Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

Cognitive performance and mortality among patients receiving autologous hematopoietic stem cell transplant.

OBJECTIVES: Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality. METHODS: Participants (N = 51; 11 patients deceased) completed tasks of processing speed, working memory, executive-mediated learning, and visual recall using the computerized CogState battery prior to HCT, 30 days post-autologous HCT, and 100 days post-autologous HCT. RESULTS: Slower processing speed (HR = 3.00) and more errors on an executive-mediated visual learning task (HR = 2.78) prior to HCT were associated with an increased risk of death following HCT. Our sample size limited longitudinal analyses of whether cognitive change predicted survival, however descriptive cognitive data of the deceased versus living patient's performances over time suggested different patterns of performance across groups. CONCLUSIONS: Pre-HCT cognition may have utility as an indicator of mortality risk following autologous HCT. More research is needed to examine whether cognitive changes after HCT could also predict mortality.

Comparison of the 3D-Exoscope and Operating Microscope in Mastoidectomy.

OBJECTIVES: The operating microscope (OM) commonly used in ear surgeries has several disadvantages, including a low depth of field, a narrow field of view, and unfavorable ergonomic characteristics. The exoscope (EX) was developed to overcome these disadvantages. Herein, we compared OM and EX during mastoidectomy and found out the feasibility of the EX. STUDY DESIGN: Prospective randomized comparative study. SETTING: Tertiary academic medical center. PATIENTS: Patients who had mastoidectomy for chronic otitis media with or without cholesteatoma between January 2022 and April 2022. INTERVENTION: Canal wall-up mastoidectomy (CWUM) or canal wall-down mastoidectomy (CWDM) using OM or EX without endoscope. MAIN OUTCOME MEASURES: Operative setting time (the time between the end of general anesthesia and incision), operative time (from incision to suture), postoperative audiologic outcomes, perioperative complications, and the decision to switch from EX to OM. RESULTS: Of 24 patients who were diagnosed with chronic otitis media or cholesteatoma, 12 each were randomly assigned to the OM or EX group. The mean operation time was 175 ± 26.5 minutes and 172 ± 34.6 minutes in the EX and OM group, respectively, which was not significantly different ( p = 0.843). The procedures in the EX group were successfully completed using a three-dimensional (3D)-EX without conversion to OM. All surgeries were completed without any complications. The postoperative difference in the air and bone conduction was 11.2 and 12.4 dB in the EX and OM groups, respectively, which was not significantly different ( p = 0.551). CONCLUSIONS: EX is comparable to OM in terms of surgical time, complications, and audiologic outcomes following mastoidectomy. The EX system is a potential alternative to OM. However, further improvements are required to overcome some drawbacks (deterioration of image resolution at high magnification, requirement of an additional controller for refocusing).

Caregiver self-efficacy providing nutritional support for pediatric patients undergoing hematopoietic stem cell transplant is associated with psychosocial factors.

Introduction: Caregiver self-efficacy in providing nutritional support to pediatric hematopoietic stem cell transplantation (HSCT) patients has been little studied despite the increased risk of these children potentially being over- or under-nourished after HSCT, and nutritional status could possibly affect treatment outcomes. The current study aimed to describe caregiver dietary self-efficacy and its associated psychosocial factors and barriers to following dietary recommendations. Methods: Caregivers completed questionnaires pre-HSCT and 30 days, 100 days, and one year post-HSCT. A subset provided a 24-h recall of food intake. Results: Results showed generally high caregiver confidence and low difficulty supporting their child nutritionally. However, lower confidence was associated with higher caregiver depression, anxiety, and stress 30 days post-HSCT. Further, higher difficulty at various time points was correlated with lower income, higher depression and anxiety, stress, and miscarried helping (i.e., negative caregiver-child interactions surrounding eating), as well as child overweight status and failure to meet protein intake guidelines. Nutritional criteria for protein, fiber, added sugar, and saturated fat were met by 65%, 0%, 75%, and 75%, respectively. Caregiver attitudes and child behavior were the most frequently reported barriers to healthy eating. Discussion: Results suggest that directing resources to caregivers struggling emotionally, economically, or transactionally could support pediatric patients undergoing HSCT in maintaining optimal nutritional status.

Return to school practices after hematopoietic cell transplantation: a survey of transplant centers in the United States.

To understand transplant center recommendations on return-to-school timing and related support for hematopoietic cell transplant (HCT) survivors, we conducted a two-phase, cross-sectional, web-based survey: In Phase I, medical directors of pediatric HCT centers from the National Marrow Donor Program/ Be The Match Registry were asked regarding the availability of a return to school standardized operating procedure (SOP). In Phase II, HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium were approached to study inter-physician practice variability regarding return to school post-HCT, factors affecting their decision-making, and support provided by HCT centers for return to school. Out of 46 respondents in Phase I (55% response rate), 28 (61%) reported having a SOP. Wide variations in recommendations were noted in 12 received SOPs. In Phase II, 122 physicians (60 centers) responded (30.6% response rate). The majority (60%) recommended autologous HCT recipients return to school within 6 months post-HCT but 65% recommended allogeneic HCT recipients return to school after 6 months or once off immunosuppression. Our findings indicate a lack of consensus within and across HCT centers regarding recommended return to school timing and underscore need for a guideline to standardize this process to ensure patient safety and re-integration into school.

Dyadic and Individual Variation in 24-Hour Heart Rates of Cancer Patients and Their Caregivers.

BACKGROUND: Twenty-four-hour heart rate (HR) integrates multiple physiological and psychological systems related to health and well-being, and can be continuously monitored in high temporal resolution over several days with wearable HR monitors. Using HR data from two independent datasets of cancer patients and their caregivers, we aimed to identify dyadic and individual patterns of 24 h HR variation and assess their relationship to demographic, environmental, psychological, and clinical variables of interest. METHODS: a novel regularized approach to high-dimensional canonical correlation analysis (CCA) was used to identify factors reflecting dyadic and individual variation in the 24 h (circadian) HR trajectories of 430 people in 215 dyads, then regression analysis was used to relate these patterns to explanatory variables. RESULTS: Four distinct factors of dyadic covariation in circadian HR were found, contributing approximately 7% to overall circadian HR variation. These factors, along with non-dyadic factors reflecting individual variation exhibited diverse and statistically robust patterns of association with explanatory variables of interest. CONCLUSIONS: Both dyadic and individual anomalies are present in the 24 h HR patterns of cancer patients and their caregivers. These patterns are largely synchronous, and their presence robustly associates with multiple explanatory variables. One notable finding is that higher mood scores in cancer patients correspond to an earlier HR nadir in the morning and higher HR during the afternoon.

Prospective Study of Nonsurgical Auricular Correction According to Timing of Treatment.

BACKGROUND AND PURPOSE: Many studies recommend nonsurgical auricular correction during the early postnatal period, when cartilage plasticity is high; however, many patients are not eligible for the procedure. This study compared different timings of nonsurgical auricular correction to investigate benefit after the optimal period for correction. METHODS: In this prospective study, 53 ears from 35 patients with congenital auricular anomaly were assigned to two groups according to age at correction: the "early-group" with correction within 2 weeks of birth and "late-group" with correction 8 weeks after birth. Aesthetic outcomes, caregiver satisfaction, detachment rates and mean device-wearing periods, were compared. RESULTS: Thirty-one ears from 20 patients comprised the early-group, and 18 ears from 12 patients comprised the late-group. Mean time to treatment after birth was 9.09 days in the early-group and 134.7 days in the late-group. In the early-group, detachment occurred in 4/31 ears (12.9%), and in the late-group, detachment occurred in 12/18 ears (66.7%), which was statistically significant (p<0.01). The average period of applying devices was 4.7 ± 1.2 weeks in the early-group and 8.5 ± 4.1 weeks in the late-group, with a significantly longer treatment time in the late-group (p=0.001). The early-group had 87.1% "good" results vs. 55.6% in the late-group, with a statistically significant difference. CONCLUSIONS: The correction period was shorter, detachment rate was lower, and treatment outcome was better in the early-group. However, successful correction was also present in the late-group, showing that the patients who have passed the optimum correction period should proceed after counselling.

The Dosing of Mobile-Based Just-in-Time Adaptive Self-Management Prompts for Caregivers: Preliminary Findings From a Pilot Microrandomized Study.

BACKGROUND: Caregivers of people with chronic illnesses often face negative stress-related health outcomes and are unavailable for traditional face-to-face interventions due to the intensity and constraints of their caregiver role. Just-in-time adaptive interventions (JITAIs) have emerged as a design framework that is particularly suited for interventional mobile health studies that deliver in-the-moment prompts that aim to promote healthy behavioral and psychological changes while minimizing user burden and expense. While JITAIs have the potential to improve caregivers' health-related quality of life (HRQOL), their effectiveness for caregivers remains poorly understood. OBJECTIVE: The primary objective of this study is to evaluate the dose-response relationship of a fully automated JITAI-based self-management intervention involving personalized mobile app notifications targeted at decreasing the level of caregiver strain, anxiety, and depression. The secondary objective is to investigate whether the effectiveness of this mobile health intervention was moderated by the caregiver group. We also explored whether the effectiveness of this intervention was moderated by (1) previous HRQOL measures, (2) the number of weeks in the study, (3) step count, and (4) minutes of sleep. METHODS: We examined 36 caregivers from 3 disease groups (10 from spinal cord injury, 11 from Huntington disease, and 25 from allogeneic hematopoietic cell transplantation) in the intervention arm of a larger randomized controlled trial (subjects in the other arm received no prompts from the mobile app) designed to examine the acceptability and feasibility of this intensive type of trial design. A series of multivariate linear models implementing a weighted and centered least squares estimator were used to assess the JITAI efficacy and effect. RESULTS: We found preliminary support for a positive dose-response relationship between the number of administered JITAI messages and JITAI efficacy in improving caregiver strain, anxiety, and depression; while most of these associations did not meet conventional levels of significance, there was a significant association between high-frequency JITAI and caregiver strain. Specifically, administering 5-6 messages per week as opposed to no messages resulted in a significant decrease in the HRQOL score of caregiver strain with an estimate of -6.31 (95% CI -11.76 to -0.12; P=.046). In addition, we found that the caregiver groups and the participants' levels of depression in the previous week moderated JITAI efficacy. CONCLUSIONS: This study provides preliminary evidence to support the effectiveness of the self-management JITAI and offers practical guidance for designing future personalized JITAI strategies for diverse caregiver groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT04556591; https://clinicaltrials.gov/ct2/show/NCT04556591.

Efficient assessment of real-world dynamics of circadian rhythms in heart rate and body temperature from wearable data.

Laboratory studies have made unprecedented progress in understanding circadian physiology. Quantifying circadian rhythms outside of laboratory settings is necessary to translate these findings into real-world clinical practice. Wearables have been considered promising way to measure these rhythms. However, their limited validation remains an open problem. One major barrier to implementing large-scale validation studies is the lack of reliable and efficient methods for circadian assessment from wearable data. Here, we propose an approximation-based least-squares method to extract underlying circadian rhythms from wearable measurements. Its computational cost is ∼ 300-fold lower than that of previous work, enabling its implementation in smartphones with low computing power. We test it on two large-scale real-world wearable datasets: [Formula: see text] of body temperature data from cancer patients and ∼ 184 000 days of heart rate and activity data collected from the 'Social Rhythms' mobile application. This shows successful extraction of real-world dynamics of circadian rhythms. We also identify a reasonable harmonic model to analyse wearable data. Lastly, we show our method has broad applicability in circadian studies by embedding it into a Kalman filter that infers the state space of the molecular clocks in tissues. Our approach facilitates the translation of scientific advances in circadian fields into actual improvements in health.

Mobile Technology to Monitor and Support Health and Well-Being: Qualitative Study of Perspectives and Design Suggestions From Patients Undergoing Hematopoietic Cell Transplantation.

BACKGROUND: In the United States, hematopoietic stem cell transplant (HCT) surpasses 22,000 procedures annually. Due to the demanding and time-intensive process of an HCT, patients and family care partners face unique challenges involving their health and well-being. Positive psychology interventions (PPIs) may offer potential solutions to help boost health and well-being. OBJECTIVE: This study aimed to explore and understand patients' experiences and perceptions about the use of the Roadmap 2.0 app, specifically its PPI features, during the acute phase of HCT. METHODS: From an ongoing randomized controlled trial, HCT patients (n=17) were recruited to participate in semistructured qualitative interviews between October 2022 and January 2023 within a large academic medical center in the Midwestern states. Using a qualitative descriptive approach, interviews were conducted in person or via Zoom. The data were analyzed through constant comparative analysis. The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines were followed. RESULTS: The majority of the participants reported Roadmap 2.0 as easy to use and enjoyed the ability to track their health data (eg, steps, mood, sleep; 9/17). Regarding the use of PPIs during the acute phase of treatment, 88% of the participants reported interest in participating in PPIs, specifically the Pleasant Activity Scheduling (11/17) followed by Gratitude Journaling (7/17) activities. Additionally, participants provided recommendations on adapting Roadmap 2.0. The major recommendations were (1) "Working Together: Need for Dyadic Involvement," (2) "Connectivity with Other Patients," and (3) "Gap in Nutritional Support." Participants (10/17) expressed the importance of caregiver involvement in activities beyond treatment-related management for maintaining healthy patient-caregiver dyadic relationships. They also expressed their desire for connectivity with other patients undergoing HCT, primarily for comparing experiences and discussing topics such as symptom management (8/17). Lastly, participants identified a gap in nutritional support during the HCT process and expressed interest in an intervention that could promote healthy eating through education and notification reminders (9/17). CONCLUSIONS: Participants openly expressed their eagerness to participate in research studies that foster connection and positive relationships with their caregivers as well as with other HCT patients. They emphasized the significance of having access to nutritional support or guidance and highlighted the potential benefits of using mobile technology to enhance these collective efforts. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094844; https://clinicaltrials.gov/study/NCT04094844. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19288.

The reliability and validity of the TBI-CareQOL system in four diverse caregiver groups.

PURPOSE: Establishing the psychometric reliability and validity of new measures is an ongoing process. More work is needed in to confirm the clinical utility of the TBI-CareQOL measurement development system in both an independent cohort of caregivers of traumatic brain injury (TBI), as well as in additional caregiver groups. METHODS: An independent cohort of caregivers of people with TBI (n = 139), as well as three new diverse caregiver cohorts (n = 19 caregivers of persons with spinal cord injury, n = 21 caregivers for persons with Huntington disease, and n = 30 caregivers for persons with cancer), completed 11 TBI-CareQOL measures (caregiver strain; caregiver-specific anxiety; anxiety; depression; anger; self-efficacy; positive affect and well-being; perceived stress; satisfaction with social roles and activities; fatigue; sleep-related impairment), as well as two additional measures to examine convergent and discriminant validity (PROMIS Global Health; the Caregiver Appraisal Scale). RESULTS: Findings support the internal consistency reliability (all alphas > 0.70 with the vast majority being > 0.80 across the different cohorts) of the TBI-CareQOL measures. All measures were free of ceiling effects, and the vast majority were also free of floor effects. Convergent validity was supported by moderate to high correlations between the TBI-CareQOL and related measures, while discriminant validity was supported by low correlations between the TBI-CareQOL measures and unrelated constructs. CONCLUSION: Findings indicate that the TBI-CareQOL measures have clinical utility in caregivers of people with TBI, as well as in other caregiver groups. As such, these measures should be considered as important outcome measures for clinical trials aiming to improve caregiver outcomes.

Prevalence of Iron Deficiency and Iron-Deficiency Anemia in US Females Aged 12-21 Years, 2003-2020.

This study examines prevalence of iron deficiency among females aged 12 to 21 years to inform future screening strategies for iron deficiency and iron-deficiency anemia.

Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats.

OBJECTIVES: Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. METHODS: Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1ß significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). CONCLUSION: The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea.

OBJECTIVES: Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. METHODS: This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. RESULTS: In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable. RESULTS: Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, -11.351; 95% confidence interval, -21.491 to -1.212; P=0.028). CONCLUSION: This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.

A pilot intervention of using a mobile health app (ONC Roadmap) to enhance health-related quality of life in family caregivers of pediatric patients with cancer.

Background: The Roadmap mobile health (mHealth) app was developed to provide health-related quality of life (HRQOL) support for family caregivers of patients with cancer. Methods: Eligibility included: family caregivers (age ≥18 years) who self-reported as the primary caregiver of their pediatric patient with cancer; patients (age ≥5 years) who were receiving cancer care at the University of Michigan. Feasibility was calculated as the percentage of caregivers who logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the 120-day study duration. Feasibility and acceptability was also assessed through a Feasibility and Acceptability questionnaire and the Mobile App Rating Scale to specifically assess app-quality. Exploratory analyses were also conducted to assess HRQOL self- or parent proxy assessments and physiological data capture. Results: Between September 2020-September 2021, 100 participants (or 50 caregiver-patient dyads) consented and enrolled in the ONC Roadmap study for 120-days. Feasibility of the study was met, wherein the majority of caregivers (N=32; 65%) logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the study duration (defined a priori in the Protocol). The Feasibility and Acceptability questionnaire responses indicated that the study was feasible and acceptable with the majority (>50%) reporting Agree or Strongly Agree with positive Net Favorability [(Agree + Strongly Agree) - (Disagree + Totally Disagree)] in each of the domains (e.g., Fitbit use, ONC Roadmap use, completing longitudinal assessments, engaging in similar future study, study expectations). Improvements were seen across the majority of the mental HRQOL domains across all groups; even though underpowered, there were significant improvements in caregiver-specific aspects of HRQOL and anxiety and in depression and fatigue for children (ages 8-17 years), and a trend toward improvement in depression for children ages 8-17 years and in fatigue for adult patients. Conclusions: This study supports that mHealth technology may be a promising platform to provide HRQOL support for caregivers of pediatric patients with cancer. Importantly, the findings suggest that the study protocol was feasible, and participants were favorable to participate in future studies of this intervention alongside routine cancer care delivery.

Deep learning-based clinical decision support system for gastric neoplasms in real-time endoscopy: development and validation study.

BACKGROUND : Deep learning models have previously been established to predict the histopathology and invasion depth of gastric lesions using endoscopic images. This study aimed to establish and validate a deep learning-based clinical decision support system (CDSS) for the automated detection and classification (diagnosis and invasion depth prediction) of gastric neoplasms in real-time endoscopy. METHODS : The same 5017 endoscopic images that were employed to establish previous models were used for the training data. The primary outcomes were: (i) the lesion detection rate for the detection model, and (ii) the lesion classification accuracy for the classification model. For performance validation of the lesion detection model, 2524 real-time procedures were tested in a randomized pilot study. Consecutive patients were allocated either to CDSS-assisted or conventional screening endoscopy. The lesion detection rate was compared between the groups. For performance validation of the lesion classification model, a prospective multicenter external test was conducted using 3976 novel images from five institutions. RESULTS : The lesion detection rate was 95.6 % (internal test). On performance validation, CDSS-assisted endoscopy showed a higher lesion detection rate than conventional screening endoscopy, although statistically not significant (2.0 % vs. 1.3 %; P = 0.21) (randomized study). The lesion classification rate was 89.7 % in the four-class classification (advanced gastric cancer, early gastric cancer, dysplasia, and non-neoplastic) and 89.2 % in the invasion depth prediction (mucosa confined or submucosa invaded; internal test). On performance validation, the CDSS reached 81.5 % accuracy in the four-class classification and 86.4 % accuracy in the binary classification (prospective multicenter external test). CONCLUSIONS : The CDSS demonstrated its potential for real-life clinical application and high performance in terms of lesion detection and classification of detected lesions in the stomach.

Auricular Reconstruction for Bilateral Auricular Deformity Caused by Relapsing Polychondritis.

This case report describes a woman in her early 20s who presented to the hospital with an acquired auricular deformity after an ear piercing and was diagnosed with recurrent polychondritis that required total auricular reconstruction.

A diagnostic classifier for pediatric chronic graft-versus-host disease: results of the ABLE/PBMTC 1202 study.

The National Institutes of Health Consensus criteria for chronic graft-versus-host disease (cGVHD) diagnosis can be challenging to apply in children, making pediatric cGVHD diagnosis difficult. We aimed to identify diagnostic pediatric cGVHD biomarkers that would complement the current clinical criteria and help differentiate cGVHD from non-cGVHD. The Applied Biomarkers of Late Effects of Childhood Cancer (ABLE) study, open at 27 transplant centers, prospectively evaluated 302 pediatric patients after hematopoietic cell transplant (234 evaluable). Forty-four patients developed cGVHD. Mixed and fixed effect regression analyses were performed on diagnostic cGVHD onset blood samples for cellular and plasma biomarkers, with individual markers declared relevant if they met 3 criteria: an effect ratio ≥1.3 or ≤0.75; an area under the curve (AUC) of ≥0.60; and a P value <5.814 × 10-4 (Bonferroni correction) (mixed effect) or <.05 (fixed effect). To address the complexity of cGVHD diagnosis in children, we built a machine learning-based classifier that combined multiple cellular and plasma biomarkers with clinical factors. Decreases in regulatory natural killer cells, naïve CD4 T helper cells, and naïve regulatory T cells, and elevated levels of CXCL9, CXCL10, CXCL11, ST2, ICAM-1, and soluble CD13 (sCD13) characterize the onset of cGVHD. Evaluation of the time dependence revealed that sCD13, ST2, and ICAM-1 levels varied with the timing of cGVHD onset. The cGVHD diagnostic classifier achieved an AUC of 0.89, with a positive predictive value of 82% and a negative predictive value of 80% for diagnosing cGVHD. Our polyomic approach to building a diagnostic classifier could help improve the diagnosis of cGVHD in children but requires validation in future prospective studies. This trial was registered at www.clinicaltrials.gov as #NCT02067832.