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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.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 amplitude25 microvolts for2 seconds, and assessed its association with sevoflurane-induced alpha power using spectral analysis and multivariable logistic regression adjusting for clinically important variables.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.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.

A retrospective review.The objective of this study was to determine whether fusing to touched vertebra (TV) on prone x-rays (XRs) with minimal rotation (Gd 0/1) allow for shorter fusion with optimal correction.Previous studies have shown risk of "adding on" when TV is not selected as lowest instrumented vertebra (LIV). Fusion proximal to TV leads to suboptimal results but fusing to TV on standing XRs can result in longer fusions. On lying down XRs, TV moves proximally, and its rotation decreases by a grade.TV patients with minimal rotation were selected on prone (TVP) or standing XRs (TVS). Patients fused to rotated (Gd 2+) TV on standing or prone XRs were considered touched vertebra rotated (TVR). In the non-TV (NTV) group, LIV was fused proximal to TV. Disk wedging ≥5° determined risk of "adding-on." To compare patients fused to minimally rotated TV, to those that were not, patients in group A (TVP + TVS) were compared with group B (TVR + NTV).In part II: TVP, TVS, TVR, and NTV patients were compared. Subanalysis compared levels saved as the difference between predicted and real LIV in TVP and TVS patients. Another subanalysis was carried out for Lenke 1+2 and Lenke 3, 4, 5.In part III: XRs of nonoperative adolescents idiopathic scoliosis patients with Cobb30 and Risser 4/5 were analyzed to determine "acceptable" end vertebra tilt and disc wedging and served as controls.There were a significantly greater number of patients in group B patients(TVR + NTV) with final disk wedging ≥5°, final LIV translation ≥1 and ≥2 cm ( P0.001).Utilizing prone XRs in TVP saved average 1 level, and 1.2 levels in TVS patients. TVP patients also had similar LIV tilt, disk wedging and coronal balance( P0.05) to controls.Choosing minimally rotated (Gd 0/1) TV on prone XR saves levels without sacrificing radiographic outcomes.

Retrospective review.The objective of this study was to evaluate and compare distribution of hospital and operating room charges and outcomes during posterior spinal fusion for adolescent idiopathic scoliosis (AIS) patients by high-volume (HV) and standard-volume (SV) surgeons at one institution and examine potential cost savings.Increased surgical volume has been associated with improved perioperative outcomes after spinal deformity correction. However, there is a lack of information on how this may affect hospital costs.Retrospective study of AIS patients undergoing posterior spinal fusion between 2013 and 2019. Demographic, x-ray, chart review and hospital costs were collected and compared between HV surgeons (≥50 AIS cases/y) and SV surgeons (50/y). Comparative analyses were computed using Wilcoxon rank-sum, Kruskal-Wallis, and the Fisher exact tests. Average values with corresponding minimum-maximum rages were reported.A total of 407 patients (HV: 232, SV: 175) operated by 4 surgeons (1 HV, 3 SV). Radiographic parameters were similar between the groups. HV surgeons had significantly lower estimated blood loss (385.3 vs. 655.6 mL, P0.001), fewer intraoperative transfusions (10.8% vs. 25.1%, P0.001), shorter surgery time (221.6 vs. 324.9 min, P0.001), and lower radiation from intraoperative fluoroscopy (4.4 vs. 6.4 mGy, P0.001). HV patients had a significantly lower length of stay (4.3 vs. 5.3, P0.001) and complication rate (0.4% vs. 4%, P =0.04).HV surgeons had significantly lower total costs ($61,716.24 vs. $72,745.93, P0.001). This included lower transfusion costs ( P0.001), operative time costs ( P0.001), screw costs ( P0.001), hospital stay costs ( P0.001), and costs associated with 30-day emergency department returns ( P0.001).HV surgeons had significantly lower operative times, lower estimated blood loss and transfusion rates and lower perioperative complications requiring readmission or return to emergency department resulting in lower health care costs.Level III.

Previous reports identified minority race/ethnicity to be an independent risk factor for prolonged length of stay (LOS); however, these cohorts consisted of predominantly White patients. This study sought to evaluate minority status as an independent risk factor for prolonged LOS after primary total knee arthroplasty (TKA) in a predominantly Hispanic and Black cohort.This was a retrospective study using an institutional database of patients who underwent primary TKA between the years 2016 and 2019. Demographic and socioeconomic data, smoking, body mass index (BMI), medical comorbidities, discharge disposition, and 30-day readmission rates were collected. Patients were first categorized into racial/ethnic groups (Hispanic, Black, or White). An univariate analysis was performed comparing patient characteristics between racial/ethnic groups using the Wilcoxon rank sum, chi-squared, and Fisher exact tests. We then categorized patients into two groups-normal LOS (discharged on postoperative day 1 to 2) and prolonged LOS (discharged after postoperative day 2). An univariate analysis was again performed comparing patient characteristics between LOS groups using Wilcoxon rank sum, chi-squared, and Fisher exact tests. After identifying risk factors markedly associated with LOS, a multivariate logistic regression analysis was performed to identify independent risk factors for prolonged LOS.A total of 3,093 patients were included-47.9% Hispanic and 38.3% Black. Mean LOS was 2.9 ± 1.6 days. An univariate analysis found race/ethnicity, age, low socioeconomic status (SES), discharge disposition, insurance type, weekday of surgery, BMI40, smoking, increased American Society of Anesthesiologists (ASA)/Charlson Comorbidity Index (CCI) and several medical comorbidities to be associated with prolonged LOS (P0.05). A multivariate logistic regression analysis found Black and Hispanic patients were less likely to have prolonged LOS after adjusting for associated risk factors. White race/ethnicity, nonhome discharge, low SES, weekday of surgery, smoking, BMI40, and increased ASA and CCI were identified as independent risk factors for prolonged LOS (P0.05). The overall 30-day readmission rate was 3.6%, with no notable difference between racial/ethnic and LOS groups (P = 0.98 and P = 0.78).In contrast to previous reports, our study found that after adjusting for associated risk factors, minority patients do not have prolonged LOS after primary TKA in an urban, socioeconomically disadvantaged, predominantly minority patient cohort. White race/ethnicity, nonhome discharge, low SES, weekday of surgery, smoking, BMI40, increased CCI, and ASA were all found to be independent risk factors for prolonged LOS. These findings highlight the need to further investigate the role of race/ethnicity on LOS after primary TKA using large-scale, randomized controlled trials with equally represented patient cohorts.

Neaodjuvant chemotherapy is used to treat high risk triple-negative breast cancer (TNBC). Residual cancer burden (RCB) is used to predict risk of relapse after neoadjuvant chemotherapy (NAC); however, it cannot predict disease recurrence with certainty. EZH2 is a targetable oncogenic protein overexpressed in TNBC and associated with metastasis and stem cell expansion. We quantified EZH2 protein expression in TNBC before NAC to examine potential utility as a predictive and prognostic biomarker.We retrospectively identified 63 patients with localized TNBC treated with NAC. We quantified EZH2 nuclear expression in pretherapy biopsies using a score which included intensity and percent of positive cells at each intensity. EZH2 expression was evaluated as a continuous variable and dichotomized at a score of 210. Logistic regression analysis was used to determine association between EZH2 expression and RCB, tumor-infiltrating lymphocytes, clinicopathologic features and disease-free survival.There was no significant association between EZH2 score and posttreatment RCB class evaluated as a continuous variable (P=0.831) or dichotomized at 210 (P=0.546). On multivariable logistic regression, adjusted for covariates including RCB, EZH2210 was associated with development of metastasis (odds ratio=14.35, 95% confidence interval: 2.69-76.66; P=0.002). Logistic regression was run with EZH2 scores as a continuous variable and increased EZH2 score was associated with metastasis (odds ratio=1.10, 95% confidence interval: 1.00-1.03; P=0.047).In our study of TNBC treated with NAC, high EZH2 expression in pretherapy core biopsies was significantly associated with metastatic recurrence independent of RCB. The potential value of EZH2 as a biomarker to improve stratification of outcome after NAC should be explored further.

Retrospective cohort study.This study aims to identify differences in perioperative outcomes between ambulatory patients with neuromuscular scoliosis (ANMS) and adolescent idiopathic scoliosis (AIS) following spinal fusion.NMS patients have severe curves with more comorbidities and procedural complexity. These patients require extensive fusion levels, increased blood loss, and suffer increased periop complications. However, NMS patients have a variable severity spectrum, including ambulation status.Chart and radiographic review of NMS and AIS patients undergoing PSF from 2005 to 2018. NNMS included NMS patients who were completely dependent (GMFCS IV-V). ANMS consisted of community ambulators without significant reliance on wheeled assistive devices (GMFCS I-III). Subanalysis matched by age, sex, levels fused and preoperative Cobb angle was conducted as well. Wilcoxon Rank-Sum, Kruskal-Wallis, χ2, and Fisher exact tests were performed.There were 120 patients in the NNMS group, 54 in ANMS and 158 in the AIS group. EBL was significantly lower for ANMS and AIS patients (P 0.001). Complications within 30 days were similar between ANMS and AIS (P = 1.0), but significantly higher for NNMS (P 0.001). Two (1.3%) AIS patients, (1.7%) nonambulatory NMS patients, and one (1.9%) ANMS patient required revision surgery (P = 1.0). However, all NMS patients had increased fusion levels, fixation points, and surgery time (P 0.05). NNMS had significantly longer ICU (P 0.001), hospital stay (P 0.001), intraoperative transfusions (P 0.001), and fewer patients extubated in the OR (P 0.001) than ANMS and AIS patients. In the subanalysis, ANMS had similar radiographic measurements, EBL, transfusion, surgery time, extubation rate, and complication rate (P 0.05) to AIS.Our data show radiographic outcomes, infections, revisions, and overall complications for ANMS were similar to the AIS population. This suggests that NMS patients who ambulate primarily without assistance can expect surgical outcomes comparable to AIS patients with further room for improvement in length of ICU and hospital stay.Level of Evidence: 4.

Database study.The purpose of this study was to use a large, nationwide database to determine prevalence of pediatric spine fractures in the United States, associated injuries, mechanisms of injury (MOI), use of safety devices, and mortality rates.Spinal fractures account for 1% to 2% of pediatric injuries. However, they are associated with significant comorbidities and complications. Motor vehicle accidents (MVAs) are most responsible for increased incidence observed.Retrospective review of National Trauma Data Bank between 2009 and 2014 (analysis in 2019) for all vertebral fractures in patients under 18 years of age. Subanalysis included those in MVAs where protective device use data were available. Patient demographics, MOI, geographical and anatomical region of injury, concomitant musculoskeletal/organ injury, protective device usage, hospital length of stay, surgical procedures, and mortality were all analyzed.A total of 34,563 patients with 45,430 fractured vertebrae included. Median age was 15 years. Most fractures (63.1%) occurred in patients aged 15 to 17 years, most frequent MOI was MVA (66.8%), and most common geographic location was the South (38%). Males sustained more spine fractures than females, overall (58.4% vs. 41.6%; P 0.001) and in MVAs (54.4% vs. 45.6%; P 0.001). Those in MVAs wearing seatbelts had lower odds of cranial (29.6% vs. 70.4%; odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.82-0.89; P 0.001) and thoracic (30.1% vs. 69.9%; OR = 0.88, 95% CI: 0.84-0.91; P 0.001) organ injury, multivertebral (30% vs. 70%; OR = 0.78, 95% CI: 0.73-0.83; P 0.001) and concomitant nonvertebral fractures (30.9% vs. 69.1%; OR = 0.89, 95% CI:0.73-0.83; P 0.001), and 21% lower odds of mortality (29.3% vs. 70.7%; OR = 0.79, 95% CI: 0.66-0.94; P = 0.009). Over 70% of drivers were not restrained during MVA, with majority of seatbelt violations incurred by males, ages 15 to 17, in the South.Over 60% of pediatric spinal fractures occur in children aged 15 to 17 years, coinciding with the beginning of legal driving. MVA is the most common cause and has significant association with morbidity/mortality. Nearly two- thirds pediatric spinal fractures sustained in MVAs occurred without seatbelts. Absence of seatbelts associated with20% greater odds of mortality. Ensuring new drivers wear protective devices can greatly reduce morbidity/ mortality associated with MVA.Level of Evidence: 3.

Single-center retrospective chart review with minimum 2-year follow up.To determine incidence of pulmonary hypertension in adolescent idiopathic scoliosis patients and to determine the effect of scoliosis surgery on pulmonary hypertension.Spinal deformity in adolescent idiopathic scoliosis can increase right atrial and ventricular pressures secondary to restrictive lung disease. Pulmonary hypertension leading to cor pulmonale is the most feared outcome, however mild pulmonary hypertension in adolescent idiopathic scoliosis (AIS) patients has been reported. No study has previously examined changes in the improvement of right heart function following scoliosis surgery.Cobb angle, 2D-echo signs of structural heart disease, aortic root dimensions, tricuspid regurgitant jet velocity (TRV), pulmonary function tests (PFTs), arterial blood gas (ABG), and patient demographics reviewed. Right ventricular systolic pressure (RVSP) estimated using Bernoulli equation (4[TRV]2) and right atrial pressure. RVSP ≥36 mmHg is a surrogate marker for pulmonary hypertension. All echocardiograms were read by board certified Pediatric Cardiologists. Logistic regression used to assess for differences in TRV between groups.Mean preoperative RVSP was significantly elevated in AIS patients (26.9 ± 0.49; P 0.001) compared with controls (17.25 + 0.88). Only 47 (21%) Group 1 patients had elevated preoperative TRV (≥2.8 m/s) versus none in Group 2 (P 0.001). Additionally, logistic regression showed AIS patients have odds ratio of 3.29 for elevated TRV (P = 0.007)-an indirect measure of pulmonary hypertension. In all Group 3 patients, the cardiac function normalized postoperatively (mean TRV = 2.09 + 0.23; P 0.001). No association found between Cobb angle, aortic root parameters, or pulmonary function tests.This study found 13.9% of patients with adolescent idiopathic scoliosis had elevated TRV while controls had no TRV abnormalities. Additionally, RVSP measurements demonstrated mild pulmonary hypertension in AIS patients. These abnormal values normalized postoperatively, indicating the benefits of scoliosis surgery on cardiac function in adolescent idiopathic scoliosis.Level of Evidence: 3.

Context.— Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) testing is used for serosurveillance and will be important to evaluate vaccination status. Given the urgency to release coronavirus disease 2019 (COVID-19) serology tests, most manufacturers have developed qualitative tests. Objective.— To evaluate clinical performance of 6 different SARS-CoV-2 IgG assays and their quantitative results to better elucidate the clinical role of serology testing in COVID-19. Design.— Six SARS-CoV-2 IgG assays were tested using remnant specimens from 190 patients. Sensitivity and specificity were evaluated for each assay with the current manufacturer's cutoff and a lower cutoff. A numeric result analysis and discrepancy analysis were performed. Results.— Specificity was higher than 93% for all assays, and sensitivity was higher than 80% for all assays (≥7 days post–polymerase chain reaction testing). Inpatients with more severe disease had higher numeric values compared with health care workers with mild or moderate disease. Several discrepant serology results were those just below the manufacturers' cutoff. Conclusions.— Severe acute respiratory syndrome coronavirus 2 IgG antibody testing can aid in the diagnosis of COVID-19, especially with negative polymerase chain reaction. Quantitative COVID-19 IgG results are important to better understand the immunologic response and disease course of this novel virus and to assess immunity as part of future vaccination programs.

In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10+ IgA-ASCs form conjugates with helper T cells, preferentially regulatory T cells, at their differentiation sites of gut-associated lymphoid organs for their coordinated co-localization into the colon to promote local homeostasis. In CCR10-knockout mice, defective migration of IgA-ASCs also resulted in defective T cell migration and homeostasis, and development of inflammatory symptoms in the colon. Antigen-specific interaction of CCR10+ IgA-ASCs and T cells is crucial for their homeostatic establishment in the colon. On the other hand, in IgA-knockout mice, preferential expansion of CCR10+ IgG1-ASCs with regulatory functions compensated for CCR10+ IgA-ASCs to help maintain colonic homeostasis. The preferential expansion of specific subclasses of CCR10+ IgG-ASCs with regulatory functions was also found in asymptomatic IgA-deficient patients. These findings suggest coordinated cell migration as a novel mechanism underlying localization and function of B and T cells in colonic homeostatic regulation.

Osteosarcoma is a highly aggressive malignancy for which treatment has remained essentially unchanged for years. Our previous studies found that the F-box protein SKP2 is overexpressed in osteosarcoma, acting as a protooncogene; p27(Kip1) (p27) is an inhibitor of cyclin-dependent kinases and a downstream substrate of SKP2-mediated ubiquitination. Overexpression of SKP2 and underexpression of p27 are common characteristics of cancer cells. The SCF(SKP2) E3 ligase ubiquitinates Thr187-phosphorylated p27 for proteasome degradation, which can be abolished by a Thr187Ala knock-in (p27(T187A) KI) mutation. RB1 and TP53 are two major tumor suppressors commonly coinactivated in osteosarcoma. We generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which developed osteosarcoma with full penetrance. When p27(T187A) KI mice were crossed on to the DKO background, p27(T187A) protein was found to accumulate in osteosarcoma tumor tissues. Furthermore, p27(T187A) promoted apoptosis in DKO tumors, slowed disease progression, and significantly prolonged overall survival. RNA sequencing analysis also linked the SCF(SKP2)–p27(T187A) axis to potentially reduced cancer stemness. Given that RB1 and TP53 loss or coinactivation is common in human osteosarcoma, our study suggests that inhibiting the SKP2–p27 axis may represent a desirable therapeutic strategy for this cancer.

There has been increasing interest in the use of stemless humeral implants for total shoulder arthroplasty when compared with both short-stem (SS) and standard-length implants. Although evidence for decreased surgical time and blood loss exists for stemless versus standard-length stems, far less literature exists comparing these clinical parameters for stemless versus SS implants.A retrospective review of consecutive anatomic total shoulder arthroplasty (aTSA) cases conducted by a single, fellowship-trained shoulder surgeon was undertaken from January 2016 through January 2022 with the exception of March 2020 through January 2021 secondary to the COVID-19 pandemic. Demographic patient and surgical data, including age, sex, body mass index, American Society of Anesthesiologists score, age-adjusted Charlson Comorbidity Index, prior ipsilateral shoulder arthroscopy, surgical time, use of a Hemovac drain and/or tranexamic acid, hospital length of stay (LOS), and both postoperative day #1 (POD 1) and discharge visual analog scores. The use of a stemless or SS implant was recorded. Intraoperative total blood volume loss (TBVL) was calculated, in addition to the need for either intraoperative or postoperative transfusions. Nonparametric analysis of covariance was used to examine effects of stemless versus SS aTSA on surgical time and intraoperative TBVL adjusted for demographic, clinical, and surgical variables.There were 47 SS and 83 stemless anatomic implants included, of which 74 patients (57%) overall were women. The median surgical time for the stemless cohort was 111 minutes (IQR 96-130) versus 137 minutes (IQR 113-169) for the SS cohort (P0.00001). The median intraoperative TBVL for the stemless cohort was 298.3 mL (IQR 212.6-402.8) versus 359.7 mL (IQR 253.9-415.0) for the SS cohort (P = 0.05). After multivariable regression analysis, use of stemless humeral implants was independently associated with both decreased surgical time and intraoperative blood loss (P0.001 and P = 0.005, respectively). There was a shorter median hospital LOS in the stemless group (2 days [IQR 1-2] versus 2 days [IQR 2-3], P = 0.03). The visual analog score pain score at discharge was lower among the stemless cohort (0 [IQR 0-3] versus 4 [IQR 2-6], P0.00001). Increased surgical time was associated with intraoperative TBVL (r = 0.340, P0.0001).Stemless aTSA is associated with a markedly decreased surgical time and intraoperative TBVL when compared with a SS aTSA. Furthermore, the use of a stemless implant results in a shorter hospital LOS and lower discharge pain scores.

The outcomes of congenital scoliosis (CS) patients undergoing hemivertebra (HV) resection surgery with a 2-level fusion versus a2-level fusion are unclear. We hypothesized that CS patients undergoing HV resection and a2-level fusion have decreased curve progression and reoperation rates compared with 2-level fusions.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.Twenty-six patients had a 2-level fusion while 27 patients had a2-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 to2-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.Two-level and2-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.

Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67gt;10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET.We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET.We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( Plt;0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant.Our results suggest that EZH2 might be a useful biomarker to predict response to NET.

Short-term cancellation of elective ambulatory orthopaedic surgery can result in disruption to the process flow of the operating room, with resultant negative financial implications for the health system. The risk factors for patient-related short-term cancellations within 24 hours of the surgical date have not been well defined.A retrospective review of a single orthopaedic surgery electronic internal database was done to identify all cancellations from January 1, 2016, through December 31, 2019, which were made within 24 hours of the surgical date. Inclusion criteria included elective arthroscopic procedures canceled solely for patient-related issues. Any cancellation for surgeon-related or ambulatory center-related reasons was excluded. Demographic patient and surgical data, including insurance type, employment status, previous history of cancellation for the same surgery, socioeconomic status based on the Area Deprivation Index, and surgery type, were tabulated. Each cancellation was matched 1:2 with noncanceled cases based on the anatomic site of the arthroscopy scheduled. Multivariable logistic regression was used to examine associations of patient demographic and medical characteristics with surgical cancellation.There were 4,715 total arthroscopic procedures done during the study period, of which 126 (2.7%) were canceled within 24 hours of the surgery date. The mean age of the canceled cases was 44.9 ± 16.1 years (range, 14 to 77 years), with 46 females (43%) included. The presence of MRI of the involved joint within 6 months of surgery (adjusted odds ratio [aOR], 0.39, 95% confidence interval [CI], 0.17 to 0.91) and current employment (aOR, 0.56, 95% CI, 0.33-0.94) were independently predictive of noncancellation. Current smokers were more likely to cancel within 24 hours of surgery (aOR, 2.63, 95% CI, 1.4-4.9). Finally, having previously canceled the same surgery was significantly associated with a current surgical cancellation (P = 0.004).Identification of the factors associated with short-term patient-related cancellation of elective arthroscopy may serve as the basis for preoperative interventions aimed specifically at those more likely to cancel. In turn, these interventions can minimize preventable cancellations.

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.

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

Hypothermia-related deaths affect vulnerable populations and are preventable. They account for the vast majority of weather-related deaths in the United States. The postmortem diagnosis of hypothermia can be challenging, as there are no pathognomonic signs. The electronic databases of the New York City Office of Chief Medical Examiner and Harris County Institute of Forensic Sciences were searched for all fatalities where the primary cause of death included hypothermia, between January 2009 and July 2019. There were 139 hypothermia deaths in New York City (NYC) with an average annualized rate of 1.7 per million. During this same time, there were 50 hypothermia deaths in Houston with an average annualized rate of 2.4 per million. Males were more likely to die of hypothermia compared to females in both cities. The rate ratio (RR) in NYC was 3.55 (95% CI 2.40, 5.25), while the RR in Houston was 2.83 (95% CI 1.50, 5.32). Age- and sex-specific standardized hypothermia mortality rates were 18.2 (95% CI 15.1, 21.2) per million in NYC and 30.1 (95% CI 21.7, 38.6) per million in Houston. The comparative hypothermia death ratio was 1.66 (95% CI 1.19, 2.30), indicating hypothermia mortality in Houston was 66% higher than in NYC. There was no correlation between zip code poverty rates and hypothermia-related deaths. The most consistent autopsy finding was Wischnewski spots (56.6%), and ethanol was the most common toxicological finding (36.5%). Local agencies can use this data to target these higher-risk populations and offer appropriate interventions to try to prevent these deaths.

STUDY DESIGN A retrospective chart review of prospectively collected data. OBJECTIVE The aim of this study was to determine whether back-to-back scoliosis surgeries can be performed safely without compromising outcomes and the reproducibility of the practice between institutions. SUMMARY OF BACKGROUND DATA During the summer, spinal surgeons will often book multiple cases in one day. The complexity and demands of spinal fusion surgery call into question the safety. Change of operating room staff including anesthesiologists, nurses, and neurologists may introduce new risks. METHODS From 2009 to 2018, index AIS surgeries were included. In Groups 1, 2, and 3, surgeries were performed by a single surgeon. In Group 4, they were performed by other institutional surgeons. Group 1: first surgery of the day, Group 2: second surgery of the day, Group 3: only surgery of the day, Group 4: only surgery of the day by different institutional surgeon. Additional analysis was done to determine reproducibility after a surgeon was moved from Institution 1 to Institution 2. RESULTS Five hundred sixty-seven AIS patients were analyzed. Group 1 patients had similar radiographic outcomes compared with Group 2 (P > 0.05). Surgical time was similar (P = 0.51), but significantly more levels fused (P = 0.01). Compared with Group 3, Group 2 had a smaller preoperative Cobb (P = 0.02), shorter surgeries (P

In this retrospective study of 319 children with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we assessed whether age, asthma, obesity, diabetes, and socioeconomic status were associated with hospitalization for coronavirus disease 2019 (COVID-19). Demographic and clinical characteristics were assessed using univariate statistics, excluding incidental or unrelated positives. There was a bimodal distribution of age among hospitalized children. Obesity ( P < .001) and a past medical history of diabetes ( P = .001) were significantly more prevalent in hospitalized children, including cases of new-onset diabetes and diabetic ketoacidosis. Neither a past medical history of asthma nor lower socioeconomic status was associated with hospitalization. Although limited to a single center, the findings in this study may have important clinical implications. Targeted, proactive health outreach to children with obesity and diabetes, with prioritization of preventative efforts such as vaccination, may be important in preventing worse SARS-CoV-2 infection in this vulnerable group.

Retrospective review.The objective of this study was to report on one institution's use of single bolus micro-dose intrathecal morphine as part of a rapid recovery pathway during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and its comparison to patients whose pain was controlled with patient-controlled analgesia (PCA).Narcotic substance addiction has risen across all patient populations, including pediatrics. Narcotics have been historically used in complex spine surgeries as a measure of pain control, predominantly provided as PCA and additional take-home medication.AIS patients undergoing PSF from 2015 to 2019 were reviewed. In 2018, we instituted a standardized rapid recovery pathway for scoliosis patients undergoing PSF utilizing micro-dose intrathecal morphine (ITM-RRP). Before this, traditional protocol with PCA was used for postoperative management. Perioperative data, morphine consumption and prescription refill requests were compared.There were 373 AIS patients total in this study, of which 250 patients were in the PCA group and 123 in the ITM-RRP Group. Preoperative Cobb angles (P = 0.195), as well as levels fused (P = 0.481) and body mass index (P = 0.075) were similar. 69.4% of ITM-RRP patients had a length of stay ≤3 days, significantly11.6% of PCA patients (P 0.001). ITM-RRP patients began ambulating significantly earlier with 84.6% patients out of bed by postoperative day 1 versus 8% PCA patients (P 0.001). Additionally, ITM-RRP patients had significantly lower VAS pain scores with activity and earlier initial bowel movements (P 0.001).Postoperative emesis was similar (P = 0.11). No patients had pruritus, respiratory depression, or required supplemental oxygenation.This is the first study to show that a rapid recovery protocol utilizing single micro-dose ITM with oral analgesics have adequate recovery, significantly better postoperative pain control and superior perioperative outcomes to traditional protocols using PCA in the AIS population following PSF.Level of Evidence: 3.

Multicenter retrospective review.This study aims to address major postoperative complications associated with Scheuermann kyphosis (SK) when compared with adolescent idiopathic scoliosis (AIS) in a large population matched by demographic characteristics, levels fused and operative technique.Prior studies have found that SK patients are 3.86 times more likely to experience major postoperative complications than in AIS. Historically, however, these studies have often had populations that were significantly different between the two groups in terms of disease severity, demographics, and small sample sizes.AIS patients were compared to SK patients between 2006 and 2018 contemporaneously. All surgeries were conducted by six surgeons among two institutions. Complications and revisions were calculated. A sub-analysis comparing SK and AIS patients by age, sex, and levels-fused in one-to-one matched pairs was performed as well as a sub-analysis matched by levels fused only in one-to-one matched pairs.One thousand three hundred twenty two patients were reviewed (1222 AIS; 100 SK). There were 52 (4.3%) complications in the AIS group compared with 20 (20%) complications in the SK group (P 0.001), with infections and revisions consisting of the majority of complication rates in both cohorts.When matched by age, sex, and levels fused, there were eight complications in the AIS group and 11 in the SK group (P = 0.63), with infection and revision rates being similar, (P = 0.29) and (P = 0.26) respectively.When matched by levels fused only, EBL, operative time and complication rates remained similar (P 0.05).Contrary to previously published literature, our analyses indicate that in a matched population, postoperative complication rates (i.e., infection and revision rates) are not significantly different between SK and AIS patients.Level of Evidence: 4.

STUDY DESIGN Retrospective review of prospective data from multicenter registry. OBJECTIVE Compare outcomes of posterior spinal fusion (PSF) versus magnetically controlled growing rods (MCGR) versus vertebral body tethers (VBT) in 8- to 11-year-old idiopathic early onset scoliosis (EOS) patients. SUMMARY OF BACKGROUND DATA In EOS, it is unclear at what age the benefit of growth-sparing strategies outweighs increased risks of surgical complications, compared with PSF. METHODS One hundred thirty idiopathic EOS patients, 81% female, aged 8-11 at index surgery (mean 10.5 yrs), underwent PSF, MCGR, or VBT. Scoliosis curve, kyphosis, thoracic and spinal height, complications, and Quality of Life (QoL) were assessed preoperatively and at most recent follow-up (prior to final fusion for VBT/MCGR). RESULTS Of 130 patients, 28.5% received VBT, 39.2% MCGR, and 32.3% PSF. The VBT cohort included more females (P

STUDY DESIGN Retrospective review of prospective case-control study. OBJECTIVE To compare minimally invasive scoliosis surgery (MIS) and posterior spinal fusion (PSF) in a large group of patients. SUMMARY OF BACKGROUND DATA MIS, has been shown to have benefits over standard PSF in adolescent idiopathic scoliosis (AIS). METHODS Radiographic, clinical, and operative review of a multi-institutional prospective database from 2013 to 2018. MIS patients with minimum 2-year XR follow up were compared with open PSF technique patients. RESULTS Four hundred eighty five patients were included; 192 MIS and 293 PSF. Preoperative Cobb (P = 0.231) and kyphosis were similar (P = 0.501). Cobb correction was comparable (P = 0.46), however percent improvement in thoracic kyphosis was significantly higher in MIS (P

The LigaSure system has been successfully used in thoracic and abdominal surgery. However, to date, its use in the resection of sarcomas has not been systematically studied. We aimed to determine whether the use of the LigaSure system reduces blood loss and blood transfusion volumes in sarcoma surgery.One hundred forty-two consecutive patients who underwent sarcoma surgeries between July 2010 and October 2016 were included. Conventional electrocautery alone (n = 91) and with LigaSure (n = 51) were compared. Case-matched samples (n = 46) from each group were additionally compared.The use of the LigaSure system resulted in a significant decrease in mean intraoperative blood loss (P = 0.02) and blood transfusion volume (P = 0.04). Likewise, a significant decrease in both mean and median intraoperative blood loss (P = 0.003; P0.0001) was seen with LigaSure in the case-matched analysis. In the soft-tissue sarcoma subgroup, a significant decrease was observed in mean hemoglobin reduction (P = 0.03) and mean intraoperative blood loss with LigaSure (P = 0.04). No adverse perioperative complications attributed to the LigaSure system were identified.The LigaSure vessel sealing and dividing system is a safe and effective hemostatic tool for deep dissection in bone and soft-tissue sarcoma surgery.Level III, therapeutic study.

Background/objective Regular physical activity (PA) has been associated with improved cognitive function, but its effect on postoperative delirium (POD) has not been established. Our objectives were to determine the effect of baseline PA on the incidence of POD in older patients undergoing elective orthopedic surgery and to determine whether these effects were independent of cognitive reserve. We hypothesize that PA protects against POD by bolstering physiologic reserve needed to withstand the stressors of surgery. Design Secondary analysis of a prospective, single-center, cohort study. Setting Urban academic hospital. Participants A total of 132 nondemented, English-speaking adults older than 60 years undergoing elective orthopedic surgery. Measurements Subjects were screened for POD and delirium severity using the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Baseline cognitive activities and PAs were assessed with a validated Leisure Activity Scale. Regular PA was categorized as 6 to 7 days per week. The association of regular PA with incidence of POD was assessed using multivariable logistic regression, adjusting for age, sex, Charlson Comorbidity Index, cognitive reserve, and cognitive function. Linear regression was used to assess the association of delirium severity with regular PA. Results Of 132 patients, 41 (31.1%) developed POD. Regular PA was associated with a 74% lower odds of developing POD (odds ratio [OR] = 0.26; 95% confidence interval [CI] = 0.08-0.82). There was no significant interaction between PA and cognitive reserve (P = .70). Of 85 women, 25 (29.4%), and of 47 men, 16 (34.0%) developed POD. In stratified analysis, women who engaged in regular PA had dramatically lower odds of POD (OR = 0.08; 95% CI = 0.01-0.63) compared with men (OR = 0.93; 95% CI = 0.18-4.97). Conclusions Regular PA is associated with decreased incidence of POD, especially among women. Future studies should address the basis of sex differences in PA benefits on delirium. J Am Geriatr Soc 67:2260-2266, 2019.

Patient-reported outcome measures (PROMs) are commonly utilized to assess patient-derived orthopaedic health status and function. The prevalence of limited musculoskeletal health literacy (MHL) has been demonstrated to be high within the orthopaedic literature. The purpose of this study was to evaluate the association between MHL and upper extremity-specific PROMs and to determine which patient- and symptom-related factors affect baseline PROMs in patients with atraumatic shoulder pain.Patients with limited MHL would demonstrate lower median scores on baseline PROMs compared with those with adequate MHL.New patients with atraumatic shoulder pain presenting to an academic practice were administered the Literacy in Musculoskeletal Problems (LiMP), in addition to the American Shoulder and Elbow Surgeons (ASES), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), and Single Assessment Numeric Evaluation (SANE) questionnaires. A detailed physical exam and history was performed by a fellowship-trained shoulder surgeon. Demographic patient data, in addition to prior imaging and orthopaedic treatment, was tabulated. The association between demographics, pain-related variables, and MHL with the ASES, SANE, and QuickDASH scores were examined using Spearman correlation coefficients for continuous variables and Wilcoxon rank-sum tests for categorical variables. Non-parametric analysis of covariance (ANCOVA) was used to examine the independent association of predictor variables with PROMs.A total of 439 patients met the inclusion criteria and were enrolled. The mean age was 58.8±12.6years (range: 24-93) with 162 (37%) being men. Overall, 172 patients (39.2%) attained a college degree or higher and 183 (41.7%) were currently employed. MHL was significantly associated with ASES (p=0.03), but not with the QuickDASH (p=0.75) or SANE score (p=0.16). Similarly, age, having been in the medical profession or having previously visited an orthopaedist were not associated with PROMs, while employment status correlated to the SANE score (p=0.002). Visual Analogue Scale (VAS) pain level demonstrated varying strengths of association with each of the scores [ASES (r=-0.729, p0.001), QuickDASH (r=0.557, p0.001), and SANE (r=-0.430, p0.001)]. MHL demonstrated no association with initial patient-derived treatment selection.The SANE and QuickDASH may be administered to patients presenting for atraumatic shoulder pain in the outpatient setting regardless of MHL. Further research should be focused on the utility of the ASES instrument amongst patients with lower educational levels and/or limited MHL.II; diagnostic.

Background Coronavirus disease 2019 (COVID-19) guidelines endorse early rehabilitation to improve outcomes in hospitalized patients, but the evidence base to support this recommendation is lacking. We examined the association between early rehabilitation and in-hospital deaths in COVID-19 patients. Method A single-center retrospective study, involving 990 COVID-19 patients (42.4% women, mean age 67.8 years) admitted between March 1, 2020 and May 31, 2020 to a community hospital, was conducted. Association of rehabilitation during hospitalization with in-hospital mortality was examined using logistic regression analysis adjusted for demographics, length of stay, body mass index, comorbid illnesses, functional status as well as for COVID-19 presentations, treatments, and complications. Results Over the 3-month study period, 475 (48.0%) inpatients were referred for rehabilitation. Patients who received rehabilitation were older (73.7 ± 14.0 vs 62.3 ± 17.2). There were 61 hospital deaths (12.8%) in the rehabilitation group and 165 (32.0%) in the nonrehabilitation group. Receiving rehabilitation was associated with an 89% lower in-hospital mortality (odds ratio [OR]: 0.11, 95% confidence interval [CI]: 0.06–0.19) after adjusting for multiple confounders and COVID-19 disease markers. In sensitivity analyses, the results were significant in subpopulations defined by age group, sex, race, length of hospitalization, or pulmonary presentations. Each additional rehabilitation session was associated with a 29% lower risk of in-hospital mortality (OR per session: 0.71, 95% CI: 0.64–0.79) in the fully adjusted model. Conclusion Among hospitalized COVID-19 patients, receiving early rehabilitation was associated with lower in-hospital mortality. Our findings support implementation of rehabilitation services for COVID-19 patients in acute care settings, but further research from randomized clinical trials is needed.

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 (p0.001). Long plate removals also took significantly longer, and RVU/min was significantly lower compared to guided-growth plate removal (p0.001). 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).

OBJECTIVES: Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Sahara Africa where HIV incidence is high. We determined the impact of Depo-Provera on cervical immune cells and mediators in healthy women. METHODS: In this longitudinal study, vaginal, endocervical, and rectal swabs were collected at baseline (visit 1), one month (visit 2), and three months (visit 3) after Depo-Provera injection. Cervical cells were collected by cytobrush and immune markers on cervical CD4(+) T cells were analyzed by multicolor flow cytometry at 3 different visits. The levels of immune mediators in cytobrush supernatants as well as vaginal, cervical, and rectal secretions from swabs were analyzed by multiplex assays and ELISA. RESULTS: Compared to baseline levels we found a significant increase in the frequency of cervical CCR5(+)CD4(+) T cells and a significant decrease in the frequency of cervical central memory CD4(+) T cells. Depo-Provera treatment had little effect on expression of immune mediators in rectal mucosa but significantly suppressed numerous immune mediators at cervicovaginal mucosa. Levels of MCP-1, G-CSF, IL-6, IL-10, GM-CSF, and IP-10 were significantly decreased in both vaginal and cervical secretions after Depo-Provera injection. In cervical samples collected by cytobrush, we found reduced levels of 22 of 25 immune mediators after Depo-Provera injection. Changes in immune mediators differed between vaginal and cervical mucosa, demonstrating compartment-specific responses. CONCLUSION: Depo-Provera altered immune profiles of cervical CD4(+) T cells and suppressed host immune response at cervicovaginal mucosa, suggesting its likely effect on transmission of sexually transmitted infections including HIV.

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

Background Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity. Objective We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity. Methods This is a cohort study simulating an intention-to-treat clinical trial, by analyzing the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours. Results Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used. Conclusion We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.

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).

MINI: The objective of this study was to evaluate the accuracy and reliability of pedicle screw placement using O-Arm at dosages below the manufactured recommended dose. O-Arm at reduced dose showed a 90% accuracy when compared with computed tomography; however, about 30% medial breaches were misclassified.Cadaveric study.The objective was to evaluate O-Arm's ability at low-dose (LD) settings to assess intraoperative screw placement.Accurate placement of pedicle screws is crucial because of proximity to vital structures. Malposition of screws may result in significant morbidity and potential mortality. O-arm provides real-time, intraoperative imaging of patient's anatomy and provides higher accuracy in scoliosis surgeries, avoiding risk to vital structures. We hypothesize using LD or ultra-low doses (ULDs) to obtain intraoperative images allow for accurate assessment of screw placement, both minimizing radiation exposure and preventing screw misplacement.Eight cadavers were instrumented with pedicle screws bilaterally from T1 to S1. Screws were randomly placed using O-arm navigation into three positions: contained within the bone, OUT-anterior/lateral, and OUT-medial. O-arm images were obtained at three dosage settings: LD (kVp120/mAs125-lowest manufacturer recommended), very-low dose (VLD) (kVp120/mAs63), and ULD (kVp120/mAs39). Computed tomography (CT) scan was performed using institution's LD protocol (kVp100/mAs50) and gross dissection to identify screw positions.LD, VLD, ULD, and CT for identifying "IN" screws relative to gross dissection had, a mean (standard deviation) sensitivity of 84.2% (±5.7), specificity of 76.1% (±9.3), and accuracy of 79.9% (±3.1) from all three observers. Across the three observers, the interobserver agreement was 0.67 (0.61-0.72) for LD, 0.74 (0.69-0.79) for VLD, 0.61 (0.56-0.66) for ULD, and 0.79 (0.74-0.84) for CT. Effective doses of radiation (mSV) for LD O-arm scan was 2.16, VLD 1.08, ULD 0.68, and our LD CT protocol was 1.05.Accuracy of pedicle screw placement is similar for O-arm at all doses and CT compared to gross dissection. Interobserver reliability was substantial for VLD and CT. Approximately 30% of medial screw breaches are, however, misclassified. ULD and VLDs can be used for intraoperative navigation and evaluation purposes within these limitations.N/A.

Study design Retrospective chart review. Objective To determine if obtaining a prone computed tomography (CT)-scan can better delineate a questionable screw-aorta relationship. Summary of background data Pedicle screw misplacement rate is reported between 6% and 15%. Studies looking at misplacements on a per patient basis show up to 14% of patients have screws at risk (impinging vital structures). A screw abutting the aorta is a management challenge and often requires vascular surgery intervention. However, CT scans routinely done in supine position may overestimate screw-aorta relationship. Change in patient position may allow the aorta to roll away and, in most cases, reveal an uncompromised aorta. This will allow safe removal of pedicle screws without any vascular intervention. Methods One hundred eleven spinal deformity patients who underwent Posterior spinal fusion from 2004 to 2009 were evaluated. Patients with concerning screw-aorta relationship underwent additional prone CT scan. Mobility of the aorta was determined and distance was compared using prone and supine CT scans. Results Two thousand two hundred ninety five screws were reviewed, 36 screws in 18 patients were in proximity to the aorta. Fourteen screws (nine patients) appeared to be impinging the aorta. On prone CT, 13 out of the 14 instances the aorta moved away from the screw. The average distance at the screw level was 13.6 ± 4.8 mm in supine position and 8.9 ± 5.4 mm in prone position (P = 0.001). In one instance the relationship was unchanged on prone CT. No screw was noted to violate the lumen or distort the aorta. Conclusion Supine CT scan alone is not entirely accurate in determining screw-aorta relationship. Prone-CT scan provides additional information for better delineation. This additional diagnostic step can change the treatment option by limiting the need for vascular intervention. When in doubt, the additional use of an arteriogram can allow for improved visualization. Level of evidence 3.

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: Multi-center, randomized, placebo-controlled clinical trial. SETTING & PARTICIPANTS: 149 patients with CKD stages 3 and 4 between 7/2011 and 4/2016 at three centers in Cleveland, OH and the Bronx, NY. INTERVENTION: Sodium bicarbonate (NaBicarb) (0.4 mEq per kilogram of ideal body weight per day) (n=74) or identical placebo (n=75). OUTCOMES: The dual primary outcomes were muscle function assessed by sit-to-stand test and bone mineral density. Muscle biopsies were collected at baseline and 2 months. Participants were seen at baseline, 2, 6, 12 and 24 months. RESULTS: The mean baseline serum bicarbonate level was 24.0 +/− 2.2 (SD) and mean baseline eGFR was 36.3 +/− 11.2 ml/min/1.7m(2). Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm over 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

Retrospective chart review of prospectively collected data. This study seeks to evaluate the effect of number of surgeons, surgeon experience, and surgeon volume on AIS surgery. Recent literature suggests that utilizing two surgeons for spine deformity correction surgery can improve perioperative outcomes. However, the surgeon’s experience and surgical volume are likely as important. AIS patients undergoing PSF from 2009 to 2019 were included. Patient demographics, X-ray and perioperative outcomes were collected and collated based on primary surgeon. Analysis was performed for single versus dual surgeons, surgeon experience (≤ 10 years in practice), and surgical volume (less/greater than 50 cases/year). Median (IQR) values, Wilcoxon Rank Sums test, Kruskal–Wallis test, and Fisher’s exact test were utilized. 519 AIS cases, performed by 4 surgeons were included. Two surgeons were highly experienced, 1 of whom was also high volume. Five cohorts were studied: a single senior high volume (S1) (n = 302), dual-junior surgeons (DJ) (n = 73), dual senior–junior (SJ) (n = 36), dual-senior (DS) (n = 21) and a single senior, standard-volume surgeon alone (S2) (n = 87). Radiographic parameters were similar between the groups (p > 0.05). Preoperative Cobb was significantly higher for DS compared to S1 (p = 0.034) Pre- and post-op kyphosis were similar (p > 0.05). Cobb correction was similar (p > 0.05). Levels fused, fixation points, anesthesia and surgical times were similar (p > 0.05). When the standard-volume surgeon operated with a second surgeon, radiographic parameters were similar (p > 0.05), but anesthesia time, surgical time, and hospital length of stay were significantly shorter (p

INTRODUCTION This study establishes the construct validity of a low-cost training platform designed for high-repetition training of the skills required for fluent use of the five specific tools described for free-hand pedicle screw placement and breach avoidance. METHODS A total of 19 participants were included and divided into three groups based on spine surgery experience. Participants were asked to place five pedicle screws into the model. The performance was assessed by recording breaches, technical criteria (0 to 44 points), time to completion, and angulation of the screws. Success (no breaches, no protrusions) frequency (success/time) was calculated and analyzed. RESULTS Participants included three spine surgeons, seven advanced trainees (who had placed >10 pedicle screws), and nine inexperienced trainees. None of the screws placed by the spine surgeons breached the pedicle wall. Eight of 35 screws placed by advanced trainees (22.9%) and 31 of 45 screws placed by inexperienced trainees (68.9%) had a pedicle breach. Spine surgeons had a higher median success frequency compared with inexperienced trainees and advanced trainees (P = 0.015). The time needed to place a screw decreased over time (P < 0.0001). There was a trend toward an association between increased training level and decreased time to place five screws (P = 0.076). Increased training level was associated with greater total points scored (P < 0.0001). More screws placed by inexperienced trainees were further away from the ideal pedicle axis compared with those placed by advanced trainees or spine surgeons. CONCLUSION An association exists between training level and performance on the pedicle screw model, which suggests construct validity when evaluating our model's use for teaching surgeon learners. The model is easily assembled and is an alternative spine surgery training tool that overcomes limited availability and considerable costs of other training platforms. It can be used in high repetition to establish tool-skill fluency. LEVEL OF EVIDENCE Level I.

Evaluation of a child's intoeing gait is one of the most common referrals made to a pediatric orthopedist. Families may have difficulty understanding the often transient and usually benign nature of intoeing. The purpose of this study was to investigate parental perceptions of an intoeing gait both before and after consultation with an orthopedic practitioner.48 parents of children referred to pediatric orthopedic surgeons for evaluation of intoeing gait completed a 22-item questionnaire that assessed demographics, anxiety, and parental perceptions of intoeing. Questionnaires were administered before and after visits. Statistical analysis was performed using Wilcoxon signed-rank tests and Fisher exact tests.Before their visits, parents reported similar levels of anxiety and understanding regarding intoeing, independent of their age or education. After the visits, anxiety decreased (P 0.001), and understanding increased (P 0.001) although younger parents (18-25 years) reported higher post-visit anxiety compared to parents older than 25 (P = 0.014). Similarly, parents with a high school degree or less reported higher post-visit anxiety compared to parents who attended college (P = 0.009). Post-visit understanding was inversely correlated with post-visit anxiety (r = -0.717; P 0.001). Additionally, parents who reported high anxiety post-visit stated they were more likely to seek additional care (P 0.001).Younger parents with lower education levels were more likely to leave visits with high anxiety and poor understanding. These parents were more likely to consider seeking further treatment for their child's intoeing, placing additional stress on their child, themselves and an overburdened healthcare system.

Retrospective review of magnetic resonance imaging (MRI) and computed tomographic (CT) scan imaging modalities.To determine MRI's capability of identifying pedicle morphology.Understanding pedicle morphology is important for accurate placement of pedicle screws. The gold standard modality to assess pedicle morphology is CT scan. However, CT scans carry the risk of radiation exposure. We have studied MRI as a potential alternative to CT scan.Nine hundred seventy pedicles in 33 spinal deformity patients were reviewed. Pedicle morphology was classified as follows: Type A (normal pedicle):4-mm cancellous channel; Type B: 2-4-mm channel; Type C: any size cortical channel; and Type D:2-mm cortical or cancellous channel. Pedicles in the same patients were classified on both low-dose CT scan and MRI. Concordance and discordance rates of MRI relative to CT scan in classification of pedicles into types A, B, C, and D were calculated for the entire length of the thoracolumbar spine and subgrouped into spinal sections. All images were evaluated by a single fellowship-trained musculoskeletal radiologist.CT scan had 809 Type A, 126 Type B, 29 Type C, and 6 Type D pedicles. Group II (MRI) had 735 Type A, 203 Type B, 30 Type C, and 2 Type D pedicles. Analysis of the entire spinal column showed a concordance rate of 86.7% in classification of the pedicles into the 4 types. In the upper thoracic region, the concordance rate was 77.1%, main thoracic 85.5%, thoracolumbar 96%, and lumbar 98.1%. MRI has a poor overall accuracy for detecting Type C pedicles, only a 44.8% concordance with CT scan. MRI overcalls Type B pedicles, often calling Type A pedicles Type B.MRI is an inferior alternative to CT scan as it has poor accuracy to properly detect pedicle abnormalities. The more severe the pedicle abnormality, the less diagnostic value the MRI has.Level III, diagnostic.

Study design A retrospective review of charts, x-rays (XRs) and computed tomography (CT) scans was performed. Objective To evaluate the accuracy of pedicle screw placement using a novel classification system to determine potentially significant screw misplacement. Summary of background data The accuracy rate of pedicle screw (PS) placement varies from 85% to 95% in the literature. This demonstrates technical ability but does not represent the impact of screw misplacement on individual patients. This study quantifies the rate of screw misplacement on a per-patient basis to highlight its effect on potential morbidity. Methods A retrospective review of charts, XRs and low-dose CT scans of 127 patients who underwent spinal fusion with pedicle screws for spinal deformity was performed. Screws were divided into four categories: screws at risk (SAR), indeterminate misplacements (IMP), benign misplacements (BMP), accurately placed (AP). Results A total of 2724 screws were placed in 127 patients. A total of 2396 screws were placed accurately (87.96%). A total of 247 screws (9.07%) were BMP, 52 (1.91%) were IMP, and 29 (1.06%) were considered SAR. Per-patient analysis showed 23 (18.11%) of patients had all screws AP. Thirty-five (27.56%) had IMP and 18 (14.17%) had SAR. Risk factor analysis showed smaller Cobb angles increased likelihood of all screws being AP. Sub-analysis of adolescent idiopathic scoliotic patients showed no curve or patient characteristic that correlated with IMP or SAR. Over 40% of patients had screws with either some/major concern. Conclusion Overall reported screw misplacement is low, but it does not reflect the potential impact on patient morbidity. Per-patient analysis reveals more concerning numbers toward screw misplacement. With increasing pedicle screw usage, the number of patients with misplaced screws will likely increase proportionally. Better strategies need to be devised for evaluation of screw placement, including establishment of a national database of deformity surgery, use of intra-operative image guidance, and reevaluation of postoperative low-dose CT imaging. Level of evidence 3.

Problem High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. Method of study Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n = 8), other HR-HPV (n = 41), and non-HR-HPV controls (n = 79). Results Compared to controls, HR-HPV groups had higher plasma viral loads (P = 0.004), lower CD4 cells (P = 0.02), more genital tract HIV RNA (P = 0.03), greater number of different HPV types (P < 0.001), higher cervicovaginal lavage (CVL) IL-1α (P = 0.03) and human beta-defensin 2 (HBD2) (P = 0.049), and less anti-HIVBal activity (P = 0.03). HPV-16 remained significantly associated with higher HBD2 (P = 0.03), higher IL-1α (P = 0.009), and lower anti-HIVBaL activity (P = 0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. Conclusion HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health.

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 (P0.0001) 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 vs1) 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.

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.

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.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.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.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.

Background The incidence and risk factors for post-traumatic cervical epidural hematoma are not well described in the current literature. Our aim was to determine the incidence and associated risk factors for post-traumatic cervical spine epidural hematoma (SEH). Methods We performed a retrospective review of our institution’s prospectively collected data submitted to the state trauma registry, using ICD-9 codes, for all patients activated as a trauma with cervical spine injuries, between the years 2010 and 2014. Patients with MRI available were classified based on the presence of cervical epidural hematoma (CEH) or no hematoma (NEH). For our second analysis, we classified patients with cord compression associated with an epidural hematoma (CC) and no cord compression (NCC). Potential risk factors evaluated included: INR, PTT, albumin and platelets levels, radiographic findings of Ankylosing Spondylitis (AS), and ISS. No conflicts of interest exist and/or funding was used for this study. Results 497 out of 1810 trauma activations met our inclusion criteria. 46 patients (2.5%) were found to have a post-traumatic cervical SEH (CEH). Of the CEH cohort, 76% were male, with 72% Caucasian, and a mean age of 55 years. 27 patients (5.4%) were found to have cervical cord compression at the level of the SEH. Of the CC arm, 78% were male, with 67% Caucasian, and a mean age of 56 years. A higher ISS and an elevated INR were found to be associated with epidural hematoma causing cord compression. Conclusions An incidence of 2.5% is reported for post-traumatic cervical spine epidural hematoma. Of these, 59% had associated spinal cord compression. Patients with a higher ISS and elevated INR levels are at a higher risk for developing this potentially devastating.

Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is partly regulated by the immune microenvironment. We evaluated immune checkpoint PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy biopsies with30% TILs were considered lymphocyte-rich IBC. We performed immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing1% PD-L1+ immune or tumor cells were considered positive. CD68 was positive if40% of tumor stroma contained CD68+ cells or atleast 50% of tumor cells showed infiltration by CD68+ cells. Residual Cancer burden (RCB) Score of 0/I represented excellent response to NAC and RCB II or III unfavorable response. Thirty-five patients had RCB 0/I and 41 pts RCB II/ III. TILs30% were present in prechemotherapy biopsies in 19 pts of whom 14 showed RCB 0/I (P=0.0075). Twenty-seven cases were PD-L1+ and 20 had an RCB 0/I (P=0.0003). Twenty-two cases were CD68+ of whom 18 showed RCB 0/I (P=0.0001) There was a significant association between TILs30%, PD-L1+ and CD68+ expression. Using atleast one of these immunologic parameters identified 26 of 35 patients with RCB 0/I and showed a higher sensitivity for response prediction than TILs alone (40% vs. 74.3%). In conclusion we demonstrate that high numbers of CD68+ monocytic/macrophage cells and PD-L1 expression in IBC shows significant association with NAC response. An immune biomarker profile including TILs, PD-LI and CD68 is more sensitive for NAC response prediction than TILs alone.

Home-based therapy optimizing biomechanics and neuromuscular control is increasingly recognized as a treatment option for chronic nonspecific low back pain (CNSLBP). However, its impact on pain, function, and gait is limited among patients in a metropolitan area.To evaluate the change of pain, function, and gait parameters with home-based therapy with the use of footwear-generated biomechanical manipulation and perturbation training in a population with CNSLBP in a metropolitan area.Prospective observational study.Outpatient rehabilitation clinic at an academic teaching hospital.One hundred sixteen patients with CNSLBP for more than 6 months.Six months of home-based therapy with a biomechanical device using 4 modular elements attached to a foot-worn platform.Instrumental gait analysis (gait velocity, step length, single limb support phase % of gait cycle), Numeric Rating Scale for pain, and Oswestry Disability Questionnaire Index for pain and function.Only 43 patients (37.1%) completed the study. Among 43 patients, mean gait velocity increased from 86.6 ± 20.7 to 99.7 ± 22.1 cm/s (P.0001) in 6 months. Mean left step length increased from 51.1 ± 8.4 to 54.8 ± 9.8 cm (P.0001). Mean right step length increased from 51.0 ± 7.9 to 55.4 ± 9.0 cm (P.0001). Mean single limb support increased from 36.4 ± 2.8 to 37.2 ± 2.5%, (P = .208) in the right side and from 36.6 ± 3.0 to 37.8 ± 4.4%, (P = .019) in the left side. Median Oswestry Disability Questionnaire Index score improved from 28 (18-44; interquartile range) to 17 (10-35) (P = .045). Mean Numeric Rating Scale for back pain improved from 7.7 ± 1.8 to 3.3 ± 3.1 (P.0001).At 6 months, patients with CNSLBP undergoing home-based therapy with footwear-generated biomechanical manipulation and perturbation training demonstrated significant improvement of objective gait parameters, pain, and function.IV.

STUDY DESIGN A retrospective study. OBJECTIVE To determine the incidence of pedicle screws close to vital structures and to identify patient or curve characteristics that increase the risk of screw misplacement. SUMMARY AND BACKGROUND Most pedicle screw misplacements are asymptomatic, thus they are frequently undetected. This study identifies the rate of screw placement in proximity to vital structures using postoperative computed tomography scans. METHODS A total of 2132 screws in 101 patients, who underwent posterior spinal fusion for spinal deformity, were reviewed. Screws adjacent to great vessels and viscera were identified and evaluated. Patients with screws at risk (group B) were compared with patients without screws at risk (group A). Patient and curve characteristics were analyzed to determine whether a correlation with screw misplacement exists. RESULTS A total of 40 at risk screws (∼2%) were identified in 25 patients (∼25%). These 40 screws were in proximity to the aorta (31), left subclavian artery (1), esophagus (3), trachea (3), pleura (1), and diaphragm (1). Of the 31 screws close to the aorta, 10 screws in 6 patients were impinging or distorting the aortic wall. One hundred percent of misplaced screws were in the thoracic spine, 50% were misplaced laterally, 50% were 35 mm long, 57.5% were in pedicles with normal morphology, and 75% were in curves between 40 and 70 degrees. Median screw misplacement rate was 10% in group A and 13% in group B. Adjusted for age and preoperative Cobb angle, patients with a higher misplacement rate were more likely to have screws adjacent to vital organs [adjusted odds ratio: 1.06 (95% confidence interval, 1.01-1.13), P=0.033]. CONCLUSIONS Although only a small number of screws were at risk, they occurred in a large percentage of patients (25%). A single at-risk screw causes a significant complication for the patient. Postoperative imaging beyond routine x-rays may be needed to detect at-risk screws in asymptomatic patients.

Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.