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The use of heparin for anticoagulation has changed the face of cardiac surgery by allowing a bloodless and motionless surgical field throughout the introduction of cardiopulmonary bypass (CPB). However, heparin is a drug with complex pharmacologic properties that can cause significant interpatient differences in terms of responsiveness. Heparin resistance during CPB is a weighty issue due to the catastrophic consequences stemming from inadequate anticoagulation, and the treatment of it necessitates a rationalized stepwise approach due to the multifactorial contributions toward this entity. The widespread use of activated clotting time (ACT) as a measurement of anticoagulation during CPB is examined, as it may be a false indicator of heparin resistance. Heparin resistance also has been repeatedly reported in patients infected with COVID-19, which deserves further exploration in this pandemic era. This review aims to examine the variability in heparin potency, underlying mechanisms, and limitations of using ACT for monitoring, as well as provide a framework towards the current management of heparin resistance.

To evaluate calcium deposition in the fetal spine in vivo during the second and third trimesters using quantitative susceptibility mapping (QSM).Fifty-four pregnant women in their second and third trimesters underwent a 2D multi-echo STrategically Acquired Gradient Echo (STAGE) MR imaging protocol at 3T covering the fetal spine. The first echo data was used for QSM processing. A linear regression model was used to assess the correlation between magnetic susceptibility and gestational age (GA). A paired sample t-test was used to compare the consistency of QSM measurements from each sequence.The magnetic susceptibility of the fetal spine decreased linearly with advancing GA, with a slope of -52.3 parts per billion (ppb)/week and a Pearson correlation coefficient (r) of 0.83 (p0.001). In 37 subjects for whom the STAGE local QSM data were available from both flip angles, the average magnetic susceptibility values were -1111 ± 278 ppb and -1081 ± 262 ppb for FA = 8° and FA = 40°, respectively. These means were not statistically different according to a paired sample t-test (p = 0.156).QSM is a reliable technique for evaluating calcium deposition and bone mineral density of fetal vertebrae. Our results demonstrate an increase in fetal calcium levels as a function of GA. These measures might be able to provide reference values for calcium content in the fetal spine during the second and third trimesters.• Calcium deposition and mineralization in the fetal spine, evaluated by vertebral magnetic susceptibility, increased with advancing gestational age. • Our results provide reference values for calcium content in the fetal spine during the second and third trimesters.

Land development intensity (LDI) is an important indicator of how much human exploitation of land resources. Against the background of rapid urbanization and industrialization, in order to curb the over-occupation of agricultural and ecological space by urbanized space, China has proposed the Major Functional Zoning Planning (MFZP) as a new spatial governance model, which attempts to implement differentiated LDI control according to the functional positioning of different regions. To observe the spatio-temporal evolution and drivers of LDI in the first five years since the implementation of the MFZP, we chose the Yangtze River Delta, the most urbanized region in China, as a case area. The multi-scale distribution pattern of LDI was analyzed by combining macro and micro scales, and a new spatial measurement method integrating global and local regression models was developed to quantitatively deconstruct the natural-human drivers of LDI in different functional zones. Results demonstrate that LDI decreases in a gradient of the urbanized zone (UZ) > main agricultural production zone (MAPZ) > key ecological function zone (KEFZ). In the UZ, LDI is influenced by natural-human multi factors, e.g., terrain conditions (SLP), proportion of cultivated land area (PCL), proportion of ecologically important area (EID), population urbanization rate (PUR), GDP per capita (PGDP), fixed asset investment size per land (FAI) and fiscal expenditure as a percentage of GDP (FD). The LDI in the MAPZ is mainly affected by the facilitating role of PCL, EID, FAI, and the prominent role of FD, while that in the KEFZ is mainly inhibited by SLP, EID, and driven by the PGDP. The diverse drivers of LDI in different functional zones remind us to implement differentiated spatial control according to functional positioning and to adopt refined policy tools of zoning and classification to ensure that land resources within each type of functional zone can be used sustainably.

Background Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. Conclusions Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

Objective We sought to clarify the effects of the preoperative K-line tilt on cervical sagittal balance and patient outcomes after laminoplasty for cervical ossification of the posterior longitudinal ligament (OPLL). Methods A retrospective analysis of 45 patients with OPLL treated by laminoplasty from January 2013 to December 2018 was performed. The radiological parameters included the K-line tilt, C2–C7 sagittal vertical axis, C2–C7 lordosis, T1 slope, and T1 slope minus C2–C7 lordosis. The patient quality of life outcomes were assessed using the neck disability index, Japanese Orthopaedic Association disability scale, and visual analog scale. The patients were classified into 2 groups according to the median preoperative K-line tilt angle (14.1°): the high K-line tilt group (n = 23) and the low K-line tilt group (n = 22). The postoperative cervical alignment changes and patient outcomes were compared and analyzed. Results The clinical outcomes demonstrated overall improvement at the final follow-up. The C2–C7 lordosis had significantly decreased from 13.5° ± 9.5° preoperatively to 10.2° ± 9.7°. The C2–C7 lordosis was less in the high K-line tilt group than that in the low K-line tilt group. In addition, the high K-line tilt group revealed significantly greater kyphotic changes and a greater loss of cervical lordosis compared with the low K-line tilt group. Finally, the quality of life outcomes and postoperative visual analog scale scores were higher in the high K-line tilt group. Conclusions The results of the present study have shown that the parameter K-line tilt is an ideal radiological parameter for predicting the outcomes and determining the need for laminoplasty for cervical ossification of the OPLL. Patients with a higher K-line tilt preoperatively experienced more kyphotic alignment changes and neck pain after laminoplasty.

Background US-based diagnosis of thyroid nodules is subjective and influenced by radiologists' experience levels. Purpose To develop an artificial intelligence model based on American College of Radiology Thyroid Imaging Reporting and Data System characteristics for diagnosing thyroid nodules and identifying nodule characteristics (hereafter, M

PURPOSE: To acquire the mobile macromolecule (MM) spectrum from healthy participants, and to investigate changes in the signals with age and sex. METHODS: 102 volunteers (49M/53F) between 20 and 69 years were recruited for in vivo data acquisition in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Spectral data were acquired at 3T using PRESS localization with a voxel size of 30 × 26 × 26 mm(3), pre-inversion (TR/TI 2000/600 ms) and CHESS water suppression. Metabolite-nulled spectra were modeled to eliminate residual metabolite signals, which were then subtracted out to yield a ‘clean’ MM spectrum using the Osprey software. Pearson’s correlation coefficient was calculated between integrals and age for the 14 MM signals. One-way ANOVA was performed to determine differences between age groups. An independent t-test was carried out to determine differences between sexes. RESULTS: MM spectra were successfully acquired in 99 (CSO) and 96 (PCC) of 102 subjects. No significant correlations were seen between age and MM signals. One-way ANOVA also suggested no age-group differences for any MM peak (all p > 0.004). No differences were observed between sex groups. WM and GM voxel fractions showed a significant (p < 0.05) negative linear association with age in the WM-predominant CSO (R = –0.29) and GM-predominant PCC regions (R = –0.57) respectively while CSF increased significantly with age in both regions. CONCLUSION: Our findings suggest that a pre-defined MM basis function can be used for linear combination modeling of metabolite data from different age and sex groups.

The neurometabolic timecourse of healthy aging is not well-established, in part due to diversity of quantification methodology. In this study, a large structured cross-sectional cohort of male and female subjects throughout adulthood was recruited to investigate neurometabolic changes as a function of age, using consensus-recommended magnetic resonance spectroscopy quantification methods.102 healthy volunteers, with approximately equal numbers of male and female participants in each decade of age from the 20s, 30s, 40s, 50s, and 60s, were recruited with IRB approval. MR spectroscopic data were acquired on a 3T MRI scanner. Metabolite spectra were acquired using PRESS localization (TE=30 ms; 96 transients) in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Water-suppressed spectra were modeled using the Osprey algorithm, employing a basis set of 18 simulated metabolite basis functions and a cohort-mean measured macromolecular spectrum. Pearson correlations were conducted to assess relationships between metabolite concentrations and age for each voxel; Spearman correlations were conducted where metabolite distributions were non-normal. Paired t-tests were run to determine whether metabolite concentrations differed between the PCC and CSO. Finally, robust linear regressions were conducted to assess both age and sex as predictors of metabolite concentrations in the PCC and CSO and separately, to assess age, signal-noise ratio, and full width half maximum (FWHM) linewidth as predictors of metabolite concentrations.Data from four voxels were excluded (2 ethanol; 2 unacceptably large lipid signal). Statistically-significant age*metabolite Pearson correlations were observed for tCho (r(98)=0.33, p0.001), tCr (r(98)=0.60, p0.001), and mI (r(98)=0.32, p=0.001) in the CSO and for NAAG (r(98)=0.26, p=0.008), tCho(r(98)=0.33, p0.001), tCr (r(98)=0.39, p0.001), and Gln (r(98)=0.21, p=0.034) in the PCC. Spearman correlations for non-normal variables revealed a statistically significant correlation between sI and age in the CSO (r(86)=0.26, p=0.013). No significant correlations were seen between age and tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region (all p0.20). Age associations for tCho, tCr, mI and sI in the CSO and for NAAG, tCho, and tCr in the PCC remained when controlling for sex in robust regressions. CSO NAAG and Asp, as well as PCC tNAA, sI, and Lac were higher in women; PCC Gln was higher in men. When including an age*sex interaction term in robust regression models, a significant age*sex interaction was seen for tCho (F(1,96)=11.53, p=0.001) and GSH (F(1,96)=7.15, p=0.009) in the CSO and tCho (F(1,96)=9.17, p=0.003), tCr (F(1,96)=9.59, p=0.003), mI (F(1,96)=6.48, p=0.012), and Lac (F(1,78)=6.50, p=0.016) in the PCC. In all significant interactions, metabolite levels increased with age in females, but not males. There was a significant positive correlation between linewidth and age. Age relationships with tCho, tCr, and mI in the CSO and tCho, tCr, mI, and sI in the PCC were significant after controlling for linewidth and FWHM in robust regressions.The primary (correlation) results indicated age relationships for tCho, tCr, mI, and sI in the CSO and for NAAG, tCho, tCr, and Gln in the PCC, while no age correlations were found for tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region. Our results provide a normative foundation for future work investigating the neurometabolic time course of healthy aging using MRS.

Promoting the downscaling and integration of zonal management and control of various environmental pollution sources is an effective way to systematically deal with the current high-intensity and complex environmental problems. Through single-factor and comprehensive pollutant emission intensity evaluation and cluster analysis, we built a full-coverage and cross-scale environmental spatial management and control system for pollution sources, then proposed environmental zoning patterns and pollution control strategies at three scales in the Yangtze River Delta (YRD), China. At the grid scale, the reclassified 7 types of pollution source spaces can be divided into 5 levels based on pollution emission intensity, and the most urgent environmental control subjects can be determined accordingly. Up to the county scale, combined with emission intensity and regional functions, 305 counties can be divided into 5 control intensity zones, which directly correspond to different environmental control intensity, requirements and policies. Finally, at the city scale, 41 cities can be clustered into 7 pollution control zones, which are classified and named as the three-level form of geographic location, development orientation and pollution source characteristics. Fully using the zoning units at different scales of cities, counties and grids can break the limitation of inherent administrative boundaries and allow environmental integration policies to be implemented across departments and regions, also let differentiated policies be more accurately implemented to different administrative levels and pollution source, and then truly improve the efficiency of environmental management.

Background According to the diagnosis criteria of the American Association of Endodontists (AAE), sensitive responses to cold and/or heat tests of suspected teeth compared with those of control teeth can be used for the diagnosis of pulpitis, but the role of electric pulp test (EPT) is not mentioned. It is believed that EPT has some limitations in determining the vitality of the pulp. The aim of this study was to explore the association between the difference in EPT values and the differential diagnoses of reversible pulpitis (RP) and symptomatic irreversible pulpitis (SIRP) caused by dental caries. Methods A total of 203 cases with pulpitis caused by dental caries were included. A diagnosis of pulpitis was made on the basis of the diagnostic criteria of AAE. Patient demographic and clinical examination data were collected. The EPT values of the suspected teeth and control teeth were measured, and the differences between them were calculated. The correlation between the difference in the EPT values and diagnosis of pulpitis was analyzed using univariate and multivariate logistic regression. Results In the 203 cases (78 males and 125 females; 115 cases of RP, 88 cases of SIRP; 9 anterior teeth, 59 premolars, and 135 molars), the mean patient age was 34.04 ± 13.02 (standard deviation) years. The unadjusted (crude) model, model 1 (adjusted for age), model 2 (adjusted for age and sex), and model 3 (adjusted for age, sex, and tooth type) were established for the statistical analyses. In model 3 [odds ratio (OR) = 1.025; 95% confidence interval (CI) 1.002–1.050; P = 0.035], the difference in EPT values between RP and SIRP was statistically significant. However, the areas under the curve of predictive probability of the crude model, model 1, model 2, and model 3 were 0.565, 0.570, 0.585, and 0.617, respectively, showing that the model accuracy was low. The P-value for the trend in differences between the EPT values as a categorical variable showed that the differences in the EPT values, comparing RP and SIRP, were not statistically significant. Conclusions Based on the present data, the difference in EPT values was not sufficient to differentiate RP from SIRP.

Background Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). Objective To compare the cost-effectiveness of different stopping ages for lung cancer screening. Design By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). Data sources The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Target population Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. Time horizon 45 years. Perspective Health care sector. Intervention Annual LDCT according to NLST, CMS, and USPSTF criteria. Outcome measures Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results of base-case analysis The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49 200, $68 600, and $96 700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Results of sensitivity analysis Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Limitation Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. Conclusion All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. Primary funding source CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.

Background The end-of-life period is a crucial time in lung cancer care. To have a better understanding of the racial-ethnic disparities in health care expenditures, access, and quality, we evaluated these disparities specifically in the end-of-life period for patients with lung cancer in the U.S. Materials and methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to analyze characteristics of lung cancer care among those diagnosed between the years 2000 and 2011. Linear and logistic regression models were constructed to measure racial-ethnic disparities in end-of-life care cost and utilization among non-Hispanic (NH) Asian, NH black, Hispanic, and NH white patients while controlling for other risk factors such as age, sex, and SEER geographic region. Results Total costs and hospital utilization were, on average, greater among racial-ethnic minorities compared with NH white patients in the last month of life. Among patients with NSCLC, the relative total costs were 1.27 (95% confidence interval [CI], 1.21-1.33) for NH black patients, 1.36 (95% CI, 1.25-1.49) for NH Asian patients, and 1.21 (95% CI, 1.07-1.38) for Hispanic patients. Additionally, the odds of being admitted to a hospital for NH black, NH Asian, and Hispanic patients were 1.22 (95% CI, 1.15-1.30), 1.47 (95% CI, 1.32-1.63), and 1.18 (95% CI, 1.01-1.38) times that of NH white patients, respectively. Similar results were found for patients with SCLC. Conclusion Minority patients with lung cancer have significantly higher end-of-life medical expenditures than NH white patients, which may be explained by a greater intensity of care in the end-of-life period. Implications for practice This study investigated racial-ethnic disparities in the cost and utilization of medical care among lung cancer patients during the end-of-life period. Compared with non-Hispanic white patients, racial-ethnic minority patients were more likely to receive intensive care in their final month of life and had statistically significantly higher end-of-life care costs. The findings of this study may lead to a better understanding of the racial-ethnic disparities in end-of-life care, which can better inform future end-of-life interventions and help health care providers develop less intensive and more equitable care, such as culturally competent advanced care planning programs, for all patients.

Background Detailed cost estimates are not widely available for esophageal cancer. Our study estimates phase‐specific costs for esophageal cancer by age, year, histology, stage, and treatment for older patients in the United States and compares these costs within stage and treatment modalities. Methods We identified 8061 esophageal cancer patients in the Surveillance, Epidemiology, and End Results‐Medicare database for years 1998‐2013. Total, cancer‐attributable, and patient‐liability costs were calculated based on separate phases of care—staging (or surgery), initial, continuing, and terminal. We estimated costs by treatment modality within stage and phase for esophageal adenocarcinoma and squamous cell carcinoma separately. We fit linear regression models using log transformation to determine cost by age and calendar year. All costs are reported in 2018 US dollars. Results Overall, mean (95% CI) monthly total cost estimates were high during the staging ($8953 [$8385‐$9485]) and initial phases ($7731 [$7492‐$7970]), decreased over the continuing phase ($2984 [$2814‐$3154]), and increased substantially during the 6‐month terminal phase ($18 150 [$17 211‐$19 089]). This pattern of high staging and initial phase costs, decreasing continuing phase costs, and increasing terminal phase costs was seen in all stages. The highest staging costs were in stages III ($9249, $8025‐$10 474) and II ($9171, $7642‐$10 699). The highest initial phase cost was in stage IV, $9263 ($8758‐49 768), the lowest continuing phase cost was in stage I, $2338 ($2160‐$2517), and the highest terminal phase costs were in stages II ($20 533, $17 772‐$23 293) and III ($20 599, $18 268‐$22 929). The linear regression models showed that cancer‐attributable costs remained stable over the study period and were unaffected by age for most histology, stage, and treatment modality subgroups. Conclusions Our estimates demonstrate that esophageal cancer costs can vary widely by histology, stage, and treatment. These cost estimates can be used to guide future resource allocation for esophageal cancer care and research.

To explore the feasibility of single-direction diffusion-weighted imaging (DWI) for assessing the fetal corpus callosum (CC).This prospective study included 67 fetuses with normal CC and 35 fetuses suspected with agenesis of the corpus callosum (ACC). The MR protocols included HASTE, TrueFISP, and single-direction DWI. Two radiologists independently evaluated the optimal visibility and the contrast ratio (CR) of the normal fetal CC. The Chi-squared test or Fisher's exact test was used to compare the proportions of "good" visibility (score ≥ 3, and the CC was almost/entirely visible) between single-direction DWI and HASTE/TrueFISP. The CR difference between single-direction DWI and HASTE/TrueFISP was detected using the paired t-test. The diagnostic accuracies were determined by comparison with postnatal imaging. In fetuses suspected of ACC, we measured and compared the length and area of the mid-sagittal CC in the single-direction DWI images.The proportion of "good" visibility in single-direction DWI was higher than that in HASTE/TrueFISP, with p0.0001. The mean CR from single-direction DWI was also higher than that of TrueFISP and HASTE (both with p0.0001). The diagnostic accuracy of the single-direction DWI combined with HASTE/TrueFisp (97.1%, 34/35) was higher than that of the Haste/TrueFISP (74.3%, 26/35) (p = 0.013). The length and area of the PACC (p0.001, p = 0.001, respectively) and HCC (p0.001, p = 0.018, respectively) groups were significantly lower than those of the normal group.The single-direction DWI is feasible in displaying fetal CC and can be a complementary sequence in diagnosing ACC.• We suggest a simple method for the display of the fetal CC. • The optimal visibility and contrast ratio from single-direction DWI were higher than those from HASTE and TrueFISP. • The diagnostic accuracy of the single-direction DWI combined with HASTE/TrueFISP sequences (97.1%, 34/35) was higher than that of the Haste/TrueFISP (74.3%, 26/35).

Purpose Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy; however the underlying epileptogenic mechanisms of FCD metabolism in epilepsy patients remain unclear. The aim of this study is to detect alterations of γ-aminobutyric acid (GABA), glutathione (GSH), and the composite of glutamate and glutamine (Glx) in MRI-typical and neuropathologically confirmed FCD-associated epilepsy using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). Materials and methods Fourteen epileptic patients suspected to be caused by FCD and 14 healthy controls were enrolled prospectively in this study; all subjects underwent a 3 T MRI scan, including 3D T1 weighted imaging and HERMES. The GABA signal detected by HERMES also contains signals from macromolecules and homocarnosine, so it is referred as GABA+. Signals of GABA+, GSH and Glx detected by HERMES from tumor foci, contralateral cerebral regions, and healthy controls were quantified using Gannet. Fitting errors and signal to noise ratios (SNRs) of GABA + signals were also recorded. Differences of GABA+, GSH, Glx, fitting error and SNR of GABA + among three groups were analyzed using linear mixed effects models. Results Twelve FCD-associated epilepsy patients (7 females, aged 21.9 ± 9.3 years) and 12 matched healthy controls (7 females, aged 22.8 ± 9.8 years) were finally enrolled in this study. ANOVA results indicated that GABA levels were significantly increased in FCD foci compared with contralateral regions (p = 0.008) and with healthy controls (p = 0.003), while no difference was found in GSH and Glx levels. No difference of fitting errors or SNR of GABA + was found among FCD foci, contralateral regions and healthy controls. Conclusions Increased GABA levels were found in FCD foci that indicated GABA may play a central role in the pathophysiology of FCD patients with epilepsy.

Background We studied trends in lung cancer treatment cost over time by phase of care, treatment strategy, age, stage at diagnosis, and histology. Methods Using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database for years 1998‐2013, we allocated total and patient‐liability costs into the following phases of care for 145 988 lung cancer patients: prediagnosis, staging, surgery, initial, continuing, and terminal. Patients served as self‐controls to determine cancer‐attributable costs based on individual precancer diagnosis healthcare costs. We fit linear regression models to determine cost by age and calendar year for each stage at diagnosis, histology, and treatment strategy and presented all costs in 2017 US dollars. Results Monthly healthcare costs prior to lung cancer diagnosis were $861 for a 70 years old in 2017 and rose by an average of $17 per year (P

Supplemental Digital Content is available in the text, Objectives: Our study provides phase-specific cost estimates for pancreatic cancer based on stage and treatment. We compare treatment costs between the different phases and within the stage and treatment modality subgroups. Methods: Our cohort included 20,917 pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed between 2000 and 2011. We allocated costs into four phases of care-staging (or surgery), initial, continuing, and terminal– and calculated the total, cancer-attributable, and patient-liability costs in 2018 US dollars. We fit linear regression models using log transformation to determine whether costs were predicted by age and calendar year. Results: Monthly cost estimates were high during the staging and surgery phases, decreased over the initial and continuing phases, and increased during the three-month terminal phase. Overall, the linear regression models showed that cancer-attributable costs either remained stable or increased by year, and either were unaffected by age or decreased with older age; continuing phase costs for stage II patients increased with age. Conclusions: Our estimates demonstrate that pancreatic cancer costs can vary widely by stage and treatment received. These cost estimates can serve as an important baseline foundation to guide resource allocation for cancer care and research in the future.

Post-hospital syndrome (PHS), a 90-day period of health vulnerability related to physiologic stressors following recent inpatient admission, has been observed in surgical and non-surgical patients. We aim to explore its effects on readmission and complication rates in patients undergoing elective female mid-urethral sling placement for the treatment of stress urinary incontinence. The Healthcare Cost and Utilization Project State Inpatient Database, State Emergency Department Database, and State Ambulatory Surgery Database for Florida between 2009 and 2014 were linked and utilized. Patients were identified as having undergone an outpatient mid-urethral sling placement with or without cystoscopy by CPT code. The primary exposure was PHS, defined as any inpatient admission within 90 days of mid-urethral sling placement. Patients with inpatient hospitalizations within 1 year of sling procedure were categorized based on timing of prior admission and analyzed. The primary outcomes were 30-day hospital readmission, rates of postoperative ED visits, minor/major complications rates, and overall 30-day cost. A multivariable logistic regression model was fit to assess independent predictors of adverse surgical outcomes. A total of 17,081 female patients who underwent mid-urethral sling procedures were identified. Patients with PHS were at higher risk for 30-day readmission [OR: 5.36 (IQR: 3.61–7.93); p

More than 50% of the world’s lung cancer cases occur in Asia and more than 20% of cancer deaths in Asia are attributable to lung cancer. The U.S. National Lung Screening Trial has shown that lung cancer screening with computed tomography (CT) can reduce lung cancer deaths. Using the Lung Cancer Policy Model–Asia (LCPM-Asia), we estimated the potential mortality reduction achievable through the implementation of CT-based lung cancer screening in China, Japan, Singapore, and South Korea. The LCPM-Asia was calibrated to the smoking prevalence of each of the aforementioned countries based on published national surveys and to lung cancer mortality rates from the World Health Organization. The calibrated LCPM-Asia was then used to simulate lung cancer deaths under screening and no-screening scenarios for the four countries. Using screening eligibility criteria recommended by the U.S. Centers for Medicare & Medicaid Services (CMS), which are based on age and smoking history, we estimated the lung cancer mortality reduction from screening through year 2040. By 2040, lung cancer screening would result in 91,362 life-years gained and 4.74% mortality reduction in South Korea; 290,325 life-years gained and 4.33% mortality reduction in Japan; 3,014,215 life-years gained and 4.22% mortality reduction in China; and 8,118 life-years gained and 3.76% mortality reduction in Singapore. As for mortality reduction by smoker type, current smokers would have the greatest mortality reduction in each country, ranging from 5.56% in Japan to 6.86% in Singapore. Among the four countries, lung cancer screening under CMS eligibility criteria was most effective in South Korea and least effective in Singapore. Singapore’s low smoking prevalence and South Korea’s aging population and higher smoking prevalence may partially explain the discrepancy in effectiveness. CT screening was shown to be promising as a means of reducing lung cancer mortality in the four countries.

Atypical choroid plexus papilloma (aCPP) is a newly introduced subtype of choroid plexus tumors (CPTs) defined by the World Health Organization (WHO) in 2007 and is characterized by intermediate characteristics between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). Currently, the available data describing the clinical features of aCPP in children are limited.We performed a retrospective review of 24 pediatric patients with CPTs in our institute and focused on the clinical, radiological and histopathological features of 9 patients with aCPP.The median age of aCPP patients was 12 (3-144) months, which was younger than the age of CPP patients (36 (5-132) months, P 0.05). Of the 9 aCPPs, there were 4 cases of giant masses in the cerebral hemisphere, which was significantly higher than that in CPPs (44.4 % vs 0.0 %, P 0.05). According to MRI analysis, cysts and necrosis (66.7 % vs 16.7 %, P 0.05), peritumoral edema (55.6 % vs 8.3 %, P 0.05) and blurred borders (55.6 % vs 8.3 %, P 0.05) were more common in aCPPs than in CPPs. T1WI isointense signals were mainly observed in aCPPs and CPPs (aCPP66.7 % vs CPP58.3 %, P0.05), while T2WI slightly low signals were more common in CPPs (CPP41.7 % vs aCPP0%, P 0.05); moreover, the tumor volume of aCPPs was significantly larger than that of CPPs (aCPP78.3 cm3 vs 8.4 cm3, P 0.05). For the DWI sequence scans, isointense signals were more common in aCPPs (aCPP77.8 %CPP25.0 %, P 0.05), while slightly low signals were more common in CPPs (CPP58.3 %aCPP0%, P 0.05). Both aCPPs and CPPs mainly showed homogeneously strong enhancement (aCPP66.7 % vs CPP91.7 %, P 0.05). Interestingly, 1 aCPP showed annular enhancement. For the pathological and immunohistochemical studies, the Ki67 proliferation index was significantly higher in aCPPs than in CPPs (13 % vs 6%, P 0.05), and the S-100(+)/Vim(+)/Syn(+) positive rate was higher in aCPPs (58.3 % vs 11.1 %, P 0.05).aCPP shows some distinctive clinical features compared with CPP, such as younger age, larger tumor size, more frequent necrosis and peritumoral edema, blurred borders, slightly low signals on T2WI and isointense signals on DWI, and a higher S-100(+)/Vim(+)/Syn(+) positive rate, which may provide more valuable evidence for differential diagnosis and clinical decisions surrounding aCPP.

Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence.

Background: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). Methods: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.

Abnormal pattern recognition receptor (PRR) signaling plays an important role in gastric mucosal damage caused by stomach microbiota; however, the underlying molecular mechanisms remain obscure. Here, we show that DC-SIGN, a surface phenotype marker of dendritic cells, is overexpressed in gastric epithelial cells facing LPS stimulation. NLRP3 expression in gastric epithelial cells are significantly increased and related to the degree of LPS stimulation. Furthermore, DC-SIGN could interact with TLR4, promote NLRP3 and related genes expression via MyD88-independent signaling pathway and regulate the secretion of IL-1β and IL-18 in gastric epithelial cells. The results of flow cytometry analysis show that DC-SIGN primarily mediates Th1 differentiation when co-cultured with gastric epithelial cells. These results reveal that LPS-induced DC-SIGN expression modulates NLRP3 inflammasomes formation via MyD88-independent TLR4 signaling in gastric epithelial cell, and induces a Th1-predominant host immune response,these findings may indicate a new function of DC-SIGN in non-immune cells, and elucidate the diversity role of gastric epithelial cells in mechanism of immune damage caused by microbial flora.

Epidemiological and basic research has suggested that Helicobacter pylori (H. pylori, Hp) infection has a protective function in inflammatory bowel disease (IBD); however, the mechanisms are not very clear. Here, we investigated the role of exosomes derived from Hp-infected patients in IBD. Human intestinal epithelial cells were treated with serum exosomes derived from Hp-positive chronic gastritis patients (Exo(Hp)), the expression of cytokines, inflammasome and signal pathway genes were detected by antibody microarray or PCR array. Furthermore, DSS-induced colitis mice were treated with exosomes by intraperitoneally injection. The results demonstrated that Exo(Hp) promoted NLRP12 expression in intestinal epithelial cells, and NLRP12 decreased chemokine MCP-1 and MIP-1α expression by inhibiting the Notch signaling pathway. Next, in vivo, results showed that Exo(Hp) attenuated the inflammatory responses in DSS-induced colitis mice and improved colitis symptoms, outcomes associated with an increase in NLRP12 expression. Furthermore, the immunohistochemistry results showed that NLRP12 was negatively correlated with the disease activity of pediatric IBD patients. These results provide new theoretical bases for further elucidation of the protective mechanisms of Hp infection in IBD, and suggest new targets for explorations of effective interventional strategies for IBD.

BackgroundOur study analyzed disparities in utilization and phase-specific costs of care among older colorectal cancer patients in the United States. We also estimated the phase-specific costs by cancer type, stage at diagnosis, and treatment modality.MethodsWe used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients aged 66 or older diagnosed with colon or rectal cancer between 2000-2013, with follow-up to death or December 31, 2014. We divided the patient's experience into separate phases of care: staging or surgery, initial, continuing, and terminal. We calculated total, cancer-attributable, and patient-liability costs. We fit logistic regression models to determine predictors of treatment receipt and fit linear regression models to determine relative costs. All costs are reported in 2019 US dollars.ResultsOur cohort included 90,023 colon cancer patients and 25,581 rectal cancer patients. After controlling for patient and clinical characteristics, Non-Hispanic Blacks were less likely to receive treatment but were more likely to have higher cancer-attributable costs within different phases of care. Overall, in both the colon and rectal cancer cohorts, mean monthly cost estimates were highest in the terminal phase, next highest in the staging phase, decreased in the initial phase, and were lowest in the continuing phase.ConclusionsRacial/ethnic disparities in treatment utilization and costs persist among colorectal cancer patients. Additionally, colorectal cancer costs are substantial and vary widely among stages and treatment modalities. This study provides information regarding cost and treatment disparities that can be used to guide clinical interventions and future resource allocation to reduce colorectal cancer burden.

To investigate the interval time to canceration, clinicopathological characteristics and prognostic factors of carcinoma in remnant stomach (CRS) in patients with primary benign diseases or primary malignant tumors.Based on the criteria of the definition of CRS proposed by Japanese Gastric Cancer Association in 2017, a retrospective analysis was conducted on clinicopathological characteristics of patients diagnosed with CRS at Peking University Cancer Hospital from March 1992 to March 2017. Between patients with primary benign diseases (CBS-B group) and primary malignant tumors (CBS-M group), continuous variables were compared using the Student's t-test or the Mann-Whitney U test; categorical variables were compared using the chi-square test or Fisher's exact test. Spearmen-Rho was used to examine correlation. Survival was estimated and compared using Kaplan-Meier methods. Cox proportional hazards regression was applied to identify independent prognostic factors. Area under ROC curve(AUC) was used to evaluate and compare prediction accuracy.A total of 89 patients were included in the study with a male: female ratio of 5.4 to 1.0. The male: female ratio in CRS-B (n=46) and CRS-M (n=43) group was 14.3 to 1.0 and 2.9 to 1.0 respectively with significant difference (χMen have more CRS than women. The interval time to canceration is correlated to the first operative procedure for CRS-B patients, while it is correlated to the age at the first operation for CRS-M patients. The major location of CRS is in the gastrointestinal anastomosis for CRS-B patients and in non-anastomosis area for CRS-M patients. Main postoperative complications include respiratory and infectious complications. Pathological T staging is an independent prognostic risk factor for CRS patients.

Background: Anesthesia for pulmonary endarterectomy (PEA) has always been one of the challenges of anesthesia. As one of the leading cardiothoracic institutions in Southeast Asia, our hospital has vast interest in this subject. A local multidisciplinary team was deployed to an expert center in the United Kingdom (UK), and the experience was then integrated to the care of our patients. We present a case series of ten patients undergoing anesthesia for PEA, a first for our institution, and discuss techniques as well as potential complications. Methods: Patients with chronic thromboembolic pulmonary hypertension were reviewed by a multidisciplinary team, and those who were suitable for surgical intervention subsequently underwent PEA. A total of ten patients were identified and operated on. The perioperative management and conduction of anesthesia for all patients followed a protocol adapted from the expert center in the UK, with revisions to cater to our Asian population. Results: In the ten patients operated on, eight of them were successfully extubated on the first postoperative day. Apart from one incident of prolonged ventilator usage due to reperfusion lung injury and pneumonia, there were no major respiratory or hemodynamic complications. Certainly, six of the ten patients developed subdural hemorrhage after the commencement of enoxaparin, although none of them sustained any permanent neurological deficits. Conclusion: We have demonstrated that with careful planning and a well-outlined protocol, anesthesia for PEA in an Asian population can be achieved with favorable outcomes. Further fine-tuning of the protocol is still required based on local expertise.

Cushing's disease (CD) presents a remarkable preponderance in female gender, and a significant minority of patients with CD presented with negative magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate gender-related and MRI classification-related differences in clinical and biochemical characteristics of CD.We retrospectively studied 169 patients with CD, comprising 132 females and 37 males, and 33 patients had no visible adenoma on MRI.We observed that male and MRI-positive patients presented with high adrenocorticotropic hormone (ACTH) values (P0.05). Female patients presented with higher prevalence of hirsutism and hyperpigmentation and lower prevalence of purple striae (P0.05). The prevalence of buffalo-hump and hypertension was greater in MRI-negative patients (P0.05). In addition, male patients with CD presented at a younger age compared with females (P0.05). Patients with fatigue and hypokalaemia presented significantly higher urinary-free cortisol, ACTH and cortisol levels compared with patients without these symptoms (P0.05). The prevalence of LH reduction, hyper total cholesterol (TC) and hyper low-density lipoprotein was more frequent in MRI-positive patients (P0.05). Hyper-TC levels and PRL reduction were more frequent in males (P0.05). T3, T4 and FT3 levels negatively correlated with age at diagnosis (r = -0.310, P0.01; r = -0.191, P0.05; r = -0.216, P0.05). T3, T4, FT3 and FT4 levels significantly negatively correlated with 8-am plasma cortisol levels (r = -0.328, P0.01; r = -0.195, P0.05; r = -0.333, P0.01; r = -0.180, P0.05). Females presented higher total protein level (P0.01) and lower blood urea nitrogen and serum creatinine levels (P0.01), compared with male patients.Carefulness and caution are required in all patients with CD, because of the complexity of clinical and biochemical characteristics in CD patients of different gender and MRI classification, particularly male patients and MRI-negative patients.

Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.