants were further divided into the group who received peritoneal irrigation (irrigation group, n = 67) and group who received gauze wiping and suction only (suction only group, n = 38). The irrigation group had a longer operative time (140 vs. 113 min, p = 0.0001), higher number of drainage tubes (38.8% vs. 0%, p < 0.0001) and a higher incidence of intra-abdominal abscess (10.4% vs. 0%, p = 0.0469) than the suction only group. Peritoneal irrigation may be associated with a prolonged operative time and a higher number of abdominal drains. Meanwhile, gauze wiping and suction may be sufficient for peritoneal decontamination during the laparoscopic repair of PPU as further infectious complications are not observed.