A Development and Implementation of a Preconception Counseling Program for Black Women and Men in the Southeastern United States: A Pilot Protocol.

Introduction: Racial/ethnic disparities in maternal mortality rates represent one of the most significant areas of disparities amongst all conventional population perinatal health measures in the U.S. The alarming trends and persistent disparities of outcomes by race/ethnicity and geographic location reinforce the need to focus on ensuring quality and safety of maternity care for all women. Despite complex multilevel factors impacting maternal mortality and morbidity, there are evidence-based interventions that, when facilitated consistently and properly, are known to improve the health of mothers before, during and after pregnancy. The objective of this project is to test implementation of pre-conception counseling with father involvement in community-based settings to improve cardiovascular health outcomes before and during pregnancy in southeastern United States. Methods and Analysis: This study has two components: a comprehensive needs and assets assessment and a small-scale pilot study. We will conduct a community informed needs and assets assessment with our diverse stakeholders to identify opportunities and barriers to preconception counseling as well as develop a stakeholder-informed implementation plan. Next, we will use the implementation plan to pilot preconception counseling with father involvement in community-based settings. Finally, we will critically assess the context, identify potential barriers and facilitators, and iteratively adapt the way preconception counseling can be implemented in diverse settings. Results of this research will support future research focused on identifying barriers and opportunities for scalable and sustainable public health approaches to implementing evidence-based strategies that reduce maternal morbidity and mortality in the southeastern United States' vulnerable communities. Discussion: Findings will demonstrate that preconception counseling can be implemented in community health settings in the southeastern United States. Furthermore, this study will build the capacity of community-based organizations in addressing the preconception health of their clients. We plan for this pilot to inform a larger scaled-up clinical trial across community health settings in multiple southeastern states.

Intramolecular Heteroatom and Styryl Diels-Alder Reactions, Asymmetric Cycloadditions of Chiral 3-Phenylallyl Maleic Esters.

Polycyclic aryl naphthalene and tetralin dihydro arylnaphthalene lactone lignans possess anticancer and antibiotic activity. Related furo[3,4-c]pyranones, typified by the sequester-terpenoid isobolivianine, show similar antiproliferative bioactivity. Efficient syntheses of compounds featuring these polycyclic cores have proven challenging due to low yields and poor stereoselectivity. We report the synthesis of chiral cinnamyl but-2-enanoates and 3,3-diphenylallyl-but-2-enoates 1 as new Diels-Alder substrates. These compounds undergo [4 + 2]-cycloadditions to give furo[3,4-c]pyranones 2 in good yield (70%) and diastereoselectivity (7:1), together with naphthyl 3 and dihydronaphthyl tetralins 4 as minor products. Molecular structures and stereochemistries of the major products were verified using X-ray diffraction. Density functional theory calculations revealed that the cycloaddition process involves a bispericyclic/ambimodal process where there is a single transition state that leads to both intramolecular styryl Diels-Alder (ISDA) 3, 4 and intramolecular hetero Diels-Alder (IHDA) cycloadducts 2. With the elevated temperature conditions after cycloaddition, the resulting ISDA cycloadduct either undergoes [3,3]-sigmatropic rearrangement to the more stable major IHDA product or aromatization leading to the phenyltetralin.

Low-Dose Short-Term Scheduled Ketorolac Reduces Opioid Use and Pain in Orthopaedic Polytrauma Patients: A Randomized Clinical Trial.

OBJECTIVE: To determine whether scheduled low-dose, short-term ketorolac is associated with reduced length of stay, opioid use, and pain in orthopaedic polytrauma patients. DESIGN: Double-blinded, randomized controlled trial. SETTING: One Level 1 trauma center. PATIENTS: From August 2018 to October 2022, 70 orthopaedic polytrauma patients between 18-75 years-old with a New Injury Severity Score (NISS) > 9 were randomized. 70 participants were enrolled, with 35 randomized to the ketorolac group and 35 to the placebo group. INTERVENTION: 15 mg of intravenous (IV) ketorolac every 6 hours for up to 5 inpatient days or 2 mL of IV saline in a similar fashion. MAIN OUTCOME MEASUREMENTS: Length of Stay (LOS), Morphine Milligram Equivalents (MME), Visual Analogue Scale (VAS), and Complications. RESULTS: Study groups were not significantly different with respect to age, BMI, and NISS (p>0.05). Median LOS was 8 days (interquartile range [IQR], 4.5 to 11.5) in the ketorolac group compared to 7 days (IQR, 3 to 10) in the placebo group (p = 0.275). Over the 5-day treatment period, the ketorolac group experienced a 32% reduction in average MME (p = 0.013) and a 12-point reduction in baseline-adjusted mean VAS (p = 0.037) compared to the placebo group. There were no apparent short-term adverse effects in either group. CONCLUSION: Scheduled low-dose, short-term IV ketorolac was associated with significantly reduced inpatient opioid use and pain in orthopaedic polytrauma patients with no significant difference in LOS and no apparent short-term adverse effects. The results support the use of scheduled low-dose, short-term IV ketorolac for acute pain control among orthopaedic polytrauma patients. Further studies are needed to delineate lasting clinical effects and potential long-term effects, such as fracture healing. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Rain, recreation and risk: Human activity and ecological disturbance create seasonal risk landscapes for the prey of an ambush predator.

Predation risk and prey responses exhibit fluctuations in space and time. Seasonal ecological disturbances can alter landscape structure and permeability to influence predator activity and efficacy, creating predictable patterns of risk for prey (seasonal risk landscapes). This may create corresponding seasonal shifts in antipredator behaviour, mediated by species ecology and trade-offs between risk and resources. Yet, how human recreation interacts with seasonal risk landscapes and antipredator behaviour remains understudied. In South Florida, we investigated the impact of a seasonal ecological disturbance, specifically flooding, which is inversely related to human activity, on interactions between Florida panthers (Puma concolor coryi) and white-tailed deer (Odocoileus virginianus). We hypothesized that human activity and ecological disturbances would interact with panther-deer ecology, resulting in the emergence of two distinct seasonal landscapes of predation risk and the corresponding antipredator responses. We conducted camera trap surveys across southwestern Florida to collect detection data on humans, panthers and deer. We analysed the influence of human site use and flooding on deer and panther detection probability, co-occurrence and diel activity during the flooded and dry seasons. Flooding led to decreased panther detections and increased deer detections, resulting in reduced deer-panther co-occurrence during the flooded season. Panthers exhibited increased nocturnality and reduced diel activity overlap with deer in areas with higher human activity. Supporting our hypothesis, panthers' avoidance of human recreation and flooding created distinct risk schedules for deer, driving their antipredator behaviour. Deer utilized flooded areas to spatially offset predation risk during the flooded season while increasing diurnal activity in response to human recreation during the dry season. We highlight the importance of understanding how competing risks and ecological disturbances influence predator and prey behaviour, leading to the generation of seasonal risk landscapes and antipredator responses. We emphasize the role of cyclical ecological disturbances in shaping dynamic predator-prey interactions. Furthermore, we highlight how human recreation may function as a 'temporal human shield,' altering seasonal risk landscapes and antipredator responses to reduce encounter rates between predators and prey.

Comparison of post-op opioid use and pain between short and long cephalomedullary nails in elderly intertrochanteric fractures.

PURPOSE: It remains unknown if cephalomedullary nail (CMN) length has an impact on pain and opioid use following fixation. Given the lack of level I evidence favoring a specific CMN length to prevent adverse surgical outcomes, we investigated if CMN length impacts acute postoperative pain and opioid use. The authors hypothesize that the use of longer CMNs results in increased pain scores and morphine milligram equivalents (MME) intake during the 0-24 h (h) and 24-36 h postoperative period. METHODS: A retrospective chart review was performed from 2010 to 2020 of patients ≥ 65 years-old who underwent CMN for IT fractures and fractures with subtrochanteric extension (STE). We compared patients who received short and long CMNs using numeric rating scale (NRS) pain scores and MME intake at 0-24 h and 24-36 h postoperatively. RESULTS: 330 patients receiving short (n = 155) and long (n = 175) CMNs met criteria. CMN length was found to not be associated with higher pain scores in the early postoperative phase. However, patients with long CMNs received higher MME from 0-24 h (25.4% estimated mean increase, p value = 0.02) and 24-36 h (22.3% estimated mean increase, p value = 0.04) postoperatively, even after adjusting for covariates, gender, and age. CONCLUSION: Patients with long CMNs received greater MME postoperatively. Additionally, differences in pain and MME were not significantly different between patients with and without STE, suggesting our findings were not influenced by this pattern. These results suggest longer CMNs are associated with higher acute postoperative opioid intake among patients with IT fractures. LEVEL OF EVIDENCE: Therapeutic level III.

Functional Outcomes of Primary Arthrodesis (PA) Versus Open Reduction and Internal Fixation (ORIF) in the Treatment of Lisfranc Injuries.

OBJECTIVES: To determine whether primary arthrodesis (PA) or open reduction and internal fixation (ORIF) results in better functional outcomes through patient-reported outcome measures (PROMs). Reoperation rates and surgical characteristics among the 2 groups are evaluated as well. DESIGN: A retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: Eighty-one patients treated using PA or ORIF for Lisfranc injuries between January 2010 and January 2019. MAIN OUTCOME MEASUREMENTS: PROMs were collected using the validated Foot and Ankle Ability Measure questionnaire. Follow-up ranged from 1 to 10 years posttreatment. RESULTS: Two hundred patients underwent ORIF, and 72 patients underwent PA. Eighty-one of 272 patients responded to the questionnaire. The Foot and Ankle Ability Measure revealed activities of daily living subscores for PA and ORIF of 69.78 ± 18.61 and 73.53 ± 25.60, respectively ( P = 0.48). The Sports subscores for PA (45.81 ± 24.65) and ORIF (56.54 ± 31.13) were not significantly different ( P = 0.11). Perceived levels of activities of daily living ( P = 0.32) and Sports ( P = 0.81) function, compared with preinjury levels, were also not significantly different between the 2 groups. Rates of reoperation were nearly identical for PA (28.1%) and ORIF (30.6%) ( P = 1.00). CONCLUSION: Our results suggest that neither PA nor ORIF is superior regarding functional outcomes or rates of reoperation in the surgical treatment of Lisfranc injuries when appropriately triaged by the treating surgeon. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Association of Talar Neck Fractures With Body Extension and Risk of Avascular Necrosis.

BACKGROUND: The objective of this study was to determine whether talar neck fractures with proximal extension (TNPE) into the talar body are associated with higher rates of avascular necrosis (AVN) compared to isolated talar neck (TN) fractures. METHODS: A retrospective review of patients sustaining talar neck fractures at a level I trauma center from 2008 to 2016 was performed. Demographic and clinical data were collected from the electronic medical record. Fractures were characterized as TN or TNPE based on initial radiographs. TNPE was defined as a fracture that originates on the talar neck and extends proximal to a line subtended from the junction of the neck and the articular cartilage dorsal to the anterior portion of the lateral process of the talus. Fractures were classified according to the modified Hawkins classification for analysis. The primary outcome was the development of AVN. Secondary outcomes included nonunion and collapse. These were measured on postoperative radiographs. RESULTS: There were 137 fractures in 130 patients, with 80 (58%) fractures in the TN group and 57 (42%) in the TNPE group. Median follow-up was 10 months (interquartile range, 6-18 months). The TNPE group was more likely to develop AVN as compared to the TN group (49% vs 19%, P < .001). Similarly, the TNPE group had a higher rate of collapse (14% vs 4%, P = .03) and nonunion (26% vs 9%, P = .01). Even after adjusting for open fracture, Hawkins fracture type, smoking, and diabetes, AVN still remained significant for the TNPE group as compared to the TN group with an odds ratio of 3.47 (95% CI, 1.51-7.99). CONCLUSION: We found a higher rate of AVN, subsequent collapse, and nonunion in patients with TNPE compared to isolated TN fractures. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer - Real-World Outcomes From UK Centres.

AIMS: Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. MATERIALS AND METHODS: We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. RESULTS: Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3-43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months - upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4-7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. CONCLUSIONS: This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.

Masquelet Technique for the Tibia: A Systematic Review and Meta-Analysis of Contemporary Outcomes.

OBJECTIVE: To systematically review outcomes of the Masquelet "induced membrane" technique (MT) in treatment of tibial segmental bone loss and to assess the impact of defect size on union rate when using this procedure. DATA SOURCES: PubMed, EBSCO, Cochrane, and SCOPUS were searched for English language studies from January 1, 2010, through December 31, 2019. STUDY SELECTION: Studies describing the MT procedure performed in tibiae of 5 or more adult patients were included. Pseudo-arthrosis, nonhuman, pediatric, technique, nontibial bone defect, and non-English studies were excluded, along with studies with less than 5 patients. Selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. DATA EXTRACTION: A total of 30 studies with 643 tibiae were included in this meta-analysis. Two reviewers systematically screened titles or abstracts, followed by full texts, to ensure quality, accuracy, and consensus among authors for inclusion or exclusion criteria of the studies. In case of disagreement, articles were read in full to assess their eligibility by the senior author. Study quality was assessed using previously reported criteria. DATA SYNTHESIS: Meta-analysis was performed with random-effects models and meta-regression. A meta-analytic estimate of union rate independent of defect size when using the MT in the tibia was 84% (95% CI, 79%-88%). There was no statistically significant association between defect size and union rate ( P = 0.11). CONCLUSIONS: The MT is an effective method for the treatment of segmental bone loss in the tibia and can be successful even for large defects. Future work is needed to better understand the patient-specific factors most strongly associated with MT success and complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Does prophylactic local tobramycin injection lower open fracture infection rates?

Objective: To determine whether local aqueous tobramycin injection in combination with systemic perioperative IV antibiotic prophylaxis will reduce the rate of fracture-related infection (FRI) after open fracture fixation. Other Outcomes of Interest: (1) To compare fracture nonunion rates and report differences between treatment and control groups and (2) compare bacterial speciation and antibiotic sensitivity among groups that develop FRI. Design: Phase 3 prospective, randomized clinical trial. Setting: Two level 1 trauma centers. Participants: Six hundred subjects (300 in study/tobramycin group and 300 in control/standard practice group) will be enrolled and assigned to the study group or control group using a randomization table. Patients with open extremity fractures that receive definitive internal surgical fixation will be considered. Intervention: Aqueous local tobramycin will be injected into the wound cavity (down to bone) after debridement, irrigation, and fixation, following closure. Main Outcome Measurements: Outcomes will look at the presence or absence of FRI, the rate of fracture nonunion, and determine speciation of gram-negative and Staph bacteria in each group with a FRI. Results: Not applicable. Conclusion: The proposed work will determine whether local tobramycin delivery plus perioperative standard antibiotic synergism will minimize the occurrence of open extremity FRI. Level of Evidence: Level 1.

Identification of the Collagen Types Essential for Mammalian Breast Acinar Structures.

Modeling human breast tissue architecture is essential to study the pathophysiological conditions of the breast. We report that normal mammary epithelial cells grown in human breast extracellular matrix (ECM) hydrogel formed acini structurally similar to those of human and pig mammary tissues. Type I, II, III and V collagens were commonly identified in human, pig, and mouse breast ECM. Mammary epithelial cells formed acini on certain types or combinations of the four collagens at normal levels of breast tissue elasticity. Comparison of the collagen species in mouse normal breast and breast tumor ECM revealed common and distinct sets of collagens within the two types of tissues. Elevated expression of collagen type I alpha 1 chain (Col1a1) was found in mouse and human breast cancers. Collagen type XXV alpha 1 chain (Col25a1) was identified in mouse breast tumors but not in normal breast tissues. Our data provide strategies for modeling human breast pathophysiological structures and functions using native tissue-derived hydrogels and offer insight into the potential contributions of different collagen types in breast cancer development.

Outcomes of Reamed Intramedullary Nailing for Lower Extremity Diaphyseal Fractures in COVID-Positive Patients: A Multi-institutional Observational Study.

OBJECTIVE: To determine if reamed intramedullary nailing (IMN) of tibial and femoral shaft fractures exacerbated the hypercoagulable state of COVID infection, resulting in increased thromboembolic and pulmonary complications. DESIGN: Retrospective chart review. SETTING: Eleven Level I trauma centers. PATIENTS: From January 1, 2020, to December 1, 2022, 163 patients with orthopaedic trauma and COVID positivity and 36 patients with tibial and femoral shaft fractures were included. INTERVENTION: Reamed IMN. MAIN OUTCOME MEASURES: Incidence of postoperative thromboembolic and respiratory complications. RESULTS: Thirty-six patients with a median age of 52 years (range, 18-92 years; interquartile range, 29-72 years) met criteria. There were 21 and 15 patients with femoral and tibial shaft fractures. There were 15 patients sustaining polytrauma; of which, 10 had a new injury severity score of >17. All patients underwent reamed IMN in a median of 1 day (range, 0-12 days; interquartile range = 1-2 days) after injury. Two patients developed acute respiratory distress syndrome (ARDS) and 3 pneumonia. No patients had pulmonary embolism, deep vein thrombosis, or died within 30 days. CONCLUSION: In this multi-institutional review of COVID-positive patients undergoing reamed IMN, there were no thromboembolic events. All patients developing pulmonary complications (ARDS or pneumonia) had baseline chronic obstructive pulmonary disease, were immune compromised, or sustained polytraumatic injuries with new injury severity score of >20. Given this, it seems reasonable to continue using reamed IMN for tibial and femoral shaft fractures after evaluation for COVID severity, comorbidities, and other injuries. LEVELS OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Impact of Infant Thoracic Non-cardiac Perioperative Critical Care on Homotopic-Like Corpus Callosum and Forebrain Sub-regional Volumes.

Previously, we reported quantitatively smaller total corpus callosum (CC) and total forebrain size in critically ill term-born and premature patients following complex perioperative critical care for long-gap esophageal atresia (LGEA) that included Foker process repair. We extended our cross-sectional pilot study to determine sub-regional volumes of CC and forebrain using structural brain MRI. Our objective was to evaluate region-specific CC as an in-vivo marker for decreased myelination and/or cortical neural loss of homotopic-like sub-regions of the forebrain. Term-born (n = 13) and premature (n = 13) patients, and healthy naïve controls (n = 21) <1-year corrected age underwent non-sedated MRI using a 3T Siemens scanner, as per IRB approval at Boston Children's Hospital following completion of clinical treatment for Foker process. We used ITK-SNAP (v.3.6) to manually segment six sub-regions of CC and eight sub-regions of forebrain as per previously reported methodology. Group differences were assessed using a general linear model univariate analysis with corrected age at scan as a covariate. Our analysis implicates globally smaller CC and forebrain with sub-region II (viz. rostral body of CC known to connect to pre-motor cortex) to be least affected in comparison to other CC sub-regions in LGEA patients. Our report of smaller subgenual forebrain implicates (mal)adaptation in limbic circuits development in selected group of infant patients following LGEA repair. Future studies should include diffusion tractography studies of CC in further evaluation of what appears to represent global decrease in homotopic-like CC/forebrain size following complex perioperative critical care of infants born with LGEA.

An Off-Label Use of a Tensioned Proximal Humerus Plate for Tibiotalar Fusion: A Case Report.

CASE: A 70-year-old man presented with a left pilon fracture after a 10-foot fall from a ladder. The severe amount of comminution, joint destruction, and impaction from this injury eventually resulted in a tibiotalar fusion. Owing to multiple tibiotalar fusion plates not being long enough to span the extent of the fracture, a tensioned proximal humerus plate was used as an alternative. CONCLUSION: We do not endorse the off-label use of a tensioned proximal humerus plate for all tibiotalar fusions; however, we do believe that this is a useful technique in certain situations with large zones of distal tibial comminution.

Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells.

Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.

Infant study of hemispheric asymmetry after long-gap esophageal atresia repair.

OBJECTIVES: Previous studies have demonstrated that infants are typically born with a left-greater-than-right forebrain asymmetry that reverses throughout the first year of life. We hypothesized that critically ill term-born and premature patients following surgical and critical care for long-gap esophageal atresia (LGEA) would exhibit alteration in expected forebrain asymmetry. METHODS: Term-born (n = 13) and premature (n = 13) patients, and term-born controls (n = 23) <1 year corrected age underwent non-sedated research MRI following completion of LGEA treatment via Foker process. Structural T1- and T2-weighted images were collected, and ITK-SNAP was used for forebrain tissue segmentation and volume acquisition. Data were presented as absolute (cm3 ) and normalized (% total forebrain) volumes of the hemispheres. All measures were checked for normality, and group status was assessed using a general linear model with age at scan as a covariate. RESULTS: Absolute volumes of both forebrain hemispheres were smaller in term-born and premature patients in comparison to controls (p < 0.001). Normalized hemispheric volume group differences were detected by T1-weighted analysis, with premature patients demonstrating right-greater-than-left hemisphere volumes in comparison to term-born patients and controls (p < 0.01). While normalized group differences were very subtle (a right hemispheric predominance of roughly 2% of forebrain volume), they represent a deviation from the expected pattern of hemispheric brain asymmetry. INTERPRETATION: Our pilot quantitative MRI study of hemispheric volumes suggests that premature patients might be at risk of altered expected left-greater-than-right forebrain asymmetry following repair of LGEA. Future neurobehavioral studies in infants born with LGEA are needed to elucidate the functional significance of presented anatomical findings.

Infant Corpus Callosum Size After Surgery and Critical Care for Long-Gap Esophageal Atresia: Qualitative and Quantitative MRI.

Previous studies in preterm infants report white matter abnormalities of the corpus callosum (CC) as an important predictor of neurodevelopmental outcomes. Our cross-sectional study aimed to describe qualitative and quantitative CC size in critically ill infants following surgical and critical care for long-gap esophageal atresia (LGEA) - in comparison to healthy infants - using MRI. Non-sedated brain MRI was acquired for full-term (n = 13) and premature (n = 13) patients following treatment for LGEA, and controls (n = 20) <1 year corrected age. A neuroradiologist performed qualitative evaluation of T1-weighted images. ITK-SNAP was used for linear, 2-D and 3-D manual CC measures and segmentations as part of CC size quantification. Qualitative MRI analysis indicated underdeveloped CC in both patient groups in comparison to controls. We show no group differences in mid-sagittal CC length. Although 2-D results were inconclusive, volumetric analysis showed smaller absolute (F(2,42) = 20.40, p < 0.001) and normalized (F(2,42) = 16.61, p < 0.001) CC volumes following complex perioperative treatment for LGEA in both full-term and premature patients, suggesting delayed or diminished CC growth in comparison to controls, with no difference between patient groups. Future research should look into etiology of described differences, neurodevelopmental outcomes, and role of the CC as an early marker of neurodevelopment in this unique infant population.

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.