Donor germ-line variants associate with outcomes of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndromes.

Overall survival probability for MDS patients who underwent allo-HCT and were matched to donors that are wild-type (red) and heterozygous (blue) for the rs111224634 SNP.

Relationship between the COVID-19 pandemic and structural inequalities within the pediatric trauma population.

BACKGROUND: The COVID-19 pandemic disrupted social, political, and economic life across the world, shining a light on the vulnerability of many communities. The objective of this study was to assess injury patterns before and after implementation of stay-at-home orders (SHOs) between White children and children of color and across varying levels of vulnerability based upon children's home residence. METHODS: A multi-institutional retrospective study was conducted evaluating patients < 18 years with traumatic injuries. A "Control" cohort from an averaged March-September 2016-2019 time period was compared to patients injured after SHO initiation-September 2020 ("COVID" cohort). Interactions between race/ethnicity or social vulnerability index (SVI), a marker of neighborhood vulnerability and socioeconomic status, and the COVID-19 timeframe with regard to the outcomes of interest were assessed using likelihood ratio Chi-square tests. Differences in injury intent, type, and mechanism were then stratified and explored by race/ethnicity and SVI separately. RESULTS: A total of 47,385 patients met study inclusion. Significant interactions existed between race/ethnicity and the COVID-19 SHO period for intent (p < 0.001) and mechanism of injury (p < 0.001). There was also significant interaction between SVI and the COVID-19 SHO period for mechanism of injury (p = 0.01). Children of color experienced a significant increase in intentional (COVID 16.4% vs. Control 13.7%, p = 0.03) and firearm (COVID 9.0% vs. Control 5.2%, p < 0.001) injuries, but no change was seen among White children. Children from the most vulnerable neighborhoods suffered an increase in firearm injuries (COVID 11.1% vs. Control 6.1%, p = 0.001) with children from the least vulnerable neighborhoods having no change. All-terrain vehicle (ATV) and bicycle crashes increased for children of color (COVID 2.0% vs. Control 1.1%, p = 0.04 for ATV; COVID 6.7% vs. Control 4.8%, p = 0.02 for bicycle) and White children (COVID 9.6% vs. Control 6.2%, p < 0.001 for ATV; COVID 8.8% vs. Control 5.8%, p < 0.001 for bicycle). CONCLUSIONS: In contrast to White children and children from neighborhoods of lower vulnerability, children of color and children living in higher vulnerability neighborhoods experienced an increase in intentional and firearm-related injuries during the COVID-19 pandemic. Understanding inequities in trauma burden during times of stress is critical to directing resources and targeting intervention strategies.

Characteristics and neighborhood-level opportunity of assault-injured children in Milwaukee.

BACKGROUND: Multiple studies have explored demographic characteristics and social determinants of health in relation to the risk of pediatric assault-related injuries and reinjury. However, few have explored protective factors. The Child Opportunity Index (COI) uses neighborhood-level indicators to measure 'opportunity' based on factors such as education, social environment, and economic resources. We hypothesized that higher 'opportunity' would be associated with less risk of reinjury in assault-injured youth. METHODS: This was a single-institution, retrospective study at a Level 1 Pediatric Trauma Center. Trauma registry and electronic medical record data were queried for children ≤ 18 years old with assault-related injuries from 1/1/2016 to 5/31/2021. Reinjured children, defined as any child who sustained more than one assault injury, were compared to non-reinjured children. Area Deprivation Index (ADI), a marker of socioeconomic status, and COI were determined through census block and tract data, respectively. A post-hoc analysis examined COI between all assault-injured children, unintentionally injured children, and a state-based normative cohort representative of non-injured children. RESULTS: There were 55,862 traumatic injury encounters during the study period. Of those, 1224 (2.3%) assault injured children were identified, with 52 (4.2%) reinjured children and 1172 (95.8%) non-reinjured children. Reinjured children were significantly more likely to be older (median age 15.0 [IQR 13.8-17.0] vs. median age 14.0 [IQR 8.8-16.0], p < 0.001) and female (55.8% vs. 37.5%, p = 0.01) than non-reinjured children. COI was not associated with reinjury. There were also no significant differences in race, ethnicity, insurance status, ADI, or mechanism and severity of injury between cohorts. Post-hoc analysis revealed that assault-injured children were more likely to live in areas of lower COI than the other cohorts. CONCLUSIONS: Compared to children who sustained only one assault during the study period, children who experienced more than one assault were more likely to be older and female. Furthermore, living in an area with more or less opportunity did not influence the risk of reinjury. However, all assault-injured children were more likely to live in areas of lower COI compared to unintentionally injured and a state-based normative cohort. Identification of factors on a social or environmental level that leads to assaultive injury warrants further exploration.

Location of Treatment Among Infants Requiring Complex Surgical Care.

INTRODUCTION: Rural children have worse health outcomes compared to urban children. One mechanism for this finding may be decreased access to specialized care at children's hospitals. The objective of this study was to evaluate the hospital types where complex surgical care in infants is performed nationally. METHODS: This study examined infants (<1 y old) in the Kids' Inpatient Database from 2009 to 2019 who underwent surgery for one of the following conditions: esophageal atresia, gastroschisis, omphalocele, Hirschsprung disease, anorectal malformation, pyloric stenosis, small bowel atresia, congenital diaphragmatic hernia, and necrotizing enterocolitis. The relationship between patient residence (rural versus urban) and location of surgical care (children's hospital versus other) was compared in relation to other covariates using multivariable logistic regression models. RESULTS: Among 29,185 infants undergoing these operations, 16.0% lived in a rural area. Rural infants were more frequently White (64.8% versus 43.4% P < 0.001), from the lowest two income quartiles (86.5% versus 52.0%, P < 0.001), and from the South or Midwest regions (P < 0.001). Surgical care was predominantly (94.1%) provided at urban teaching hospitals but frequently not at children's hospitals, especially among rural infants. After adjusting for other covariates, rural infants were significantly less likely to undergo care at a children's hospital for both 2009 (adjusted odds ratio 0.66, P < 0.001) and 2012-2019 (adjusted odds ratio 0.78, P < 0.001). CONCLUSIONS: A sizable portion of complex surgical care in infants is performed outside children's hospitals, especially among those from rural areas. Further work is necessary to ensure adequate access to children's hospitals for rural children.

Evaluating the Regional Differences in Pediatric Injury Patterns During the COVID-19 Pandemic.

INTRODUCTION: Reports of pediatric injury patterns during the COVID-19 pandemic are conflicting and lack the granularity to explore differences across regions. We hypothesized there would be considerable variation in injury patterns across pediatric trauma centers in the United States. MATERIALS AND METHODS: A multicenter, retrospective study evaluating patients <18 y old with traumatic injuries meeting National Trauma Data Bank criteria was performed. Patients injured after stay-at-home orders through September 2020 ("COVID" cohort) were compared to "Historical" controls from an averaged period of equivalent dates in 2016-2019. Differences in injury type, intent, and mechanism were explored at the site level. RESULTS: 47,385 pediatric trauma patients were included. Overall trauma volume increased during the COVID cohort compared to the Historical (COVID 7068 patients versus Historical 5891 patients); however, some sites demonstrated a decrease in overall trauma of 25% while others had an increase of over 33%. Bicycle injuries increased at every site, with a range in percent change from 24% to 135% increase. Although the greatest net increase was due to blunt injuries, there was a greater relative increase in penetrating injuries at 7/9 sites, with a range in percent change from a 110% increase to a 69% decrease. CONCLUSIONS: There was considerable discrepancy in pediatric injury patterns at the individual site level, perhaps suggesting a variable impact of the specific sociopolitical climate and pandemic policies of each catchment area. Investigation of the unique response of the community during times of stress at pediatric trauma centers is warranted to be better prepared for future environmental stressors.

Pediatric injury trends and relationships with social vulnerability during the COVID-19 pandemic: A multi-institutional analysis.

BACKGROUND: The impact of the COVID-19 pandemic on pediatric injury, particularly relative to a community's vulnerability, is unknown. The objective of this study was to describe the change in pediatric injury during the first 6 months of the COVID-19 pandemic compared with prior years, focusing on intentional injury relative to the social vulnerability index (SVI). METHODS: All patients younger than 18 years meeting inclusion criteria for the National Trauma Data Bank between January 1, 2016, and September 30, 2020, at nine Level I pediatric trauma centers were included. The COVID cohort (children injured in the first 6 months of the pandemic) was compared with an averaged historical cohort (corresponding dates, 2016-2019). Demographic and injury characteristics and hospital-based outcomes were compared. Multivariable logistic regression was used to estimate the adjusted odds of intentional injury associated with SVI, moderated by exposure to the pandemic. Interrupted time series analysis with autoregressive integrated moving average modeling was used to predict expected injury patterns. Volume trends and observed versus expected rates of injury were analyzed. RESULTS: There were 47,385 patients that met inclusion criteria, with 8,991 treated in 2020 and 38,394 treated in 2016 to 2019. The COVID cohort included 7,068 patients and the averaged historical cohort included 5,891 patients (SD, 472), indicating a 20% increase in pediatric injury ( p = 0.031). Penetrating injuries increased (722 [10.2%] COVID vs. 421 [8.0%] historical; p < 0.001), specifically firearm injuries (163 [2.3%] COVID vs. 105 [1.8%] historical; p = 0.043). Bicycle collisions (505 [26.3%] COVID vs. 261 [18.2%] historical; p < 0.001) and collisions on other land transportation (e.g., all-terrain vehicles) (525 [27.3%] COVID vs. 280 [19.5%] historical; p < 0.001) also increased. Overall, SVI was associated with intentional injury (odds ratio, 7.9; 95% confidence interval, 6.5-9.8), a relationship which increased during the pandemic. CONCLUSION: Pediatric injury increased during the pandemic across multiple sites and states. The relationship between increased vulnerability and intentional injury increased during the pandemic. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

A Multi-institutional Study Evaluating Pediatric Burn Injuries During the COVID-19 Pandemic.

During the COVID-19 pandemic, children were out of school due to Stay-at-Home Orders. The objective of this study was to investigate how the COVID-19 pandemic may have impacted the incidence of burn injuries in children. Eight Level I Pediatric Trauma Centers participated in a retrospective study evaluating children <18 years old with traumatic injuries defined by the National Trauma Data Bank. Patients with burn injuries were identified by ICD-10 codes. Historical controls from March to September 2019 ("Control" cohort) were compared to patients injured after the start of the COVID-19 pandemic from March to September 2020 ("COVID" cohort). A total of 12,549 pediatric trauma patients were included, of which 916 patients had burn injuries. Burn injuries increased after the start of the pandemic (COVID 522/6711 [7.8%] vs Control 394/5838 [6.7%], P = .03). There were no significant differences in age, race, insurance status, burn severity, injury severity score, intent or location of injury, and occurrence on a weekday or weekend between cohorts. There was an increase in flame burns (COVID 140/522 [26.8%] vs Control 75/394 [19.0%], P = .01) and a decrease in contact burns (COVID 118/522 [22.6%] vs Control 112/394 [28.4%], P = .05). More patients were transferred from an outside institution (COVID 315/522 patients [60.3%] vs Control 208/394 patients [52.8%], P = .02), and intensive care unit length of stay increased (COVID median 3.5 days [interquartile range 2.0-11.0] vs Control median 3.0 days [interquartile range 1.0-4.0], P = .05). Pediatric burn injuries increased after the start of the COVID-19 pandemic despite Stay-at-Home Orders intended to optimize health and increase public safety.

Pediatric Injury Transfer Patterns During the COVID-19 Pandemic: An Interrupted time Series Analysis.

INTRODUCTION: With the expected surge of adult patients with COVID-19, the Children's Hospital Association recommended a tiered approach to divert children to pediatric centers. Our objective was understanding changes in interfacility transfer to Pediatric Trauma Centers (PTCs) during the first 6 mo of the pandemic. METHODS: Children aged < 18 y injured between January 1, 2016 and September 30, 2020, who met National Trauma Databank inclusion criteria from 9 PTCs were included. An interrupted time-series analysis was used to estimate an expected number of transferred patients compared to observed volume. The "COVID" cohort was compared to a historical cohort (historical average [HA]), using an average across 2016-2019. Site-based differences in transfer volume, demographics, injury characteristics, and hospital-based outcomes were compared between cohorts. RESULTS: Twenty seven thousand thirty one/47,382 injured patients (57.05%) were transferred to a participating PTC during the study period. Of the COVID cohort, 65.4% (4620/7067) were transferred, compared to 55.7% (3281/5888) of the HA (P < 0.001). There was a decrease in 15-y-old to 17-y-old patients (10.43% COVID versus 12.64% HA, P = 0.003). More patients in the COVID cohort had injury severity scores ≤ 15 (93.25% COVID versus 87.63% HA, P < 0.001). More patients were discharged home after transfer (31.80% COVID versus 21.83% HA, P < 0.001). CONCLUSIONS: Transferred trauma patients to Level I PTC increased during the COVID-19 pandemic. The proportion of transferred patients discharged from emergency departments increased. Pediatric trauma transfers may be a surrogate for referring emergency department capacity and resources and a measure of pediatric trauma triage capability.

Distribution of acute appendicitis care in children: A statewide assessment of the surgeons and facilities providing surgical care.

BACKGROUND: Pediatric appendicitis is managed by general and pediatric surgeons at both children's hospitals and non-children's hospitals. A statewide assessment of surgeons and facilities providing appendicitis care was performed to identify factors associated with location of surgical care. METHODS: Children aged <18 years undergoing appendectomy for appendicitis in Wisconsin from 2018-2020 were identified through the International Classification of Diseases, 10th revision, and Current Procedural Terminology codes using Wisconsin Hospital Association data. Patient residence and hospital locations were used to determine travel distance, rurality, and neighborhood-level socioeconomic status. RESULTS: Among 3,604 children with appendicitis, 36.0% and 12.8% had an appendectomy at 2 major children's hospitals and 4 other children's hospitals, respectively, and 51.2% had an appendectomy at 99 non-children's hospitals. Pediatric surgeons performed 76.1% of appendectomies at children's hospitals and 2.9% at non-children's hospitals. Only 32.2% of patients received care at the hospital closest to their homes. Non-children's hospitals disproportionally cared for older, non-Hispanic White, and privately insured children, those with uncomplicated appendicitis, and those living in rural areas, in mid-socioeconomic status neighborhoods, and greater distances from children's hospitals (all P < .001). After multivariable adjustment, receipt of care at children's hospitals was associated with younger age, minority race, complicated appendicitis, shorter distance to children's hospitals, and urban residence. CONCLUSION: Over half of surgical care for pediatric appendicitis occurred at non-children's hospitals, especially among older children and those living in rural areas far from children's hospitals. Future work is necessary to determine which children benefit most from care at children's hospitals and which can safely receive care at non-children's hospitals to avoid unnecessary time and resource utilization associated with travel to children's hospitals.

Utilization and Adequacy of Telemedicine for Outpatient Pediatric Surgical Care.

INTRODUCTION: Telemedicine (TM) use accelerated out of necessity during the COVID-19 pandemic, but the utility of TM within the pediatric surgery population is unclear. This study measured utilization, adequacy, and disparities in uptake of TM in pediatric surgery during the COVID-19 pandemic. METHODS: Scheduled outpatient pediatric surgery clinic encounters at a large academic children's hospital from January 2020 through March 2021 were reviewed. Sub-group analysis examined post-operative (PO) visits after appendectomy and umbilical, epigastric, and inguinal hernia repairs. RESULTS: Of 9149 scheduled visits, 87.9% were in-person and 12.1% were TM. TM visits were scheduled for PO care (76.9%), new consultations (7.1%), and established patients (16.0%). Although TM visits were more frequently canceled or no shows (P < 0.001), most canceled TM visits were PO visits, of which 41.7% were canceled via electronic communication reporting the absence of any PO concerns. TM visits were adequate for accomplishing visit goals in 98.2%, 95.5%, and 96.2% of PO, new, and established patient visits, respectively. Patients utilizing TM visits were more frequently of white race, privately-insured, from less disadvantaged neighborhoods, and living a greater distance from clinic (P < 0.001 for all comparisons). CONCLUSIONS: TM was adequate for the majority of visits in which it was utilized, including the basic PO visits that occurred via TM. TM was used more by patients with greater travel and less by those of minority race, with public insurance, and from more disadvantaged neighborhoods. Future work is necessary to ensure broad access to this useful tool for all children requiring surgical care.

The COVID-19 pandemic and associated rise in pediatric firearm injuries: A multi-institutional study.

BACKGROUND: Firearm sales in the United States (U.S.) markedly increased during the COVID-19 pandemic. Our objective was to determine if firearm injuries in children were associated with stay-at-home orders (SHO) during the COVID-19 pandemic. We hypothesized there would be an increase in pediatric firearm injuries during SHO. METHODS: This was a multi institutional, retrospective study of institutional trauma registries. Patients <18 years with traumatic injuries meeting National Trauma Data Bank (NTDB) criteria were included. A "COVID" cohort, defined as time from initiation of state SHO through September 30, 2020 was compared to "Historical" controls from an averaged period of corresponding dates in 2016-2019. An interrupted time series analysis (ITSA) was utilized to evaluate the association of the U.S. declaration of a national state of emergency with pediatric firearm injuries. RESULTS: Nine Level I pediatric trauma centers were included, contributing 48,111 pediatric trauma patients, of which 1,090 patients (2.3%) suffered firearm injuries. There was a significant increase in the proportion of firearm injuries in the COVID cohort (COVID 3.04% vs. Historical 1.83%; p < 0.001). There was an increased cumulative burden of firearm injuries in 2020 compared to a historical average. ITSA showed an 87% increase in the observed rate of firearm injuries above expected after the declaration of a nationwide emergency (p < 0.001). CONCLUSION: The proportion of firearm injuries affecting children increased during the COVID-19 pandemic. The pandemic was associated with an increase in pediatric firearm injuries above expected rates based on historical patterns.

Impact of "Stay-at-Home" orders on non-accidental trauma: A multi-institutional study.

BACKGROUND: It is unclear how Stay-at-Home Orders (SHO) of the COVID-19 pandemic impacted the welfare of children and rates of non-accidental trauma (NAT). We hypothesized that NAT would initially decrease during the SHO as children did not have access to mandatory reporters, and then increase as physicians' offices and schools reopened. METHODS: A multicenter study evaluating patients <18 years with ICD-10 Diagnosis and/or External Cause of Injury codes meeting criteria for NAT. "Historical" controls from an averaged period of March-September 2016-2019 were compared to patients injured March-September 2020, after the implementation of SHO ("COVID" cohort). An interrupted time series analysis was utilized to evaluate the effects of SHO implementation. RESULTS: Nine Level I pediatric trauma centers contributed 2064 patients meeting NAT criteria. During initial SHO, NAT rates dropped below what was expected based on historical trends; however, thereafter the rate increased above the expected. The COVID cohort experienced a significant increase in the proportion of NAT patients age ≥5 years, minority children, and least resourced as determined by social vulnerability index (SVI). CONCLUSIONS: The COVID-19 pandemic affected the presentation of children with NAT to the hospital. In times of public health crisis, maintaining systems of protection for children remain essential. LEVEL OF EVIDENCE: III.

The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem.

Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases. Here, we present a simple relationship between disease association statistics and the decline of linkage disequilibrium from a causal site. Specifically, the ratio of Chi-square disease association statistics at a marker site and causal site is equivalent to the standard measure of pairwise linkage disequilibrium, r2. A complete derivation of this relationship from a general disease model is shown. Quite interestingly, this relationship holds across all modes of inheritance. Extensive Monte Carlo simulations using a disease genetics model applied to chromosomes subjected to a standard model of recombination are employed to better understand the variation around this fine mapping theorem due to sampling effects. We also use this relationship to provide a framework for estimating properties of a non-interrogated causal site using data at closely linked markers. Lastly, we apply this way of examining association data from high-density genotyping in a large, publicly-available data set investigating extreme BMI. We anticipate that understanding the patterns of disease association decay with declining linkage disequilibrium from a causal site will enable more powerful fine mapping methods and provide new avenues for identifying causal sites/genes from fine-mapping studies.