Scalp Cooling in Preventing Persistent Chemotherapy-Induced Alopecia: A Randomized Controlled Trial.

PURPOSE: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 µm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.

Vessel Wall Imaging Features of Spontaneous Intracranial Carotid Artery Dissection.

BACKGROUND AND OBJECTIVES: Intracranial dissection is an important cause of stroke often with nonspecific angiographic features. Vessel wall imaging (VWI) can detect dissections, but intracranial applications remain unvalidated by pathologic specimens. We sought to determine the ability of VWI to identify the rarely reported spontaneous intracranial carotid dissection (sICD) guided by postmortem validation. METHODS: VWI features of sICD, validated by postmortem specimen analysis in 1 patient, included luminal enhancement within a hypoenhancing outer wall, narrowing the mid to distal ophthalmic (C6) segment, relatively sparing the communicating (C7) segment. VWI examinations were reviewed to identify patients (1) with matching imaging features, (2) no evidence of other vasculopathies (i.e., inflammatory, intracranial atherosclerotic disease [ICAD]), and (3) adequate image quality. These sICD VWI features were compared with those in patients with known ICAD causing similar narrowing of C6 and relative sparing of C7 by a Fisher exact test accounting for multiple samples. RESULTS: Among 407 VWI examinations, 8 patients were identified with 14 sICDs, all women aged 30-56 years, 6 (75%) bilateral. All patients with sICD had risk factors of dissection (e.g., recently postpartum, fibromuscular dysplasia, and hypertension) and 3 (37.5%) had intracranial dissections elsewhere. Seven (87.5%) were diagnosed as moyamoya syndrome on initial angiography. Enhancing lesions varied from thin flap-like defects (n = 6) to thick tissue along the superolateral wall of the internal carotid artery, within the hypoenhancing outer wall. Compared with 10 intracranial carotid plaques in 8 patients with ICAD, sICD demonstrated stronger (84.6% vs 20.0%, p = 0.003-0.025) and more homogeneous (61.5% vs 0.0%, p = 0.005-0.069) enhancement and less positive remodeling (0.0% vs 60.0%, p = 0.004-0.09). T1 hyperintensity was identified in 5 sICDs in 3 patients but not identified in ICAD. Three patients with serial imaging (8- to 39.8-month maximum intervals) revealed little to no changes in stenosis, wall thickening, or enhancement. DISCUSSION: sICD is distinguishable on VWI from ICAD by enhancement characteristics, less positive remodeling, and clinical parameters. These VWI features should raise suspicion especially in young women with risk factors of dissection. Temporal stability and a lack of T1 hyperintensity should not discourage diagnosing sICD.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Obesity paradox in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy.

BACKGROUND: The obesity paradox in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival. METHODS: This retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non-small cell lung cancer between October 2015 and October 2021. We used abdominal cross-sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2 /m2 ) by dividing the cross-sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional-hazards regression was performed to determine the correlation between BMI according to the Asia-Pacific classification, body composition metrics and overall survival. RESULTS: We analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1-year mortality rate of 0.58 (95% confidence interval, 0.55-0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52-0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41-0.70). No association was observed between sex and the impact of BMI on overall survival (P-value for interaction >0.05). CONCLUSIONS: In Asian patients with advanced non-small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.

Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality.

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.

Air pollution and mortality in patients with chronic obstructive pulmonary disease: a cohort study in South Korea.

Background: Evidence on whether long-term exposure to air pollution increases the mortality risk in patients with chronic obstructive pulmonary disease (COPD) is limited. Objectives: We aimed to investigate the associations of long-term exposure to particulate matter with diameter <10 µm (PM10) and nitrogen dioxide (NO2) with overall and disease-specific mortality in COPD patients. Design: We conducted a nationwide retrospective cohort study of 121,423 adults ⩾40 years diagnosed with COPD during 1 January to 31 December 2009. Methods: Exposure to PM10 and NO2 was estimated for residential location using the ordinary kriging method. We estimated the risk of overall mortality associated with 1-, 3-, and 5-years average concentrations of PM10 and NO2 using Cox proportional hazards models and disease-specific mortality using the Fine and Gray method adjusted for age, sex, income, body mass index, smoking, comorbidities, and exacerbation history. Results: The adjusted hazard ratios (HRs) for overall mortality associated with a 10 µg/m3 increase in 1-year PM10 and NO2 exposures were 1.004 [95% confidence interval (CI) = 0.985, 1.023] and 0.993 (95% CI = 0.984, 1.002), respectively. The results were similar for 3- and 5-year exposures. For a 10-µg/m3 increase in 1-year PM10 and NO2 exposures, the adjusted HRs for chronic lower airway disease mortality were 1.068 (95% CI = 1.024, 1.113) and 1.029 (95% CI = 1.009, 1.050), respectively. In stratified analyses, exposures to PM10 and NO2 were associated with overall mortality in patients who were underweight and had a history of severe exacerbation. Conclusion: In this large population-based study of patients with COPD, long-term PM10 and NO2 exposures were not associated with overall mortality but were associated with chronic lower airway disease mortality. PM10 and NO2 exposures were both associated with an increased risk of overall mortality, and with overall mortality in underweight individuals and those with a history of severe exacerbation.

Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Introduction-Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods-Oxidative stress was measured in 475 women and 266 men, aged 48-55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results-Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions-Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.

Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number.

Inter-individual variation in the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), reflects mitochondrial function and has been associated with various aging-related diseases. We examined 415,422 exomes of self-reported White ancestry individuals from the UK Biobank and tested the impact of rare variants, at the level of single variants and through aggregate variant-set tests, on mtDNA-CN. A survey across nine variant sets tested enrichment of putatively causal variants and identified 14 genes at experiment-wide significance and three genes at marginal significance. These included associations at known mtDNA depletion syndrome genes (mtDNA helicase TWNK, p = 1.1 × 10-30; mitochondrial transcription factor TFAM, p = 4.3 × 10-15; mtDNA maintenance exonuclease MGME1, p = 2.0 × 10-6) and the V617F dominant gain-of-function mutation in the tyrosine kinase JAK2 (p = 2.7 × 10-17), associated with myeloproliferative disease. Novel genes included the ATP-dependent protease CLPX (p = 8.4 × 10-9), involved in mitochondrial proteome quality, and the mitochondrial adenylate kinase AK2 (p = 4.7 × 10-8), involved in hematopoiesis. The most significant association was a missense variant in SAMHD1 (p = 4.2 × 10-28), found on a rare, 1.2-Mb shared ancestral haplotype on chromosome 20. SAMHD1 encodes a cytoplasmic host restriction factor involved in viral defense response and the mitochondrial nucleotide salvage pathway, and is associated with Aicardi-Goutières syndrome 5, a childhood encephalopathy and chronic inflammatory response disorder. Rare variants were enriched in Mendelian mtDNA depletion syndrome loci, and these variants implicated core processes in mtDNA replication, nucleoid structure formation, and maintenance. These data indicate that strong-effect mutations from the nuclear genome contribute to the genetic architecture of mtDNA-CN.

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome.

BACKGROUND & AIMS: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. METHODS: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. RESULTS: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). CONCLUSION: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

OBJECTIVE: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. BACKGROUND: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. METHODS: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. RESULTS: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). CONCLUSIONS: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study.

PURPOSE: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. METHOD: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10-20 mg or rosuvastatin 5-10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. RESULTS: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86-1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74-1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. CONCLUSIONS: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

Obstructive Sleep Apnea and Its Influence on Intracranial Aneurysm.

Obstructive sleep apnea syndrome (OSAS) is associated with cerebrovascular disease, which can lead to life-threatening outcomes. The purpose of the study was to investigate the relationship between OSAS and comorbid intracranial aneurysms. We retrospectively reviewed 564 patients who underwent a polysomnography and brain magnetic resonance angiography as part of their health checkup. We calculated the prevalence of an intracranial aneurysm and OSAS in patients and measured the size of the intracranial aneurysm if present. The mean patient age was 55.6 ± 8.5 years, and 82.3% of them were men. The prevalence of an intracranial aneurysm in patients with OSAS was 12.1%, which is significantly higher than patients with non-OSAS (5.9%, p = 0.031). Patients with OSAS had a much higher prevalence of intracranial aneurysms, after adjusting all possible confounding factors such as age, sex, smoking status, alcohol drinking, and body mass index (odds ratio: 2.32; 95% confidence interval: 1.07-5.04). Additionally, the OSAS group had noticeably larger aneurysms compared with those of the non-OSAS group (3.2 ± 2.0 mm vs. 2.0 ± 0.4 mm, p = 0.013). We found a significant association between OSAS and intracranial aneurysms. OSAS could be another risk factor for the development of intracranial aneurysms.

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease.

BACKGROUND/AIMS: This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. METHODS: This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. RESULTS: The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56). CONCLUSION: HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

Association Between Retinopathy of Prematurity in Very-Low-Birth-Weight Infants and Neurodevelopmental Impairment.

PURPOSE: To evaluate the impact of retinopathy of prematurity (ROP) severity and the treatment of very-low-birth-weight infants (VLBWIs) on neurodevelopmental impairment in early childhood. DESIGN: Prospective cohort study. METHOD: This was a prospective cohort study. The data were obtained from the Korean Neonatal Network (KNN), a nationwide registry for VLBWIs. Infants who were born from 2013 to 2015 and underwent ROP evaluation at birth and neurodevelopmental examinations at corrected ages of 18 to 24 months were included in the study. Infants with a history of meningitis or severe congenital anomalies were excluded. The VLBWI patients were grouped into no ROP, no treatment-requiring ROP (non-TR-ROP), and treatment-requiring ROP (TR-ROP) groups. Neurodevelopmental impairment was defined as participants who had at least 1 developmental problem according to the Bayley Scales of Infant and Toddler Development-2nd Edition (Bayley-II; <70), Bayley Scales of Infant and Toddler Development-3rd Edition (Bayley-III; <70), and Korean Developmental Screening Test (K-DST) tests (below -1 SD), and the Korean Ages and Stages Questionnaire (K-ASQ) (below the threshold) and Gross Motor Function Classification System (GMFCS; at level 2 or above). Multivariable logistic regression analysis was performed to evaluate the association between ROP and neurodevelopmental impairment. RESULT: Among 3132 infants, 1093 (34.9%) had ROP. Among the ROP infants, 644 were not treated for ROP (non-TR-ROP group) and 449 received ROP treatments (TR-ROP group). The patients in the TR-ROP group had an increased risk of developing neurodevelopmental problems compared to those in the no ROP group (odds ratio [OR] = 1.72, 95% CI = 1.33-2.21). The TR-ROP group had a higher risk of all 3 types of neurodevelopmental problems: mental (OR = 1.62, 95% CI = 1.25-2.09), social (OR = 1.62, 95% CI = 1.12-2.09), and motor (OR = 1.69, 95% CI = 1.31-2.18). The risk of neurodevelopmental problems in patients treated with laser therapy did not differ from that in patients treated with anti-vascular endothelial growth factor (anti-VEGF) therapy (OR = 1.17, 95% CI = 0.73-1.88). CONCLUSION: ROP was independently associated with neurodevelopmental impairment in early childhood. The type of ROP treatment (anti-VEGF or laser treatment) did not affect neurodevelopmental impairment in patients in the TR-ROP group.

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.

Oxidative Stress and Menopausal Status: The Coronary Artery Risk Development in Young Adults Cohort Study.

Background: Low endogenous estrogen concentrations after menopause may contribute to higher oxidative stress and greater cardiovascular disease (CVD) risk. However, differences in oxidative stress between similarly aged premenopausal and postmenopausal women are not well-characterized on a population level. We hypothesized that urinary isoprostane concentrations, a standard measure of systemic oxidative stress, are higher in women who have undergone menopause compared to premenopausal women. Methods and Results: We examined differences in urinary 8-isoprostane (iPF2α-III) and 2,3-dinor-8-isoprostane (iPF2α-III-M) indexed to urinary creatinine between 279 postmenopausal and 196 premenopausal women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, using linear regression with progressive adjustment for sociodemographic factors and traditional CVD risk factors. Unadjusted iPF2α-III-M concentrations were higher among postmenopausal compared to premenopausal women (Median [25th, 75th percentile]: 1762 [1178, 2974] vs. 1535 [1067, 2462] ng/g creatinine; p = 0.01). Menopause was associated with 25.5% higher iPF2α-III-M (95% confidence interval [6.5-47.9]) adjusted for age, race, college education, and field center. Further adjustments for tobacco use (21.2% [2.9-42.6]) and then CVD risk factors (18.8% [0.1-39.6]) led to additional partial attenuation. Menopause was associated with higher iPF2α-III in Black but not White women. Conclusions: We conclude that postmenopausal women had higher oxidative stress, which may contribute to greater CVD risk. ClinicalTrials.gov Identifier: NCT00005130.

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study.

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11-4.51), cardiomyopathy (HR 2.65; 95% CI 1.90-3.68), endometrial cancer (HR 3.53; 95% CI 2.76-4.53), hypothyroidism (HR 1.29; 95% CI 1.19-1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12-3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20-1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Outcomes and Revenue Generation of a Community-based Screening at a Center in the United States: The SToP Glaucoma Program.

PRCIS: Of 611 individuals seen at referral clinic visits following community screenings, 76% were diagnosed with ≤1 eye condition needing treatment, generating a total of $213,110 in collections for the institution over 2.5 years. PURPOSE: The purpose of this study was to examine the outcomes and revenue generation of community-based eye screenings. MATERIALS AND METHODS: Individuals aged 50 years and above screened at community sites in Baltimore, MD, with abnormal ophthalmic findings were referred for one free-of-charge definitive eye examination at the Wilmer Eye Institute. Diagnoses, treatment, and billing information were abstracted from electronic medical records of patients subsequently seen at Wilmer from January 1, 2016, to July 31, 2018. RESULTS: A total of 611 individuals attended 3696 encounters at Wilmer during this time period. Most patients were female (60.3%) and African American (83.7%). At the screening event, 82.9% reported difficulty seeing when not wearing corrective eyewear, although only 49.8% reported having visited an eye doctor within the last 2 years. The majority (60.2%) reported having Medicare/Medicaid coverage, and 8.1% reported being uninsured. At the definitive eye examination after the screening, 75.5% of patients were diagnosed with ≥1 eye condition, most commonly cataract (30.3%), suspicion of glaucoma (24.9%), manifest glaucoma (11.9%), diabetic retinopathy (5.4%), and ocular hypertension (2.6%). Overall, 430 (70.4%) individuals required treatment including surgery (n=106), intravitreal injections (n=14), laser procedures (n=9), and medications (n=48). A total of $213,110 was collected for visits and procedures after the initial referral visit during the study period. CONCLUSIONS: A large community-based vision screening program in Baltimore was able to identify ocular conditions requiring treatment in underserved older adults and connect them to eyecare. Our findings also highlight that this model simultaneously generates new revenue streams for the institution organizing the community screenings.