Longitudinal associations of reproductive factors and exogeneous estrogens with neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease.

INTRODUCTION: Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies. METHODS: We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures. RESULTS: Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume. DISCUSSION: HC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies. HIGHLIGHTS: Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

Factors determining utilization of stem cell transplant for initial therapy of multiple myeloma by patient race: exploring intra-racial healthcare disparities.

Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed, stem cell transplant (SCT) remains an important modality that provides excellent disease control and delays the progression of disease. Over the years, SCT use has increased overall in the U.S., but two distinct gaps remain, including suboptimal use overall and racial-ethnic disparities. We evaluated the National Cancer Database (NCDB) to study what sociodemographic factors might play a role within a given racial-ethnic group leading to disparate SCT utilization, such that targeted approaches can be developed to optimize SCT use for all. In nearly 112,000 cases belonging to mutually exclusive categories of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA), and others, we found certain factors including age, comorbidity index, payor type, facility type (academic vs. community) and facility volume to be uniformly associated with SCT use for all the racial-ethnic groups, while gender was not significant for any of the groups. There were several other factors that had a differential impact on SCT utilization among the various race-ethnicity groups studied, including year of diagnosis (significant for NHW, NHB, and Hispanics), income level (significant for NHW and Hispanics), literacy level (significant for NHW and NHB), and geographic location of the treatment facility (significant for NHW and NHA). The suboptimal SCT utilization overall in the U.S. suggests that there may be room for improvement for all, even including the majority NHW, while we continue to work on factors that lead to disparities for the traditionally underserved populations. This study helps identify sociodemographic factors that may play a role specifically in each group and paves the way to devise targeted solutions such that resource utilization and impact can be maximized.

Associations of reproductive factors and exogenous estrogens with global and domain-specific cognition in later life.

INTRODUCTION: Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain-specific cognition in later life. METHODS: We studied a population-based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing. RESULTS: The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular-related covariates did not attenuate the results. DISCUSSION: Multiple reproductive risk factors are associated with cognitive decline in later life. HIGHLIGHTS: The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain-specific z-scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

BACKGROUND AND OBJECTIVES: Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life. METHODS: Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record-abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined. RESULTS: Of the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p < 0.05) in age- and education-adjusted models. There was an interaction (p = 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p < 0.001) vs 12 + years (b = -0.11, p = 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p < 0.001), language (beta = -0.03, p = 0.001), and attention (beta = -0.04, p < 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results. DISCUSSION: Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

BACKGROUND: ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. METHODS: This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. RESULTS: One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13-3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91-0.99], P = .02), lower bicarbonate (OR 0.94 [0.88-0.99], P = .035), and higher creatinine (OR 1.91 [1.23-2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48-3.94], P < .001), opioids (OR 2.94 [1.67-5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30-1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34-2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33-1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2-301.7], P < .001), bloodstream infection (OR 4.59 [2.46-8.57], P < .001), and pneumonia (OR 9.76 [5.01-19.00], P < .001). CONCLUSIONS: Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Performance of plasma phosphorylated tau 181 and 217 in the community.

Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30-98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid positron-emission tomography (PET) (area under the receiver operating characteristic curve (AUROC) = 0.81-0.86) and tau PET entorhinal cortex (AUROC > 0.80), but was less predictive of a tau PET temporal region of interest (AUROC < 0.70). Multiple comorbidities were associated with higher plasma P-tau181 and P-tau217 levels; the difference between participants with and without chronic kidney disease (CKD) was similar to the difference between participants with and without elevated brain amyloid. The exclusion of participants with CKD and other comorbidities affected the establishment of a normal reference range and cutpoints. Understanding the effect of comorbidities on P-tau181 and P-tau217 levels is important for their future interpretation in the context of clinical screening, diagnosis or prognosis at the population level.

Plasma, platelet and red blood cell transfusion ratios for life-threatening non-traumatic haemorrhage in medical and post-surgical patients: An observational study.

BACKGROUND AND OBJECTIVES: Despite the broad utilization of component-based transfusion strategies that aim to reconstitute whole blood during acute traumatic haemorrhage, data for haemorrhage occurring outside of trauma and surgery are limited. METHODS: This is an observational cohort study of adults experiencing critical non-traumatic, non-intraoperative haemorrhage during hospitalization at an academic medical centre from 2011 to 2015. The primary goal was to evaluate differences in plasma and platelet to red blood cell (RBC) transfusion ratios across patient demographic, clinical and laboratory characteristics. Secondarily, associations between transfusion ratios and clinical outcomes were assessed. RESULTS: Seven hundred nine patients were included: 498 (70.2%) medical and 211 (29.8%) post surgical. The gastrointestinal tract (36.7%) was the most common site of bleeding. Most patients received RBCs without plasma (35.5%) or platelets (54.2%). Among those receiving plasma, 82.3% received a plasma to RBC ratio < 1:1 at 24 h. For platelets, the most common ratio was 1-2:1 (52.9%). Transfusion ratios were generally consistent across comorbid disease severity, admission type and anatomic sites of bleeding. Higher plasma utilization was observed in the emergency department, while greater platelet utilization occurred in intensive care units. Higher transfusion ratios were observed in those with greater laboratory haemostatic abnormalities prior to the haemorrhagic event. Clinical outcome differences were limited, though greater platelet utilization in the first 24 h was associated with higher mortality and fewer hospital-free days. CONCLUSIONS: Transfusion ratios for critical non-traumatic haemorrhage were primarily related to laboratory abnormalities preceding the haemorrhagic event and practice environments. Clinical outcome differences across ratios were limited.

Association Between Antifibrinolytic Therapy and Perioperative Outcomes in Patients With Coronary Artery Stents Undergoing Noncardiac Surgery.

BACKGROUND: Patients with existing coronary artery stents are at an increased risk for major adverse cardiac events (MACEs) when undergoing noncardiac surgery (NCS). Although the use of antifibrinolytic (AF) therapy in NCS has significantly increased in the past decade, the relationship between perioperative AF use and its association with MACEs among patients with existing coronary artery stents has yet to be assessed. In this study, we aim to evaluate the association of MACEs in patients with existing coronary artery stents who receive perioperative AF therapy during orthopedic surgery. METHODS: A single-center retrospective cohort study was conducted in adult patients with existing coronary artery stents who underwent orthopedic surgery from 2008 to 2018. Two cohorts were established: patients with existing coronary artery stents who did not receive perioperative AF and patients with coronary artery stents who received perioperative AF. Associations between AF use and the primary outcome of MACEs within 30 days postoperatively and the secondary outcomes of thrombotic complications, excessive surgical bleeding, and intensive care unit (ICU) admissions were analyzed using logistic regression models. Inverse probability of treatment weighting was used to control for confounding. Secondary analyses examining the association between coronary stent type/timing and the outcomes of interest were performed using unadjusted logistic regression models. RESULTS: A total of 473 patients met study criteria, including 294 who did not receive AF and 179 patients who received AF. MACEs occurred in 15 (5.1%) patients who did not receive AF and 1 (0.6%) who received AF (P = .007). In weighted analyses, no significant difference was found in patients who received AF with regard to MACEs (odds ratio [OR] = 0.13, 95% confidence interval [CI], 0.01-1.74, P = .12), thrombotic complications (OR = 1.19, 95% CI, 0.53-2.68, P = .68), or excessive surgical bleeding (OR = 0.13, 95% CI, 0.01-2.23, P = .16) compared to patients who did not receive AF. CONCLUSIONS: The results of this study are inconclusive whether an association exists between perioperative AF use in patients with coronary artery stents and the outcome of MACEs compared to patients who did not receive perioperative AF therapy. The authors acknowledge that the imprecise CI hinders the ability to definitively determine whether an association exists in the study population. Further large prospective studies, powered to detect differences in MACEs, are needed to assess the safety of perioperative AF in patients with existing coronary artery stents and to clarify the mechanism of perioperative MACEs in this high-risk population.

Idiopathic pulmonary fibrosis and gastroesophageal reflux disease: A population-based, case-control study.

BACKGROUND: It is unknown whether gastroesophageal reflux disease (GERD) is a risk factor or consequence of idiopathic pulmonary fibrosis (IPF). This study aimed to determine whether patients with IPF were more likely to have GERD compared with age- and sex-matched controls who either had 1) interstitial lung disease (ILD) other than IPF or 2) no diagnosed lung disease (population control). METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project (REP) to identify patients with IPF who resided in Olmsted County, Minnesota, from January 1, 1997, through June 30, 2017. IPF cases were each matched with patients from 2 control groups (non-IPF ILD controls and population controls). We used conditional logistic regression to model associations between GERD diagnosis and IPF case status. P values were adjusted for multiple comparisons by using the Bonferroni adjustment (P values < .025 were considered statistically significant). RESULTS: One hundred thirteen IPF cases were identified and matched to 226 population controls and 226 controls with non-IPF ILD. After multivariable adjustment, the odds of having GERD were 1.78 times higher (95% CI, 1.09-2.91; P = .02) in IPF cases compared with population controls. After multivariable adjustment, the odds of having GERD were 0.46 times lower (95% CI, 0.23-0.94; P = .03) in IPF cases compared with non-IPF ILD controls. CONCLUSION: GERD may be an important contributor to the development of lung fibrosis. Thus, it should be investigated and addressed adequately when detected in patients with IPF and patients with non-IPF ILD.

Pretransplant Risk Factors Can Predict Development of Acute Respiratory Distress Syndrome after Hematopoietic Stem Cell Transplantation.

Rationale: Acute respiratory distress syndrome (ARDS) is a common complication after hematopoietic stem cell transplantation (HCT) and is a major contributor to nonrelapse mortality. Objectives: To better understand pretransplant risk factors for developing ARDS after HCT. Methods: This is a single-center observational study comparing risk factors for ARDS development in 164 patients who went on to develop post-HCT ARDS compared with 492 patients who did not. The patients were matched 1 to 3 on age, sex, type of transplant (allogeneic vs. autologous), and underlying disease. Pertinent risk factors were analyzed separately in multivariable conditional logistic regression after adjustment for a priori variables known to be associated with ARDS development. Results: Patients with ARDS were more likely to have a lower pretransplant pulmonary function as measured by forced vital capacity (FVC) (odds ratio [OR], 0.54 [0.42-0.70] per liter increase in FVC; P < 0.001), forced expiratory volume in one second (FEV1) (OR, 0.52 [0.38-0.71] per liter increase in FEV1; P < 0.001) and diffusing capacity (OR, 0.92 [0.88-0.96] per ml/min/mm Hg increase in diffusing capacity; P < 0.001). Several laboratory indices were predictive of subsequent ARDS development including elevated AST (aspartate aminotransferase) (OR, 1.01 [1.00-1.01]; P < 0.008), lower serum albumin (OR, 0.44 [0.30-0.66]; P < 0.001), lower pretransplant hemoglobin (OR, 0.82 [0.73-0.92]; P = 0.001), and lower leukocyte count (OR, 0.88 [0.79-0.99]; P < 0.03). Patients who went on to develop ARDS were more likely to have been hospitalized in the year before the transplant (OR, 1.11 [1.04-1.20]; P = 0.003), and required invasive or noninvasive ventilation during that hospitalization. Lastly, patients with ARDS were significantly more likely to have received carboplatin, thalidomide, methotrexate, and cisplatin than the non-ARDS control subjects. Conclusions: Several risk factors for developing ARDS after HCT are identifiable at the time of transplantation, well before the development of critical illness and ARDS. The identification of risk factors long before ARDS develops is relatively unique to the HCT population. Further work is needed to develop usable risk prediction tools in this setting.

Hospital discharge hemoglobin values and posthospitalization clinical outcomes in transfused patients undergoing noncardiac surgery.

BACKGROUND: Red blood cell (RBC) transfusion is common in surgical patients, yet optimal transfusion targets are incompletely defined in the perioperative period. Hemoglobin levels at the time of hospital discharge may provide insight into transfusion practices, anemia management, and patient outcomes. STUDY DESIGN AND METHODS: This is an observational cohort study of adults receiving RBC transfusion during noncardiac surgery from 2010 to 2014. Multivariable regression was used to assess the relationships between hospital discharge hemoglobin concentrations, anemia severity (severe: <8 g/dL; moderate: 8-10 g/dL; mild/none: ≥10 g/dL), and clinical outcomes, including a primary outcome of 30-day hospital readmission and secondary outcomes of posthospitalization RBC transfusion, composite stroke or myocardial infarction, and mortality. RESULTS: A total of 3129 patients were included: 165 (5%) with severe discharge anemia, 1962 (63%) moderate, and 1002 (32%) with mild/none. Five hundred ninety-two (19%) were readmitted, with the highest rates observed with severe anemia (26% vs 19% for mild/none). Readmissions were not significantly different after multivariable adjustment (overall P = .216); however, in those receiving postoperative intensive care, severe anemia was associated with increased readmission rates (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.09-2.71; reference mild/none]. Posthospitalization RBC transfusion rates were highest with severe anemia (25% vs 10% for mild/none; adjusted HR, 2.2; 95% CI, 1.5-3.3; P < .001). There were no significant differences in composite stroke/myocardial infarction, or mortality. RBC transfusion volumes did not modify anemia-outcome relationships. CONCLUSION: Hospital discharge hemoglobin values for transfused surgical patients were not associated with hospital readmission rates except for those receiving postoperative intensive care. Further evaluation is warranted to understand downstream consequences of postsurgical anemia.

Neuraxial anesthesia is associated with improved survival after total joint arthroplasty depending on frailty: a cohort study.

BACKGROUND: Frailty increases risk for complications after total joint arthroplasty (TJA). Whether this association is influenced by anesthetic administered is unknown. We hypothesized that use of neuraxial (spinal or epidural) anesthesia is associated with better outcomes compared with general anesthesia, and that the effect of anesthesia type on outcomes differs by frailty status. METHODS: This single-institution cohort study included all patients (≥50 years) from January 2005 through December 2016 undergoing unilateral, primary and revision TJA. Using multivariable Cox regression, we assessed relationships between anesthesia type, a preoperative frailty deficit index (FI) categorized as non-frail (FI <0.11), vulnerable (FI 0.11 to 0.20), and frail (FI >0.20), and complications (mortality, infection, wound complications/hematoma, reoperation, dislocation, and periprosthetic fracture) within 1 year after surgery. Interactions between anesthesia type and frailty were tested, and stratified models were presented when an interaction (p<0.1) was observed. RESULTS: Among 18 458 patients undergoing TJA, more patients were classified as frail (21.5%) and vulnerable (36.2%) than non-frail (42.3%). Anesthesia type was not associated with complications after adjusting for age, joint, and revision type. However, in analyzes stratified by frailty, vulnerable patients under neuraxial block had less mortality (HR=0.49; 95% CI 0.27 to 0.89) and wound complications/hematoma (HR=0.71; 95% CI 0.55 to 0.90), whereas no difference in risk by anesthesia type was observed among patients found non-frail or frail. CONCLUSIONS: Neuraxial anesthesia use among vulnerable patients was associated with improved survival and less wound complications. Calculating preoperative frailty prior to TJA informs perioperative risk and enhances shared-decision making for selection of anesthesia type.

Intraoperative Fluid Balance and Perioperative Outcomes After Aortic Valve Surgery.

BACKGROUND: The effect of intraoperative fluid balance on postoperative acute kidney injury (AKI) in cardiac surgical patients is poorly defined. METHODS: In this retrospective study of patients undergoing aortic valve replacement for aortic stenosis, the primary outcome of interest was postoperative AKI. Secondary outcomes were postoperative fluid balance, cardiac index, vasopressor use, hospital-free days, stroke, myocardial infarction, hospital readmission, and 30- and 90-day mortality. RESULTS: A total of 2327 patients were analyzed. Positive intraoperative fluid balance was associated with lower odds of AKI; the lowest odds were in the 20- to 39-mL/kg group (odds ratio, 0.56; 95% confidence interval, 0.38-0.81; P = .002). Positive intraoperative fluid balance was associated with a lower postoperative fluid balance. Increased ultrafiltration volume was associated with increased postoperative fluid resuscitation and vasopressor use. AKI was associated with increased 30- and 90-day mortality. Increased fluid balance was associated with increased odds of myocardial infarction and 30-day mortality. Increased ultrafiltration volume was associated with increased odds of 30- and 90-day mortality. CONCLUSIONS: In patients who underwent aortic valve replacement for aortic stenosis, positive intraoperative fluid balance was associated with decreased odds of AKI. Patients developing AKI had increased 30- and 90-day mortality. Although the overall incidence was low, increased intraoperative fluid balance was associated with myocardial infarction and 30-day mortality, whereas increased ultrafiltration volume was associated with 30- and 90-day morality. Prospective studies are needed to better define proper intraoperative fluid management in patients undergoing cardiac surgery.

Intraoperative Plasma Transfusion Volumes and Outcomes in Cardiac Surgery.

OBJECTIVE: Assess outcomes after intraoperative plasma transfusion in patients undergoing cardiac surgery. DESIGN: Retrospective study of adult cardiac surgical between 2011 and 2015. Relationships between plasma transfusion volume, coagulation test values, and a primary outcome of early postoperative red blood cell (RBC) transfusion were assessed via multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit and hospital-free days, intraoperative RBCs, estimated blood loss, and reoperation for bleeding. SETTING: Academic tertiary referral center. PARTICIPANTS: A total of 1,794 patients received intraoperative plasma transfusions during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher plasma transfusion volumes were associated with worse clinical outcomes, with each 1-unit increase being associated with greater odds for postoperative RBCs [odds ratio (OR) 1.12 (confidence interval [CI] 1.04-1.20); p = 0.002], intraoperative [OR 1.85 (CI 1.69-2.03); p < 0.001], and fewer hospital-free days [mean -0.20 (-0.39, -0.01); p = 0.04]. Each 0.1 increase in pretransfusion International Normalized Ratio (INR) was associated with increased odds of postoperative and intraoperative RBCs, reoperation for bleeding, and fewer intensive care unit and hospital-free days. For given plasma volumes, patients achieving greater reduction in elevated pretransfusion INR values experienced more favorable outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who received intraoperative plasma transfusion, higher plasma transfusion volumes were associated with inferior clinical outcomes. Higher pretransfusion INR values also were associated with worse outcomes; however, those achieving a greater degree of INR correction after plasma transfusion demonstrated more favorable outcomes. Prospective studies related to plasma transfusion are needed to address this important topic.

Influence of Sociodemographic Factors on Treatment Decisions in Non-Small-Cell Lung Cancer.

INTRODUCTION: In stage IV non-small-cell lung cancer (NSCLC), survival has significantly improved. Despite such trends, it has been noted that patients frequently refuse treatment. Therefore, we explored the factors associated with treatment refusal in NSCLC. PATIENTS AND METHODS: Utilizing the National Cancer Data Base (NCDB), we identified all stage IV NSCLC cases from 2004 to 2014. Patients who received cancer treatment outside of the reporting facility were excluded. Multivariable logistic regression models were used to determine associations with treatment refusal. RESULTS: A total of 341,993 patients were identified; 5.4% of patients refused radiotherapy and 10.3% refused chemotherapy despite provider recommendations. The proportion of patients refusing radiotherapy and chemotherapy increased over time from 4.2% to 7.3% and 7.9% to 15%, respectively (P < .001). In multivariable analysis, men were less likely to refuse treatment compared to women (respectively, odds ratio = 0.80; 95% confidence interval, 0.76-0.84; P < .001; odds ratio = 0.82; 95% confidence interval, 0.80-0.85; P < .001, respectively). Factors associated with radiotherapy refusal included: Medicaid or Medicare as primary insurance, uninsured status, low household median income, and lower educational level. Regarding chemotherapy, uninsured patients, Medicaid patients, and patients with a high comorbidity index were more likely to refuse chemotherapy. Asians had lower rates of chemotherapy refusal relative to non-Hispanic whites. Non-Hispanic whites, Hispanics, and Asians had increasing chemotherapy refusal rates over time, while non-Hispanic blacks had less pronounced trends over time. CONCLUSION: Socioeconomic factors rather than race/ethnicity appear to influence the refusal of cancer treatment in patients with stage IV NSCLC. Assessing socioeconomic challenges should be an essential part of patient evaluation when discussing treatment options.

Ratios of Plasma and Platelets to Red Blood Cells in Surgical Patients With Acute Intraoperative Hemorrhage.

BACKGROUND: The relationships between the ratios of transfused allogeneic blood products and clinical outcomes in patients with acute intraoperative hemorrhage are poorly defined. METHODS: To better define these ratios, we undertook a single-center, observational cohort study of all surgical patients (≥18 years) who received rapid transfusion defined by a critical administration threshold of 3 or more units of red blood cells (RBCs) intraoperatively within 1 hour between January 1, 2011 and December 31, 2015. Multivariable regression analyses were used to assess relationships between ratios of plasma to RBCs and platelets to RBCs at 3, 12, and 24 hours and clinical outcomes. The primary outcome was hospital mortality, with secondary outcomes of intensive care unit and hospital-free days. RESULTS: The study included 2385 patients, of whom 14.9% had a plasma-to-RBC ratio of 1.0+, and 47.6% had a platelet-to-RBC ratio of 1.0+. Higher plasma-to-RBC and platelet-to-RBC ratios were observed for patients who underwent cardiac, transplant, and vascular surgery and in patients with greater derangements in hemostatic laboratory values. Ratios did not differ by patient age or severity of illness. Higher ratios were not associated with improved clinical outcomes. Mortality differed by platelet-to-RBC but not plasma-to-RBC ratio, with the highest mortality observed with a platelet-to-RBC ratio of 0.1-0.9 at 24 hours (odds ratio, 3.34 [1.62-6.88]) versus no platelets (P= .001). Higher plasma-to-RBC ratios were associated with decreased hospital-free days, although differences in clinical outcomes were not significant after exclusion of patients receiving only RBCs without component therapies. CONCLUSIONS: Transfusion ratios in surgical patients with critical intraoperative hemorrhage were largely related to surgical and hemostatic features rather than baseline patient characteristics. Higher ratios were not associated with improved outcomes.

Initial Postoperative Hemoglobin Values and Clinical Outcomes in Transfused Patients Undergoing Noncardiac Surgery.

BACKGROUND: Intraoperative red blood cell (RBC) transfusion is common, yet transfusion strategies remain controversial as pretransfusion hemoglobin triggers are difficult to utilize during acute bleeding. Alternatively, postoperative hemoglobin values may provide useful information regarding transfusion practices, though optimal targets remain undefined. METHODS: This is a single-center observational cohort study of adults receiving allogeneic RBCs during noncardiac surgery from 2010 through 2014. Multivariable regression analyses adjusting for patient illness, laboratory derangements, and surgical features were used to assess relationships between initial postoperative hemoglobin values and a primary outcome of hospital-free days. RESULTS: A total of 8060 patients were included. Those with initial postoperative hemoglobin <7.5 or ≥11.5 g/dL had decreased hospital-free days [mean (95% confidence interval [CI]), -1.45 (-2.50 to -0.41) and -0.83 (-1.42 to -0.24), respectively] compared to a reference range of 9.5-10.4 g/dL (overall P value .003). For those with hemoglobin <7.5 g/dL, the odds (95% CI) for secondary outcomes included acute kidney injury (AKI) 1.43 (1.03-1.99), mortality 2.10 (1.18-3.74), and cerebral ischemia 3.12 (1.08-9.01). The odds for postoperative mechanical ventilation with hemoglobin ≥11.5 g/dL were 1.33 (1.07-1.65). Secondary outcome associations were not significant after multiple comparisons adjustment (Bonferroni P < .0056). CONCLUSIONS: In transfused patients, postoperative hemoglobin values between 7.5 and 11.5 g/dL were associated with superior outcomes compared to more extreme values. This range may represent a target for intraoperative transfusions, particularly during active bleeding when pretransfusion hemoglobin thresholds may be impractical or inaccurate. Given similar outcomes within this range, targeting hemoglobin at the lower aspect may be preferable, though prospective validation is warranted.

Timing of Postoperative CSF Leak after Endoscopic Skull Base Surgery in Patients with Obstructive Sleep Apnea.

Background There is little data regarding postoperative outcomes of patients with obstructive sleep apnea (OSA) undergoing skull base surgery. The purpose of this study is to determine an association between risk factors and proximity of cerebrospinal fluid (CSF) leak to surgery in patients with OSA undergoing endoscopic skull base surgery. Methods A retrospective review of neurosurgical inpatients, with and without OSA, at a tertiary care institution from 2002 to 2015 that experienced a postoperative CSF leak after undergoing endoscopic skull base surgery. Results Forty patients met inclusion criteria, 12 (30%) with OSA. OSA patients had significantly higher body mass index (BMI; median 39.4 vs. 31.7, p < 0.01) and were more likely to have diabetes (41.7 vs. 10.7%, p = 0.04) than non-OSA patients; otherwise there were no significant differences in clinical comorbidities. No patients restarted positive pressure ventilation (PPV) in the inpatient setting. The type of repair was not a significant predictor of the time from surgery to leak. Patients with OSA experienced postoperative CSF leak 49% sooner than non-OSA patients (Hazard Ratio 1.49, median 2 vs. 6 days, log-rank p = 0.20). Conclusion Patients with OSA trended toward leaking earlier than those without OSA, and no OSA patients repaired with a nasoseptal flap (NSF) had a leak after postoperative day 5. Due to a small sample size this trend did not reach significance. Future studies will help to determine the appropriate timing for restarting PPV in this high risk population. This is important given PPV's significant benefit to the patient's overall health and its ability to lower intracranial pressure.

Impact of Frailty on Outcomes After Primary and Revision Total Hip Arthroplasty.

BACKGROUND: Frailty and disability from arthritis are closely intertwined and little is known about the impact of frailty on total hip arthroplasty (THA) outcomes. We hypothesized that higher preoperative frailty is associated with more adverse events following THA. METHODS: All patients (≥50 years) undergoing unilateral primary or revision THA at a single institution from 2005 through 2016 were included. We analyzed the association of frailty (measured by a frailty deficit index) with postoperative outcomes in hospital, within 90 days, and within 1 year using multivariable logistic and Cox regression, adjusting for age. RESULTS: Among 8640 patients undergoing THA (6502 primary and 2138 revisions; median age 68 years), 22.7%, 32.9%, and 44.4% were classified as frail, vulnerable, and nonfrail, respectively. Frail patients tended to be female, older, sicker (American Society of Anesthesiologists ≥3), and received general anesthesia more frequently. Relative to nonfrail patients, frail patients had significantly increased odds of wound complications/hematoma (odds ratio 2.01) and reoperation (odds ratio 2.74) while in hospital, and increased risks for mortality (1-year hazards ratio [HR] 5.65), infection (1-year HR 3.63), dislocation (1-year HR 2.10), wound complications/hematoma (1-year HR 2.61), and reoperation (1-year HR 2.22) within 90 days and 1 year. Frailty was also associated with >5.5-fold increased mortality risk 1 year following THA. No significant associations with aseptic loosening, periprosthetic fracture, or heterotopic ossification were observed. CONCLUSION: A higher preoperative frailty index is associated with increased mortality and perioperative complications following primary and revision THA. The proposed frailty deficit index provides clinically important information for healthcare providers to use when counseling patients prior to decision for surgery.