Chemically induced cone degeneration in the 13-lined ground squirrel.

Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.

Isolation and survival: The impact of local and MSA isolation on survival among non-Hispanic Black women diagnosed with breast cancer in the United States using a SEER-Medicare cohort.

BACKGROUND: Residential segregation is an important factor that negatively impacts cancer disparities, yet studies yield mixed results and complicate clear recommendations for policy change and public health intervention. In this study, we examined the relationship between local and Metropolitan Statistical Area (MSA) measures of Black isolation (segregation) and survival among older non-Hispanic (NH) Black women with breast cancer (BC) in the United States. We hypothesized that the influence of local isolation on mortality varies based on MSA isolation-specifically, that high local isolation may be protective in the context of highly segregated MSAs, as ethnic density may offer opportunities for social support and buffer racialized groups from the harmful influences of racism. METHODS: Local and MSA measures of isolation were linked by Census Tract (CT) with a SEER-Medicare cohort of 5,231 NH Black women aged 66-90 years with an initial diagnosis of stage I-IV BC in 2007-2013 with follow-up through 2018. Proportional and cause-specific hazards models and estimated marginal means were used to examine the relationship between local and MSA isolation and all-cause and BC-specific mortality, accounting for covariates (age, comorbidities, tumor stage, and hormone receptor status). FINDINGS: Of 2,599 NH Black women who died, 40.0% died from BC. Women experienced increased risk for all-cause mortality when living in either high local (HR = 1.20; CI = 1.08-1.33; p < 0.001) or high MSA isolation (HR = 1.40; CI = 1.17-1.67; p < 0.001). A similar trend existed for BC-specific mortality. Pairwise comparisons for all-cause mortality models showed that high local isolation was hazardous in less isolated MSAs but was not significant in more isolated MSAs. INTERPRETATION: Both local and MSA isolation are independently associated with poorer overall and BC-specific survival for older NH Black women. However, the impact of local isolation on survival appears to depend on the metropolitan area's level of segregation. Specifically, in highly segregated MSAs, living in an area with high local isolation is not significantly associated with poorer survival. While the reasons for this are not ascertained in this study, it is possible that the protective qualities of ethnic density (e.g., social support and buffering from experiences of racism) may have a greater role in more segregated MSAs, serving as a counterpart to the hazardous qualities of local isolation. More research is needed to fully understand these complex relationships. FUNDING: National Cancer Institute.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Historical redlining and breast cancer treatment and survival among older women in the United States.

BACKGROUND: Breast cancer (BC) is the most common cancer among US women, and institutional racism is a critical cause of health disparities. We investigated impacts of historical redlining on BC treatment receipt and survival in the United States. METHODS: Home Owners' Loan Corporation (HOLC) boundaries were used to measure historical redlining. Eligible women in the 2010-2017 Surveillance, Epidemiology, and End Results-Medicare BC cohort were assigned a HOLC grade. The independent variable was a dichotomized HOLC grade: A and B (nonredlined) and C and D (redlined). Outcomes of receipt of various cancer treatments, all-cause mortality (ACM), and BC-specific mortality (BCSM) were analyzed using logistic or Cox models. Indirect effects by comorbidity were examined. RESULTS: Among 18 119 women, 65.7% resided in historically redlined areas (HRAs), and 32.6% were deceased at a median follow-up of 58 months. A larger proportion of deceased women resided in HRAs (34.5% vs 30.0%). Of all deceased women, 41.6% died of BC; a larger proportion resided in HRAs (43.4% vs 37.8%). Historical redlining is a statistically significant predictor of poorer survival after BC diagnosis (hazard ratio = 1.09, 95% confidence interval [CI] = 1.03 to 1.15 for ACM, and hazard ratio = 1.26, 95% CI = 1.13 to 1.41 for BCSM). Indirect effects via comorbidity were identified. Historical redlining was associated with a lower likelihood of receiving surgery (odds ratio = 0.74, 95% CI = 0.66 to 0.83, and a higher likelihood of receiving palliative care odds ratio = 1.41, 95% CI = 1.04 to 1.91). CONCLUSION: Historical redlining is associated with differential treatment receipt and poorer survival for ACM and BCSM. Relevant stakeholders should consider historical contexts when designing and implementing equity-focused interventions to reduce BC disparities. Clinicians should advocate for healthier neighborhoods while providing care.

Association of Self-Reported Coping Strategies With Speech Recognition Outcomes in Adult Cochlear Implant Users.

OBJECTIVE: To characterize the degree to which individual coping strategies may influence speech perception after cochlear implantation. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adult, postlingually deaf cochlear implant recipients. INTERVENTIONS: The Coping Orientation to Problems Experience inventory, a validated, multidimensional self-reported coping scale, was administered preoperatively. MAIN OUTCOME MEASURES: Speech perception was measured using consonant-nucleus-consonant (CNC) phoneme and word scores, AzBio sentence accuracy in quiet and noise, and Hearing in Noise Test sentences in quiet preoperatively and at 1, 3, and 6 months postoperatively. Quality of life was measured with the Hearing Implant Sound Quality Index and the Nijmegen Cochlear Implant Questionnaire. RESULTS: Thirty-six patients were included in this study. Mean age at surgery was 70.7 ± 11.4 years. Acceptance was associated with a decreased AzBio in noise score in the 6 months after CI (regression coefficient b = -0.05; 95% confidence interval [CI], -0.07 to -0.03; p < 0.01). Denial was associated with a decreased AzBio in quiet score (b = -0.05; 95% CI, -0.09 to -0.01; p < 0.05), whereas humor was associated with an increased AzBio in quiet score (b = 0.02; 95% CI, 0.01 to 0.04; p < 0.05). Humor was also associated with an increased Hearing in Noise Test score (b = 0.05; 95% CI, 0.02 to 0.07; p < 0.05). Denial was associated with decreased CNC word (b = -0.04; 95% CI, -0.06 to -0.02; p < 0.01) and phoneme (b = -0.04; 95% CI, -0.07 to -0.02; p < 0.01) scores, whereas substance use was associated with increased CNC word (b = 0.03; 95% CI, 0.01 to 0.05, p < 0.01) and phoneme (b = 0.04; 95% CI, 0.02 to 0.06; p < 0.01) scores. Scores on self-reported quality of life measures were not significantly correlated with coping strategies. CONCLUSION: A variety of adaptive and maladaptive coping strategies are used by postlingually deaf adult cochlear implant users. Denial and acceptance may be more predictive of poor speech performance, whereas humor and substance use may be more predictive of improved speech performance.

Combinatorial genetics reveals the Dock1-Rac2 axis as a potential target for the treatment of NPM1;Cohesin mutated AML.

Acute myeloid leukemia (AML) is driven by mutations that occur in numerous combinations. A better understanding of how mutations interact with one another to cause disease is critical to developing targeted therapies. Approximately 50% of patients that harbor a common mutation in NPM1 (NPM1cA) also have a mutation in the cohesin complex. As cohesin and Npm1 are known to regulate gene expression, we sought to determine how cohesin mutation alters the transcriptome in the context of NPM1cA. We utilized inducible Npm1cAflox/+ and core cohesin subunit Smc3flox/+ mice to examine AML development. While Npm1cA/+;Smc3Δ/+ mice developed AML with a similar latency and penetrance as Npm1cA/+ mice, RNA-seq suggests that the Npm1cA/+; Smc3Δ/+ mutational combination uniquely alters the transcriptome. We found that the Rac1/2 nucleotide exchange factor Dock1 was specifically upregulated in Npm1cA/+;Smc3Δ/+ HSPCs. Knockdown of Dock1 resulted in decreased growth and adhesion and increased apoptosis only in Npm1cA/+;Smc3Δ/+ AML. Higher Rac activity was also observed in Npm1cA/+;Smc3Δ/+ vs. Npm1cA/+ AMLs. Importantly, the Dock1/Rac pathway is targetable in Npm1cA/+;Smc3Δ/+ AMLs. Our results suggest that Dock1/Rac represents a potential target for the treatment of patients harboring NPM1cA and cohesin mutations and supports the use of combinatorial genetics to identify novel precision oncology targets.

Improving Child Development Screening: Implications for Professional Practice and Patient Equity.

INTRODUCTION AND OBJECTIVES: A pediatric group with 25 clinics and 150 providers used multifaceted approaches to implement workflow processes and an electronic health record (EHR) flowsheet to improve child developmental screening. The key outcome was developmental screening done for every patient during 3 periods between ages 8 and 36 months. Identification of developmental concerns was the secondary study outcome. Screening rates and referrals were hypothesized to be optimized for children regardless of demographic backgrounds. METHODS: During preventive visits, developmental screens targeted patients in age groups 8 to 12, 13 to 24, and 25 to 36 months. EHRs were analyzed for screening documentation, results, and referrals by patient demographics. Fifteen pediatric professionals were interviewed about their qualitative experiences. Quality improvement interventions included appointing clinic champions, training staff about the screening process and responsibilities, using a standardized tool, employing plan-do-study-act cycles, posting EHR prompts, providing financial incentives, and monitoring screening rates using control charts. RESULTS: Within 25 months, screening rates improved from 60% to >95% within the 3 preventive visit age groups for a total of more than 30 000 children. Professionals valued the team process improvements. Children enrolled in Medicaid, black children, and those living in lower income zip codes had lower screening rates than privately insured, white children, and those living in higher income areas. Ages and Stages Questionnaire 3rd edition results were significantly different by gender, race/ethnicity, insurance, and income categories across all groups. Referral rates varied by race/ethnicity and zip code of residence. CONCLUSIONS: This project resulted in an effective and efficient process to improve child developmental screening that was valued by pediatric professionals. Analyses of patient demographics revealed disparities in services for the most vulnerable families. Ongoing quality improvement, health services research, and advocacy offer hope to improve health equity.

Association Between Nonsurgical Weight Loss From Body Mass Index >40 to Body Mass Index <40 and Complications and Readmissions Following Total Hip Arthroplasty.

BACKGROUND: Elevated body mass index (BMI) is a risk factor for adverse outcomes following total hip arthroplasty (THA). It is unknown if preoperative weight loss to a BMI <40 kg/m2 is associated with reduced risk of adverse outcomes. METHODS: We retrospectively reviewed elective, primary THA performed at an academic center from 2015 to 2019. Patients were split into groups based on their BMI trajectory prior to THA: BMI consistently <40 ("BMI <40"); BMI >40 at the time of surgery ("BMI >40"); and BMI >40 within 2 years preoperatively, but <40 at the time of surgery ("Weight Loss"). Length of stay (LOS), 30-day readmissions, and complications as defined by Centers for Medicare and Medicaid Services were compared between groups using parsimonious regression models and Fisher's exact testing. Adjusted analyses controlled for sex, age, and American Society of Anesthesiologists class. RESULTS: In total, 1589 patients were included (BMI <40: 1387, BMI >40: 96, Weight Loss: 106). The rate of complications in each group was 3.5%, 6.3%, and 8.5% and the rate of 30-day readmissions was 3.0%, 4.2%, and 7.5%, respectively. Compared to the BMI <40 group, the weight loss group had a significantly higher risk of 30-day readmission (odds ratio [OR] 2.70, 95% confidence interval [CI] 1.19-6.17, P = .02), higher risk of any complication (OR 2.47, 95% CI 1.09-5.59, P = .03), higher risk of mechanical complications (OR 3.07, 95% CI 1.14-8.25, P = .03), and longer median LOS (16% increase, P = .002). The BMI >40 group had increased median LOS (10% increase, P = .03), but no difference in readmission or complications (P > .05) compared to BMI <40. CONCLUSION: Weight loss from BMI >40 to BMI <40 prior to THA was associated with increased risk of readmission and complications compared to BMI <40, whereas BMI >40 was not. LEVEL OF EVIDENCE: Level III - Retrospective Cohort Study.

Multi-segment foot kinematics during gait following ankle arthroplasty.

Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty-nine patients with end-stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi-segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1-6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF-36] questionnaire) and temporal-spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF-36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal-spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi-segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli-segment gait kinematics despite improved patient-reported outcomes and gait mechanics.

Budesonide Prophylaxis Reduces the Risk of Engraftment Syndrome After Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.

BACKGROUND: Engraftment syndrome (ES) after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) encompasses a continuum of periengraftment complications characterized by noninfectious fever, rash, diarrhea, and capillary leak features. PATIENTS AND METHODS: We analyzed the ES outcomes in 257 consecutive patients MM patients who underwent AHCT at our institution from 12/2017 to 11/2019 with budesonide prophylaxis (3 mg PO daily at day +5 post-AHCT till the time of discharge) (N = 109) and no prophylaxis (N = 148). RESULTS: The rates of ES were significantly higher in the no prophylaxis group versus prophylaxis group [69 (46%) vs. 23 (21%); P< .001]. There was no significant difference in length of stay (LOS) [mean 15 (±3.2) vs. 16 (±2.8); P = .27] and 30-day readmission [9 (6%) vs. 8 (7%); P = .81] between the no prophylaxis and prophylaxis groups, respectively. On adjusted analysis, budesonide prophylaxis was associated with a significantly lower risk of developing ES [odds ratio (OR) 0.29 (95% confidence interval [CI], 0.16-0.51); P< .0001]. There was no difference in the 30-day readmission rates [OR 1.12 (95% CI, 0.41-3.03); P = .81], but a trend for shorter LOS in the prophylaxis group [7.3% reduction in LOS (95% CI, -14.4% to 0%); P = .06]. CONCLUSION: Budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing AHCT. These promising results suggest the need for a randomized study investigate the role of budesonide for ES prophylaxis.

Cribriform prostate cancer: Morphologic criteria enabling a diagnosis, based on survey of experts.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

Comparative influence of cribriform growth and percent Gleason 4 in prostatic biopsies with Gleason 3+4 cancer.

The International Society of Urological Pathology endorses specifying presence of cribriform architecture in Gleason (G)4 prostate cancer because of cribriform's aggressiveness. The relative effect of cribriform presence versus percentage G4 within grade group (GG)2 or 3 was uncertain. 194 men's biopsies with GG2 with or without cribriform (excluding glomeruloid from cribriform) and GG3 without cribriform (controls) from 4 years were reviewed. 173 cases had follow-up including 147 GG2 (15/147 or 10% had cribriform) and 26 GG3. Effects of total tumor specimen involvement, %Gleason 4, and cribriform were stratified into prostatectomy (n = 90), radiotherapy (n = 61), and watching waiting (n = 22) groups. Median follow-up duration was 3.32 years (range 1.90-6.18). Biochemical failures in the above 3 cohorts numbered 9 (9/90; 10%), 5 (5/61; 8%), and 13 (13/22; 59%) respectively. In all groups, (GG2+ GG3, n = 173), the HR for C pattern was 1.64. In GG2, cribriform presence (considering glomeruloid as non-cribriform) conferred a hazard ratio (HR) of 1.51 (p = 0.48). It was 1.38, excluding glomeruloid. In watchful waiting cohort only, presence of C conferred a HR of 2.62 (p = 0.086). All remaining comparisons including percent G4, remained not significant. Thus, only in WW group did cribriform pattern presence approach significance. Detection of differences otherwise was not feasible, probably because: 1) biochemical failure is too rare in GG2 cancer; 2) cribriform frequency was only 10% in GG2 (in current study), less than in higher-grade cancer. 3) Use of biopsy tissue is subject to sampling variation which may undersample cribriform pattern, though biopsy forms the basis of treatment decisions.

Validation of an Objective Assessment Tool for Tonsillectomy in Otolaryngology Resident Training.

OBJECTIVE: Create and validate an objective structured assessment of technical skills (OSATS) for otolaryngology residents learning how to perform a tonsillectomy. STUDY DESIGN: Multicenter prospective longitudinal validation study. METHODS: A multi-institutional study at six tertiary academic otolaryngology residency programs from July 2009 to May 2012. Using the modified Delphi technique, a panel of pediatric otolaryngologists created a tonsillectomy task-based checklist (TBC) for a tonsil OSATS using a 5-point Likert-type scale. Residents were assessed by pediatric otolaryngology staff at the time of surgery with the TBC and a global rating scale. Procedure time, patient age, number of previously performed tonsillectomies, and surgical technique were also collected. RESULTS: One hundred sixty-seven tonsil OSATS were completed for 38 residents, and competency was recorded for 99 (59.2%). Residents scored as competent had performed significantly more previous tonsillectomies than those deemed noncompetent, 44.4 ± 35.6 and 13.5 ± 11.6, respectively (P < .001). The mean overall score on the tonsil TBC was 4.0 ± 0.8 and 2.6 ± 1.0 for competent and noncompetent, respectively (P < .001). Higher number of tonsillectomies performed and mean tonsil TBC score significantly increased the likelihood of competency (P < .001). Each additional tonsillectomy performed increased the likelihood of achieving competency by 6.3% (P = .006, 95% confidence interval (CI): 1.330-1.110), and each 1.0 point increase in mean tonsil TBC score increased the likelihood of competency by a factor of 2.71 (P = .006, 95% CI:1.330-5.513). There is a 95% likelihood of competency at 48 tonsillectomies or a tonsil TBC score of 4.91. CONCLUSION: The tonsil OSATS is a valid and feasible instrument to assess resident competency with tonsillectomy and provides timely objective feedback. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E359-E366, 2021.

Wound Trauma Exacerbates Acute, but not Delayed, Effects of Radiation in Rats: Mitigation by Lisinopril.

The goal of this study is to understand and mitigate the effects of wounds on acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), for preparedness against a radiological attack or accident. Combined injuries from concomitant trauma and radiation are likely in these scenarios. Either exacerbation or mitigation of radiation damage by wound trauma has been previously reported in preclinical studies. Female WAG/RijCmcr rats received 13 Gy X-rays, with partial-body shielding of one leg. Within 2 h, irradiated rats and non-irradiated controls were given full-thickness skin wounds with or without lisinopril, started orally 7 days after irradiation. Morbidity, skin wound area, breathing interval and blood urea nitrogen were measured up to 160 days post-irradiation to independently evaluate wound trauma and DEARE. Wounding exacerbated morbidity in irradiated rats between 5 and 14 days post-irradiation (during the ARS phase), and irradiation delayed wound healing. Wounding did not alter delayed morbidities from radiation pneumonitis or nephropathy after 30 days post-irradiation. Lisinopril did not mitigate wound healing, but markedly decreased morbidity during DEARE from 31 through 160 days. The results derived from this unique model of combined injuries suggest different molecular mechanisms of injury and healing of ARS and DEARE after radiation exposure.

Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low-grade cancer.

BACKGROUND: Corpora amylacea (CAM), in benign prostatic acini, contain acute-phase proteins. Do CAM coincide with carcinoma? METHODS: Within 270 biopsies, 83 prostatectomies, and 33 transurethral resections (TURs), CAM absence was designated CAM 0; corpora in less than 5% of benign acini: CAM 1; in 5% to 25%: CAM 2; in more than 25%: CAM 3. CAM were compared against carcinoma presence, clinicopathologic findings, and grade groups (GG) 1 to 2 vs 3 to 5. The frequency of CAM according to anatomic zone was counted. A pilot study was conducted using paired initial benign and repeat biopsies (33 benign, 24 carcinoma). RESULTS: A total of 68.9% of biopsies, 96.4% of prostatectomies, and 66.7% of TURs disclosed CAM. CAM ≥1 was common at an older age (P = .019). In biopsies, 204 cases (75%) had carcinoma; and CAM of 2 to 3 (compared to 0-1) were recorded in 25.0% of carcinomas but only 7.4% of benign biopsies (P = .005; odds ratio [OR] = 5.1). CAM correlated with high percent Gleason pattern 3, low GG (P = .035), and chronic inflammation (CI). CI correlated inversely with carcinoma (P = .003). CAM disclosed no association with race, body mass index, serum prostate specific antigen (PSA), acute inflammation (in biopsies), atrophy, or carcinoma volume. With CAM 1, the odds of GG 3 to 5 carcinoma, by comparison to CAM 0, decreased more than 2× (OR = 0.48; P = .032), with CAM 2, more than 3× (OR = 0.33; P = .005), and with CAM 3, almost 3× (OR = 0.39, P = .086). For men aged less than 65, carcinoma predictive model was: Score = (2 × age) + (5 × PSA) - (20 × degree of CAM); using our data, area under the ROC curve was 78.17%. When the transition zone was involved by cancer, it showed more CAM than in cases where it was uninvolved (P = .012); otherwise zonal distributions were similar. In the pilot study, CAM ≥1 predicted carcinoma on repeat biopsy (P < .05; OR = 8), as did CAM 2 to 3 (P < .0001; OR = 30). CI was not significant, and CAM retained significance after adjusting for CI. CONCLUSION: CAM correlate with carcinoma. Whether abundant CAM in benign biopsies adds value amidst high clinical suspicion, warrants further study.

Magnetic resonance-guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study.

OBJECTIVE: This study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors. METHODS: Data from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed. RESULTS: A total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created. CONCLUSIONS: SLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Youth Victims of Violence Report Worse Quality of Life Than Youth With Chronic Diseases.

OBJECTIVES: Measuring health-related quality of life (HRQOL) provides the patient's perspective of his/her well-being and offers a unique outcome measure to demonstrate the impact of violence on the victim. To date, no study has described HRQOL in youth victims of violence in the United States. The purpose of this study was to describe HRQOL in youth victims of violence as compared with healthy youth and youth with chronic disease. METHODS: We conducted an exploratory cross-sectional study of the HRQOL of victims of violence aged 8 to 18 years. Descriptive statistics were reported for participant and injury demographics. One sample t tests were used to compare the sample population's HRQOL to known HRQOL of healthy populations and specific disease populations. RESULTS: Fifty-eight victims of violence participated in the study. Youth victims of violence had significantly worse mean HRQOL scores (mean, 71.4) compared with healthy youth in overall functioning (mean, 83.9), P < 0.001. Youth victims of violence reported worse psychosocial (mean, 67.6), emotional (mean, 62.9), and school (mean, 63.8) functioning than youth with obesity (mean, 72.1, 68.6, 75.0, respectively) and cancer (mean, 72.1, 72.2, 68.3, respectively). Mean Patient-Reported Outcomes Measurement Information System T scores for youth victims of violence were significantly worse in anxiety (T = 51.9) and depression (T = 52.4) compared with youth with obesity (T = 48.3, 49.2), cancer (T = 47.7, 47.6), and sickle cell disease (T = 43, 44). CONCLUSIONS: Youth victims of violence suffer significant impairment in HRQOL compared with healthy populations and youth with specific disease burdens. Future studies into violence prevention effectiveness should use HRQOL as a comparative outcome measure to better tailor post injury management and interventions.

Intervention Reach and Sexual Risk Reduction of a Multi-level, Community-Based HIV Prevention Intervention for Crack Users in San Salvador, El Salvador.

This article examines the effects of a multi-level, community-based HIV prevention intervention for crack users residing in low-income neighborhoods in San Salvador, El Salvador conducted between August 2011 and June 2016. The intervention consisted of three components introduced sequentially: (1) rapid HIV testing in community settings; (2) a social network HIV testing intervention; and (3) small group interventions with crack users who were members of the same social network. The intervention was evaluated with an interrupted time series design in which we used respondent-driven sampling to conduct 7 cross-sectional surveys with crack users along a 3-4 month period for each assessment (total n = 1597). Results revealed a significant increase in exposure to the intervention over time with 50% of the participants reporting exposure to one or more of the three components. Getting an HIV test at the community site was associated with reductions in total times each individual had sex without a condom (p < 0.05) compared to those who had been exposed to no intervention components. Being referred by another crack user through the Social Network HIV intervention was also associated with reductions in total numbers of condomless sex (p < 0.05) The cumulative effect of being exposed to more than one intervention component was associated with reductions in total number of times individuals had condomless sex (p < 0.05). In spite of the high level of intervention reach and that self-reported exposure to intervention components was associated with lower sexual risk, reductions in sexual risk over time were not observed in the full sample, indicating that the penetration of HIV prevention components was not sufficient to produce population level change.

Risk Factors Linked to Central Catheter-Associated Thrombosis in Critically Ill Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: Our study identified risk factors for the development of clinically identifiable catheter-associated thrombosis (CT). STUDY DESIGN: We performed a retrospective cohort study of neonates in whom a central catheter was present. A total of 1,475 catheters were identified in 766 patients during a 36-month study period. The odds ratio (OR) of thrombi formation in catheterized neonates was modeled using simple (single predictor) and multiple (multiple predictors) logistic regressions as well as simple and multiple Cox's proportional hazard models. RESULT: The incidence of CT was 1.17 per 100 neonates. Unadjusted factors including age at insertion, history of surgery before or during line placement, cholestasis, femoral location, and line size significantly increased the OR or hazards ratio (HR) of developing thrombi formation. In multiple logistic and Cox's regression analyses, three factors continued to be significantly associated with OR or HR of thrombi formation: line size, femoral location, and cholestasis. CONCLUSION: We conclude that clinically identifiable CT is rare in the neonatal population. Furthermore, catheter-specific characteristics are predictive for CT and require further investigation.

Effects of Spinal Fusion for Idiopathic Scoliosis on Lower Body Kinematics During Gait.

STUDY DESIGN: Prospective. OBJECTIVES: The purpose of this study was to compare gait among patients with scoliosis undergoing posterior spinal fusion and instrumentation (PSFI) to typically developing subjects and determine if the location of the lowest instrumented vertebra impacted results. SUMMARY OF BACKGROUND DATA: PSFI is the standard of care for correcting spine deformities, allowing the preservation of body equilibrium while maintaining as many mobile spinal segments as possible. The effect of surgery on joint motion distal to the spine must also be considered. Very few studies have addressed the effect of PSFI on activities such as walking and even fewer address how surgical choice of the lowest instrumented vertebra (LIV) influences possible motion reduction. METHODS: Individuals with scoliosis undergoing PSFI (n = 38) completed gait analysis preoperatively and at postoperative years 1 and 2 along with a control group (n = 24). Comparisons were made with the control group at each time point and between patients fused at L2 and above (L2+) versus L3 and below (L3-). RESULTS: The kinematic results of the AIS group showed some differences when compared to the Control Group, most notably decreased range of motion (ROM) in pelvic tilt and trunk lateral bending. When comparing the LIV groups, only minor differences were observed, and the results showed decreased coronal trunk and pelvis ROM at the one-year visit and decreased hip rotation ROM at the two-year visit in the L3- group. CONCLUSIONS: Patients with AIS showed decreased ROM preoperatively with further decreases postoperatively. These changes remained relatively consistent following the two-year visit, indicating that most kinematic changes occurred in the first year following surgery. Limited functional differences between the two LIV groups may be due to the lack of full ROM used during normal gait, and future work could address tasks that use greater ROM. LEVEL OF EVIDENCE: Level II.