A pragmatic methodology to extract anesthetic and physiological data from the electronic health record.

BACKGROUND/AIMS: Traditional manual methods of extracting anesthetic and physiological data from the electronic health record rely upon visual transcription by a human analyst that can be labor-intensive and prone to error. Technical complexity, relative inexperience in computer coding, and decreased access to data warehouses can deter investigators from obtaining valuable electronic health record data for research studies, especially in under-resourced settings. We therefore aimed to develop, pilot, and demonstrate the effectiveness and utility of a pragmatic data extraction methodology. METHODS: Expired sevoflurane concentration data from the electronic health record transcribed by eye was compared to an intermediate preprocessing method in which the entire anesthetic flowsheet narrative report was selected, copy-pasted, and processed using only Microsoft Word and Excel software to generate a comma-delimited (.csv) file. A step-by-step presentation of this method is presented. Concordance rates, Pearson correlation coefficients, and scatterplots with lines of best fit were used to compare the two methods of data extraction. RESULTS: A total of 1132 datapoints across eight subjects were analyzed, accounting for 18.9 h of anesthesia time. There was a high concordance rate of data extracted using the two methods (median concordance rate 100% range [96%, 100%]). The median time required to complete manual data extraction was significantly longer compared to the time required using the intermediate method (240 IQR [199, 482.5] seconds vs 92.5 IQR [69, 99] seconds, p = .01) and was linearly associated with the number of datapoints (rmanual = .97, p < .0001), whereas time required to complete data extraction using the intermediate approach was independent of the number of datapoints (rintermediate = -.02, p = .99). CONCLUSIONS: We describe a pragmatic data extraction methodology that does not require additional software or coding skills intended to enhance the ease, speed, and accuracy of data collection that could assist in clinician investigator-initiated research and quality/process improvement projects.

Risk Factors for Increased Hospital Costs for Primary Total Hip Arthroplasty.

BACKGROUND: Patient medical complexity increases the cost of primary total hip arthroplasty (THA). The goal of this study was to quantify the impact of specific medical comorbidities on the real hospital cost of primary THA. METHODS: This study consisted of a retrospective analysis of 1,222 patient encounters for Current Procedural Terminology code 27130 (primary THA) between January 2017 and March 2020 at a high-volume urban academic medical center. Patient demographics, comorbidities, and admission data were collected, and univariate and multivariate gamma regression analyses were performed to identify associations with increased costs incurred during THA admission. RESULTS: The median total cost for THA was $30,580. Univariate analysis showed increased cost for body mass index (BMI) > 35 versus BMI < 35 ($31,739 versus 30,071; P < .05), American Society of Anesthesiologists (ASA) score 3 to 4 versus ASA 1 to 2 ($32,268 versus 30,045; P < .05), prevalence of diabetes ($31,523 versus 30,379; P < .05), congestive heart failure ($34,814 versus 30,584; P < .05), peripheral vascular disease (PVD) ($35,369 versus 30,573; P < .05), chronic pulmonary disease (CPD) ($34,625 versus 30,405; P < .05), renal disease ($31,973 versus 30,352; P < .05), and increased length of stay (r = 0.424; P < .05). Multivariate gamma regression showed that BMI > 35 (relative risk [RR] = 1.05), ASA 3 to 4 (RR = 1.07), PVD (RR = 1.29), CPD (RR = 1.13), and renal disease (RR = 1.09) were independently associated with increased THA hospital cost (P < .01). Increased costs seen in BMI > 35 versus BMI < 35 patients were largely due to hospital room and board ($6,345 versus 5,766; P = .01) and operating room costs ($5,744 versus 5,185; P < .05). CONCLUSIONS: A BMI > 35, PVD, CPD, renal disease, and ASA 3 to 4 are associated with higher inpatient hospital costs for THA. LEVEL OF EVIDENCE: Level III; Retrospective cohort study.

Pediatric Fractures: Does Vitamin D Play a Role?

BACKGROUND: Vitamin D (25-OHD) deficiency and insufficiency are reported in about half of all children. The literature on low 25-OHD and pediatric fracture risk presents inconsistent results. This study evaluates the association between pediatric fractures and 25-OHD, parathyroid hormone (PTH), and calcium. METHODS: This is a prospective case-control study in 2 urban pediatric emergency departments (2014-2017). Patients aged 1 to 17 requiring intravenous access were enrolled. Demographics, nutrition, and activity information were recorded and levels of 25-OHD, calcium, and PTH were measured. RESULTS: Two hundred forty-five subjects were enrolled: 123 fractures and 122 controls. Overall, the mean 25-OHD level was 23 ng/mL±8.5: 52 (21%) of patients were 25-OHD sufficient; 193 (79%) were not. Ninety-six percent of patients with lower extremity fractures had low 25-OHD versus 77% of patients with upper extremity fractures ( P =0.024). The fracture cohort was younger ( P =0.002), included more males ( P =0.020), and spent more time playing outdoor sports ( P =0.011) than the control cohort. The 25-OHD level (fracture 22.8 ng/mL±7.6 vs. nonfracture 23.5 ng/mL±9.3, P =0.494) and median calcium level (fracture 9.8 mg/dL vs. nonfracture 10.0 mg/dL, P =0.054) were similar between cohorts. The median PTH level was higher in the fracture than the control cohort (33 vs. 24.5 pg/mL; P <0.0005); PTH was elevated to hyperparathyroidism (>65 pg/mL) in 13% of fractures and 2% of controls ( P =0.006). Matched subgroup analysis of 81 fracture patients and 81 controls by age, gender, and race showed that PTH was the only variable independently associated with increased odds of fracture (odds ratio=1.10, 95% CI, 1.01-1.19, P =0.021) in a model adjusted for vitamin D sufficiency and time spent playing outdoor sports. CONCLUSIONS: Low 25-OHD is common in children with fractures but we found no difference in 25-OHD levels between fracture and nonfracture cohorts. This research can impact evidence-based guidelines on vitamin D level screening and/or supplementation after fracture. LEVEL OF EVIDENCE: Diagnostic level IV-case-control study.

Decreased Electroencephalographic Alpha Power During Anesthesia Induction Is Associated With EEG Discontinuity in Human Infants.

BACKGROUND: Electroencephalogram (EEG) discontinuity can occur at high concentrations of anesthetic drugs, reflecting suppression of electrocortical activity. This EEG pattern has been reported in children and reflects a deep state of anesthesia. Isoelectric events on the EEG, a more extreme degree of voltage suppression, have been shown to be associated with worse long-term neurologic outcomes in neonates undergoing cardiac surgery. However, the clinical significance of EEG discontinuities during pediatric anesthesia for noncardiac surgery is not yet known and merits further research. In this study, we assessed the incidence of EEG discontinuity during anesthesia induction in neurologically normal infants and the clinical factors associated with its development. We hypothesized that EEG discontinuity would be associated with sevoflurane-induced alpha (8-12 Hz) power during the period of anesthesia induction in infants. METHODS: We prospectively recorded 26 channels of EEG during anesthesia induction in an observational cohort of 54 infants (median age, 7.6 months; interquartile range [IQR] [4.9-9.8 months]). We identified EEG discontinuity, defined as voltage amplitude <25 microvolts for >2 seconds, and assessed its association with sevoflurane-induced alpha power using spectral analysis and multivariable logistic regression adjusting for clinically important variables. RESULTS: EEG discontinuity was observed in 20 of 54 subjects (37%), with a total of 25 discrete events. Sevoflurane-induced alpha power in the posterior regions of the head (eg, parietal or occipital regions) was significantly lower in the EEG discontinuity group (midline parietal channel on the electroencephalogram, International 10-20 System [Pz]; 8.3 vs 11.2 decibels [dBs]; P = .004), and this association remained after multivariable adjustment (adjusted odds ratio [aOR] = 0.51 per dB increase in alpha power [95% CI, 0.30-0.89]; P = .02). There were no differences in the baseline (unanesthetized) EEG between groups in alpha power or power in any other frequency band. CONCLUSIONS: We demonstrate that EEG discontinuity is common during anesthesia induction and is related to the level of sevoflurane-induced posterior alpha power, a putative marker of cortical-thalamic circuit development in the first year of life. This association persisted even after adjusting for age and propofol coadministration. The fact that this difference was only observed during anesthesia and not in the baseline EEG suggests that otherwise hidden brain circuit properties are unmasked by general anesthesia. These neurophysiologic markers observed during anesthesia may be useful in identifying patients who may have a greater chance of developing discontinuity.

Posterior-only Resection of Single Hemivertebrae With 2-Level Versus >2-Level Fusion: Can We Improve Outcomes?

BACKGROUND: The outcomes of congenital scoliosis (CS) patients undergoing hemivertebra (HV) resection surgery with a 2-level fusion versus a >2-level fusion are unclear. We hypothesized that CS patients undergoing HV resection and a >2-level fusion have decreased curve progression and reoperation rates compared with 2-level fusions. METHODS: Retrospective review of prospectively collected data from a multicenter scoliosis database. Fifty-three CS patients (average age 4.5, range 1.2 to 10.9 y) at index surgery were included. Radiographic and surgical parameters, complications, as well as revision surgery rates were tracked at a minimum of 2-year follow-up. RESULTS: Twenty-six patients had a 2-level fusion while 27 patients had a >2-level fusion with similar age and body mass index between groups. The HV was located in the lumbar spine for 69% (18/26) 2-level fusions and 30% (8/27) >2-level fusions ( P =0.006). Segmental HV scoliosis curve was smaller in 2-level fusions compared to >2-level fusions preoperatively (38 vs. 50 degrees, P =0.016) and at follow-up (25 vs. 34 degrees, P =0.038). Preoperative T2-T12 (28 vs. 41 degrees, P =0.013) and segmental kyphosis (11 vs. 23 degrees, P =0.046) were smaller in 2-level fusions, but did not differ significantly at postoperative follow-up (32 vs. 39 degrees, P =0.22; 13 vs. 11 degrees, P =0.64, respectively). Furthermore, the 2 groups did not significantly differ in terms of surgical complications (27% vs. 22%, P =0.69; 2-level fusion vs. >2-level fusion, respectively), unplanned revision surgery rate (23% vs. 22%, 0.94), growing rod placement or extension of spinal fusion (15% vs. 15%, P =0.95), or health-related quality of life per the EOS-Questionnaire 24 (EOSQ-24). Comparison of patients with or without the need for growing rod placement or posterior spinal fusion revealed no significant differences in all parameters analyzed. CONCLUSIONS: Two-level and >2-level fusions can control congenital curves successfully. No differences existed in curve correction, proximal junctional kyphosis or complications between short and long-level fusion after HV resection. Both short and long level fusions are viable options and generate similar risk of revision. The decision should be individualized by patient and surgeon.

Are All Hardware Removals Equal?

The objective of this study is to report operative time and associated complications of six types of implants and to determine if surgeons are adequately compensated. Hardware removals were analyzed from 2014-2019. Implants were flexible nails, intramedullary rigid nails, long plates, screw(s), single guided-growth plates, and multiple guided-growth plates. Patient demographics, operative time, blood loss, complications, and relative value units (RVU)/min were collected. RVU/min was used to maximize rate. In total, 392 patients were analyzed. Long plate removals took significantly longer than screw removal, therefore RVU/min was significantly lower (p < 0.001). Long plate removals also took significantly longer, and RVU/min was significantly lower compared to guided-growth plate removal (p < 0.001). Intramedullary nails took significantly longer compared to flexible nails, nearly double the RVU/min (p = 0.02). The results from this study indicate that the RVU/ minute for these six different types of implant removals are not equal. Surgeons can use this data to set up their schedule to ensure maximum utilization. (Journal of Surgical Orthopaedic Advances 30(1):020-023, 2021).

Effects of Fellowship Training on Pediatric Anterior Cruciate Ligament Reconstruction Techniques and Outcomes.

The purpose of this study is to examine differences in pediatric anterior cruciate ligament reconstruction (ACLR) between surgeons with either pediatric or sports medicine fellowship training. Patients were divided into two groups, those performed by either a pediatric or sports medicine fellowship-trained surgeon. One hundred and forty-one patients were identified: 91 (64.5%) by pediatric trained surgeons and 50 (35.4%) by sports medicine trained surgeons. Patients that had ACLR by a pediatric trained surgeon were younger (p = 0.02), had larger body mass index (BMI) (p = 0.027), and more likely to have government assisted insurance (p = 0.006). Pediatric trained surgeons had longer procedure time (p < 0.001), used smaller graft sizes (p = 0.016), used soft tissue grafts (p < 0.001) and used button fixation at both the femur and tibia (p < 0.001). There were no differences regarding meniscus surgery, surgical technique (transphyseal versus physeal sparing), arthrofibrosis, graft failure, and intraoperative complications (p > 0.05). This study shows favorable and comparable results after ACLRs with either pediatric or sports medicine fellowship training. (Journal of Surgical Orthopaedic Advances 30(3):161-165, 2021).

Community Racial Composition and Hospitalization Among Patients Receiving In-Center Hemodialysis.

RATIONALE & OBJECTIVE: Community racial composition has been shown to be associated with mortality in patients receiving maintenenance dialysis. It is unclear whether living in communities with predominantly Black residents is also associated with risk for hospitalization among patients receiving hemodialysis. STUDY DESIGN: Retrospective analysis of prospectively collected data from a cohort of patients receiving hemodialysis. SETTING & PARTICIPANTS: 4,567 patients treated in 154 dialysis facilities located in 127 unique zip codes and enrolled in US Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 5 (2010-2015). EXPOSURE: Tertile of percentage of Black residents within zip code of patients' dialysis facility, defined through a link to the American Community Survey. OUTCOME: Rate of hospitalizations during the study period. ANALYTIC APPROACH: Associations of patient-, facility-, and community-level variables with community's percentage of Black residents were assessed using analysis of variance, Kruskal-Wallis, or χ2/Fisher exact tests. Negative binomial regression was used to estimate the incidence rate ratio for hospitalizations between these communities, with and without adjustment for potential confounding variables. RESULTS: Mean age of study patients was 62.7 years. 53% were White, 27% were Black, and 45% were women. Median and threshold percentages of Black residents in zip codes in which dialysis facilities were located were 34.2% and≥14.4% for tertile 3 and 1.0% and≤1.8% for tertile 1, respectively. Compared with those in tertile 1 facilities, patients in tertile 3 facilities were more likely to be younger, be Black, live in urban communities with lower socioeconomic status, have a catheter as vascular access, and have fewer comorbid conditions. Patients dialyzing in communities with the highest tertile of Black residents experienced a higher adjusted rate of hospitalization (adjusted incidence rate ratio, 1.32; 95% CI, 1.12-1.56) compared with those treated in communities within the lowest tertile. LIMITATIONS: Potential residual confounding. CONCLUSIONS: The risk for hospitalization for patients receiving maintenance dialysis is higher among those treated in communities with a higher percentage of Black residents after adjustment for dialysis care, patient demographics, and comorbid conditions. Understanding the cause of this association should be a priority of future investigation.

Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial.

RATIONALE & OBJECTIVE: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN: Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS: Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS: Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING: National Institutes of Health grant. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01452412.

Tumour-infiltrating lymphocytes in ductal carcinoma in situ (DCIS)-assessment with three different methodologies and correlation with Oncotype DX DCIS Score.

AIMS: Tumour-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer; however, their prognostic significance in ductal carcinoma in situ (DCIS) has not been established. The Oncotype DX (ODX) Breast DCIS Score test is a genomic assay used to predict the local recurrence risk. The aims of this study were to quantify TILs in DCIS by the use of three methodologies, and correlate them with the ODX DCIS Score. METHODS AND RESULTS: We studied 97 DCIS cases, all with an ODX DCIS Score. Cases with a low ODX DCIS Score were considered as one group, and those with an intermediate/high ODX Score were considered together. TILs were quantified on haematoxylin and eosin-stained slides. The methodologies used to quantify TILS included assessment of stromal TILs, assessment of touching TILs, and assessment of circumferential TILS. In cases with >5% stromal TILS, the percentage of stromal TILS was considered to be high. In cases with a mean number of more than five touching TILs per DCIS duct, TILs were considered to be present. The ODX DCIS Score was intermediate/high in 27 (28%) cases and low in 70 (72%) cases. There were >5% stromal TILs in 33 (34%) cases, and more than five touching TILs per DCIS duct in 15 (15%) cases; circumferential TILs were present in nine (9%) cases. In univariate analysis, a low ODX DCIS Score showed significant associations with absent touching TILS (P = 0.027), stromal TILs < 5% (P = 0.031), and absent circumferential TILs (P = 0.002). In logistic regression analysis adjusted for necrosis and nuclear grade, touching TILs and circumferential TILs showed significant associations with the ODX DCIS Score, whereas stromal TILs did not. CONCLUSIONS: Our results suggest that both the presence of TILs and the spatial arrangement of TILs or close proximity of TILs to DCIS, and TILs touching or encircling DCIS, may be predictive of recurrence.

End Vertebra Versus Apical Vertebra: Where Are We More Likely to Misplace in Spine Deformity?

BACKGROUND DATA: Pedicle screws placement remains technically demanding. The thoracic curve apex is considerably difficult due to its unique morphology and severe rotation. In comparison the upper end vertebrae have smaller pedicles and limited soft tissue exposure. This study seeks to evaluate the likelihood of screw misplacement at the end vertebra and apex. METHODS: A retrospective review of preoperative and postoperative computed tomographic (CT) scans of spinal deformity patients who underwent posterior spinal fusion with pedicle screw constructs between 2004 and 2011 was performed. Pedicles located at the upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV), and the major and minor apices were evaluated. Pedicle morphology was studied on preoperative CT and screw placement on postoperative CT. RESULTS: In total, 188 patients met the inclusion criteria, 172 had preoperative CT scans and 133 had postoperative CT scans. The UIV had a significantly lower percentage of normal pedicles (type A) compared with apex major, apex minor, or LIV (59.1% vs. 76.1% vs. 77.3% vs. 98.7%; P<0.001). UIV had significantly the lowest percentage of normal normally placed screws compared with LIV, apex major, or apex minor (69.4% vs. 97.3% vs. 87.6% vs. 92.1%; P<0.001). In a logistic regression adjusted for preoperative Cobb angles, UIV was more likely to have screws misplaced (odds ratio =7.56; 95% confidence interval, 4.01-14.30; P<0.001) and abnormal pedicles (odds ratio=2.81; 95% confidence interval, 1.52-5.19; P=0.001) compared with any other location studied. In abnormal pedicles, 41 (39.8%) of the 103 UIV screws were misplaced, whereas 10 (16.4%) of the 61 apex major, apex minor, or LIV screws were misplaced (P=0.007). CONCLUSIONS: The UIV presents more of a risk for pedicle screw misplacement and abnormal morphology when compared with LIV and apical vertebra. We believe these findings can aid in the surgeon's preoperative and intraoperative management to ensure increased success in accurate and safe pedicle screw placement. LEVEL OF EVIDENCE: Level III.

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P < .0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50. © 2018 American Cancer Society.

Holocrine Poroma: A Distinctive Adnexal Tumor.

There are 36 cases of complex poroid tumors with folliculosebaceous and apocrine differentiation reported in the literature. The authors evaluated 111 poroid tumors including 63 typical eccrine poromas and 48 poroid tumors with folliculosebaceous elements. Folliculosebaceous poroid tumors (FSPT) had basaloid and squamous cells (100%), ducts with steatocystoma-like cuticles and holocrine secretions (89.6%), infundibular follicular structures (66.7%), and entrapped sebocytes (56.3%). No definite apocrine decapitation secretions in FSPT were found. Immunohistochemistry was strongly positive for CK903 and focally positive for CAM5.2, epithelial membrane antigen, and carcinoembryonic antigen. No loss of MLH-1, MSH-2, or MSH-6 mismatch repair proteins was found. FSPT had distinctive features that differentiate them from eccrine poromas including the frequent head and neck locations (62.5% vs. 20.6%, P < 0.01), squamous cytology (100% vs. 1.6%, P < 0.01), more prominent cytoplasmic vacuolization (score 1.4/4.0 vs. 0.3/4.0, P < 0.01), presence of infundibular follicular structures (score 1.2/4.0 vs. 0.03/4.0, P < 0.01), presence of ducts with steatocystoma-like cuticles (89.6% vs. 0.0%, P < 0.01), and less stromal hyalinization (score 1.0/4.0 vs. 2.5/4.0, P < 0.01). The authors propose that FSPT are distinctive benign tumors originating from the sebaceous gland duct and are therefore best categorized as holocrine poroma.

Breast pathology and mammography BI-RADS category correlation study - A single institute experience.

Although recent technological advances, there is still discordance between mammography findings and pathologic diagnoses, especially for certain racial/ethnic populations. In this study we correlated the mammography BI-RADS categories with pathologic diagnoses, aiming to evaluate the performance of mammography in breast cancer detection in a unique poor population consisting of mostly Hispanics and African Americans. A total of 3935 female patients with a breast mammography and a subsequent breast pathology report within 90 days were retrospectively analyzed. There were 875 (22.2%) patients with a negative or probably benign mammography (BI-RADS 1, 2 and 3), and 33 (3.8%) of them had a malignant pathologic diagnosis. Patients with malignant pathologic diagnoses were older, higher in socioeconomic status (SES), and more likely to be African American or White, compared to those with non-malignant pathologic findings. They mostly presented with related symptoms (e.g. breast pain, mass or discharge) and/or family history or past history of breast cancers, which triggered secondary imaging examination and subsequent breast biopsy/excision, and eventually resulted to the diagnosis of breast cancers. In conclusion, our studies indicated that the performance of mammography is comparable in detection of breast cancers among Hispanics, African American and White populations, if it was done in the same facility. Our results also suggested that for patients with presenting symptoms, past history of breast cancer or strong family history of breast cancer, a secondary breast imaging examination may be warranted following a negative to probably benign mammography (BI-RADS 1-3).

Mechanical analysis of the vascularized fibular graft prosthetic composite (VFGPC) for internal hemipelvectomy reconstruction.

INTRODUCTION: The vascularized fibular graft prosthetic composite (VFGPC) is used for reconstruction after internal hemipelvectomy. The purpose of this study was to create a mathematical model that calculates the mechanical effects of the vascularized fibular graft on the VFGPC. METHODS: The effects of the VFG positioning were calculated based on three-dimensional static analyzes to determine the direction, magnitude, and distribution of the forces through the prosthesis and VFG. The shear stress (SS) and cyclic loads to failure (CLF) were calculated. By varying the location of the VFG on the sacrum the zone of acceptable placement was calculated. RESULTS: Utilization of the VFG decreased the forces through the implant by 15-35% and decreased SS 20-54%, depending on stance. The CLF improved by 94%. The zone of acceptable placement for the VFG was found to be between 0° and 15° of the vertical axis in the sagittal plane and 0° and 30° of the posterior axis in coronal plane. CONCLUSION: Determining the position of the VFG pre-operatively allows for the creation of a customized cutting jig can be utilized to create graft allowing for accurate fibular osteotomies, minimization of ischemia time, and decreased intra-operative handling of the graft.

Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals.

BACKGROUND: Clinically significant dysregulation of the insulin-like growth factor (IGF) family proteins occurs in HIV-infected individuals, but the details including whether the deficiencies in IGFs contribute to CNS dysfunction are unknown. METHODS: We measured the levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGF2 receptor (IGF2R) in matching plasma and cerebrospinal fluid (CSF) samples of 107 HIV+ individuals from CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and analyzed their associations with demographic and disease characteristics, as well as levels of several soluble inflammatory mediators (TNFα, IL-6, IL-10, IL-17, IP-10, MCP-1, and progranulin). We also determined whether IGF1 or IGF2 deficiency is associated with HIV-associated neurocognitive disorder (HAND) and whether the levels of soluble IGF2R (an IGF scavenging receptor, which we also have found to be a cofactor for HIV infection in vitro) correlate with HIV viral load (VL). RESULTS: There was a positive correlation between the levels of IGF-binding proteins (IGFBPs) and those of inflammatory mediators: between plasma IGFBP1 and IL-17 (ß coefficient 0.28, P = 0.009), plasma IGFBP2 and IL-6 (ß coefficient 0.209, P = 0.021), CSF IGFBP1 and TNFα (ß coefficient 0.394, P < 0.001), and CSF IGFBP2 and TNF-α (ß coefficient 0.14, P < 0.001). As IGFBPs limit IGF availability, these results suggest that inflammation is a significant factor that modulates IGF protein expression/availability in the setting of HIV infection. However, there was no significant association between HAND and the reduced levels of plasma IGF1, IGF2, or CSF IGF1, suggesting a limited power of our study. Interestingly, plasma IGF1 was significantly reduced in subjects on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) compared to protease inhibitor-based therapy (174.1 ± 59.8 vs. 202.8 ± 47.3 ng/ml, P = 0.008), suggesting a scenario in which ART regimen-related toxicity can contribute to HAND. Plasma IGF2R levels were positively correlated with plasma VL (ß coefficient 0.37, P = 0.021) and inversely correlated with current CD4+ T cell counts (ß coefficient -0.04, P = 0.021), supporting our previous findings in vitro. CONCLUSIONS: Together, these results strongly implicate (1) an inverse relationship between inflammation and IGF growth factor availability and the contribution of IGF deficiencies to HAND and (2) the role of IGF2R in HIV infection and as a surrogate biomarker for HIV VL.

Correlation of histopathologic features of ductal carcinoma in situ of the breast with the oncotype DX DCIS score.

The Oncotype DX Breast Cancer Assay for ductal carcinoma in situ is used to determine local recurrence risk in patients with ductal carcinoma in situ. The results help select patients with low-risk ductal carcinoma in situ who could forgo radiation therapy after conservative surgery. The genes assessed include five proliferation genes, progesterone receptor (PR), and GSTM-1. Our objective was to determine if PR, mitotic counting, or any other pathologic feature of ductal carcinoma in situ could predict the Oncotype DX DCIS Score. We identified 46 cases of ductal carcinoma in situ with a Oncotype DX DCIS Score. In addition to information obtained from routine pathology, we counted mitotic figures in the ductal carcinoma in situ and noted presence of dense chronic inflammatory infiltrate surrounding ductal carcinoma in situ. We found that PR ≥ 90% (P = 0.004), mitotic count ≤ 1 (P = 0.045), estrogen receptor ≥ 90% (P = 0.046), and low nuclear grade (P < 0.0001) were associated with a low score. Dense chronic inflammation surrounding ductal carcinoma in situ was associated with a high score (P = 0.034).All 13 cases with PR ≥ 90%, ≤ 1 mitotic figure and absence of dense chronic inflammation around ductal carcinoma in situ had a low score (100% specificity). A low score was not observed in any case with at least two of the following--negative PR, >1 mitotic figure, and/or presence of dense chronic inflammation around ductal carcinoma in situ (100% specificity). Our study suggests using a combination of PR (≥ 90% vs negative) with mitotic count in ductal carcinoma in situ (≤ 1 vs >1) and dense chronic inflammation around ductal carcinoma in situ one could predict the Oncotype DX DCIS score. Mitotic counting and evaluation of immune response might provide prognostic information in ductal carcinoma in situ.

Binary regression with differentially misclassified response and exposure variables.

Misclassification is a long-standing statistical problem in epidemiology. In many real studies, either an exposure or a response variable or both may be misclassified. As such, potential threats to the validity of the analytic results (e.g., estimates of odds ratios) that stem from misclassification are widely discussed in the literature. Much of the discussion has been restricted to the nondifferential case, in which misclassification rates for a particular variable are assumed not to depend on other variables. However, complex differential misclassification patterns are common in practice, as we illustrate here using bacterial vaginosis and Trichomoniasis data from the HIV Epidemiology Research Study (HERS). Therefore, clear illustrations of valid and accessible methods that deal with complex misclassification are still in high demand. We formulate a maximum likelihood (ML) framework that allows flexible modeling of misclassification in both the response and a key binary exposure variable, while adjusting for other covariates via logistic regression. The approach emphasizes the use of internal validation data in order to evaluate the underlying misclassification mechanisms. Data-driven simulations show that the proposed ML analysis outperforms less flexible approaches that fail to appropriately account for complex misclassification patterns. The value and validity of the method are further demonstrated through a comprehensive analysis of the HERS example data.