The relationship between parameters measured using intravoxel incoherent motion and dynamic contrast-enhanced MRI in patients with breast cancer undergoing neoadjuvant chemotherapy: a longitudinal cohort study.

Purpose: The primary aim of this study was to explore whether intravoxel incoherent motion (IVIM) can offer a contrast-agent-free alternative to dynamic contrast-enhanced (DCE)-MRI for measuring breast tumor perfusion. The secondary aim was to investigate the relationship between tissue diffusion measures from DWI and DCE-MRI measures of the tissue interstitial and extracellular volume fractions. Materials and methods: A total of 108 paired DWI and DCE-MRI scans were acquired at 1.5 T from 40 patients with primary breast cancer (median age: 44.5 years) before and during neoadjuvant chemotherapy (NACT). DWI parameters included apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudo-diffusion coefficient (Dp), perfused fraction (f), and the product f×Dp (microvascular blood flow). DCE-MRI parameters included blood flow (Fb), blood volume fraction (vb), interstitial volume fraction (ve) and extracellular volume fraction (vd). All were extracted from three tumor regions of interest (whole-tumor, ADC cold-spot, and DCE-MRI hot-spot) at three MRI visits: pre-treatment, after one, and three cycles of NACT. Spearman's rank correlation was used for assessing between-subject correlations (r), while repeated measures correlation was employed to assess within-subject correlations (rrm) across visits between DWI and DCE-MRI parameters in each region. Results: No statistically significant between-subject or within-subject correlation was found between the perfusion parameters estimated by IVIM and DCE-MRI (f versus vb and f×Dp versus Fb; P=0.07-0.81). Significant moderate positive between-subject and within-subject correlations were observed between ADC and ve (r=0.461, rrm=0.597) and between Dt and ve (r=0.405, rrm=0.514) as well as moderate positive within-subject correlations between ADC and vd and between Dt and vd (rrm=0.619 and 0.564, respectively) in the whole-tumor region. Conclusion: No correlations were observed between the perfusion parameters estimated by IVIM and DCE-MRI. This may be attributed to imprecise estimates of fxDp and vb, or an underlying difference in what IVIM and DCE-MRI measure. Care should be taken when interpreting the IVIM parameters (f and f×Dp) as surrogates for those measured using DCE-MRI. However, the moderate positive correlations found between ADC and Dt and the DCE-MRI parameters ve and vd confirms the expectation that as the interstitial and extracellular volume fractions increase, water diffusion increases.

Economic Burden of Health Conditions Associated With Adverse Childhood Experiences Among US Adults.

Importance: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events in childhood, such as experiencing abuse or neglect, witnessing violence, or living in a household with substance use disorder, mental health problems, or instability from parental separation or incarceration. Adults who had ACEs have more harmful risk behaviors and worse health outcomes; the economic burden associated with these issues is uncertain. Objective: To estimate the economic burden of ACE-associated health conditions among US adults. Design, Setting, and Participants: In this economic evaluation, regression models of cross-sectional survey data from the 2019-2020 Behavioral Risk Factor Surveillance System (BRFSS) and previous studies were used to estimate ACE population-attributable fractions (PAFs) (ie, the fraction of total cases associated with a specific exposure) for selected health outcomes (anxiety, arthritis, asthma, cancer, chronic obstructive pulmonary disease, depression, diabetes, heart disease, kidney disease, stroke, and violence) and risk factors (heavy drinking, illicit drug use, overweight and obesity, and smoking) among the 2019 US adult population. Adverse childhood experience PAFs were used to calculate the proportion of total condition-specific medical spending and lost healthy life-years related to ACEs using Global Burden of Disease Study data. Data analysis was performed from September 10, 2021, to November 29, 2022. Exposure: Adverse childhood experiences (age <18 years). Main Outcomes and Measures: Monetary valuation of ACE-associated morbidity and mortality using standard US value of statistical life methods and presented in terms of annual and lifetime per affected person and total population estimates at the national and state levels. Results: A total of 820 673 adults, representing 255 million individuals, participated in the BRFSS in 2019 and 2020. An estimated 160 million of the total 255 million US adult population (63%) had 1 or more ACE, associated with an annual economic burden of $14.1 trillion ($183 billion in direct medical spending and $13.9 trillion in lost healthy life-years). This was $88 000 per affected adult annually and $2.4 million over their lifetimes. The lifetime economic burden per affected adult was lowest in North Dakota ($1.3 million) and highest in Arkansas ($4.3 million). Twenty-two percent of adults had 4 or more ACEs and comprised 58% of the total economic burden-the estimated per person lifetime economic burden for those adults was $4.0 million. Conclusions and Relevance: In this cross-sectional analysis of the US adult population, the economic burden of ACE-related health conditions was substantial. The findings suggest that measuring the economic burden of ACEs can support decision-making about investing in strategies to improve population health.

Nrf2 Downregulation Contributes to Epithelial-to-Mesenchymal Transition in Helicobacter pylori-Infected Cells.

BACKGROUND: Gastric cancer, the fifth most common cancer worldwide, is mainly linked to Helicobacter pylori infection. H. pylori induces chronic inflammation of the gastric mucosa associated with high oxidative stress. Our study aimed at assessing the implication of Nrf2, a major regulator of cellular redox homeostasis, in H. pylori-induced gastric carcinogenesis. METHODS: Using three different gastric epithelial cell lines, a non-cancerous (HFE-145) and two different subtypes of gastric cancer (AGS and MKN74), we analyzed the modulation of Nrf2 expression over time. After invalidation of Nrf2 by CRISPR-cas9, we assessed its role in H. pylori-induced epithelial-to-mesenchymal transition (EMT). Finally, we evaluated the expression of Nrf2 and ZEB1, a central EMT transcription factor, in human gastric tissues. RESULTS: We first demonstrated that the Nrf2 signaling pathway is differentially regulated depending on the infection stage. Rapidly and transiently activated, Nrf2 was downregulated 24 h post-infection in a VacA-dependent manner. We then demonstrated that Nrf2 invalidation leads to increased EMT, which is even exacerbated after H. pylori infection. Finally, Nrf2 expression tended to decrease in human patients' gastric mucosa infected with H. pylori. CONCLUSIONS: Our work supports the hypothesis that Nrf2 downregulation upon H. pylori infection participates in EMT, one of the most important events in gastric carcinogenesis.

Evaluation of Monoexponential, Stretched-Exponential and Intravoxel Incoherent Motion MRI Diffusion Models in Early Response Monitoring to Neoadjuvant Chemotherapy in Patients With Breast Cancer-A Preliminary Study.

BACKGROUND: There has been a growing interest in exploring the applications of stretched-exponential (SEM) and intravoxel incoherent motion (IVIM) models of diffusion-weighted imaging (DWI) in breast imaging, with the focus on differentiation of breast lesions. However, the use of SEM and IVIM models to predict early response to neoadjuvant chemotherapy (NACT) has received less attention. PURPOSE: To investigate the value of monoexponential, SEM, and IVIM models to predict early response to NACT in patients with primary breast cancer. STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with primary breast cancer (aged 46 ± 11 years) due to undergo NACT. FIELD STRENGTH/SEQUENCES: A 1.5-T MR scanner, T1 -weighted three-dimensional spoiled gradient-echo, two-dimensional single-shot spin-echo echo-planar imaging sequence (DWI) at six b-values (0-800 s mm-2 ). ASSESSMENT: Tumor volume, apparent diffusion coefficient, tissue diffusion (Dt ), pseudo-diffusion coefficient (Dp ), perfusion fraction (f), distributed diffusion coefficient, and alpha (α) were extracted, following volumetric sampling of the tumors, at three time-points: pretreatment, post one and three cycles of NACT. STATISTICAL TESTS: Mann-Whitney test, receiver operating characteristic (ROC) curve. Statistical significance level was P < 0.05. RESULTS: Following NACT, 17 patients were determined to be pathological responders and 20 nonresponders. Tumor volume was significantly larger in nonresponders at each MRI time-point and demonstrated reasonable performance in predicting response (area under the ROC curve [AUC] = 0.83-0.87). No significant differences between groups were found in the diffusion coefficients at each time-point (P = 0.09-1). The parameters α (SEM), f, and f × Dp (IVIM) were able to differentiate between response groups after one cycle of NACT (AUC = 0.73, 0.72, and 0.74, respectively). CONCLUSION: Diffusion coefficients derived from the monoexponential, SEM, and IVIM models did not predict pathological response. However, the IVIM-derived parameters f and f × Dp and the SEM-derived parameter α were able to predict response to NACT in breast cancer patients following one cycle of NACT. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Impact of Various Weights in the Intraoperative Skull-Skeletal Traction on Correction of Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVES: Intraoperative skull-skeletal traction (ISST) facilitates the surgical scoliosis correction, but it is also associated with neurological risk. The objective of the present study was to investigate the impact of various traction weights on neurophysiological change and curve correction in surgery for adolescent idiopathic scoliosis (AIS). METHODS: A retrospective review of a consecutive series of posterior spinal fusions for AIS patients undergoing corrections with the use of ISST by 2 surgeons in one institution was performed. Intraoperative prone, post-traction radiographs were performed on all cases. The cases were divided into 2 groups, high and low traction weights, based on whether the weight used was ≥35% or <35% of body weight. The frequency of neurophysiological changes and the curve correction were compared between the 2 groups. RESULTS: The intraoperative correction magnitudes by ISST were significantly larger in the high ISST group than in the low ISST group (35° vs 26°, P < .001). Changes in motor-evoked potential (MEP) were more frequently observed in the high ISST group (47% vs 26%, P = .049). A multivariate analysis showed that high ISST was associated with 3 times higher risk of MEP change (95% confidence interval = 1.1-8.0, P = .03) and higher final postoperative correction rates (68% vs 60%, P = .001). CONCLUSIONS: The high ISST for AIS was associated with increased intraoperative and ultimate curve corrections, and potentially facilitated better final correction. However, the high weight group was associated with an increased frequency of intraoperative MEP changes.

Upper instrumented vertebral fractures in long lumbar fusions: what are the associated risk factors?

STUDY DESIGN: A retrospective comparative study. OBJECTIVE: To investigate the risk factors associated with upper instrumented vertebral (UIV) fractures in adult lumbar deformity. SUMMARY OF BACKGROUND DATA: Long segment lumbar fusions may lead to junctional failures. The purpose of this study was to determine factors associated with junctional failures. METHODS: Twenty-seven consecutive patients from 2001 to 2008 with minimum 4 levels fused, lower instrumented vertebra (LIV) of L5 or S1, upper instrumented vertebra of T10 or distal, and no previous surgery proximal to the instrumentation were retrospectively reviewed. We describe the UIV angle, the sagittal angle of the upper instrumented vertebra with the horizontal. Patients were divided into 3 groups: group 1, 7 patients with UIV fractures; group 2, 6 patients with other proximal failures; and group 3, 14 patients with no proximal complications. RESULTS: The mean number of levels fused was 5.7 (4-7), 5.2 (4-8), and 6.2 (4-8); mean age was 64.1, 61.8, and 64.1, and mean body mass index was 33.5, 30.0, and 31.6 for groups 1, 2, and 3, respectively (P > 0.05). Osteotomies were performed in 5 of 7 in group 1, 1 of 6 in group 2, and 5 of 14 in group 3. Mean follow-up was 26.3 months. The average intraoperative UIV angle (UIV0) and immediate postoperative UIV angle (UIV1) were 18.6°/15.4° for group 1, 5.7°/5.3° for group 2, and 10.3°/7.1° for group 3 (P < 0.05). Surgical revision rates were higher in group 1 (71%) compared with groups 2 (50%) and 3 (43%). Eight of 11 (73%) patients with upper instrumented vertebra of L1 or L2 had either UIV fracture or other proximal failure compared with 5 of 16 (31%) in patients with upper instrumented vertebra of T10, T11, or T12. CONCLUSION: Our series of long lumbar fusions had a high long-term complication and revision rate. A high UIV angle on intraoperative lateral radiograph was strongly associated with UIV fractures. UIVs of L1 or L2 had a higher rate of adjacent segment or UIV failure.

Posterior column reconstruction with autologous rib graft after en bloc tumor excision.

STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To evaluate the efficacy of using autologous rib graft for fusion across long posterior column defects. SUMMARY OF BACKGROUND DATA: Achieving fusion across large posterior column defects after en bloc tumor resection can be difficult. Rib graft can be harvested from the local wound, and its shape and structural properties are well suited for reconstruction of thoracic posterior column deficits. METHODS: After Research Ethics Board approval, a retrospective review of the charts of 17 consecutive patients undergoing posterior column reconstruction after en bloc tumor resections was carried out. Autologous vascularized and nonvascularized rib grafts were utilized in 8 and 9 cases, respectively; 14 patients with malignant tumors and 3 with benign etiology. After surgery, patients underwent routine clinical and radiographic follow-up, with a computed tomographic scan performed at a minimum of 6 months in all surviving patients. Clinical and radiographic films were analyzed. RESULTS: Computed tomographic scans at a minimum of 6 months demonstrated graft incorporation in all surviving cases. There was no obvious difference at 6-month imaging to differentiate vascularized from nonvascularized grafts. There were no cases of graft dislodgement or fracture. Graft site morbidity was difficult to isolate from the morbidity of these large procedures. No complications related to the graft were identified. CONCLUSION: The use of autologous rib graft with a proximal step-cut and distal saddle-cut supplemented with posterior instrumentation allowed immediate stabilization of the posterior column defect created by the en bloc tumor resection. This technique of fashioning the graft and taking advantage of its natural curved structure for immediate press-fit was associated with graft incorporation in our cases.

Posterior transdiscal three-column shortening in the surgical treatment of vertebral discitis/osteomyelitis with collapse.

STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To evaluate the early surgical results and complications of thoracic transdiscal osteotomies and vertebral shortening for the treatment of thoracic discitis/osteomyelitis. SUMMARY OF BACKGROUND DATA: Thoracic discitis/osteomyelitis leads to collapse of the disc space and/or vertebral body. We propose a novel technique to achieve the same goals as anterior column reconstruction through an entirely posterior approach. Shortening of the vertebral column provides structural support without the morbidity of an anterior approach. METHODS: Following REB approval, retrospective review of the charts of five patients that underwent posterior only thoracic transdiscal osteotomies and vertebral shortening for discitis/osteomyelitis was carried out. Posterior only surgery was performed in these patients with excision of the affected disc space and corresponding posterior elements. Instrumented fusion was performed across the segment spanning multiple vertebral levels. Clinical outcome, radiographic correction, and perioperative complications were analyzed. RESULTS: Three patients had bacterial discitis, and 2 had tuberculosis. Mean age at the time of surgery was 61 years (50-76). Mean follow-up was 45 months (25-63). There was no neurologic deterioration; 2 patients with Frankel grade B improved to grade D and E, respectively. Mean kyphosis corrected from 36 degrees (14-90) to 4 degrees (0-8), and the mean construct spanned 9 levels (6-15). No major complications were encountered during surgery. Two patients underwent revision surgeries, 1 patient died of unrelated causes at 6 months. All patients were treated with a full course of postoperative antibiotic treatment. No cases of recurrent infection were recorded. CONCLUSION: Thoracic transdiscal osteotomy with vertebral shortening is a safe and effective option for the treatment of infectious discitis/osteomyelitis with associated kyphosis. With adjuvant antibiotics, it effectively eradicates the infection through a posterior only approach, avoiding the need for anterior procedures and long anterior struts.