Simultaneous Co-surgeon Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstructions: Feasibility and Clinical Outcomes.

BACKGROUND: A co-surgeon model is known to be favorable in microvascular breast reconstruction, but simultaneous co-surgeon deep inferior epigastric perforator (DIEP) flap cases have not been well-studied. The authors hypothesize that performing two simultaneous co-surgeon bilateral DIEP flap reconstructions results in non-inferior clinical outcomes and may improve patient access to care. METHODS: A single-institution, retrospective cohort study was performed utilizing record review to identify all cases of co-surgeon free-flap breast reconstructions over a 38-month period. Patients who underwent simultaneous bilateral DIEP flap breast reconstructions with the same two co-surgeons were identified. The control group consisted of subjects who underwent non-simultaneous reconstruction by the same co-surgeons within the same, preceding, or following month of those in the study group. Primary outcome variables were 90-day postoperative complications, while secondary outcomes were operating time, ischemia time, and length of stay. Descriptive statistics, univariate and multivariable regression analyses were performed. RESULTS: Overall, 137 subjects were identified and 64 met the inclusion criteria (n = 28 study, n = 36 control). There were no statistically significant differences between groups in body mass index, radiation, trainee experience, flap perforator number, immediate/delayed reconstruction, or length of stay. There were also no statistically significant differences in complications, including flap loss, anastomosis revision, take-back to the operating room, or re-admission. Operative time was longer in the simultaneous DIEP group (540.5 vs. 443.5 min, p < 0.01), but ischemia time was shorter in the simultaneous group (64.0 vs. 80.5 min, p < 0.01). CONCLUSIONS: A simultaneous co-surgeon approach to bilateral DIEP flap reconstruction may improve access to care and does not result in a higher complication rate compared with non-simultaneous bilateral DIEP flaps.

ROUTE-T1D: A behavioral intervention to promote optimal continuous glucose monitor use among racially minoritized youth with type 1 diabetes: Design and development.

BACKGROUND: Type 1 diabetes management is often challenging during adolescence, and many youth with type 1 diabetes struggle with sustained and optimal continuous glucose monitor (CGM) use. Due to racial oppression and racially discriminatory policies leading to inequitable access to quality healthcare and life necessities, racially minoritized youth are significantly less likely to use CGM. METHODS: ROUTE-T1D: Research on Optimizing the Use of Technology with Education is a pilot behavioral intervention designed to promote optimal CGM use among racially minoritized youth with type 1 diabetes. Intervention strategies include problem solving CGM challenges and promoting positive caregiver-youth communication related to CGM data. RESULTS: This randomized waitlist intervention provides participants with access to three telemedicine sessions with a Certified Diabetes Care and Education Specialist. Caregiver participants are also connected with a peer-parent coach. CONCLUSION: Hypothesized findings and anticipated challenges are discussed. Future directions regarding sustaining and optimizing the use of diabetes technology among racially minoritized pediatric populations are reviewed.

Evaluating Transition Readiness in Older Adolescents and Young Adults With Type 1 Diabetes.

For older adolescents and young adults (AYAs) with type 1 diabetes, successful transition from pediatric to adult diabetes care requires ongoing planning and support. Yet, the transition to adult care is not always smooth. Some AYAs struggle to leave pediatric care or experience significant gaps between pediatric and adult diabetes care. The use of diabetes-specific transition readiness assessments can inform transition planning and support successful preparation for adult care. This study evaluated transition readiness in a diverse sample of AYAs nearing transition to adult diabetes care. Findings suggest that AYAs may benefit from additional preparation and education related to sexual health, tobacco use, and diabetes complications.

Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus.

Introduction: Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown. Methods: We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI). Results: cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis. Discussion: This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.

Factors Influencing Recurrence in Medial Breast Cancer Tumors After Skin Sparing Mastectomy and Immediate Breast Reconstruction.

BACKGROUND: Skin sparing mastectomy (SSM) with immediate breast reconstruction (IBR) has been established as a safe option for curative-intent surgical resection. Prior studies have shown that medial location of the primary tumor is associated with increased risk of local recurrence. The purpose of this study is to determine the factors associated with recurrence and survival in individuals with breast cancers located in the inner quadrants (medial) who underwent SSM with IBR. METHODS: A retrospective chart review was done on individuals with medial breast cancer who received SSM with IBR in British Columbia between 1980 and 2012. RESULTS: Of 136 individuals with medial breast cancer undergoing SSM with IBR, 27.9% experienced local recurrence and 42.6% overall recurrence. Factors associated with recurrence were T-stage (44.8 vs. 22.4% with T2 disease, P = .02), transverse rectus abdominis muscle (TRAM) flap reconstruction (48.3 vs. 29.5%, P = .00395), prior breast surgery (87.9 vs. 63%, P = .002), and prior radiation therapy (74.1 vs. 38.5%, P < .0001). LR was associated with higher mortality (OR 2.78, 95% CI: 1.26-6.09). CONCLUSION: For patients with medial tumors undergoing SSM with IBR, potential risk factors for recurrence are T-stage, TRAM flap reconstruction, prior breast surgery, and prior radiation therapy. Local recurrence is associated with poor survival.

Type I Interferonopathies: A Clinical Review.

This review will discuss when clinicians should consider evaluating for Type I interferonopathies, review clinical phenotypes and molecular defects of Type I interferonopathies, and discuss current treatments.

Normal multiple sleep latency test values in adults: A systematic review and meta-analysis.

Sleep latency is a measure of time it takes to enter sleep. Very short sleep latencies are indicative of excessive daytime sleepiness and pathological sleep conditions such as narcolepsy. The normal range of mean sleep latency calculated from the multiple sleep latency test in healthy adults is not well-established. We provide a review of normative mean sleep latency values on the multiple sleep latency test by synthesizing data from 110 healthy adult cohorts. We also examine the impact of demographic variables such as age, sex, body mass index, sleep architecture and sleep-disordered breathing as well as methodological variables such as sleep onset definitions and multiple sleep latency test protocols. The average mean sleep latency was 11.7 min (95% CI: 10.8-12.6; 95% PI: 5.2-18.2) for cohorts evaluated using the earlier definition of sleep onset and 11.8 min (95% CI: 10.7-12.8; 95% PI: 7.2-16.3) for those evaluated using the later definition. There were no significant associations between mean sleep latency and demographic or methodological variables. A negative association of -0.29 per one unit increase (95% CI: -0.55 to -0.04) was found between mean sleep latency and apnea-hypopnea index on prior night polysomnography. Establishing updated ranges for mean sleep latency among healthy adults may guide clinical decision-making surrounding sleep pathologies and inform future research into the associations between patient variables, daytime sleepiness, and sleep pathologies.

Satisfaction With Participation in the First STEPS Behavioral Intervention: Experiences of Parents of Young Children With Newly Diagnosed Type 1 Diabetes.

OBJECTIVE: Parents of young children with new-onset type 1 diabetes (T1D) often experience significant distress and struggle with T1D management during a challenging developmental stage. The First STEPS (Study of Type 1 in Early childhood and Parenting Support) trial evaluated a stepped-care behavioral intervention comprising increasingly intensive intervention steps (peer parent coach, cognitive-behavioral counseling, consultations with diabetes educator and psychologist) based on need. The intervention improved parental depressive symptoms compared to usual care. Subsequently, we examined parent satisfaction with the intervention to guide potential implementation and refinement for future trials. METHODS: Participants were 157 parents of young children newly diagnosed with T1D. At 9 months post randomization, n = 153 completed satisfaction questionnaires and n = 17 completed qualitative interviews. Satisfaction ratings about trial procedures and each intervention step were summarized. We used thematic analysis with the interview transcripts to generate themes related to participants' experiences in the trial overall and intervention specifically. We explored differences in themes between participants who did versus did not respond to the intervention and among those who experienced different intervention steps. RESULTS: Most participants in both arms rated study participation and methods positively (>95%), and those completing interviews described high satisfaction with study procedures overall, retention incentives, and contact with study staff. Intervention participants' satisfaction ratings were high across steps. Two qualitative themes reflected satisfaction with the intervention enhancing self-efficacy and social support. CONCLUSIONS: High satisfaction suggests implementing a stepped-care behavioral intervention as part of routine clinical care following T1D diagnosis would be well received.

Comparison of Functional Outcomes After Acute Inpatient Rehabilitation After Acquired Brain Injury Before and During the COVID-19 Pandemic.

OBJECTIVE: The objective of this study was to characterize and compare functional outcomes of acquired brain injury patients in an inpatient rehabilitation facility in the year before (April 2019-March 2020) and during the first year (April 2020-March 2021) of the COVID-19 pandemic, when the most drastic changes in the delivery of health care occurred. DESIGN: In this retrospective single-center chart review study, functional outcomes, based on the Center for Medicare and Medicaid Services Inpatient Rehabilitation Facility-Patient Assessment Instrument, were obtained and analyzed for patients in acute inpatient rehabilitation with acquired brain injury. RESULTS: Data from 1330 patients were included for analysis. Functional outcomes of average self-care, bed mobility, and transfer scores were statistically, but not clinically, different between groups. More patients in the pandemic group were discharged home (prepandemic n = 454 [65.4%]; pandemic n = 461 [72.6%]; P = 0.011), although they had significantly longer lengths of stay (prepandemic median = 14.0 [interquartile range = 9.0-23.0]; pandemic = 16.0 [10.0-23.0]; P = 0.037). CONCLUSIONS: Despite the impact of hospital policies due to the COVID-19 pandemic, similar functional outcomes were obtained for those with acquired brain injury after inpatient rehabilitation.

Patient, disease, and survival outcomes for stage IB to stage IV cervical cancer-A population study.

BACKGROUND: Factors that impact recurrence in stages IB to IV include larger tumor, high-risk histology, older age, and lymphovascular invasion (LVI); however, local studies on risk factors for recurrence in British Columbia and our local recurrence patterns have not been well studied. Furthermore, the efficacy of treatment modalities including surgery and chemoradiation in the different stages of cervical cancer have not been clarified in this population. OBJECTIVES: The purpose of this study is to determine the disease and treatment characteristics of stages IB to IV cervical cancer which are associated with survival differences within British Columbia. METHODS/DESIGN: We performed a retrospective population study. A chart review on cervical cancer patients in British Columbia between 1 January 2010 and 31 December 2017 was done. Demographic data and treatment details were collected. Data were analyzed using multivariate Cox regressions, pairwise comparison using the Log-Rank test, and chi-square tests. RESULTS: We included 780 patients (stage I: 31.5%, II: 20.0%, III: 34.5%, and IV: 3.3%). LVI and p16 negativity were associated with decreased overall survival (OS), and multivariate analyses show them to be independent risk factors for poorer survival. Surgical resection in stage I was associated with improved survival, but not with stages II-IV. The use of radical radiation therapy (RT), brachytherapy, and concurrent chemotherapy were independently associated with improved survival in stages II-IV. Peri-RT chemotherapy was not associated with survival benefit in adeno/adenosquamous carcinoma. There were 180 recurrences (23.1%), mostly distant metastases (42.8%). There were fewer recurrences after resection of tumors <2 cm compared to tumors 2 cm or larger (6.49% vs 31.3%, p = 0.00011). Only 37.7% of recurrence/metastases were treated with first-line carboplatin/paclitaxel/bevacizumab, but it was associated with better OS compared to other regimens (median OS 40.1 vs 24.8 months, p = 0.03). CONCLUSION: A significant portion of patients with localized cervical cancer relapse despite radical therapy, with LVI and p16 negativity associated with poorer survival. Surgical resection may still play a role in stage IB disease, while RT, brachytherapy, and concurrent chemotherapy should be considered first-line therapy in stage II-IV diseases. First-line carboplatin, paclitaxel, and bevacizumab for recurrence shows improved survival.

Parent Perspectives of School/Daycare Experiences in Young Children Newly Diagnosed With Diabetes.

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis. METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods design to describe and contextualize parents' experiences with school/daycare. Qualitative data were collected via open-ended responses, and quantitative data were collected from a demographic/medical from. RESULTS: While most children were enrolled in school/daycare at all time points, over 50% of parents endorsed that T1D affected their child's enrollment, rejection, or removal from school/daycare at 9 or 15 months. We generated five themes related to parents' school/daycare experiences: Child factors, Parent factors, School/Daycare factors, Cooperation between Parents and Staff, and Socio-historical factors. Parents of younger children and those with lower subjective socioeconomic status were significantly more likely to endorse challenges with school/daycare enrollment. CONCLUSIONS: School/daycare settings present challenges for parents of young children with T1D. Changes may need to occur across contexts to support early childhood education, including advocacy resources for parents to navigate school policies, increased training for school staff, and healthcare team outreach initiatives to parents and schools.

Psychosocial, Medical, and Demographic Variables Associated with Parent Mealtime Behavior in Young Children Recently Diagnosed with Type 1 Diabetes.

OBJECTIVE: Managing young children's mealtime concerns can be challenging after type 1 diabetes (T1D) diagnosis because of developmental factors and diabetes management demands. To identify potential intervention targets, we evaluated medical, psychosocial, and demographic factors in relation to parents' engagement in problem mealtime behaviors (e.g., pressure to eat, restriction). METHOD: Parents (N = 157) of young children (age 1-6 years) reported on psychosocial variables (parent fear of hypoglycemia, family functioning, parent problem solving, and parents' problem mealtime behavior frequency and perceptions of being problematic) within 2 months after T1D diagnosis. Hierarchical regression analyses examined associations among psychosocial variables, demographics (child sex, parent race/ethnicity), child continuous glucose monitor (CGM) use, and parents' problem mealtime behaviors. RESULTS: Parents of children using CGMs reported parents' mealtime behaviors as more problematic than nonusers, but there were no differences for other medical or demographic variables. Models predicting parents' problem mealtime behavior frequency and problem perceptions that included psychosocial variables, demographic variables, and CGM use led to significant R 2 of 0.14 and 0.16, respectively. CGM use and parent problem solving were significantly associated with parent mealtime behaviors being perceived as more problematic. CONCLUSION: Shortly after T1D diagnosis in young children, medical and parent psychosocial factors related to how frequently parents engaged in problem mealtime behaviors and the degree to which parents perceived them as problematic. Other factors may further explain the complexities of mealtime management. Considering parents' problem-solving skills and child treatment regimens may help guide interventions targeting mealtime challenges during the new diagnosis period.

Weight Management Behaviors are Associated with Elevated Glycemic Outcomes in Adolescents and Young Adults with Type 1 Diabetes.

Many adolescents and young adults (AYAs) with type 1 diabetes (T1D) engage in weight management behaviors (i.e., trying to lose weight), and efforts to manage weight may impact glycemic control. We assessed objective/subjective weight status and weight management behaviors in a diverse sample of 76 AYAs with T1D, and examined differences in sociodemographic characteristics and A1c levels by the following categories: (1) Overweight BMI/weight management (n = 21), (2) overweight BMI/no weight management (n = 6), (3) in/below-range BMI/weight management (n = 25), (4) in/below-range BMI/no weight management (n = 24). Subjective overweight status was more common among late adolescents and females; female gender was associated with weight management behaviors. AYAs endorsing weight management behaviors evidenced higher A1c values than those who did not. Clinicians working with AYAs should be aware of associations among weight management and glycemic indicators and routinely screen for weight management behaviors. Future research should explore interventions to promote healthy lifestyle behaviors among AYAs.

Initiating daily acute intermittent hypoxia (dAIH) therapy at 1-week after contusion spinal cord injury (SCI) improves lower urinary tract function in rat.

Spinal cord injury (SCI) above the level of the lumbosacral spinal cord produces lower urinary tract (LUT) dysfunction, resulting in impairment of urine storage and elimination (voiding). While spontaneous functional recovery occurs due to remodeling of spinal reflex micturition pathways, it is incomplete, indicating that additional strategies to further augment neural plasticity following SCI are essential. To this end, acute intermittent hypoxia (AIH) exposure has been proposed as a therapeutic strategy for improving recovery of respiratory and other somatic motor function following SCI; however, the impact of AIH as a therapeutic intervention to improve LUT dysfunction remains to be determined. Therefore, we examined the effects of daily AIH (dAIH) on both spontaneous micturition patterns and reflex micturition event (rME) behaviors in adult female Sprague-Dawley rats with mid-thoracic moderate contusion SCI. For these experiments, dAIH gas exposures (five alternating 3 min 12% O2 and 21% O2 episodes) were delivered for 7 consecutive days beginning at 1-week after SCI, with awake micturition patterns being evaluated weekly for 2-3 sessions before and for 4 weeks after SCI and rME behaviors elicited by continuous infusion of saline into the bladder being evaluated under urethane anesthesia at 4-weeks after SCI; daily normoxia (dNx; 21% O2 episodes) served as a control. At 1-week post-SCI, both an areflexic phenotype (i.e., no effective voiding events) and a functional voiding phenotype (i.e., infrequent voiding events with large volumes) were observed in spontaneous micturition patterns (as expected), and subsequent dAIH, but not dNx, treatment led to recovery of spontaneous void frequency pattern to pre-SCI levels; both dAIH- and dNx-treated rats exhibited slightly increased void volumes. At 4-weeks post-SCI, rME behaviors showed increased effectiveness in voiding in dAIH-treated (compared to dNx-treated) rats that included an increase in both bladder contraction pressure (delta BP; P = 0.014) and dynamic voiding efficiency (P = 0.018). Based on the voiding and non-voiding bladder contraction behaviors (VC and NVC, respectively) observed in the BP records, bladder dysfunction severity was classified into mild, moderate, and severe phenotypes, and while rats in both treatment groups included each severity phenotype, the primary phenotype observed in dAIH-treated rats was mild and that in dNx-treated rats was moderate (P = 0.044). Taken together, these findings suggest that 7-day dAIH treatment produces beneficial improvements in LUT function that include recovery of micturition pattern, more efficient voiding, and decreased NVCs, and extend support to the use of dAIH therapy to treat SCI-induced LUT dysfunction.

Assessing Unique Risk Factors for COVID-19 Complications Among Cancer Patients: A Multi-ethnic Cohort Study.

A myriad of organ-specific complications have been observed with COVID-19. While racial/ethnic minorities have been disproportionately burdened by this disease, our understanding of the unique risk factors for complications among a diverse population of cancer patients remains limited. This is a multi-institutional, multi-ethnic cohort study evaluating COVID-19 complications among cancer patients. Patients with an invasive cancer diagnosis and confirmed SARS-CoV-2 infection were identified from March to November 2020. Demographic and clinical data were obtained and a multivariate logistic regression was employed to evaluate the impact of demographic and clinical factors on COVID-19 complications. The study endpoints were evaluated independently and included any complication, sepsis, pulmonary complications and cardiac complications. A total of 303 patients were evaluated, of whom 48% were male, 79% had solid tumors, and 42% were Hispanic/Latinx (Hispanic). Malignant hematologic cancers were associated with a higher risk of sepsis (OR 3.93 (95% CI 1.58-9.81)). Male patients had a higher risk of sepsis (OR 4.42 (95% CI 1.63-11.96)) and cardiac complications (OR 2.02 (95% CI 1.05-3.89)). Hispanic patients had a higher odds of any complication (OR 2.31 (95% CI 1.18-4.51)) and other race was associated with a higher odds of cardiac complications (OR 2.41 (95% CI 1.01-5.73)). Clinically, fever, cough, and ≥2 co-morbidities were independently significantly associated with any complication. This analysis evaluated covariates that can significantly predict a myriad of complications among a multi-ethnic cohort of cancer patients. The conclusions drawn from this analysis elucidate a mechanistic understanding of differential illness severity from COVID-19.