A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection.

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

Effect of low-power laser irradiation on the shear bond strength and thermal changes across different zirconia thicknesses using different irradiation times.

PURPOSE: To investigate the effect of irradiation time and zirconia thickness using low power Er,Cr:YSGG laser irradiation (for debonding purposes) on the thermal changes and shear bond strength of resin-bonded 3% mol yttrium oxide stabilized tetragonal zirconia polycrystal (3Y-TZP) specimens. MATERIALS AND METHODS: 3Y-TZP slices of 0.5, 2, and 3 mm thick were used. The temperature during laser irradiation using single spot irradiation at different times (30, 60, 90, and 120 s) and line scanning irradiation from one spot tanother at three different distances (2-, 4-, and 6- mm) were recorded. Single spot and line scanning irradiation data were analyzed using three-way ANOVA (α: 0.05) and generalized linear mixed model, respectively. Non-irradiated (control) and irradiated resin-bonded 3Y-TZP specimens were shear tested, and the data were analyzed using two-way ANOVA (α: 0.05). RESULTS: Under single spot irradiation, the laser-induced temperature was higher through thin 3Y-TZP at any time compared to thick 3Y-TZP. For the line scanning method, short distances (2 and 4 mm) resulted in a significant increase in temperature in 0.5 mm thick specimens. Laser irradiation significantly decreased the shear bond strength of the 0.5 mm group compared to the non-irradiated group. After irradiation, the bond strength of the 2- and 3-mm thick 3Y-TZP was similar to the non-irradiated group. CONCLUSION: The temperature and bond strength of low-power laser irradiated 3Y-TZP specimens was affected by the specimen thickness but not by the irradiation time tested. Low-power laser irradiation is an effective debonding method for thin Y-TZP restorations.

Pulmonary Surface Irregularity Score as a New Quantitative CT Marker for Idiopathic Pulmonary Fibrosis-a Pilot Study.

The purpose of this study is to evaluate the accuracy and inter-observer agreement of a quantitative pulmonary surface irregularity (PSI) score on high-resolution chest CT (HRCT) for predicting transplant-free survival in patients with IPF. For this IRB-approved HIPAA-compliant retrospective single-center study, adult patients with IPF and HRCT imaging (N = 50) and an age- and gender-matched negative control group with normal HRCT imaging (N = 50) were identified. Four independent readers measured the PSI score in the midlungs on HRCT images using dedicated software while blinded to clinical data. A t-test was used to compare the PSI scores between negative control and IPF cohorts. In the IPF cohort, multivariate cox regression analysis was used to associate PSI score and clinical parameters with transplant-free survival. Inter-observer agreement for the PSI score was assessed by intraclass correlation coefficient (ICC). The technical failure rate of the midlung PSI score was 0% (0/100). The mean PSI score of 5.38 in the IPF cohort was significantly higher than 3.14 in the negative control cohort (p < .001). In the IPF cohort, patients with a high PSI score (≥ median) were 8 times more likely to die than patients with a low PSI score (HR: 8.36; 95%CI: 2.91-24.03; p < .001). In a multivariate model including age, gender, FVC, DLCO, and PSI score, only the PSI score was associated with transplant-free survival (HR:2.11 per unit increase; 95%CI: 0.26-3.51; p = .004). Inter-observer agreement for the PSI score among 4 readers was good (ICC: 0.88; 95%CI: 0.84-0.91). The PSI score had high accuracy and good inter-observer agreement on HRCT for predicting transplant-free survival in patients with IPF.

Do outcomes for heart transplantation differ based on donor and recipient race?

PURPOSE: There are limited data examining the impact of both donor and recipient race on outcomes following orthotopic heart transplant (OHT). The purpose of this study was to evaluate the relationship between donor and recipient race and OHT outcomes. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. A comparison was conducted based on donor and recipient race (White, Black, Hispanic, Other/Unknown). Races for which there were limited numbers were excluded from the analysis (Asian, n = 1292; American Indian, n = 132; Pacific Islander, n = 132, Multiple ethnicities, n = 225). The primary endpoint was survival at 30 days, 1 year survival, and post-transplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: A total of 41 841 OHT were included. Of the recipients, 29 894 (71%) were White, 8475 (20%) were Black, and 3472 (8%) were Hispanic. Of the donors 27 783 (66%) were White, 6277 (15%) were Black, 6576 (16%) were Hispanic, and 1205 (3%) were Unknown/Other race. In a comparison of recipient demographics, White recipients were older (54.09 ± 12.21 years) compared to Black (49.44 ± 12.83 years) and Hispanic (49.97 ± 13.27 years) recipients. All other differences between groups were not clinically significant. Black recipients were more likely to receive a heart with an "urgent" status (probability .80) compared to White (.73) and Hispanic (.75) recipients (p < .001). Hispanic recipients were more likely to receive a transplant when listed as "non-urgent" (Probability .47) compared to White (.37) and Black (.30) recipients (p < .001). In terms of outcomes, compared to White recipients, Hispanic patients experienced a decreased 30-day survival (OR 1.27; p = .011) and 1-year survival (OR 1.17; p = .016). In comparing Donor/Recipient combinations compared to a White Donor/White Recipient combination, overall survival was decreased in White donor/African American recipient (HR 1.36; p < .001), African American donor/African American recipient (HR 1.41; p < .001) and Hispanic donor/African American recipient (HR 1.30; p < .001) combinations (Table 1). CONCLUSIONS: African American and Hispanic recipients have decreased survival compared to White recipients after heart transplant. The African American donor does not decrease survival. Racial differences still exist in donor and recipient characteristics and recipient outcomes after OHT. Increasing the donor pool for all races and ethnicities would potentially benefit all recipients. Continued study is warranted in order to minimize these differences among recipients and identify factors that could be contributing to decreased survival, in order to optimize outcomes for African American and Hispanic recipients post-transplant and eliminate disparities.

Are Academic Emergency Radiologists Systematically Disadvantaged Compared With Diagnostic Radiology Subspecialty Counterparts When It Comes to Promotion?

PURPOSE: The aim of this study was to assess academic rank differences between academic emergency and other subspecialty diagnostic radiologists. METHODS: Academic radiology departments likely containing emergency radiology divisions were identified by inclusively merging three lists: Doximity's top 20 radiology programs, the top 20 National Institutes of Health-ranked radiology departments, and all departments offering emergency radiology fellowships. Within departments, emergency radiologists (ERs) were identified via website review. Each was then matched on career length and gender to a same-institutional nonemergency diagnostic radiologist. RESULTS: Eleven of 36 institutions had no ERs or insufficient information for analysis. Among 283 emergency radiology faculty members from 25 institutions, 112 career length- and gender-matched pairs were included. Average career length was 16 years, and 23% were women. The mean h indices for ERs and non-ERs were 3.96 ± 5.60 and 12.81 ± 13.55, respectively (P < .0001). Non-ERs were twice as likely as ERs (0.21 versus 0.1) to be associate professors at h index < 5. Men had nearly 3 times the odds of advanced rank compared with women (odds ratio, 2.91; 95% confidence interval, 1.02-8.26; P = .045). Radiologists with at least one additional degree had nearly 3 times the odds of advancing rank (odds ratio, 2.75; 95% confidence interval, 1.02-7.40; P = .045). Each additional year of practice increased the odds of advancing rank by 14% (odds ratio, 1.14; 95% confidence interval, 1.08-1.21; P < .001). CONCLUSIONS: Academic ERs are less likely to achieve advanced rank compared with career length- and gender-matched non-ERs, and this persists even after adjusting for h index, suggesting that academic ERs are disadvantaged in current promotions systems. Longer term implications for staffing and pipeline development merit further attention as do parallels to other nonstandard subspecialties such as community radiology.

Immune marker reductions in black and white Americans following sleeve gastrectomy in the short-term phase of surgical weight loss.

BACKGROUND: Surgical weight loss procedures like vertical sleeve gastrectomy (SG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro-inflammatory cytokines and augment the release of anti-inflammatory cytokines. Recent reports suggest a reduced improvement in weight resolution after SG in Black Americans (BA) versus White Americans (WA). The goal of this study was to determine if differences in immunoglobulin levels and general markers of inflammation after SG in Black Americans (BA) and White Americans (WA) may contribute to this differential resolution. METHODS: Personal information, anthropometric data, and plasma samples were collected from 58 participants (24 BA and 34 WA) before and 6 weeks after SG for the measurement of immunoglobulin A (IgA), IgG, IgM, C-reactive protein (CRP), and transforming growth factor (TGFß). Logistic regression analysis was used to determine the relationship of measures of body size and weight and inflammatory markers. RESULTS: Both IgG and CRP were significantly elevated in BA in comparison to WA prior to weight loss. Collectively, IgG, TGFß, and CRP were all significantly reduced at six weeks following SG. CRP levels in BA were reduced to a similar extent as WA, but IgG levels were more dramatically reduced in BA than WA despite the overall higher starting concentration. No change was observed in IgA and IgM. CONCLUSIONS: These data suggest that SG improves markers of immune function in both BA and WA. More diverse markers of immune health should be studied in future work.

Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients' healthcare costs.

Background: Glioblastoma (GBM) is a lethal disease. At least in part, the recurrence of GBM is caused by cancer stem cells (CSCs), which are resistant to chemotherapy. Personalized anticancer therapy against CSCs can improve treatment outcomes. We present a prospective cohort study of 40 real-world unmethylated Methyl-guanine-methyl-transferase-promoter GBM patients treated utilizing a CSC chemotherapeutics assay-guided report (ChemoID). Methods: Eligible patients who underwent surgical resection for recurrent GBM were included in the study. Most effective chemotherapy treatments were chosen based on the ChemoID assay report from a panel of FDA-approved chemotherapies. A retrospective chart review was conducted to determine OS, progression-free survival, and the cost of healthcare costs. The median age of our patient cohort was 53 years (24-76). Results: Patients treated prospectively with high-response ChemoID-directed therapy, had a median overall survival (OS) of 22.4 months (12.0-38.4) with a log-rank P = .011, compared to patients who could be treated with low-response drugs who had instead an OS of 12.5 months (3.0-27.4 months). Patients with recurrent poor-prognosis GBM treated with high-response therapy had a 63% probability to survive at 12 months, compared to 27% of patients who were treated with low-response CSC drugs. We also found that patients treated with high-response drugs on average had an incremental cost-effectiveness ratio (ICER) of $48,893 per life-year saved compared to $53,109 of patients who were treated with low-response CSC drugs. Conclusions: The results presented here suggest that the ChemoID Assay can be used to individualize chemotherapy choices to improve poor-prognosis recurrent GBM patient survival and to decrease the healthcare cost that impacts these patients.

Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial.

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world.

Retrospective analysis of SGLT2 inhibitors in heart failure with preserved ejection fraction.

AIMS: Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality. HF with preserved ejection fraction (HFpEF), or diastolic failure, accounts for half of all HF cases and differs from HF with reduced ejection fraction (HFrEF). Patients with HFpEF are typically older, female, and commonly seen with chronic kidney disease (CKD), one of the leading independent risk factors for mortality in these patients. Unfortunately, drugs that had shown significant improvements in mortality in HFrEF have not shown similar benefits in HFpEF. Recently, sodium glucose transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular morbidity and mortality in HFrEF patients and slow down CKD progression. This study aimed to elucidate the impact of this drug class on mortality and risk of end stage renal disease in patients with HFpEF, which is currently unclear. METHODS AND RESULTS: We retrospectively analysed the Research Data Warehouse containing electronic health records from de-identified patients (n = 1 266 290) from the University of Mississippi Medical Center from 2013 to 2022. HFpEF patients had an average follow-up of 4 ± 2 years. Factors associated with increased all-cause mortality during HFpEF included age, male sex, and CKD. Interestingly, the only treatments associated with significant improvements in survival were angiotensin converting enzyme inhibitors/angiotensin receptor blockers and SGLT2i, regardless of CKD or diabetes status. Additionally, SGLT2i use was also associated with significant decrease in the risk of end stage renal disease. CONCLUSIONS: Our results support the use of SGLT2i in an HFpEF population with relatively high rates of hypertension, CKD, and black race and suggests that improvements in mortality may be through preserving kidney function.

Increasing Utilization and Improving Documentation in a Radiology Critical Alert System.

Effective communication of critical imaging findings is an important patient safety issue. Despite an increase in exam volumes, our institution saw a decrease in the number of alerts sent through our critical alert system, indicating that critical findings were not being communicated. The purpose of our interventions was to increase the number of critical alerts, while also improving documentation and improving our provider database. We used a program of education for our radiologists and systematic reinforcement to increase the usage of our critical alert system. We also implemented a new time-stamp macro in our dictation system to improve documentation of emergency alerts, and engaged with other departments to improve the contact information in our provider database. Our interventions led to an increase in the monthly number of critical alerts, most notably for findings that require clinical or imaging follow-up (17 alerts per month). There was also a steady improvement in documentation (96.9% compliance), along with an increase in the number of alerts to providers with current contact information (0.5% per month). Our efforts show that educational and collaborative efforts can result in improved communication of radiologic critical results.

Real World and Public Health Perspectives of Intraoperative Radiotherapy in Early-Stage Breast Cancer: A Multidisciplinary Analysis Beyond the Statistical Facts.

Breast conservation therapy (BCT) (usually a lumpectomy plus radiotherapy (RT)) has become a standard alternative to radical mastectomy in early-stage breast cancers with equal, if not higher, survival rates. The established standard of the RT component of the BCT had been about six weeks of Monday through Friday external beam RT to the whole breast (WBRT). Recent clinical trials have shown that partial breast radiation therapy (PBRT) to the region surrounding the lumpectomy cavity with shorter courses can result in equal local control, survival, and slightly improved cosmetic outcomes. Intraoperative RT (IORT) wherein RT is administered at the time of operation for BCT to the lumpectomy cavity as a single-fraction RT is also considered PBRT. The advantage of IORT is that weeks of RT are avoided. However, the role of IORT as part of BCT has been controversial. The extreme views go from "I will not recommend to anyone" to "I can recommend to all early-stage favorable patients." These divergent views are due to difficulty in interpreting the clinical trial results. There are two modalities of delivering IORT, namely, the use of low-energy 50 kV beams or electron beams. There are several retrospective, prospective, and two randomized clinical trials comparing IORT versus WBRT. Yet, the opinions are divided. In this paper, we try to bring clarity and consensus from a highly broad-based multidisciplinary team approach. The multidisciplinary team included breast surgeons, radiation oncologists, medical physicists, biostatisticians, public health experts, nurse practitioners, and medical oncologists. We show that there is a need to more carefully interpret and differentiate the data based on electron versus low-dose X-ray modalities; the randomized study results have to be extremely carefully dissected from biostatistical points of view; the importance of the involvement of patients and families in the decision making in a very transparent and informed manner needs to be emphasized; and the compromise some women may be willing to accept between 2-4% potential increase in local recurrence (as interpreted by some of the investigators in IORT randomized studies) versus mastectomy. We conclude that, ultimately, the choice should be that of women with detailed facts of the pros and cons of all options being presented to them from the angle of patient/family-focused care. Although the guidelines of various professional societies can be helpful, they are only guidelines. The participation of women in IORT clinical trials is still needed, and as genome-based and omics-based fine-tuning of prognostic fingerprints evolve, the current guidelines need to be revisited. Finally, the use of IORT can help rural, socioeconomically, and infrastructure-deprived populations and geographic regions as the convenience of single-fraction RT and the possibility of breast preservation are likely to encourage more women to choose BCT than mastectomy. This option can also likely lead to more women choosing to get screened for breast cancer, thus enabling the diagnosis of breast cancer at an earlier stage and improving the survival outcomes.

Impact of 2016 UNOS pediatric heart allocation policy changes on VAD utilization, waitlist, and post-transplant survival outcomes in children with CHD versus Non-CHD.

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.

Side-firing intraoperative ultrasound applied to resection of pituitary macroadenomas and giant adenomas: A single-center retrospective case-control study.

Introduction: Multiple intraoperative navigation and imaging modalities are currently available as an adjunct to endoscopic transsphenoidal resection of pituitary adenomas, including intraoperative CT and MRI, fluorescence guidance, and neuronavigation. However, these imaging techniques have several limitations, including intraoperative tissue shift, lack of availability in some centers, and the increased cost and time associated with their use. The side-firing intraoperative ultrasound (IOUS) probe is a relatively new technology in endoscopic endonasal surgery that may help overcome these obstacles. Methods: A retrospective analysis was performed on patients admitted for resection of pituitary adenomas by a single surgeon at the University of Mississippi Medical Center. The control (non-ultrasound) group consisted of twelve (n=12) patients who received surgery without IOUS guidance, and the IOUS group was composed of fifteen (n=15) patients who underwent IOUS-guided surgery. Outcome measures used to assess the side-firing IOUS were the extent of tumor resection, postoperative complications, length of hospital stay (LOS) in days, operative time, and self-reported surgeon confidence in estimating the extent of resection intraoperatively. Results: Preoperative data analysis showed no significant differences in patient demographics or presenting symptoms between the two groups. Postoperative data revealed no significant difference in the rate of gross total resection between the groups (p = 0.716). Compared to the non-US group, surgeon confidence was significantly higher (p < 0.001), and operative time was significantly lower for the US group in univariate analysis (p = 0.011). Multivariate analysis accounting for tumor size, surgeon confidence, and operative time confirmed these findings. Interestingly, we noted a trend for a lower incidence of postoperative diabetes insipidus in the US group, although this did not quite reach our threshold for statistical significance. Conclusion: Incorporating IOUS as an aid for endonasal resection of pituitary adenomas provides real-time image guidance that increases surgeon confidence in intraoperative assessment of the extent of resection and decreases operative time without posing additional risk to the patient. Additionally, we identified a trend for reduced diabetes insipidus with IOUS.

Relationship between fracture toughness and fractal dimensional increment in two types of dental glass-ceramics with different fracture surface roughness.

OBJECTIVES: Previous studies have reported the fractal dimensional increment of glass-ceramic fracture surfaces. The objective of this study was to determine the relationship between fracture toughness and fractal dimensional increment of two dental glass-ceramics with different volume fraction of crystals and different fracture surface roughness. METHODS: Bar-shaped specimens were prepared from lithium disilicate (LDS) and nanofluorapatite (NFA) glass-ceramics. One face of each specimen was indented using a Knoop diamond at 25 N (LDS) or 10 N (NFA) followed by loading in 4-point, or 3-point flexure, respectively, until failure. Fracture toughness (Kc) was calculated using the surface crack in flexure (SCF) technique (ASTM C1421). Epoxy replicas of the fracture surfaces were scanned using the atomic force microscope (AFM) followed by noise filtering. The FRACTALS software was used to determine the fractal dimensional increment (D*) by the Minkowski cover algorithm. RESULTS: Median (25%, 75% quartiles) fracture toughness of LDS bars were 1.62 (1.59, 1.69) MPa m1/2 and NFA bars were 0.68 (0.66, 0.74) MPa m1/2, respectively. The median fractal dimension (D) value (25%, 75% quartiles) before noise filtering were 2.16 (2.15, 2.17) and after noise filtering were 2.14 (2.14, 2.15) for LDS and before noise filtering were 2.29 (2.21, 2.38) and after noise filtering were 2.17 (2.17, 2.18) for NFA. Median (25%, 75% quartiles) surface roughness (Ra) before noise filtering were 139 (119, 188) nm and after noise filtering were 137 (118, 187) nm for LDS and before noise filtering were 7 (6, 15) nm and after noise filtering were 7 (6, 15) nm for NFA. SIGNIFICANCE: Noise filtering successfully eliminated noise from the material with smooth fracture surfaces (NFA), decreasing the measured fractal dimension. The NFA data fit a Kc vs. D*1/2 statistical model for fused silica previously tested using a similar technique. The equation relating fracture toughness to the fractal dimension was modified, accounting for the toughening mechanisms. Fractal analysis with noise filtering can be used to estimate the fracture toughness of dental glass-ceramics that do not exhibit crack bridging.

Mediation effects of diabetes and inflammation on the relationship of obesity to cognitive impairment in African Americans.

BACKGROUND: Whether diabetes and adipokine-driven inflammation explain the association of obesity to cognitive impairment is unknown. METHODS: Structural equation models estimated the total effects of waist circumference on cognitive outcomes among African American participants cross-sectionally (index exam) and longitudinally. Total effects were deconstructed into direct pathways of waist circumference to cognitive impairment and indirect mediation pathways through leptin, soluble tumor necrosis factor receptor 2 (sTNFR2), and diabetes. Waist circumference, leptin, and sTNFR2 were standardized. Cognitive impairment was defined as MMSE <21 or a z-score < -1.5 standard deviation (SD). Incident cognitive impairment was defined among those without cognitive impairment at the index exam as follow-up MMSE<21, z- score < -1.5, MMSE decline >1 point/year, or z-score decline of >0.1 SD/year. RESULTS: Among 1008 participants (70% women, mean age 62.9 years, 14.5% with obesity, 26% with diabetes), 132 (13%) had baseline cognitive impairment. Each SD higher waist circumference was associated with higher odds of cognitive impairment, odds ratio (OR) = 1.63; (95% confidence interval: 1.17, 2.24), with mediating pathways explaining 65% of the total effect (58% from diabetes; 7% from inflammation). At follow-up (mean 6.8 years), 106 of 535 (19.8%) had developed cognitive impairment. Each SD higher waist circumference was associated with higher odds of developing cognitive impairment (OR = 1.87; 95%CI: 1.18, 2.74); the direct effect of waist circumference explained 37% of the total effect and mediating pathways explained 63% (61% from diabetes; 2% from inflammation), although individual pathways were not statistically supported in the smaller sample. CONCLUSION: Diabetes, and to a lesser degree, adiposity-driven inflammation, appear to explain a substantial proportion of abdominal adiposity relationships with cognitive impairment. The impact of preventing and treating obesity on cognitive outcomes merits study.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

BACKGROUND: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. OBJECTIVE: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. DESIGN: Cross-sectional study. SETTING: Four U.S. community-based epidemiologic cohort studies with mGFR. PATIENTS: 3223 participants in 4 studies. MEASUREMENTS: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. RESULTS: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR - eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. LIMITATION: Single measurement of mGFR and serum markers without short-term replicates. CONCLUSION: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. PRIMARY FUNDING SOURCE: National Institutes of Health.

Repeated Transarterial Radioembolization Adverse Event and Hepatotoxicity Profile in Cirrhotic Patients With Hepatocellular Carcinoma: A Single-Center Experience.

Purpose The study aimed to evaluate the adverse event (AE) and hepatotoxicity profile, including radioembolization induced liver disease (REILD), following repeat radioembolization (RE) to the same or overlapping vascular territories in patients with hepatocellular carcinoma (HCC) and limited functional hepatic reserve/cirrhosis. Methods Nine patients (seven male and two female; median age, 66 years) with cirrhosis and HCC who underwent repeat RE (cycle 1 and cycle 2) between January 2012 and August 2019 were included. Patient demographics, clinical and treatment history, and pertinent laboratory values were recorded at baseline and post-treatment time points over a period of four months. Post-RE AE/hepatotoxicity was assessed, organized by type and frequency, and graded by severity according to the National Cancer Institute common terminology criteria for adverse events, version 5.0 (CTCAE v5.0). To assess rudimentary comparisons for post-RE hepatotoxicity vs. factors of interest, Spearman's rank correlation/rho was calculated, and all relevant plots were constructed. Kaplan-Meier analysis was performed along with associated median survival time. All statistical analyses were performed with Stata v16.1. Results Following cycle 1, 22 objective AE were identified according to CTCAE v.5 (17 grade I, four grade II, and one grade III), with grade I, II, and III AE experienced by 78%, 33%, and 11% of patients, respectively. Following cycle 2, 19 objective AE were identified according to CTCAE v.5 (11 grade I, seven grade II, and one grade III), with grade I, II, and III AE experienced by 89%, 56%, and 11% of patients, respectively. A single patient developed REILD after cycle 1, which progressed to fatal REILD following cycle 2. Following cycle 2, an additional patient advanced from less severe hepatotoxicity to REILD. Following cycle 2, positive correlations between the higher model for end-stage liver disease (MELD; rho=0.70) and Child-Pugh (rho=0.74) scores and degree of post-RE hepatotoxicity/REILD appear to emerge. Post-repeat RE median overall survival was 12.5 months. Conclusion Post-RE hepatotoxicity following repeat RE to the same or overlapping vascular territories in patients with limited functional hepatic reserve/cirrhosis is a common occurrence with variable severity ranging from transient laboratory derangement to fatal REILD. Lack of a consensus REILD definition and grading scale results in non-uniform reporting of incidence as well as clinical and laboratory features of the disease process. Strides aimed at improving clinical characterization, forming a more complete diagnostic definition, and establishing a uniform grading system with respect to REILD are of particular importance and would ultimately improve repeat RE patient selection and risk management.

IgG Antibody Response to the Pfizer BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers with Healthy Weight, Overweight, and Obesity.

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.