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Increased exposure to ultraviolet radiation (UVR) is associated with an increased risk of nonmelanoma skin cancer. Cutaneous surgery can be negatively influenced by UVR, causing delayed wound healing, hyperpigmentation of the scar, and an increased incidence of additional skin cancers. By changing sun protection behavior, these risks can be limited. Therefore, this study evaluates changes in patients' sun protective behavior after Mohs micrographic surgery (MMS). Patients undergoing MMS between December 2017 and November 2019 were included. Patients were asked to complete the FACE-Q Skin Cancer - Sun Protection Behavior checklist before and 3 months and 1 year post-surgery. A total of 125 patients completed the pre-operative and 3-months post-operative checklists, and 89 (71.2%) completed the 1-year post-operative checklist. Reported sun protective behaviors increased post-surgery at all time points (p < 0.001). Patients with a prior history of facial skin cancer demonstrated a larger increase in sun protection behaviors after surgery than patients without a history of facial skin cancer (p = 0.04). Patients with defects located on the ear or scalp demonstrated a lesser increase in sun protection behaviors than patients with defects located in more conspicuous areas as the face (p = 0.02). Our study demonstrates a change in sun protection behavior, with an increase in sun protection behavior over time in patients after MMS. However, more improvement is possible. Targeted counseling can increase sun protection behavior in patients without a history of facial skin cancer and patients with skin cancer located on the ears or scalp.

Background Women undergoing cancer-related mastectomy and reconstruction are facing multiple treatment choices where post-surgical satisfaction with breasts is a key outcome. We developed and validated machine learning algorithms to predict patient-reported satisfaction with breasts at 2-year follow-up to better inform the decision-making process for women with breast cancer. Methods We trained, tested, and validated three machine learning algorithms (logistic regression (LR) with elastic net penalty, Extreme Gradient Boosting (XGBoost) tree, and neural network) to predict clinically important differences in satisfaction with breasts at 2-year follow-up using the validated BREAST-Q. We used data from 1553 women undergoing cancer-related mastectomy and reconstruction who were followed-up for two years at eleven study sites in North America from 2011 to 2016. 10-fold cross-validation was used to train and test the algorithms on data from 10 of the 11 sites which were further validated using the additional site's data. Area-under-the-receiver-operating-characteristics-curve (AUC) was the primary outcome measure. Results Of 1553 women, 702 (45.2%) experienced an improved satisfaction with breasts and 422 (27.2%) a decreased satisfaction. In the validation set (n = 221), the algorithms showed equally high performance to predict improved or decreased satisfaction with breasts (all P > 0.05): For improved satisfaction AUCs were 0.86–0.87 and for decreased satisfaction AUCs were 0.84–0.85. Conclusion Long-term, individual patient-reported outcomes for women undergoing mastectomy and breast reconstruction can be accurately predicted using machine learning algorithms. Our algorithms may be used to better inform clinical treatment decisions for these patients by providing accurate estimates of expected quality of life., Highlights • Optimal treatment for women undergoing mastectomy and reconstruction is unclear. • Can machine learning algorithms predict long-term patient-reported outcomes? • An international cohort of 1553 women was used for the algorithm development. • External validation showed good performance with AUCs of 0.84–0.87 • accurate estimates of expected quality of life may help inform treatment decisions.

Key Points Variation in initial systemic therapy for chronic graft-versus-host disease includes varied prednisone dose and use of nonsteroid agents.Prospective trials are needed to verify efficacy of reduced-dose prednisone or prednisone-free initial therapy approaches., Visual Abstract, Prior clinical trials largely considered prednisone 1 mg/kg per day with or without calcineurin inhibitor as standard initial therapy for chronic graft-versus-host disease (cGVHD), but uncertainty remains regarding the extent of practice variation and whether this affects subsequent outcomes. We assembled a cohort of 745 patients with cGVHD treated with initial systemic immune suppressive (IS) therapy from 3 prior cGVHD Consortium observational studies. Initial therapy was defined as first IS therapy started for cGVHD or prednisone increased to ≥0.4 mg/kg per day from lower doses within 30 days before cGVHD diagnosis to any time afterward. Initial therapies were nonprednisone IS therapies (n = 137, 18%), prednisone alone (n = 411, 55%), or prednisone plus other IS therapy (n = 197, 26%). In multivariate analysis, initial therapy group was not associated with failure-free survival (FFS; a composite of death, relapse, and new IS therapy), overall survival (OS), or nonrelapse mortality (NRM). Among the prednisone-based approaches, steroid dose was 1.25 mg/kg per day (13%). Prednisone dose within the patients treated with steroids was not significantly associated with FFS, OS, or NRM. No significant interactions were detected between overall cGVHD severity and either initial therapy group or prednisone dose for the outcomes of FFS, OS, or NRM. These observational data document heterogeneity in more contemporary cGVHD initial treatment practices, including prednisone dose and use of nonsteroid approaches. This variation was not associated with FFS, OS, or NRM. Prospective trials are needed to verify efficacy of reduced-dose prednisone or prednisone-free initial therapy approaches.

Purpose: A limited number of studies have examined the impact of type of axillary lymph node surgery on breast cancer-related lymphedema (BCRL) from the patient’s perspective. The objective of this study was to assess the impact of sentinel lymph node dissection (SLND) and axillary lymph node dissection (ALND) on the health-related quality of life (HRQOL) in women diagnosed with BCRL using a condition specific patient-reported outcome measure (PROM), the LYMPH-Q upper extremity (UE) module. Methods: Adult women diagnosed with BCRL were identified from the Danish National Health Data Authority database for the period 2008 to 2020 and were sent an online REDCap survey with the LYMPH-Q UE module. Information pertaining to axillary surgery was obtained from an online pathology repository. Multivariable linear regression was used to examine differences in the SLND and ALND groups on the LYMPH-Q UE scale scores. Results: Three thousand and fourty four women with BCRL were included in the analysis. The mean follow-up duration was 8.6 ± 5.15 years (range, 0–36 years). The majority of participants underwent ALND (n = 2805, 92.1%) and only 7.9% (n = 239) received SLND. The mean number of lymph nodes removed in the SLND group was 2.2 ± 1.4. No statistically significant difference was found in the two groups on the LYMPH-Q UE scale scores. Conclusion: There is no difference in women with upper extremity lymphedema after SLND or ALND on the LYMPH-Q UE module scales measuring arm symptoms, function, distress, and appearance.

PURPOSE Standard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy. PATIENTS AND METHODS One hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital. RESULTS Mean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed. CONCLUSION Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

Summary Background There is currently a lack of patient-reported outcome measures for ear reconstruction. We developed the EAR-Q to measure ear appearance and post-operative adverse effects from the patient perspective. Methods Field-test data were collected from children and young adults in eight countries between 13 May 2016 and 12 December 2019. Rasch measurement theory (RMT) analysis was used to refine the scales and to examine their psychometric properties. Results Participants had microtia (n = 607), prominent ears (n = 145) or another ear condition (n = 111), and provided 960 assessments for the Appearance scale (e.g., size, shape, photos), and 137 assessments for the Adverse Effects scale (e.g., itchy, painful, numb). RMT analysis led to the reduction of each scale to 10-items. Data fit the Rasch model for the Appearance (X2(80) = 90.9, p = 0.19) and Adverse Effects (X2(20) = 24.5, p = 0.22) scales. All items in each scale had ordered thresholds and good item fit. There was no evidence of differential item function for the Appearance scale by age, gender, language, or type of ear condition. Reliability was high for the Appearance scale, with person separation index (PSI) and Cronbach alpha values with and without extremes ≥0.92. Reliability for the Adverse Effects scale was adequate (i.e., PSI and Cronbach alpha values ≥0.71). Higher scores (liked appearance more) correlated with higher scores (better) on Psychological, Social and School scales. Interpretation The EAR-Q can be used in those 8–29 years of age to understand the patient perspective in clinical practice and research, and in addition, can be used to benchmark outcomes for ear reconstruction internationally.

Accurate measurement of healthcare costs is required to assess and improve the value of oncology care. We aimed to determine the cost of breast cancer care provision across collaborating health care organizations. We used time-driven activity-based costing (TDABC) to calculate the complete cost of breast cancer care—initial treatment planning, chemotherapy, radiation therapy, surgical resection and reconstruction, and ancillary services (e.g., psychosocial oncology, physical therapy)—across multiple hospital sites. Data were collected between December 2019 and February 2020. TDABC steps involved (1) developing process maps for care delivery pathways; (2) determine capacity cost rates for staff, medical equipment, and hospital space; (3) measure the time required for each process step, both manually through clinic observation and using data from the Real-Time Location System (RTLS); and (4) calculate the total cost of care delivery. Surgical care costs ranged from $1431 for a lumpectomy to $12,129 for a mastectomy with prepectoral implant reconstruction. Radiation therapy was costed at $1224 for initial simulation and patient education, and $200 for each additional treatment. Base costs for chemotherapy delivery were $382 per visit, with additional costs driven by chemotherapy agent(s) administered. Personnel expenses were the greatest contributor to the cost of surgical care, except in mastectomy with implant reconstruction, where device costs equated to up to 60% of the cost of surgery. The cost of complete breast cancer care depended on (1) treatment protocols; (2) patient choice of reconstruction; and (3) the need for ancillary services (e.g., physical therapy). Understanding the actual costs and cost drivers of breast cancer care delivery may better inform resource utilization to lower the cost and improve the quality of care.

Background A multiphased mixed-methods study was performed to develop and validate a comprehensive patient-reported outcome measure (PROM) for arm lymphedema in women with breast cancer (i.e., the LYMPH-Q Upper Extremity Module). Methods Qualitative interviews (January 2017 and June 2018) were performed with 15 women to elicit concepts specific to arm lymphedema after breast cancer treatment. Data were audio-recorded, transcribed, and coded. Scales were refined through cognitive interviews (October and Decemeber 2018) with 16 patients and input from 12 clinical experts. The scales were field-tested (October 2019 and January 2020) with an international sample of 3222 women in the United States and Denmark. Rasch measurement theory (RMT) analysis was used to examine reliability and validity. Results The qualitative phase resulted in six independently functioning scales that measure arm symptoms, function, appearance, psychological function, and satisfaction with information and with arm sleeves. In the RMT analysis, all items in each scale had ordered thresholds and nonsignificant chi-square p values. For all the scales, the reliability statistics with and without extremes for the Person Separation Index were 0.80 or higher, Cronbach’s alpha was 0.89 or higher, and the Intraclass Correlation Coefficients were 0.92 or higher. Lower (worse) scores on the LYMPH-Q Upper Extremity scales were associated with reporting of more severe arm swelling, an arm problem caused by cancer and/or its treatment, and wearing of an arm sleeve in the past 12 months. Conclusions The LYMPH-Q Upper Extremity Module can be used to measure outcomes that matter to women with upper extremity lymphedema. This new PROM was designed using a modern psychometric approach and, as such, can be used in research and in clinical care.

OBJECTIVE We implemented routine daily electronic monitoring of patient-reported outcomes (PROs) for 10 days after discharge after ambulatory cancer surgery, with alerts to clinical staff for worrying symptoms. We sought to determine whether enhancing this monitoring by adding immediate automated normative feedback to patients regarding expected symptoms would further improve the patient experience. SUMMARY OF BACKGROUND DATA PRO monitoring reduces symptom severity in cancer patients. In ambulatory cancer surgery, it reduces potentially avoidable urgent care center (UCC) visits, defined as those UCC visits without readmission. METHODS Patients undergoing ambulatory cancer surgery (n = 2624) were randomized to receive standard PRO monitoring or enhanced feedback. The primary study outcome was UCC visits without readmission within 30 days; secondary outcomes included patient anxiety and nursing utilization. RESULTS There was no significant difference in the risk of a potentially avoidable UCC visit [1.0% higher in enhanced feedback, 95% confidence interval (CI) -0.2-3.1%; P = 0.12]. There were similarly no significant differences in UCC visits with readmission or readmission overall (P = 0.4 for both). Patients randomized to enhanced feedback demonstrated a quicker reduction in anxiety (P < 0.001) and required 14% (95% CI 8-19%; P < 0.001) and 10% (95% CI 5-16%, P < 0.001) fewer nursing calls over 10 and 30 days postoperatively. CONCLUSIONS Providing patients with feedback about symptom severity during recovery from ambulatory cancer surgery reduces anxiety and nursing workload without affecting UCC visits or readmissions. These results support wider incorporation of normative feedback in systems for routine PRO monitoring.

The BREAST-Q is a patient-reported outcome measure for women with breast cancer. The aim of this study was to develop new BREAST-Q scales to measure Cancer Worry, Fatigue and Impact on Work. Data were collected between January 2017 and November 2019. Phase 1 (qualitative) included participants from Canada and the USA, pre/post any type of breast cancer treatment (surgery, adjuvant, neoadjuvant). Interviews were audio-recorded, transcribed verbatim and coded line-by-line. New scales were drafted and refined through cognitive interviews and expert input. Phase 2 (field-test study) involved USA members of the Love Research Army (LRA). Rasch measurement theory analysis was used to examine reliability and validity. In phase 1, 57 women were interviewed. Three concepts were identified as important to the breast cancer experience that are not currently covered in the BREAST-Q and developed into scales, i.e., Cancer Worry, Fatigue and Impact on Work. Feedback from nine women and 23 experts was used to establish content validity. The scales were field-tested in the LRA sample (n = 1680), of whom 1006 completed a test-retest. Reliability was > 0.81 for the person separation index, > 0.89 for Cronbach’s alpha and > 0.83 for interclass correlation coefficients. Lower scores on all three scales were significantly associated with being closer in time to diagnosis and having a higher cancer stage at diagnosis (p

Reconstructive techniques for restoring sensation to the breast after mastectomy continue to evolve. The BREAST-Q is a patient-reported outcome measure that can be used to evaluate outcomes of breast cancer treatments; however, it previously lacked scales to measure breast sensation. This paper outlines the development and validation of the BREAST-Q Sensation Module. Phase 1 (January 2017 through December 2018) involved qualitative and cognitive interviews with women who had undergone breast reconstruction, as well as expert input, to develop and refine the scales. In phase 2 (March through June 2019), Love Research Army (LRA) members completed the scales, and Rasch Measurement Theory (RMT) analysis was performed to examine the reliability and validity of the scales. In this study, 36 qualitative and 7 cognitive interviews were conducted, and input from 18 experts was obtained. Three scales were developed to measure breast Symptoms (e.g., throbbing, burning, tingling), Sensation (e.g., feeling with light touch, through clothing, sexually), and Quality of Life impact of sensation loss. In phase 2, 1204 LRA members completed the scales. Data for each scale fit the RMT model. Reliability was high, with Person Separation Index, Cronbach alpha, and intraclass correlation coefficient values of 0.81 or higher (with and without extremes) for all three scales. Mean scores were higher (better) on the Symptoms and Quality of Life impact scales for the participants with unilateral (vs. bilateral) and autologous (vs. alloplastic) reconstruction, and for the participants who were farther out from their reconstruction. The BREAST-Q Sensation Module can be used alone or in conjunction with other BREAST-Q scales to inform clinical care and to evaluate outcomes of new surgical approaches to restoration of breast sensation.

Environmental enrichment produces beneficial effects in the brain at genetic, molecular, cellular and behavior levels, and has long been studied as a therapeutic intervention for a wide variety of neurological disorders. However, the complexity of applying a robust environmental enrichment paradigm makes clinical use difficult. Accordingly, there has been increased interest in developing environmental enrichment mimetics, also known as enviromimetics. Here we review the benefits of environmental enrichment for migraine treatment, and discuss the potential of using extracellular vesicles derived from interferon gamma-stimulated dendritic cells as an effective mimetic.

To assess the impact of animation deformity on health-related quality of life, a content-specific, valid, and reliable patient-reported outcome measure is needed. This report describes the development and validation of the BREAST-Q Animation Deformity scale. Women with breast cancer who had an implant-based reconstruction provided data. In phase 1 (January 2017 and December 2018), qualitive and cognitive patient interviews and expert input were used to develop and refine scale content. In phase 2 (March to June 2019), a field test study with members of the Love Research Army (LRA) was conducted. Rasch Measurement Theory (RMT) analysis was used to examine psychometric properties. In phase 1 of the study, qualitative (n = 11) and cognitive (n = 4) interview data and expert input (n = 9) led to the development of a 12-item scale measuring animation deformity. In phase 2, 651 LRA members provided data and 349 participated in a test-retest study. In the RMT analysis, the data fit the Rasch model (X2(96) = 104.06; p = 0.27). The scale’s reliability was high, with person separation index and Cronbach alpha values with/without extremes of ≥ 0.84 and ≥ 0.92 respectively, and an intraclass correlation coefficient of 0.92 (95% confidence interval, 0.90–0.94). Mean scores on the Animation Deformity scale varied as predicted across subgroups of participants who reported differing amounts of change in breast appearance when their arms were lifted overhead or when they lifted something heavy, and for increasing happiness with the overall outcome of their breast reconstruction. The 12-item Animation Deformity scale forms a new scale in the BREAST-Q Reconstruction Module that can be used in comparative effectiveness research or to inform clinical care.

OBJECTIVE. To address the lack of validated patient-reported outcome (PRO) instruments that define and quantify patient expectations in thyroid cancer surgery, we developed and initially validated ThyroidEx, a novel disease-specific PRO instrument. STUDY DESIGN. Survey study. SETTING. Single-institution tertiary care cancer center. METHODS. An expert panel drafted an initial set of thyroid cancer–specific concepts, which was used in semistructured concept elicitation interviews with patients with thyroid cancer 4 weeks before and 8 weeks after surgery. Candidate items were generated per patient responses and refined via cognitive interviewing and additional review by the expert panel. The draft ThyroidEx was then preoperatively administered to a separate cohort undergoing thyroid cancer surgery to establish a final item set and initial psychometric evidence. RESULTS. Prospective concept elicitation interviews generated 358 patient-elicited concepts (n = 15 patients). These were then placed into 70 unique subcategories from which 41 items were generated for cognitive interviews with 20 patients preoperatively and 28 postoperatively. After expert panel review, ThyroidEx included 18 items across 2 scales (Expectations and Concerns), with an additional item about beliefs. In the preoperative cohort in phase 2 (n = 67), internal consistency Cronbach’s α values ranged from 0.81 to 0.89. Descriptive analysis showed significant differences between patients’ concerns and expectations and clinicians’ perceptions. CONCLUSION. Defining expectations represents an important modifier in the measurement of PROs. Preliminary validation of ThyroidEx revealed incongruent expectations between expert opinion and patients. Future development and implementation of ThyroidEx may affect preoperative consultation and the consent process.

Natural killer (NK) cells are an emerging cancer cellular therapy and potent mediators of antitumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in patients with acute myeloid leukemia (AML). However, the dynamic changes in phenotype that occur after NK-cell transfer that affect patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML NK cell–treated patients with AML using mass cytometry. These data identify a unique in vivo differentiated ML NK–cell phenotype distinct from conventional NK cells. Moreover, the inhibitory receptor NKG2A is a dominant, transcriptionally induced checkpoint important for ML, but not conventional NK-cell responses to cancer. The frequency of CD8α+ donor NK cells is negatively associated with AML patient outcomes after ML NK therapy. Thus, elucidating the multidimensional dynamics of donor ML NK cells in vivo revealed critical factors important for clinical response, and new avenues to enhance NK-cell therapeutics. Significance: Mass cytometry reveals an in vivo memory-like NK-cell phenotype, where NKG2A is a dominant checkpoint, and CD8α is associated with treatment failure after ML NK–cell therapy. These findings identify multiple avenues for optimizing ML NK–cell immunotherapy for cancer and define mechanisms important for ML NK–cell function. This article is highlighted in the In This Issue feature, p. 1775

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to aBCR-ABL1fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

New therapeutic approaches are needed to improve outcomes of patients with advanced chronic graft vs. host disease (GVHD). Pre-clinical and clinical data suggest proteasome inhibition may modulate GVHD. In a phase II, single-arm, multi-center trial conducted by the Chronic GVHD Consortium, we examined the efficacy of ixazomib in advanced chronic GVHD treatment. Ixazomib was given as a 4 mg oral dose weekly on days 1, 8, and 15 of a 28-day cycle for up to 6 total cycles. An amendment permitted additional cycles beyond 6 for those with responsive chronic GVHD. The primary endpoint was 6 month treatment failure, a composite endpoint including death, relapse, and requirement for an additional line of systemic immune suppressive (IS) therapy, compared with a historical 6 month treatment failure rate of 44% based on 312 patients treated with secondary therapy. Key eligibility criteria included age ≥ 18, NIH Consensus defined chronic GVHD, failure of at least one prior line of systemic IS therapy, and adequate hematologic parameters, hepatic, and renal function. A total of 50 subjects were enrolled at 6 institutions. Median age was 58 years. Median time from transplant to enrollment was 3.6 years (IQR 2.6-5.5), and from chronic GVHD onset to enrollment 2.8 years (IQR 1.5-4.3). Chronic GVHD was NIH moderate (16%) or severe (84%), predominantly classic (80% vs. overlap 20%), with 52% having 4 or more involved organs. Patients were heavily pretreated with 39 (78%) having 3 or more prior lines of systemic therapy for chronic GVHD. Of the 50 treated subjects, 26 completed all 6 months of planned therapy. Dose reductions most commonly occurred for thrombocytopenia, fatigue, diarrhea, and infection. SAEs occurred in 38% of subjects, and 5 deaths occurred in study participants (2 deemed possibly related to ixazomib). The 6 month treatment failure rate was significantly improved vs. the historical benchmark (28% vs. 44%, p=0.01), Figure 1. No patient, transplant, or chronic GVHD variables were significantly associated with 6 month treatment failure. NIH response rates at 3, 6, and 12 months are presented in Figure 2; the ORR was 34% (17/50) at 6 months. Overall survival at 6 and 12 months was 92% and 90%. No subjects completely discontinued IS by 12 months. Ixazomib met the primary endpoint of low treatment failure at 6 months in the setting of advanced chronic GVHD. At 6 months the ORR rate was 34% and 50% remained on ixazomib suggesting the low treatment failure rate was in part due to prevention of progressive disease that would have required additional treatment. Randomized studies are warranted.

Objectives: Although comorbidities play an essential role in risk adjustment and outcomes measurement, there is little consensus regarding the best source of this data. The aim of this study was to identify general patient-reported morbidity instruments and their measurement properties. Methods: A systematic review was conducted using multiple electronic databases (Embase, Medline, Cochrane Central, and Web of Science) from inception to March 2018. Articles focusing primarily on the development or subsequent validation of a patient-reported morbidity instrument were included. After including relevant articles, the measurement properties of each morbidity instrument were extracted by 2 investigators for narrative synthesis. Results: A total of 1005 articles were screened, of which 34 eligible articles were ultimately included. The most widely assessed instruments were the Self-Reported Charlson Comorbidity Index (n = 7), the Self-Administered Comorbidity Questionnaire (n = 3), and the Disease Burden Morbidity Assessment (n = 3). The most commonly included conditions were diabetes, hypertension, and myocardial infarction. Studies demonstrated substantial variability in item-level reliability versus the gold standard medical record review (κ range 0.66-0.86), meaning that the accuracy of the self-reported comorbidity data is dependent on the selected morbidity. Conclusions: The Self-Reported Charlson Comorbidity Index and the Self-Administered Comorbidity Questionnaire were the most frequently cited instruments. Significant variability was observed in reliability per comorbid condition of patient-reported morbidity questionnaires. Further research is needed to determine whether patient-reported morbidity data should be used to bolster medical records data or serve as a stand-alone entity when risk adjusting observational outcomes data.

Nipple-sparing mastectomy (NSM) is being performed increasingly for risk reduction in high-risk groups. There are limited data regarding complications and oncological outcomes in women undergoing bilateral prophylactic NSM. This study reviewed institutional experience with prophylactic NSM, and examined the indications, rates of postoperative complications, incidence of occult malignant disease and subsequent breast cancer diagnosis.Women who had bilateral prophylactic NSM between 2000 and 2016 were identified from a prospectively maintained database. Rates of postoperative complications, incidental breast cancer, recurrence and overall survival were evaluated.A total of 192 women underwent 384 prophylactic NSMs. Indications included BRCA1 or BRCA2 mutations in 117 patients (60·9 per cent), family history of breast cancer in 35 (18·2 per cent), lobular carcinoma in situ in 29 (15·1 per cent) and other reasons in 11 (5·7 per cent). Immediate breast reconstruction was performed in 191 patients. Of 384 NSMs, 116 breasts (30·2 per cent) had some evidence of skin necrosis at follow-up, which resolved spontaneously in most; only 24 breasts (6·3 per cent) required debridement. Overall, there was at least one complication in 129 breasts (33·6 per cent); 3·6 and 1·6 per cent had incidental findings of ductal carcinoma in situ and invasive breast cancer respectively. The nipple-areola complex was preserved entirely in 378 mastectomies. After a median follow-up of 36·8 months, there had been no deaths and no new breast cancer diagnoses.These findings support the use of prophylactic NSM in high-risk patients. The nipples could be preserved in the majority of patients, postoperative complication rates were low, and, with limited follow-up, there were no new breast cancers.La mastectomía con preservación del pezón (nipple-sparing mastectomy, NSM) se realiza cada vez más para reducir riesgos en los grupos de pacientes de alto riesgo. Se dispone de pocos datos sobre complicaciones y resultados oncológicos en mujeres sometidas a NSM bilateral profiláctica. Este estudio revisó la experiencia institucional de la NSM profiláctica, y analizó las indicaciones, tasas de complicaciones postoperatorias, incidencia de enfermedad maligna oculta y diagnóstico de subsiguiente cáncer de mama. MÉTODOS: Se identificaron mujeres sometidas a NSM bilateral profiláctica durante el periodo 2000-2016 a partir de una base de datos prospectiva. Se evaluaron tasas de complicaciones postoperatorias, cáncer de mama incidental, recidiva y supervivencia global.Un total de 192 mujeres fueron sometidas a 384 NSMs profilácticas. Las indicaciones incluyeron mutaciones BRCA1 o BRCA2 en 117 (61%) pacientes, historia familiar de cáncer de mama en 35 (18%), carcinoma lobulillar in situ en 29 (15%) y otros motivos en 11 (5,7%). La reconstrucción mamaria inmediata se realizó en 191 pacientes. De las 384 NSMs, 116 (30%) presentaron alguna evidencia de necrosis de la piel durante el seguimiento y la mayoría se resolvieron de forma espontánea, con solo 24 (6,2%) mamas que requirieron desbridamiento. Globalmente hubo al menos una complicación en 129 (34%) mamas; 3,6% y 1,6% tuvieron hallazgos incidentales de carcinoma ductal in situ o cáncer de mama invasivo, respectivamente. El complejo areola-pezón se preservó completamente en 378 mastectomías. Tras una mediana de seguimiento de 36,8 meses, no hubo fallecimientos ni ningún diagnóstico nuevo de cáncer de mama. CONCLUSIÓN: Estos hallazgos apoyan la utilización de la NSM profiláctica en pacientes de alto riesgo. En la mayoría pacientes fue posible la preservación del pezón, las tasas de complicaciones postoperatorias fueron bajas y, con un seguimiento limitado, no hubo nuevos casos de cáncer de mama.

Background Cellulite is a localized metabolic disorder of the subcutaneous tissue. To measure the impact of cellulite and its treatment(s) on patients’ health-related quality of life, a psychometrically sound patient-reported outcome measure is needed. Objectives The authors sought to develop and field test a new BODY-Q cellulite scale to measure the appearance of cellulite. Methods Appearance-related codes from the original BODY-Q qualitative interviews were reexamined, and a set of cellulite-specific items was developed and refined through cognitive patient interviews (n = 10) and expert input (n = 17). This scale was field-tested in adults with cellulite through 2 crowdworking platforms. Rasch Measurement Theory analysis was employed to refine the scale and examine its psychometric properties. Results The field-test sample included 2129 participants. The 15-item scale was reduced in length to 11 items. Data from the sample fit the Rasch model (X2 [99] = 21.32, P = 0.06). All items had ordered thresholds and mapped out a targeted clinical hierarchy. The reliability statistics for the person separation index was 0.94 and for Cronbach’s alpha was 0.97. In terms of validity, worse scores on the cellulite scale were associated with being more bothered by how the cellulite looked overall, having more severe cellulite on the Patient-Reported Photo-numeric Cellulite Severity Scale, and having more self-reported cellulite and more areas of the body with cellulite. Conclusions The BODY-Q cellulite scale can be utilized to measure appearance of cellulite and provides a solid basis for future studies evaluating the impact of cellulite and its treatment.

Background: Generic preference-based measures (pbms), though commonly used, may not be optimal for use in the economic evaluations assessing the impact of breast cancer interventions. Concerns that are unique to women with breast cancer (for example, body image, appearance, treatment-specific adverse effects) are not adequately captured by the existing generic measures. No breast cancer–specific pbm exists. The objective of this study was to construct a health state classification system specific to breast cancer which is amenable to valuation. Methods: We conducted semi-structured interviews in a heterogeneous sample of women with breast cancer [stages 0–4, any stage of treatment(s)]. Interviews were audio recorded, transcribed verbatim, and coded using the constant comparison approach to develop the conceptual framework. Patients were also asked to describe their most and least important concerns during the interview and to rate items in the related breast-q module (that is, mastectomy, breast-conserving therapy, or reconstruction) on a modified 5-point Likert scale (ranging from Not important to Very important). A faceto- face meeting with an expert panel of health care professionals, health economists, and hrqol researchers was used to obtain feedback on the health state classification system, response levels, and wording of the items. Results: Interviews (n = 59) with patients aged 59.9 years were completed. The resultant conceptual framework included site-specif ic (that is, abdomen, arm, breast) and overall (that is, body image, appearance, cancer, psychological, sexual, and social) domains. Triangulation of the qualitative and quantitative evidence led to the selection of key constructs for inclusion in the new pbm. The field test version of the breast-q utility health state classification system consisted of 13 attributes with 4 response levels each. Conclusions: The health state classification system for the preference-based module of the breast-q (breast-q-u) was derived using patient and expert feedback. The next phase will involve establishing psychometric properties of the breast-q-u, followed by a valuation study to generate utility weights.

Implementation of the 2014 National Institutes of Health (NIH) response algorithm for joint/fascia graft-versus-host disease (GVHD) has identified real-world limits to its application. To refine the 2014 NIH response algorithm, we analyzed multicenter prospective observational data from the Chronic GVHD Consortium. The training cohort included 209 patients and the replication cohort included 191 patients with joint/fascia involvement during their course of chronic GVHD. Linear mixed models with random patient effect were used to evaluate correlations between response categories and clinician- or patient-perceived changes in joint status as an anchor of response. Analysis of the training cohort showed that a 2-point change in total photographic range of motion (P-ROM) score was clinically meaningful. The results also suggested that a change from 0 to 1 on the NIH joint/fascia score should not be considered as worsening and suggested that both the NIH joint/fascia score and total P-ROM score, but not individual P-ROM scores, should be used for response assessment. On the basis of these results, we developed an evidence-based refined algorithm, the utility of which was examined in an independent replication cohort. Using the refined algorithm, ∼40% of responses were reclassified, largely mitigating most divergent responses among individual joints and changes from 0 to 1 on the NIH joint/fascia score. The refined algorithm showed robust point estimates and tighter 95% confidence intervals associated with clinician- or patient-perceived changes, compared with the 2014 NIH algorithm. The refined algorithm provides a superior, evidence-based method for measuring therapeutic response in joint/fascia chronic GVHD.

Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24–75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p

Obesity is a significant public health concern and clear risk factor for complications following breast reconstruction. To date, few have assessed patient-reported outcomes (PROs) focused on this key determinant. Our study aimed to investigate the impact of obesity (body mass index ≥ 30) on postoperative satisfaction and physical function utilizing the BREAST-Q in a cohort of autologous breast reconstruction patients. An Institutional Review Board-approved prospective investigation was conducted to evaluate PROs in patients undergoing autologous breast reconstruction from 2009 to 2017 at a tertiary academic medical center. The BREAST-Q reconstruction module was used to assess outcomes between cohorts preoperatively and at 6 months, 1 year, 2 years, and 3 years after reconstruction. Overall, 404 patients underwent autologous breast reconstruction with abdominal free-tissue transfer (244 non-obese, 160 obese) and completed the BREAST-Q. Although obese patients demonstrated lower satisfaction with breasts preoperatively (p = 0.04), no significant differences were noted postoperatively (p = 0.58). However, physical well-being of the abdomen was lower in the obese cohort compared with their non-obese counterparts at long-term follow-up (3 years; p = 0.04). Obesity significantly impacts autologous breast reconstruction patients. Although obese patients are more likely to present with dissatisfaction with breasts preoperatively, they exhibit comparable PROs overall compared with their non-obese counterparts, despite increased complications.

BACKGROUND This study aims to present normative values for satisfaction with breasts among preoperative breast reconstruction patients as assessed using the BREAST-Q instrument and to delineate factors associated with preoperative breast satisfaction. METHODS A retrospective analysis of prospectively collected data was performed examining women undergoing postmastectomy breast reconstruction at a tertiary care center who preoperatively completed the BREAST-Q from 2010 to 2017. Because breast satisfaction scores were nonnormally distributed, scores were categorized into quartiles for analysis. Patient- and treatment-level variables were tested in a multivariable ordinal logistic regression model as predictors of breast satisfaction. Preoperative satisfaction was also tested for association with choice of reconstructive modality. RESULTS Among 1306 postmastectomy reconstruction patients included in the study, mean preoperative Satisfaction with Breasts score was 61.8 ± 21.5 and the median score was 58.0 (interquartile range, 48 to 70). Factors associated with significantly lower preoperative satisfaction included history of psychiatric diagnosis, preoperative radiotherapy, marital status (married), and higher body mass index. Factors associated with significantly higher scores were malignancy (localized tumor), medium bra size (B to C cup), and self-identification as black. Preoperative breast satisfaction was lower among patients who elected autologous reconstruction than among those with implant reconstruction (p < 0.001). CONCLUSIONS Preoperative breast satisfaction is influenced by multiple factors. Understanding these factors may improve preoperative counseling and expectation management for patients who undergo postmastectomy breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity presented with different symptoms such as visual disturbances, headaches, seizures, severe hypertension and altered mental status. It has been recognized in a different pathological conditions, although preeclampsia/eclampsia is the most common cause of PRES. The pathogenesis of PRES is still not fully understood, but it seems that failure of cerebrovascular autoregulation causing vasogenic edema, cerebral vasoconstriction, and disruption of the blood brain barrier plays an important role. Cortical blindness, hypertensive retinopathy, serous retinal detachment (SRD), central retinal artery and vein occlusions, retinal or vitreous hemorrhages, anterior ischemic optic neuropathy (AION) and Purtscher’s retinopathy are ophthalmic disorders that may occur in PRES associated with preeclampsia. Among these, cortical blindness is the best documented complication of preeclampsia. Magnet resonance imaging (MRI) is a gold standard to establish the diagnosis of PRES because clinical findings are not sufficiently specific. Typically, there are bilateral cortical occipital lesions with hyperdensity on T2-weighted MRI. Blindness due to occipital lesions is reversible and the vision loss is usually regained within 4 h to 8 days.

Background: Skin cancer is among the most frequently occurring malignancies worldwide, which creates a great need for an effective patient-reported outcome measure. Providing shorter questionnaires reduces patient burden and increases patients' willingness to complete forms. The authors set out to use computerized adaptive testing to reduce the number of items needed to predict results for scales of the FACE-Q Skin Cancer Module, a validated patient-reported outcome measure that measures health-related quality of life and patient satisfaction in facial surgery. Methods: Computerized adaptive testing generates tailored questionnaires for patients in real time based on their responses to previous questions. The authors used an open-source computerized adaptive testing simulation software to run item responses for the five scales from the FACE-Q Skin Cancer Module (i.e., scar appraisal, satisfaction with facial appearance, appearance-related psychosocial distress, cancer worry, and satisfaction with information about appearance). Each simulation continued to administer items until prespecified levels of precision were met, estimated by standard error. Mean and maximum item reductions between the original fixed-length short forms and the simulated versions were evaluated. Results: The number of questions that patients needed to answer to complete the FACE-Q Skin Oncology Module was reduced from 41 items in the original form to a mean of 23 +/- 0.55 items (range, 15 to 29) using the computerized adaptive testing version. Simulated computerized adaptive testing scores maintained a high correlation (0.98 to 0.99) with the score from the fixed-length short forms. Conclusions: Applying computerized adaptive testing to the FACE-Q Skin Cancer Module can reduce the length of assessment by more than 50 percent, with virtually no loss in precision. It is likely to play a critical role in the implementation in clinical practice.

Introduction: Haploidentical peripheral blood allogeneic hematopoietic cell transplantation (PB haplo-HCT) can be complicated by graft-versus-host disease (GVHD) and cytokine release syndrome (CRS). Acute GVHD rates are higher with PB grafts compared with bone marrow, affecting 35-45% of patients and outcomes are poor in steroid refractory cases. Severe CRS occurs in 10-15% of patients receiving PB haplo-HCT and is associated with high non-relapse mortality and dismal one year overall survival between 25-30%. As interferon-γ and IL-6 are important mediators in both acute GVHD and CRS, we hypothesized that JAK1 inhibition with itacitinib could prevent these toxicities without impairing engraftment. Here we report the clinical outcomes from our pilot study of itacitinib with haplo-HCT (NCT03755414). Methods: Patients with AML, ALL, or NHL in remission undergoing PB haplo-HCT were treated with itacitinib 200 mg/day on days -3 through +100, followed by a taper. Myeloablative and reduced intensity conditioning were allowed. GVHD prophylaxis was tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide. Primary outcomes were incidence of primary graft failure and incidence of grade III-IV acute GVHD. Secondary outcomes included incidence and severity of CRS (graded by Lee criteria). Peripheral blood and serum samples were banked prior to conditioning and on days -1, 1, 3, 7, 14, 28, 60, 100, end of treatment, and time of diagnosis of acute GVHD. Matched control samples were collected from patients undergoing haplo-HCT off clinical trials. Correlative studies include flow cytometry (FACS) with five 28-color panels for cellular subsets, mass cytometry (CyTOF) with 40-colors for intracellular signaling events, single cell RNA sequencing, and serum cytokine and chemokine measurements. Results: Twenty of a planned 20 patients completed enrollment and underwent haplo-HCT between 11/2019 and 3/2021. Median age at transplant was 49 (21-74). Diagnoses were AML (13), ALL (5) and NHL (2). Median follow up is 319 days, with 18/20 beyond 180 days. There were no cases of engraftment failure with short median times to neutrophil (14 days, range 12-20) and platelet (14 days, range 7-54) engraftment (historical 16 and 25 days, respectively). There were no cases of grade III-IV acute GVHD. The incidence of grade II acute GVHD on day 100 was 15%. Two patients developed grade I-II skin acute GVHD during itacitinib taper and responded to resumption of a higher dose. There were no cases of extensive chronic GVHD. There were no cases of severe CRS (historical rate 17%), with 90% of patients having grade 1 CRS and 10% having no CRS. Furthermore, no anti-IL6R or steroid therapy was used. Overall survival at day 180 was 90% (95% CI 75-100%) by Kaplan-Meier estimate. Incidence of relapse at 180 days was 5.5% (95% CI 0-15.6%). Refined GVHD and relapse-free survival at 180 days was 83% (95% CI 68-100%). All patients had full donor engraftment and >95% chimerism at day 100. FACS and CyTOF have been performed and analyzed for the day 28 time point from 14 patients and four controls. Flow cytometry revealed no difference in cell subset numbers between controls and patient samples. CyTOF revealed differences in intracellular signaling molecules between itacitinib and control patients - including higher Ki-67, pNF-κB, and Caspase3 in controls. Phospho-Stat1 and pStat3 were lower CD4 T subsets. FACS and CyTOF at remaining time points, single cell RNA sequencing, and serum cytokine and chemokine measurements are underway and will be presented at the ASH 2021 meeting. Conclusions: Itacitinib with PB haplo-HCT was safe with no engraftment failure and prompt engraftment. Rates of acute and chronic GVHD were low, without increased risk of relapse or transplant related mortality. Severe CRS was not seen in this trial, and no anti-IL6 or steroid therapy was used. Flow cytometry demonstrated comparable immune reconstitution in terms of cell lineage and number between treated patients and controls. Mass cytometry revealed lower Ki-67, pNF-κB, and caspase3 levels, among other markers, which suggest lower immune cell activity, proliferation, and apoptosis. An extension cohort of 20 additional patients is enrolling. Multi-platform correlative studies are underway, comparing samples from haplo-HCT patients treated with and without itacitinib. Figure 1 Figure 1. Disclosures Uy: Astellas: Honoraria, Speakers Bureau; Novartis: Consultancy; Agios: Consultancy; Jazz: Consultancy; Genentech: Consultancy; AbbVie: Consultancy; GlaxoSmithKline: Consultancy; Macrogenics: Research Funding. Ghobadi: Atara: Consultancy; Amgen: Consultancy, Research Funding; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Jacoby: Abbvie: Research Funding; Jazz: Research Funding. Pusic: Syndax: Other: Advisory Board. Schroeder: Equillium Inc: Honoraria; Janssen: Honoraria; Sanofi Genzyme: Honoraria.

Background: Post-operative changes in eating behavior, eating-related distress and eating-related symptoms play an important role in the lives of bariatric surgery patients. However, there are no studies that assess these outcomes using a specifically designed patient-reported outcome measure (PROM) for patients undergoing bariatric surgery. We use our newly developed and validated scales as part of the well-established BODY-Q PROMs to compare laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass patients (LRYGB). Methods: We analyzed data from an international multi-center prospective cohort study of patients over 18 who underwent bariatric surgery. We used multivariable linear regression models to assess the difference between LRYGB and LSG for the new BODY-Q scales, which include eating behavior, eating-related distress and eating-related symptoms. All analyses were corrected for significant confounding variables. Results: Out of 1420 patients, 920 underwent LRYGB and 500 underwent LSG. The LRYGB group had a higher percentage total weight loss (p < 0.001). There was no significant difference in eating behavior (e.g., stop eating before feeling full, avoiding unhealthy snacks, etc.) or eating-related distress (e.g., feeling ashamed or out of control after eating). Patients who underwent LSG scored significantly better on the post-prandial eating-related symptoms scale (e.g., vomiting, reflux; p < 0.001). Symptoms more prevalent in the LRYGB patients were related to dumping syndrome whereas symptoms more prevalent in LSG patients were related to reflux. Conclusion: Patients who underwent LRYGB had a significantly better weight loss after surgery, but they scored worse on post-prandial symptoms in comparison to LSG patients. This information may be relevant for patients in the pre-operative counseling setting, as it may influence their decision for surgical procedure selection.

Objectives. This systematic review evaluates breast reconstruction options for women after mastectomy for breast cancer (or breast cancer prophylaxis). We addressed six Key Questions (KQs): (1) implant-based reconstruction (IBR) versus autologous reconstruction (AR), (2) timing of IBR and AR in relation to chemotherapy and radiation therapy, (3) comparisons of implant materials, (4) comparisons of anatomic planes for IBR, (5) use versus nonuse of human acellular dermal matrices (ADMs) during IBR, and (6) comparisons of AR flap types. Data sources and review methods. We searched Medline®, Embase®, Cochrane CENTRAL, CINAHL®, and ClinicalTrials.gov from inception to March 23, 2021, to identify comparative and single group studies. We extracted study data into the Systematic Review Data Repository Plus (SRDR+). We assessed the risk of bias and evaluated the strength of evidence (SoE) using standard methods. The protocol was registered in PROSPERO (registration number CRD42020193183). Results. We found 8 randomized controlled trials, 83 nonrandomized comparative studies, and 69 single group studies. Risk of bias was moderate to high for most studies. KQ1: Compared with IBR, AR is probably associated with clinically better patient satisfaction with breasts and sexual well-being but comparable general quality of life and psychosocial well-being (moderate SoE, all outcomes). AR probably poses a greater risk of deep vein thrombosis or pulmonary embolism (moderate SoE), but IBR probably poses a greater risk of reconstructive failure in the long term (1.5 to 4 years) (moderate SoE) and may pose a greater risk of breast seroma (low SoE). KQ 2: Conducting IBR either before or after radiation therapy may result in comparable physical well-being, psychosocial well-being, sexual well-being, and patient satisfaction with breasts (all low SoE), and probably results in comparable risks of implant failure/loss or need for explant surgery (moderate SoE). We found no evidence addressing timing of IBR or AR in relation to chemotherapy or timing of AR in relation to radiation therapy. KQ 3: Silicone and saline implants may result in clinically comparable patient satisfaction with breasts (low SoE). There is insufficient evidence regarding double lumen implants. KQ 4: Whether the implant is placed in the prepectoral or total submuscular plane may not be associated with risk of infections that are not explicitly implant related (low SoE). There is insufficient evidence addressing the comparisons between prepectoral and partial submuscular and between partial and total submuscular planes. KQ 5: The evidence is inconsistent regarding whether human ADM use during IBR impacts physical well-being, psychosocial well-being, or satisfaction with breasts. However, ADM use probably increases the risk of implant failure/loss or need for explant surgery (moderate SoE) and may increase the risk of infections not explicitly implant related (low SoE). Whether or not ADM is used probably is associated with comparable risks of seroma and unplanned repeat surgeries for revision (moderate SoE for both), and possibly necrosis (low SoE). KQ 6: AR with either transverse rectus abdominis (TRAM) or deep inferior epigastric perforator (DIEP) flaps may result in comparable patient satisfaction with breasts (low SoE), but TRAM flaps probably increase the risk of harms to the area of flap harvest (moderate SoE). AR with either DIEP or latissimus dorsi flaps may result in comparable patient satisfaction with breasts (low SoE), but there is insufficient evidence regarding thromboembolic events and no evidence regarding other surgical complications. Conclusion. Evidence regarding surgical breast reconstruction options is largely insufficient or of only low or moderate SoE. New high-quality research is needed, especially for timing of IBR and AR in relation to chemotherapy and radiation therapy, for comparisons of implant materials, and for comparisons of anatomic planes of implant placement.

Leukemia stem cells utilize cell adhesion molecules like CXCR4/CXCL12 to home to bone marrow stromal niches where they are maintained in a dormant, protected state. Dociparstat sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action, including inhibition of the CXCR4/CXCL12 axis, blocking HMGB1, and binding platelet factor 4 (PF-4). We conducted a pilot study adding DSTAT to azacitidine for patients with AML or MDS unresponsive to or relapsed after prior hypomethylating agent therapy, hypothesizing that DSTAT may improve response rates. Twenty patients were enrolled, with a median of 2 prior lines of therapy and 6 cycles of prior hypomethylating agents. Among fifteen patients evaluable for response, there was 1 complete remission, and 3 marrow complete remissions, for a response rate of 27 % among evaluable patients (20 % overall). Hematologic improvement was observed in 5 additional patients. The median overall survival for all enrolled patients was 205 days (95 % CI 119–302). While cytopenias and infections were common, these were not out of proportion to what would be expected in this population of patients undergoing treatment with azacitidine alone. In summary, this trial demonstrated the feasibility of combining DSTAT with azacitidine, with several responses observed, suggesting this combination warrants further study.

IMPORTANCE: Increasingly complex surgical procedures are being performed in the outpatient setting, increasing the burden on patients and caregivers to manage their postoperative symptoms. Electronic patient-reported symptom tracking may reduce this burden and help patients distinguish between expected symptoms and those requiring intervention. OBJECTIVE: To determine whether electronic symptom reporting with clinical alerts for 10 days after ambulatory cancer surgery is associated with a reduction in potentially avoidable urgent care visits, defined as a visit not leading to admission. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at the Josie Robertson Surgery Center (JRSC), Memorial Sloan Kettering Cancer Center’s ambulatory surgery center with overnight stay capacity from September 20, 2016, to December 31, 2018. Patients undergoing prostatectomy, nephrectomy, mastectomy with or without immediate reconstruction, hysterectomy, or thyroidectomy at the surgery center before (n = 4195) and after (n = 2970) implementation of the Recovery Tracker (RT) electronic postoperative symptom survey were included. Data analyses were conducted from February 1 to November 24, 2020. EXPOSURES: A short electronic survey assessing symptoms daily for 10 days after surgery, administered via the patient portal, with alerts to the clinical team and follow-up for concerning responses. MAIN OUTCOMES AND MEASURES: The main outcome was Memorial Sloan Kettering urgent care center visits with and without readmission and any readmission within 30 days after surgery. Nursing workload was measured by patient phone calls, emails, and secure messages as documented in the electronic medical record. RESULTS: A total of 7165 patients were analyzed, including 4195 (median age, 53 [interquartile range (IQR), 44-63] years; 3490 women [83%]) from the pre-RT implementation period and 2970 (median age, 56 [IQR, 46-65] years; 2221 women [75%]) from after full implementation. On multivariable, intent-to-treat analysis by study period, having surgery in the post-RT period was associated with a 22% decrease in the odds of an urgent care center visit without readmission (OR, 0.78; 95% CI, 0.60-1.00; P = .047). Having responded to at least 1 survey was associated with a 42% reduction in the odds of an urgent care center visit without readmission (OR, 0.58; 95% CI, 0.39-0.87; P = .007). There was no change in the risk of admission. Nursing calls increased by a mean of 0.86 (95% CI, 0.75-0.98) calls per patient after RT implementation (P

As high breast cancer survival rates are achieved nowadays, irrespective of type of surgery performed, prediction of long‐term physical, sexual, and psychosocial outcomes is very important in treatment decision‐making. Patient‐reported outcomes (PROs) can help facilitate this shared decision‐making. Given the significance of more personalized medicine and the growing trend on the application of machine learning techniques, we are striving to develop an algorithm using machine learning techniques to predict PROs in breast cancer patients treated with breast surgery. This short communication describes the bottlenecks in our attempt to predict PROs.

Objective Our objectives were to investigate case-mix adjusted hospital variations in 2-year clinical and patient-reported outcomes following immediate breast reconstruction. Background Over the past few decades, variations in medical practice have been viewed as opportunities to promote best practices and high-value care. Methods The Mastectomy Reconstruction Outcomes Consortium Study is an National Cancer Institute-funded longitudinal, prospective cohort study assessing clinical and patient-reported outcomes of immediate breast reconstruction after mastectomy at 11 leading medical centers. Case-mix adjusted comparisons were performed using generalized linear mixed-effects models to assess variation across the centers in any complication, major complications, satisfaction with outcome, and satisfaction with breast. Results Among 2252 women in the analytic cohort, 1605 (71.3%) underwent implant-based and 647 (28.7%) underwent autologous breast reconstruction. There were significant differences in the sociodemographic and clinical characteristics, and distribution of procedure types at the different Mastectomy Reconstruction Outcomes Consortium Study centers. After case-mix adjustments, hospital variations in the rates of any and major postoperative complications were observed. Medical center odds ratios for major complication ranged from 0.58 to 2.13, compared with the average major complication rate across centers. There were also meaningful differences in satisfaction with outcome (from the lowest to highest of -2.79-2.62) and in satisfaction with breast (-2.82-2.07) compared with the average values. Conclusions Two-year postoperative complications varied widely between hospitals following post-mastectomy breast reconstruction. These variations represent an important opportunity to improve care through dissemination of best practices and highlight the limitations of extrapolating single-institution level data and the ongoing challenges of studying hospital-based outcomes for this patient population.

INTRODUCTION: There is a subset of patients who initially had implant based breast reconstruction but later change to autologous reconstruction after failure of the implant reconstruction. The purpose of this study was to examine our series of patients in whom autologous reconstruction was performed after initial failed implant reconstruction, using the BREAST-Q to examine patient satisfaction and quality of life. METHODS: After Institutional Review Board approval, a retrospective chart review of a prospectively maintained database was performed as well as evaluation of BREAST-Q surveys. RESULTS: One hundred thirty-seven patients underwent autologous breast reconstruction following failed implant based reconstruction with 192 total flaps. Failure of implant reconstruction was defined as follows: capsular contracture causing pain and/or cosmetic deformity (n=106, 77%), dissatisfaction with the aesthetic result without capsular contracture (n=15, 11%), impending exposure of the implant/infection (n=8, 6%), and unknown (n=8, 6%). Complications requiring operative intervention included: partial flap loss (n=5, 3%), hematoma (n=5, 3%), vascular compromise requiring intervention for salvage (n=2, 1%), and total flap loss (n=1, 1%). Thirty-four patients (23%) had BREAST-Q surveys available for analysis both during implant and autologous phases of reconstruction. There was a statistically significant increase in satisfaction with appearance of breasts(p

Objective We developed, tested, and validated machine learning algorithms to predict individual patient-reported outcomes at 1-year follow-up to facilitate individualized, patient-centered decision-making for women with breast cancer. Summary background data Satisfaction with breasts is a key outcome for women undergoing cancer-related mastectomy and reconstruction. Current decision-making relies on group-level evidence which may lead to sub-optimal treatment recommendations for individuals. Methods We trained, tested, and validated three machine learning algorithms using data from 1921 women undergoing cancer-related mastectomy and reconstruction conducted at eleven study sites in North America from 2011 to 2016. Data from 1921 women undergoing cancer-related mastectomy and reconstruction were collected prior to surgery and at 1-year follow-up. Data from 10 of the 11 sites was randomly split into training and test samples (2:1 ratio) to develop and test three algorithms (logistic regression with elastic net penalty, Extreme Gradient Boosting tree, and neural network) which were further validated using the additional site's data.Accuracy and area-under-the-receiver-operating-characteristics-curve (AUC) to predict clinically-significant changes in satisfaction with breasts at 1-year follow-up using the validated BREAST-Q were the outcome measures. Results The three algorithms performed equally well when predicting both improved or decreased satisfaction with breasts in both testing and validation datasets: For the testing dataset median accuracy= 0.81 (range 0.73-0.83), median AUC= 0.84 (range 0.78-0.85). For the validation dataset median accuracy= 0.83 (range 0.81-0.84), median AUC= 0.86 (range 0.83-0.89). Conclusion Individual patient-reported outcomes can be accurately predicted using machine learning algorithms, which may facilitate individualized, patient-centered decision-making for women undergoing breast cancer treatment.

OBJECTIVES: Using a sample of pediatric chest radiographs (pCXR) taken to rule out pneumonia, we obtained diagnostic interpretations from physicians and used learning analytics to determine the radiographic variables and participant review processes that predicted for an incorrect diagnostic interpretation. METHODS: This was a prospective cross‐sectional study. A convenience sample of frontline physicians with a range of experience levels interpreted 200 pCXR presented using a customized online radiograph presentation platform. Participants were asked to determine absence or presence (with respective location) of pneumonia. The pCXR were categorized for specific image‐based variables potentially associated with interpretation difficulty. We also generated heat maps displaying the locations of diagnostic error among normal pCXR. Finally, we compared image review processes in participants with higher versus lower levels of clinical experience. RESULTS: We enrolled 83 participants (20 medical students, 40 postgraduate trainees, and 23 faculty) and obtained 12,178 case interpretations. Variables that predicted for increased pCXR interpretation difficulty were pneumonia versus no pneumonia (β = 8.7, 95% confidence interval [CI] = 7.4 to 10.0), low versus higher visibility of pneumonia (β = –2.2, 95% CI = –2.7 to –1.7), nonspecific lung pathology (β = 0.9, 95% CI = 0.40 to 1.5), localized versus multifocal pneumonia (β = –0.5, 95% CI = –0.8 to –0.1), and one versus two views (β = 0.9, 95% CI = 0.01 to 1.9). A review of diagnostic errors identified that bony structures, vessels in the perihilar region, peribronchial thickening, and thymus were often mistaken for pneumonia. Participants with lower experience were less accurate when they reviewed one of two available views (p

BACKGROUND. Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence. METHODS. This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months. RESULTS. The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain. CONCLUSIONS. This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.

BackgroundGeneric preference-based measures (PBM), though commonly used, may not be optimal for use in economic evaluations of breast cancer interventions. No breast cancer-specific PBM currently exists, and the generic PBMs fail to capture the unique concerns of women with breast cancer (e.g., body image, appearance, treatment-specific adverse effects). Hence, the objective of this study was to develop a breast cancer-specific PBM, the BREAST-Q Utility module.MethodsWomen diagnosed with breast cancer (stage 0–4, any treatment) were recruited from two tertiary hospitals in Canada and one in the US. The study followed an exploratory sequential mixed methods approach, whereby semi-structured interviews were conducted and at the end of the interview, participants were asked to list their top five health-related quality of life (HRQOL) concerns and to rate the importance of each item on the BREAST-Q. Interviews were audio-recorded, transcribed verbatim, and coded. Constant comparison was used to refine the codes and develop a conceptual framework. Qualitative and quantitative data were triangulated to develop the content of the Utility module that was refined through 2 rounds of cognitive debriefing interviews with women diagnosed with breast cancer and feedback from experts.ResultsInterviews were conducted with 57 women aged 55 ± 10 years. A conceptual framework was developed from 3948 unique codes specific to breasts, arms, abdomen, and cancer experience. Five top-level domains were HRQOL (i.e., physical, psychological, social, and sexual well-being) and appearance. Data from the interviews, top 5 HRQOL concerns, and BREAST-Q item ratings were used to inform dimensions for inclusion in the Utility module. Feedback from women with breast cancer (N = 9) and a multidisciplinary group of experts (N = 27) was used to refine the module. The field-test version of the HSCS consists of 10 unique dimensions. Each dimension is measured with 1 or 2 candidate items that have 4–5 response levels each.ConclusionThe field-test version of the BREAST-Q Utility module was derived from extensive patient and expert input. This comprehensive approach ensured that the content of the Utility module is relevant, comprehensive, and includes concerns that matter the most to women with breast cancer.

Infection or vaccination induces a population of long-lived bone marrow plasma cells (BMPCs) that are a persistent and essential source of protective antibodies1–5. Whether this population is induced in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. Recent reports have suggested that SARS-CoV-2 convalescent patients experience a rapid decay in their antigen-specific serum antibodies, raising concerns that humoral immunity against this virus may be short-lived6–8. Here we show that in patients who experienced mild infections (n=73), serum anti-SARS-CoV-2 spike (S) antibodies indeed decline rapidly in the first 3 to 4 months after infection. However, this is followed by a more stable phase between 4- and 8-months after infection with a slower serum anti-S antibody decay rate. The level of serum antibodies correlated with the frequency of S-specific long-lived BMPCs obtained from 18 SARS-CoV-2 convalescent patients 7 to 8 months after infection. S-specific BMPCs were not detected in aspirates from 11 healthy subjects with no history of SARS-CoV-2 infection. Comparable frequencies of BMPCs specific to contemporary influenza virus antigens or tetanus and diphtheria vaccine antigens were present in aspirates in both groups. Circulating memory B cells (MBCs) directed against the S protein were detected in the SARS-CoV-2 convalescent patients but not in uninfected controls, whereas both groups had MBCs against influenza virus hemagglutinin. Overall, we show that robust antigen specific long-lived BMPCs and MBCs are induced after mild SARS-CoV-2 infection of humans.

Migraine is a common headache disorder characterized by unilateral, intense headaches. In migraine with aura, the painful headache is preceded by focal neurological symptoms that can be visual, sensory, or motor in nature. Spreading depression (the most likely cause of migraine with aura and perhaps related headache pain) results in increased neuronal excitability and related increases in inflammation and production of reactive oxygen species. This in turn can promote the transformation of low-frequency, episodic migraine into higher-frequency and eventually chronic migraine. Though migraine affects 11% of adults worldwide, with 3% experiencing chronic headache, existing therapies offer only modest benefits. Here, we focus on the mechanisms by which environmental enrichment (i.e., volitionally increased intellectual, social, and physical activity) mitigates spreading depression. In prior work, we have shown that exposure to environmental enrichment reduces susceptibility to spreading depression in rats. This protective effect is at least in part due to environmental enrichment-mediated changes in the character of serum exosomes produced by circulating immune cells. We went on to show that environmental enrichment-mimetic exosomes can be produced by stimulating dendritic cells with low levels of interferon gamma (a cytokine that is phasically increased during environmental enrichment). Interferon gamma-stimulated dendritic cell exosomes (IFNγ-DC-Exos) significantly improve myelination and reduce oxidative stress when applied to hippocampal slice cultures. Here, we propose that they may also be effective against spreading depression. We found that administration of IFNγ-DC-Exos reduced susceptibility to spreading depression in vivo and in vitro, suggesting that IFNγ-DC-Exos may be a potential therapeutic for migraine.

Background: Lymphedema is a chronic and debilitating condition that affects many cancer survivors. Patient-reported outcome measures (PROMs) can give valuable insight into the impact of lymphedema on a patient’s quality of life and can play an essential role in treatment decisions. This study aims to (1) identify PROMs used to assess health-related quality of life (HRQoL) in patients with lymphedema; and (2) assess the quality of the lymphedema-specific PROMs. Methods: We performed a systematic search to identify articles on lymphedema, quality of life, and PROMs. An overview was created of all PROMs used to assess HRQoL in patients with lymphedema. The methodological quality of the lymphedema-specific PROMs was assessed using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria. Results: A total of 235 articles met the inclusion criteria, of which 200 described studies using one or more PROMs as an outcome measure in patients with lymphedema. The other 35 studies described the development and/or validation of a lymphedema-specific PROM. The COSMIN assessment demonstrated that none of these PROMs met all quality standards for development. Conclusion: The use of PROMs in lymphedema is increasing; however, based on our findings, we cannot fully support the use of any of the existing instruments. A well-developed lymphedema-specific PROM, based on patient input, is needed to gain better insight into the impact of this condition, and can be used to measure the effect of possible medical and surgical treatments.

BACKGROUND In the past decade, surgeons have increasingly advocated for a return to prepectoral breast reconstruction with claims that surgical mesh (including acellular dermal matrix) can reduce complication rates. However, numerous surgical and implant advancements have occurred in the decades since the initial prepectoral studies, and it is unclear whether mesh is solely responsible for the touted benefits. METHODS The authors conducted a systematic review of all English language articles reporting original data for prepectoral implant-based breast reconstruction. Articles presenting duplicate data were excluded. Complications were recorded and calculated on a per-breast basis and separated as mesh-assisted, no-mesh prior to 2006, and no-mesh after 2006 (date of first silicone gel-filled breast implant approval). Capsular contracture comparisons were adjusted for duration of follow-up. RESULTS A total of 58 articles were included encompassing 3120 patients from 1966 to 2019. The majority of the included studies were retrospective case series. Reported complication outcomes were variable, with no significant difference between groups in hematoma, infection, or explantation rates. Capsular contracture rates were higher in historical no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts. CONCLUSIONS Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are needed to better understand the specific role of mesh for these procedures. Existing data are inconclusive but suggest that prepectoral breast reconstruction can be safely performed without surgical mesh.

In most states, prehospital professionals (PHPs) are mandated reporters of suspected abuse but cite a lack of training as a challenge to recognizing and reporting physical abuse. We developed a learning platform for the visual diagnosis of pediatric abusive versus non-abusive burn and bruise injuries and examined the amount and rate of skill acquisition.This was a prospective cross-sectional study of PHPs participating in an online educational intervention containing 114 case vignettes. PHPs indicated whether they believed a case was concerning for abuse and would report a case to child protection services. Participants received feedback after submitting a response, permitting deliberate practice of the cases. We describe learning curves, overall accuracy, sensitivity (diagnosis of abusive injuries) and specificity (diagnosis of non-abusive injuries) to determine the amount of learning. We performed multivariable regression analysis to identify specific demographic and case variables associated with a correct case interpretation. After completing the educational intervention, PHPs completed a self-efficacy survey on perceived gains in their ability to recognize cutaneous signs of abuse and report to social services.We enrolled 253 PHPs who completed all the cases; 158 (63.6%) emergency medical technicians (EMT), 95 (36.4%) advanced EMT and paramedics. Learning curves demonstrated that, with one exception, there was an increase in learning for participants throughout the educational intervention. Mean diagnostic accuracy increased by 4.9% (95% CI 3.2, 6.7), and the mean final diagnostic accuracy, sensitivity, and specificity were 82.1%, 75.4%, and 85.2%, respectively. There was an increased odds of getting a case correct for bruise versus burn cases (OR = 1.4; 95% CI 1.3, 1.5); if the PHP was an Advanced EMT/Paramedic (OR = 1.3; 95% CI 1.1, 1.4) ; and, if the learner indicated prior training in child abuse (OR = 1.2; 95% CI 1.0, 1.3). Learners indicated increased comfort in knowing which cases should be reported and interpreting exams in children with cutaneous injuries with a median Likert score of 5 out of 6 (IQR 5, 6).An online module utilizing deliberate practice led to measurable skill improvement among PHPs for differentiating abusive from non-abusive burn and bruise injuries.

Summary Background The FACE-Q Craniofacial Module is a patient-reported outcome measure designed for patients aged 8 to 29 years with conditions associated with a facial difference. In part 1, we describe the psychometric findings for the original CLEFT-Q scales tested in patients with cleft and noncleft facial conditions. The aim of this study was to examine psychometric performance of new FACE-Q Craniofacial Module scales. Methods Data were collected between December 2016 and December 2019 from patients aged 8 to 29 years with conditions associated with a visible or functional facial difference. Rasch measurement theory (RMT) analysis was used to examine psychometric properties of each scale. Scores were transformed from 0 (worst) to 100 (best) for tests of construct validity. Results 1495 participants were recruited with a broad range of conditions (e.g., birthmarks, facial paralysis, craniosynostosis, craniofacial microsomia, etc.) RMT analysis resulted in the refinement of 7 appearance scales (Birthmark, Cheeks, Chin, Eyes, Forehead, Head Shape, Smile), two function scales (Breathing, Facial), and an Appearance Distress scale. Person separation index and Cronbach alpha values met criteria. Three checklists were also formed (Eye Function, and Eye and Face Adverse Effects). Significantly lower scores on eight of nine scales were reported by participants whose appearance or functional difference was rated as a major rather than minor or no difference. Higher appearance distress correlated with lower appearance scale scores. Conclusion The FACE-Q Craniofacial Module scales can be used to collect and compare patient reported outcomes data in children and young adults with a facial condition.

Objective This study sought to estimate the incidence and incidence rate of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) at a high-volume single institution, which enables vigorous long-term follow-up and implant tracking for more accurate estimates. Summary background data The reported incidence of BIA-ALCL is highly variable, ranging from 1 in 355 to 1 in 30,000 patients, demonstrating a need for more accurate estimates. Methods All patients who underwent implant-based breast reconstruction from 1991 to 2017 were retrospectively identified. The incidence and incidence rate of BIA-ALCL were estimated per patient and per implant. A time-to-event analysis was performed using the Kaplan-Meier estimator and life table. Results During the 26-year study period, 9373 patients underwent reconstruction with 16,065 implants, of which 9589 (59.7%) were textured. Eleven patients were diagnosed with BIA-ALCL, all of whom had a history of textured implants. The overall incidence of BIA-ALCL was 1.79 per 1000 patients (1 in 559) with textured implants and 1.15 per 1000 textured implants (1 in 871), with a median time to diagnosis of 10.3 years (range, 6.4-15.5 yrs). Time-to-event analysis demonstrated a BIA-ALCL cumulative incidence of 0 at up to 6 years, increasing to 4.4 per 1000 patients at 10 to 12 years and 9.4 per 1000 patients at 14 to 16 years, although a sensitivity analysis showed loss to follow-up may have skewed these estimates. Conclusions BIA-ALCL incidence and incidence rates may be higher than previous epidemiological estimates, with incidence increasing over time, particularly in patients exposed to textured implants for longer than 10 years.