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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

The optimal order of vasopressor discontinuation during shock resolution remains unclear. We evaluated the incidence of hypotension in patients receiving concomitant vasopressin (VP) and norepinephrine (NE) based on the order of their discontinuation. In this retrospective cohort study, consecutive patients receiving concomitant VP and NE infusions for shock admitted to intensive care units were evaluated. The primary outcome was hypotension incidence following discontinuation of VP or NE (VP1 and NE1 groups, respectively). Secondary outcomes included the incidence of acute kidney injury (AKI) and arrhythmias. Subgroup analysis was conducted by examining outcomes based on the type of shock. Of the 2,035 included patients, 952 (46.8%) were VP1 and 1,083 (53.2%) were NE1. VP1 had a higher incidence of hypotension than NE1 (42.1% vs. 14.2%; P P = .009), higher hospital [29% (278/952) vs. 24% (258/1083); P = .006], and 28-day mortality [37% (348/952) vs. 29% (317/1,083); P p-value p-value p-value

Introduction The impact of albumin resuscitation on sepsis outcomes is debated, particularly in the initial phase of resuscitation. We aimed to investigate the association between albumin use in the initial six hours of resuscitation and subsequent outcomes in adult septic patients. Methods This single-center, retrospective, propensity score-matched cohort study included adult patients admitted to intensive care units (ICUs) with sepsis or septic shock from January 1, 2006, to May 4, 2018, at a tertiary referral hospital. We compared two groups based on albumin receipt within the initial six resuscitation hours (albumin group vs. non-albumin group). We performed a 1:2 propensity score matching to assess shock-free time in ICU as the primary outcome. Results Of 2,732 patients with medical sepsis, 286 cases in the albumin group were matched with 549 individuals in the non-albumin group. Compared to the non-albumin group, the albumin group required more intravenous fluids and had higher net fluid balance, lower mean arterial pressure, and lower serum base excess level in the initial 6 and 24 hours of resuscitation. Shock-free time, ICU and hospital length of stay, and 28-day mortality were not different between albumin and non-albumin groups (56 vs. 66 hours, P = 0.18; 3.5 vs. 3.7 days, P = 0.61; 9.1 vs. 9.5 days, P = 0.27; 36 vs. 32%, P = 0.25, respectively). Conclusions Using albumin during the initial six hours of resuscitation was not associated with benefits in clinical outcomes of patients with medical sepsis.

Background/aimsTo determine if nasolacrimal massage or topical antibiotics are associated with higher rates of resolution compared with observation alone in a population-based cohort of infants with congenital nasolacrimal duct obstruction (CNLDO).MethodsThe medical records of all children ResultsAmong 1958 infants diagnosed and followed for CNLDO, 516 (26.4%) were merely observed, 506 (25.8%) were prescribed massage alone, 485 (24.8%) were prescribed at least one course of topical antibiotics, 397 (20.3%) were prescribed both topical antibiotics and massage, and 54 (2.8%) had no documented therapy. Non-surgical resolution, occurring in 1669 (85.2%) during a median follow-up of 3.1 months (range: 1 week–248 months), was 74.6% for the merely observed, 89.7% for those prescribed digital massage, 87.0% for those prescribed antibiotics and 90.7% for those treated with both. This comparison was significant in unadjusted (pConclusionPrescribing topical antibiotics or digital massage for infants with CNLDO in this cohort, individually or in combination, was associated with a higher rate of spontaneous resolution than observation alone.

Plasma cell disorders including plasmacytomas and multiple myeloma (MM) are exquisitely radiosensitive, and thus, radiation therapy (XRT) is used effectively in their management. The role of XRT in the setting of novel MM therapeutics has not been explored. The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004 and 2013 was studied. Association between utilization of XRT as part of initial therapy and patient, disease, or treating facility characteristics was studied. A total of 111,281 cases with 91.6% MM, 7% osseous plasmacytoma (PLA-O), and 1.4% extramedullary plasmacytoma (PLA-E) were identified. XRT was utilized as part of initial therapy in 25.4% cases, including 69.3% of PLA-O, 60% of PLA-E, and 21.5% of MM patients. Patients with PLA-E and MM were significantly less likely to receive XRT as compared to PLA-O (p

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

Background: Little is known about the impact of socioeconomic status (SES) as a key element of social determinants of health on intensive care unit (ICU) outcomes for adults. Objective: We assessed whether a validated individual SES index termed HOUSES (HOUsing-based SocioEconomic status index) derived from housing features was associated with short-term outcomes of critical illness including ICU mortality, ICU-free days, hospital-free days, and ICU readmission. Methods: We performed a population-based cohort study of adult patients living in Olmsted County, Minnesota, admitted to 7 intensive care units at Mayo Clinic from 2011 to 2014. We compared outcomes between the lowest SES group (HOUSES quartile 1 [Q1]) and the higher SES group (HOUSES Q2-4). We stratified the cohort based on age (Results: Among 4134 eligible patients, 3378 (82%) patients had SES successfully measured by the HOUSES index. Baseline characteristics, severity of illness, and reason for ICU admission were similar among the different SES groups as measured by HOUSES except for larger number of intoxications and overdoses in younger patients from the lowest SES. In all adult patients, there were no overall differences in mortality, ICU-free days, hospital-free days, or ICU readmissions in patients with higher SES compared to lower SES. Among older patients (>50 years), those with higher SES (HOUSES Q2-4) compared to those with lower SES (HOUSES Q1) had lower mortality rates (hazard ratio = 0.72; 95% CI: 0.56-0.93; adjusted P = .01), increased ICU-free days (mean 1.08 days; 95% CI: 0.34-1.84; adjusted P = .004), and increased hospital-free days (mean 1.20 days; 95% CI: 0.45-1.96; adjusted P = .002). There were no differences in ICU readmission rates (OR = 0.74; 95% CI: 0.55-1.00; P = .051). Conclusion: Individual-level SES may be an important determinant or predictor of critical care outcomes in older adults. Housing-based socioeconomic status may be a useful tool for enhancing critical care research and practice.

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.

Epidural blood patch (EBP) is an accepted treatment modality for postdural puncture headache (PDPH) refractory to conservative approaches.[1–5][1] Despite the established efficacy of EBP, some patients require more than one EBP intervention to achieve symptom resolution. The rate of repeat image

BACKGROUND: Several markers of oxygenation are used as prognostic markers in acute hypoxemic respiratory failure. Real-world use is limited by the need for invasive measurements and unreliable availability in the electronic health record. A pragmatic, reliable, and accurate marker of acute hypoxemic respiratory failure is needed to facilitate epidemiologic studies, clinical trials, and shared decision-making with patients. F IO 2 is easily obtained at the bedside and from the electronic health record. The F IO 2 trajectory may be a valuable marker of recovery in patients with acute hypoxemic respiratory failure. METHODS: This was a historical cohort study of adult subjects admitted to an ICU with acute hypoxemic respiratory failure secondary to community-acquired pneumonia and/or ARDS. RESULTS: Our study included 2,670 subjects. F IO 2 and S pO 2 were consistently more available than was P aO 2 in the electronic health record: ( F IO 2 vs S pO 2 vs P aO 2 : 100 vs 100 vs 72.8% on day 1, and 100 vs 99 vs 21% on day 5). A worsening F IO 2 trajectory was associated with reduced ventilator-free days. From days 2 to 5, every increase in F IO 2 by 10% from the previous day was associated with fewer ventilator-free days (on day 2: adjusted mean –1.25 [95% CI –1.45 to –1.05] d, P S pO 2 /F IO 2 trajectory also provided prognostic information. On days 3 – 5, an increase in S pO 2 /F IO 2 from the previous day was associated with increased ventilator-free days (on day 3: adjusted mean 2.09 (95% CI 1.44–2.74) d; P S pO 2 /F IO 2 models did not add predictive information compared with models with F IO 2 alone (on day 2: adjusted F IO 2 vs S pO 2 /F IO 2 R2 0.122 vs 0.119; and on day 3: 0.153 vs 0.163). CONCLUSIONS: F IO 2 and S pO 2 /F IO 2 are pragmatic and readily available intermediate prognostic markers in acute hypoxic respiratory failure. The F IO 2 trajectory in the first 5 d of ICU admission provided important prognostic information (ventilator-free days). Although the S pO 2 /F IO 2 trajectory was also associated with ventilator-free days, it did not provide more information than the F IO 2 trajectory alone.

Objective: Anemia is common during critical illness and often persists after hospital discharge; however, its potential association with physical outcomes after critical illness is unclear. Our objective was to assess the associations between hemoglobin at intensive care unit (ICU) and hospital discharge with physical status at 3-month follow-up in acute respiratory distress syndrome (ARDS) survivors. Methods: This is a secondary analysis of a multisite prospective cohort study of 195 mechanically ventilated ARDS survivors from 13 ICUs at 4 teaching hospitals in Baltimore, Maryland. Multivariable regression was utilized to assess the relationships between ICU and hospital discharge hemoglobin concentrations with measures of physical status at 3 months, including muscle strength (Medical Research Council sumscore), exercise capacity (6-minute walk distance [6MWD]), and self-reported physical functioning (36-Item Short-Form Health Survey [SF-36v2] Physical Function score and Activities of Daily Living [ADL] dependencies). Results: Median (interquartile range) hemoglobin concentrations at ICU and hospital discharge were 9.5 (8.5-10.7) and 10.0 (9.0-11.2) g/dL, respectively. In multivariable regression analyses, higher ICU discharge hemoglobin concentrations (per 1 g/dL) were associated with greater 3-month 6MWD mean percent of predicted (3.7% [95% confidence interval 0.8%-6.5%]; P = .01) and fewer ADL dependencies (−0.2 [−0.4 to −0.1]; P = .02), but not with percentage of maximal muscle strength (0.7% [−0.9 to 2.3]; P = .37) or SF-36v2 normalized Physical Function scores (0.8 [−0.3 to 1.9]; P = .15). The associations of physical outcomes and hospital discharge hemoglobin concentrations were qualitatively similar, but none were statistically significant. Conclusions: In ARDS survivors, higher hemoglobin concentrations at ICU discharge, but not hospital discharge, were significantly associated with improved exercise capacity and fewer ADL dependencies. Future studies are warranted to further assess these relationships.

Background: Sepsis and septic shock are life-threatening causes of acute kidney injury (AKI) frequently seen and managed in intensive care units (ICUs). Sepsis-associated AKI (SA-AKI) independently contributes to the mortality of sepsis. Understanding the potential factors involved in kidney function recovery may further aid in the prevention and management of SA-AKI. This study aimed to describe the clinical characteristics of septic shock patients who required kidney replacement therapy and factors associated with kidney function recovery. Methods: We conducted a retrospective cohort study of adult septic shock patients who received in-hospital kidney replacement therapy at medical intensive care unit (MICU) at the Mayo Clinic, Rochester, from January 1, 2006, to May 31, 2018. Kidney function recovery was defined as liberation from kidney replacement therapy before hospital discharge. Associations between clinical features and kidney recovery were analyzed using multivariable Fine and Gray regression accounting for death as a competing event. Results: Our retrospective cohort consisted of 229 patients with a median (interquartile range [IQR]) age of 64 (52–74) years: 55% were men, 89% were Caucasians, 39% had diabetes mellitus (DM), 16% had heart failure, APACHE (Acute Physiology and Chronic Health Evaluation) III score was 105 (84–123), and SOFA (Sequential [Sepsis-related] Organ Failure Assessment) score was 12 (9–14). The patients received 1,567 (524–4,108) mL of intravenous fluids in the first 3 h, 92% required vasopressor support, and 83% required mechanical ventilation. The median MICU and hospital stays were 7 (4–13) and 19 (10–31) days, respectively. Median (IQR) kidney replacement therapy duration was 7 (3.5–17.1) days. Among 158 ICU survivors, 73 (46%) patients were weaned from RRT in ICU and 85 (54%) were transitioned to intermittent RRT. A higher volume of fluid resuscitation in the first 3 h (hazard ratio [HR] = 1.07 per 1 L, CI: 1.01–1.14, p = 0.04) and a history of DM (HR = 1.70, CI: 1.14–2.54, p = 0.009) were associated with kidney function recovery. Conclusion: Among septic shock patients who initiated kidney replacement therapy in the MICU, 41% recovered kidney function before discharge. A higher initial fluid resuscitation volume was associated with recovery, and interestingly, patients with DM had a higher chance of recovery.

Background It is not known whether the neurotoxicity produced by anaesthetics administered to young animals can also occur in children. Exposure of infant macaques to ketamine impairs performance in selected domains of the Operant Test Battery (OTB), which can also be administered to children. This study determined whether a similar pattern of results on the OTB is found in children exposed to procedures requiring general anaesthesia before age 3 yr. Methods We analysed data from the Mayo Anesthesia Safety in Kids (MASK) study, in which unexposed, singly-exposed, and multiply-exposed children born in Olmsted County, MN, USA, from 1994 to 2007 were sampled using a propensity-guided approach and prospectively underwent OTB testing at ages 8–12 or 15–20 yr, using five tasks that generated 15 OTB test scores. Results In primary analysis, none of the OTB test scores depended upon anaesthesia exposure status when corrected for multiple comparisons. Cluster analysis identified four clusters of subjects, with cluster membership determined by relative performance on the OTB tasks. There was no evidence of association between exposure status and cluster membership. Exploratory factor analysis showed that the OTB scores loaded onto four factors. The score for one factor was significantly less in multiply-exposed children (mean standardised difference –0.28 [95% confidence interval, –0.55 to –0.01; P=0.04]), but significance did not survive a sensitivity analysis accounting for outlying values. Conclusions These findings provide little evidence to support the hypothesis that children exposed to procedures requiring anaesthesia show deficits on OTB tasks that are similar to those observed in non-human primates.

Several markers of oxygenation are used as prognostic markers in acute hypoxemic respiratory failure. Real-world use is limited by the need for invasive measurements and unreliable availability in the electronic health record. A pragmatic, reliable, and accurate marker of acute hypoxemic respiratory failure is needed to facilitate epidemiologic studies, clinical trials, and shared decision-making with patients. [Formula: see text] is easily obtained at the bedside and from the electronic health record. The [Formula: see text] trajectory may be a valuable marker of recovery in patients with acute hypoxemic respiratory failure.This was a historical cohort study of adult subjects admitted to an ICU with acute hypoxemic respiratory failure secondary to community-acquired pneumonia and/or ARDS.Our study included 2,670 subjects. [Formula: see text] and [Formula: see text] were consistently more available than was [Formula: see text] in the electronic health record: ([Formula: see text] vs [Formula: see text] vs [Formula: see text] : 100 vs 100 vs 72.8% on day 1, and 100 vs 99 vs 21% on day 5). A worsening [Formula: see text] trajectory was associated with reduced ventilator-free days. From days 2 to 5, every increase in [Formula: see text] by 10% from the previous day was associated with fewer ventilator-free days (on day 2: adjusted mean -1.25 [95% CI -1.45 to -1.05] d,[Formula: see text] and [Formula: see text] are pragmatic and readily available intermediate prognostic markers in acute hypoxic respiratory failure. The [Formula: see text] trajectory in the first 5 d of ICU admission provided important prognostic information (ventilator-free days). Although the [Formula: see text] trajectory was also associated with ventilator-free days, it did not provide more information than the [Formula: see text] trajectory alone.

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.

The possible causative role of gastroesophageal reflux disease(GERD)in idiopathic pulmonary fibrosis (IPF)has been quite controversial. Another question is if GERD is a consequence of exaggerated negative intrathoracic pressure in IPF rather than an etiology.The objective of this population-based study was to investigate if patients with IPF were at increased risk of GERD exposure(within 5 years prior to the diagnosis) compared to age and sex matched two groups of controls.The two groups of controls were: interstitial lung disease(ILD)other than IPF and subjects with no diagnosed lung disease (population controls).Rochester Epidemiology Project (REP)was used to identify cases of IPF as well as controls (matching between cases and controls 1:2).American Thoracic Society/European Respiratory Society criteria for the diagnosis of IPF were used.A total of 113 IPF cases were identified between Jan 1, 1997 and Jun 30, 2017.When comparing IPF cases with population controls the odds of being exposed to GERD was 1.80(95% CI 1.11-2.93,p-value 0.02)times higher in IPF patients after multivariable adjustments. When comparing with non-IPF controls the odds of GERD were 0.60 times lower(95% CI =0.35-1.03,p=0.06) after multivariable adjustment.This comparison did not reach statistical significance.We conclude from this study when compared to the population control, patients with IPF were at significantly increased risk to have exposure to GERD. This difference was not observed when IPF was compared to non-IPF ILD.GERD can be one of the important contributors to the development of lung fibrosis,it should be addressed adequately when detected in patients with pulmonary fibrosis especially IPF.

Key Points Question Is anemia in patients with critical illness associated with persistent anemia following discharge? Findings In this cohort study of 6901 adults hospitalized for critical illness, 41% had prevalent anemia preceding hospitalization and 74% of those without prehospitalization anemia developed incident anemia, for an overall anemia prevalence of 80% at hospital discharge. Rates of complete recovery from hospital discharge anemia at 12 months posthospitalization for those alive with available hemoglobin assessments were 58% for mild anemia, 39% for moderate anemia, and 24% for severe anemia. Meaning The findings of this study suggest that anemia is common and often persistent in the first year after critical illness., Importance Anemia is common and has been associated with poor outcomes in the critically ill population, yet the timing and extent of hemoglobin recovery remains incompletely described, which may have important implications for clinical outcomes following discharge from intensive care. Objectives To describe longitudinal changes in anemia status during and after critical illness and assess the associations between hemoglobin concentrations and postdischarge mortality. Design, Setting, and Participants A population-based cohort study was conducted from January 1, 2010, to December 31, 2016, in Olmsted County, Minnesota; data analysis was performed from June 1 to December 30, 2019. Participants included 6901 adults (age ≥18 years) admitted to intensive care. Main Outcomes and Measures Hemoglobin concentrations in the 12 months before hospitalization, during hospitalization, and in the 12 months after discharge, categorized by anemia severity (mild, hemoglobin ≥10.0 to, This cohort study examines the presence of anemia in critically ill patients and outcomes after discharge.

Background Fluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution. Method We retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25–0.49, group 3 0.17–0.24, and group 4 Result A total of 1052 patients met eligibility criteria and were included in the analysis. The time-to-shock reversal was significantly different among the groups (P P = .01) when compared with group 4 with a median (IQR) time-to-shock reversal of 1.7 (1.5, 2.0) vs. 2.8 (2.6, 3.3) days, respectively. Using 0.25 ml/kg/min as cutoff, the higher fluid infusion rate was associated with a shorter time to shock reversal (HR = 1.22; 95% CI 1.06–1.41; P = .004) and with decreased odds of 28-day mortality (HR = 0.71; 95% CI 0.60–0.85; P Conclusion In septic shock patients, initial fluid resuscitation rate of 0.25–0.50 ml/kg/min (i.e., completion of the initial 30 ml/kg IV fluid resuscitation within the first 2 h), may be associated with early shock reversal and lower 28-day mortality compared with slower rates of infusion.

Objective To determine whether treatment of delirium affects outcomes. Patients and Methods A retrospective cohort study of patients admitted to the medical intensive care unit (ICU) from July 1, 2015, through June 30, 2016, was conducted. Patients with ICU delirium, defined by a positive Confusion Assessment Method for the ICU score, were included. Patients were stratified into 4 treatment groups based on exposure to melatonin and antipsychotic agents during ICU stay: no pharmacologic treatment, melatonin only, antipsychotics only, and both melatonin and antipsychotics. A time-dependent cause-specific hazards model with death as a competing risk was used to evaluate the effect of melatonin or antipsychotic drug use for delirium on duration of ICU delirium, length of ICU stay, and length of hospitalization. A logistic regression was used to evaluate 28-day mortality. Covariates significantly associated with exposure to melatonin and antipsychotics were included in the minimally adjusted model. Covariates significantly associated in the minimally adjusted model were included in a final adjusted model. Results A total of 449 admissions to the medical ICU were included in the analysis. Exposure to melatonin or antipsychotic agents did not reduce the duration of ICU delirium, ICU/hospital length of stay, or 28-day mortality. However, antipsychotic use only was associated with longer hospitalization. Conclusion Antipsychotic drugs for the treatment ICU delirium may not provide the benefit documented in earlier literature. Further investigation on patient selection, type of antipsychotic, and dosing is needed.

BACKGROUND Intraoperative plasma transfusion is common, yet little is known regarding its effects on perioperative coagulation tests or clinical outcomes. STUDY DESIGN AND METHODS This is a retrospective cohort study of adults receiving intraoperative plasma transfusion at a single center from 2011 to 2015. Relationships between plasma transfusion volume, changes in coagulation test values, and clinical outcomes, including a primary outcome of early postoperative red blood cell (RBC) transfusion, were assessed with multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit (ICU)- and hospital-free days, intraoperative RBC transfusions, and estimated blood loss. RESULTS A total of 3393 unique patients were included, with median (IQR) transfusion of 2 (2-4) units. In multivariable analyses, higher plasma volumes were associated with worse outcomes, with each 1 mL/kg increase associated with increased odds for postoperative (1.02 [1.01-1.03], p < 0.001) and intraoperative RBCs (1.17 [1.16-1.19], p < 0.001) and fewer ICU- and hospital-free days (mean difference [95% CI], -0.08 [-0.12 to -0.05], p < 0.001; and -0.09 [-0.13 to -0.06], p < 0.001, respectively). Greater decreases in international normalized ratio (INR) following plasma transfusion were associated with decreased odds of postoperative RBCs (0.35 [0.25-0.47], p < 0.001), decreased mortality (0.50 [0.31-0.83], p = 0.007), and increased mean ICU- (1.31 [0.41-2.21], p = 0.004) and hospital-free days (1.15 [0.19-2.10], p = 0.018). CONCLUSION In patients receiving intraoperative plasma transfusion, higher transfusion volumes were associated with inferior clinical outcomes; however, greater improvements in INR were associated with improved outcomes. Future prospective studies are necessary to better define these relationships and to explore plasma transfusion triggers beyond the limitations of INR.

Background More than 1.5 million women per year have a benign breast biopsy resulting in concern about their future breast cancer (BC) risk. This study examined the performance of 2 BC risk models that integrate clinical and histologic findings in this population. Methods The BC risk at 5 and 10 years was estimated with the Breast Cancer Surveillance Consortium (BCSC) and Benign Breast Disease to Breast Cancer (BBD-BC) models for women diagnosed with benign breast disease (BBD) at the Mayo Clinic from 1997 to 2001. Women with BBD were eligible for the BBD-BC model, but the BCSC model also required a screening mammogram. Calibration and discrimination were assessed. Results Fifty-six cases of BC were diagnosed among the 2142 women with BBD (median age, 50 years) within 5 years (118 were diagnosed within 10 years). The BBD-BC model had slightly better calibration at 5 years (0.89; 95% confidence interval [CI], 0.71-1.21) versus 10 years (0.81; 95% CI, 0.70-1.00) but similar discrimination in the 2 time periods: 0.68 (95% CI, 0.60-0.75) and 0.66 (95% CI, 0.60-0.71), respectively. In contrast, among the 1089 women with screening mammograms (98 cases of BC within 10 years), the BCSC model had better calibration (0.94; 95% CI, 0.85-1.43) and discrimination (0.63; 95% CI, 0.56-0.71) at 10 years versus 5 years (calibration, 1.31; 95% CI, 0.94-2.25; discrimination, 0.59; 95% CI, 0.46-0.71) where discrimination was not different from chance. Conclusions The BCSC and BBD-BC models were validated in the Mayo BBD cohort, although their performance differed by 5-year risk versus 10-year risk. Further enhancement of these models is needed to provide accurate BC risk estimates for women with BBD.

Background: Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. Objective: To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Methods: Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. Results: A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Conclusions: Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

Approximately one third of cancer patients suffer from comorbid mood disorders that are associated with increased cost and poorer outcomes. The majority of patients with multiple myeloma (MM) are treated with corticosteroids; as many as three fourths of those taking corticosteroids develop neuropsychiatric complications, likely increasing morbidity and cost of care. MM patients diagnosed between 1991 and 2010 and reported in the Surveillance Epidemiology, and End Results-Medicare database were characterized as MM-Only, MM+Psychiatric (any psychiatric condition, preexisting or post-MM), or MM+Depression (depression as the only psychiatric diagnosis, preexisting or post-MM). Differences in demographic characteristics, occurrence of clinical myeloma-defining events (MDEs), health care utilization (inpatient, outpatient, ambulatory claims), and cost of care during the first 6 months of MM diagnosis were analyzed. Psychiatric comorbidities were reported more frequently in females, and racial minorities had lower rates of psychiatric comorbidities. All clinical MDEs were more common in the MM+Psychiatric and MM+Depression groups; within them, the majority were more common in patients diagnosed with the psychiatric condition or depression after MM compared with it being a preexisting condition. Health care utilization in all treatment settings was higher in those with psychiatric comorbidities. Cost of care within the first 6 months after MM diagnosis was significantly higher in the MM+Psychiatric and MM+Depression groups. This increase in cost was more pronounced for patients from racial minorities diagnosed with a psychiatric condition, including depression. Psychiatric comorbidities significantly impact the clinical presentations, health care utilization, and cost among patients with MM. These findings need to be addressed for improved survivorship of MM patients.

Total joint arthroplasty (TJA) is prevalent and offered to patients regardless of frailty status experiencing pain, disability, and functional decline. This study aims to describe changes in levels of frailty 1 year after TJA.We identified a retrospective cohort of adult patients undergoing primary TJA between 2005 and 2016 using an institutional total joint registry. Associations between categorized frailty deficit index (FI) and change in FI were analyzed using linear regression models. Mortality, deep periprosthetic joint infection, and reoperation were analyzed using time to event methods.In total, 5341 patients (37.6% non-frail, 39.4% vulnerable, and 23.0% frail) with items necessary to determine FI at 1 year after TJA were included. Preoperatively, 29% of vulnerable patients improved to non-frail 1 year later, compared to only 11% regressing to frail. Four in 10 frail patients improved to vulnerable/non-frail. Improvements in activities of daily living (ADL) were more evident in frail and vulnerable patients, with30% reduction in the percentage of patients expressing difficulties with walking, climbing stairs, and requiring ADL assistance 1 year after TJA. Increases in frailty 1 year after TJA were associated with significantly increased rates of mortality (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.24-1.82, P.001), deep periprosthetic joint infection (HR 3.98, 95% CI 1.85-8.58, P.001), and reoperation (HR 1.80, 95% CI 1.19-2.72, P = .005).Frailty states are dynamic with patient frailty shown to be modifiable 1 year after TJA. Preoperative frailty measurement is an important step toward identifying those that may benefit most from TJA and for postoperative frailty surveillance.

Background: There has been an overall decline in intensive care unit mortality over the past 2 decades, including in patients undergoing intubation and mechanical ventilation (MV). Whether this decline extends to patients with metastatic cancer remains unknown. We analyzed the outcomes of patients with metastatic cancer undergoing intubation/MV using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010. Methods: Diagnosis and procedure codes were used to identify patients with metastatic cancer who underwent intubation/MV. Demographics, diagnoses, length of stay (LOS), and discharge information were abstracted. Multivariate linear and logistic regression models with weighted analysis were conducted to study trends in outcomes. Results: During the 10-year study period, 200,350 patients with metastatic cancer and who underwent intubation/MV were identified; the mean age was 65.3 years and 46.2% were men. There was an increase in the total number of patients with metastatic cancer who underwent intubation/MV during the study period, from 36,881 in 2001-2002 to 51,003 in 2009-2010 (P

We conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P

Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial‐ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER‐Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time‐dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4‐year follow‐up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African‐Americans (P

Purpose Sclerosing adenosis (SA), found in ¼ of benign breast disease (BBD) biopsies, is a histological feature characterized by lobulocentric proliferation of acini and stromal fibrosis and confers a two-fold increase in breast cancer risk compared to women in the general population. We evaluated a NanoString-based gene expression assay to model breast cancer risk using RNA derived from formalin-fixed, paraffin-embedded (FFPE) biopsies with SA. Methods The study group consisted of 151 women diagnosed with SA between 1967 and 2001 within the Mayo BBD cohort, of which 37 subsequently developed cancer within 10 years (cases) and 114 did not (controls). RNA was isolated from benign breast biopsies, and NanoString-based methods were used to assess expression levels of 61 genes, including 35 identified by previous array-based profiling experiments and 26 from biological insight. Diagonal linear discriminant analysis of these data was used to predict cancer within 10 years. Predictive performance was assessed with receiver operating characteristic area under the curve (ROC-AUC) values estimated from 5-fold cross-validation. Results Gene expression prediction models achieved cross-validated ROC-AUC estimates ranging from 0.66 to 0.70. Performing univariate associations within each of the five folds consistently identified genes DLK2, EXOC6, KIT, RGS12, and SORBS2 as significant; a model with only these five genes showed cross-validated ROC-AUC of 0.75, which compared favorably to risk prediction using established clinical models (Gail/BCRAT: 0.57; BBD-BC: 0.67). Conclusions Our results demonstrate that biomarkers of breast cancer risk can be detected in benign breast tissue years prior to cancer development in women with SA. These markers can be assessed using assay methods optimized for RNA derived from FFPE biopsy tissues which are commonly available. Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4441-z) contains supplementary material, which is available to authorized users.

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.

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.

Importance Cerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is needed. Objective To conduct a head-to-head comparison of plasma p-tau181 and p-tau231 measured on the single-molecule array (Simoa) platform and p-tau181 and p-tau217 measured on the Meso Scale Discovery (MSD) platform on amyloid and tau positron emission tomography (PET) measures, neurodegeneration, vascular pathology, and cognitive outcomes. Design, Setting, and Participants This study included data from the Mayo Clinic Study on Aging collected from March 1, 2015, to September 30, 2017, and analyzed between December 15, 2020, and May 17, 2021. Associations between the 4 plasma p-tau measures and dichotomous amyloid PET, metaregion of interest tau PET, and entorhinal cortex tau PET were analyzed using logistic regression models; the predictive accuracy was summarized using area under the receiver operating characteristic curve (AUROC) statistic. Of 1329 participants without dementia and with p-tau181 and p-tau217 on MSD, 200 participants with plasma p-tau181 and p-tau231 on Simoa and magnetic resonance imaging and amyloid and tau PET data at the same study visit were eligible. Main Outcomes And Measures Primary outcomes included amyloid (greater than 1.48 standardized uptake value ratio) and tau PET, white matter hyperintensities, white matter microstructural integrity (fractional anisotropy genu of corpus callosum and hippocampal cingulum bundle), and cognition. Results Of 200 included participants, 101 (50.5%) were male, and the median (interquartile range [IQR]) age was 79.5 (71.1-84.1) years. A total of 177 were cognitively unimpaired (CU) and 23 had mild cognitive impairment. Compared with amyloid-negative CU participants, among amyloid-positive CU participants, the median (IQR) Simoa p-tau181 measure was 49% higher (2.58 [2.00-3.72] vs 1.73 [1.45-2.13] pg/mL), MSD p-tau181 measure was 53% higher (1.22 [0.91-1.56] vs 0.80 [0.66-0.97] pg/mL), MSD p-tau217 measure was 77% higher (0.23 [0.17-0.34] vs 0.13 [0.09-0.18] pg/mL), and Simoa p-tau231 measure was 49% higher (20.21 [15.60-25.41] vs 14.27 [11.27-18.10] pg/mL). There were no differences between the p-tau species for amyloid PET and tau PET metaregions of interest. However, among CU participants, both MSD p-tau181 and MSD p-tau217 more accurately predicted abnormal entorhinal cortex tau PET than Simoa p-tau181 (MSD p-tau181: AUROC, 0.80 vs 0.70;P = .046; MSD p-tau217: AUROC, 0.81 vs 0.70;P = .04). MSD p-tau181 and p-tau217 and Simoa p-tau181, but not p-tau231, were associated with greater white matter hyperintensity volume and lower white matter microstructural integrity. Conclusions and Relevance In this largely presymptomatic population, these results suggest subtle differences across plasma p-tau species and platforms for the prediction of amyloid and tau PET and magnetic resonance imaging measures of cerebrovascular and Alzheimer-related pathology.

We evaluated whether single-layer renorrhaphy (SLR) without collecting system (CS) closure is sufficient following robot-assisted partial nephrectomy (RAPN).One hundred fifty consecutive patients underwent RAPN by a single surgeon and were prospectively labeled with regard to CS entry during surgery. Patients with CS entry were subdivided into two groups: those with classical renorrhaphy (CR) (i.e., two-layer repair) and those with SLR (i.e., without CS repair). Perioperative variables and outcomes were compared between CR and SLR groups.Ninety patients had CS entry during RAPN. Of these 90 patients, 64 had CR, and 26 had SLR, with mean ages of 62 and 59 years (p = 0.22), tumor sizes of 3.4 and 3.3 cm (p = 0.61), Mayo Adhesive Probability scores of 1.8 and 1.8 (p = 0.95), and radius, exophytic/endophytic, nearness to CS, and laterality scores of 8.5 and 8.0 (p = 0.16), respectively. Mean warm ischemia times (WITs) were 19.6 and 17.3 minutes (p = 0.04), hospital stays of 3.0 and 2.8 days (p = 0.62), and drain times of 2.9 and 2.7 days (p = 0.65), for the CR and SLR groups, respectively. Using the Clavien-Dindo classification, there were a total of six grade III or higher complications, with no difference between the CR and SLR subgroups (p = 1.0). Renal function using creatinine or glomerular filtration rate as surrogates showed no difference between groups preoperatively or up until 2 years postoperatively.Omitting CS repair during RAPN with SLR decreases WIT without altering complications, hospital stay, or drain time. Long-term renal function was not associated with CS repair.

This cohort study of adult (≥50 years) patients aimed to calculate a validated, preoperative frailty deficit index (FI) and used it to compare outcomes following total knee arthroplasty (TKA), primary and revision, from 2005 through 2016. Using multivariable logistic and Cox regression, the authors analyzed whether FI, adjusted for age, predicts outcomes prior to hospital discharge, within 90 days, and within 365 days. They classified 9818 patients undergoing TKA (7920 primary and 1898 revision; median age, 69 years) as frail (21%), vulnerable (39%), and non-frail (40%). Frail, relative to non-frail, patients were more often female with more systemic diseases (American Society of Anesthesiologists classification, ≥III). While in-hospital, frail patients were found to have increased odds of reoperation (odds ratio, 2.52) and wound complications/hematoma (odds ratio, 2.15). Within 90 days, there was increased risk for periprosthetic fracture (>4-fold) and mortality (>9-fold) following TKA after age adjustment. Within the first year, frail patients were at heightened risk for death (hazard ratio, 8.08), any patient infection (hazard ratio, 1.97), wound complications/hematoma (hazard ratio, 2.16), periprosthetic fracture (hazard ratio, 3.03), and reoperation (hazard ratio, 1.41). At no time point were significant associations found with arthrofibrosis, aseptic loosening, or patellar clunk syndrome. One-fifth of patients undergoing primary and revision TKAs are frail and at notable risk for complications. Calculating a preoperative FI should guide pre-habilitation efforts (eg, chronic disease management, wellness) before and postoperative surveillance after TKA. [ Orthopedics . 2019; 42(6):335–343.]

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.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.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.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.

BACKGROUND Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. METHODS This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. RESULTS A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9-9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

Purpose To determine if the use of oral contraceptive pills (OCP) and other hormonal contraceptives are associated with a higher incidence of idiopathic intracranial hypertension (IIH). Design Retrospective, population-based, case-control study. Methods Setting : Female IIH patients evaluated between January 1, 1990, and December 31, 2016 were identified using the Rochester Epidemiology Project (REP), a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. Study Population : Fifty-three female residents of Olmsted County diagnosed with IIH between 15 and 45 years of age. The use of OCPs and other hormonal contraceptives was compared to controls matched for age, sex, and body mass index. Interventions/Exposures : Hormonal contraceptives. Main Outcome Measure : Odds of developing IIH. Results Of the 53 women diagnosed with IIH between 15 and 45 years of age, 11 (20.8%) had used hormonal contraceptives within ≤30 days of the date of IIH diagnosis, in contrast to 30 (31.3%) among the control patients. The odds ratio of hormonal contraceptive use and IIH was 0.55 (95% conficence interval [CI]: 0.24-1.23, P = .146). The odds ratio of OCP use was 0.52 (95% CI: 0.20-1.34, P = .174). Conclusions OCP and other hormonal contraceptives were not significantly associated with a higher incidence of IIH, arguing against the need for women with IIH to discontinue their use.

Although the overall rate of spontaneous resolution in congenital nasolacrimal duct obstruction (CNLDO) and efficacy of probing have been documented in the literature, the optimal timing of intervention has not been established.To report new findings regarding spontaneous resolution in a large cohort of children with CNLDO.The medical records of 1998 consecutive infants diagnosed with CNLDO from January 1, 1995, through December 31, 2004, while residing in Olmsted County, Minnesota, were retrospectively reviewed. Data were analyzed between January 1, 2015, and January 2017.Rate of spontaneous resolution over time and by sex.The cohort, diagnosed at a median age of 1.2 months (interquartile range, 0.4-3.6), was 48% girls (n = 959) and 89% white (n = 1626; 173 were unreported). Among the 1998 cases, 1669 (83.5%) spontaneously resolved, 289 (14.5%) underwent treatment, and the remaining 40 (2.0%) were lost to follow-up. Of the 1958 infants followed up, CNLDO in 925 (47.3%) spontaneously resolved by age 3 months, in 1300 (66.4%) by 6 months, in 1472 (75.7%) by 9 months, and in 1516 (78.4%) by 12 months. The rate of resolution was 35% faster (95% CI, 23%-47%; P .001) at less than 1 month vs 3 months, 43% faster (95% CI, 27%-64%; P .001) at 3 months vs 6 months, 39% faster (95% CI, 16%-64%; P .001) at 6 months vs 9 months, and 1% slower at 9 months vs 12 months (hazard ratio, 0.99; 95% CI, 0.80-1.22; P = .78). Congenital nasolacrimal duct obstruction resolved in boys 0.5 months (95% CI, 0.2-0.8; P .001) faster than girls (median, 2.9 vs 3.4 months), and unilateral obstructions resolved 0.2 months (95% CI, 0.1-0.4; P = .002) faster than bilateral (median, 3.1 vs 3.3 months) ones. Children probed at 15 months or older had decreased odds of resolution after probing (odds ratio, 0.11; 95% CI, 0.01-0.89; P = .04) compared with children probed at age 12 to 14 months.Based on this large cohort of children with CNLDO, probing between age 9 and 15 months may be reasonable given that the rate of spontaneous resolution plateaued after 9 months and initial probing success declined after 15 months. This time frame supports both an earlier and narrower range of ages for intervention compared with the current practice of probing after age 1 year.

Palliative treatment may be associated with prolonged survival and improved quality of life, but remains underutilized in stage IV colorectal (CRC). We examined a national cohort of stage IV CRC patients to determine the factors associated with palliative treatment.Stage IV CRC patients, classified based on their survival length (6 months, 6-24 months, and 24 + months), were analyzed using the American College of Surgeons National Cancer Data Base (2004-2013). Multivariable analysis was performed to evaluate factors associated with palliative treatment.Of 85,981 patients analyzed, 10.9% received palliative treatment. For 6-24 months survival, a more recent year of diagnosis, Medicaid, uninsured status, Mountain and Pacific regions were associated with higher odds of palliative treatment. For those who survived6months, older patients had lower odds, while academic centers and residence20 miles from treating institutions were associated with increased likelihood of palliative treatment.Palliative treatment in stage IV CRC is associated with a more recent year of diagnosis, Medicaid, academic centers, Mountain and Pacific regions of the US.

Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. Electronic supplementary material The online version of this article (doi:10.1007/s10549-016-3691-5) contains supplementary material, which is available to authorized users.

Benign breast disease (BBD) is diagnosed in 1–2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), which represent ¼ of all BBD patients. A training set was developed from 86 patients diagnosed with SA, of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). An diagonal linear discriminate analysis-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of FFPE biopsy-derived RNA. This model was tested on a separate validation case–control set composed of 65 SA patients. The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, demonstrating that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA. Electronic supplementary material The online version of this article (doi:10.1007/s10549-015-3513-1) contains supplementary material, which is available to authorized users.

Background: Palliative care is associated with improved survival and quality of life, but its use among patients with colorectal cancer varies nationwide and the determinants of those variations are not clear. Objective: To determine the factors associated with palliative care use among patients who died of colorectal cancer. Methods: Deceased patients treated for colorectal cancer (2004-2013) were identified within the National Cancer Database. Multivariable logistic regression was used to evaluate patient and institutional characteristics associated with palliative care use. Patients were classified based on their length of survival (Results: A total of 287 923 patients were analyzed. Overall, 4.3% of the patients received palliative care. Patients who received palliative care were more likely to be younger, recently diagnosed, treated at academic hospitals, and have stage IV disease. Patients living in Mountain and Pacific regions had higher odds of palliative care receipt than those in the East Coast. Patients without insurance had higher odds of palliative care if they survived 9 miles from the institution received more palliative care. Conclusion: Palliative care use among patients with colorectal cancer is associated with a younger age, a more recent year of diagnosis, insurance status, academic hospitals, and living in Mountain and Pacific regions.

Background/aimsThe literature on the prevalence and demographics of congenital nasolacrimal duct obstruction (CNLDO) is 30–70 years old and largely comprises small sample sizes. This study provides epidemiological findings of this common disorder from the largest cohort reported to date.MethodsThe medical records of all children (ResultsOf 17 713 newborns born during the 10-year study period, 1998 were diagnosed with CNLDO, yielding a birth prevalence of one in nine live births. The diagnosis was made in approximately 90% by a primary care physician, at a median age of 5 weeks, with no gender predilection. Compared with the reference population, CNLDO was associated with premature birth (p=0.005) and was more prevalent among Caucasians (pConclusionsIn this large population-based cohort, CNLDO occurred in one in nine live births with no gender predilection. Prematurity and Caucasian race were associated with the development of CNLDO. Mucopurulent discharge was a much more common feature than tearing at initial presentation.

Objectives To describe the effect of implementing a contemporary perioperative pulmonary hypertension (PH)-targeted protocol in patients with pulmonary arterial hypertension (PAH) undergoing noncardiac surgery (NCS). Methods The data of consecutive patients with PAH diagnosed by right heart catheterization who underwent NCS between January 1, 2006 and February 9, 2016 were reviewed. Patient demographics, etiology of PAH, clinical features, diagnostic data, utilization of PH-specific medications, and trend of perioperative complications rate were recorded during the study period. Results In the base cohort of 375 patients, 37 had NCS. The mean age at surgery was 62 years. Most patients were women (78%) classified in group 1 PAH. At the time of the surgery, 86% were New York Heart Association functional class III/IV and 97% had American Society of Anesthesiologists classifications 3 and 4. A larger proportion of patients displayed lower PAH risk scores between 2006 and 2011 (P = 0.045). Conversely, a higher percentage of patients exhibited moderately high to very high PAH risk scores between 2012 and 2016 (P = 0.003). Perioperative and anesthetic-related morbidity was 27%, and no difference was observed between either period (P = 0.944). Most of the complications (70%) were related to general anesthesia. Two deaths (5%) occurred in our study group, both during the 2006-2011 period. Conclusions The combination of a multidisciplinary perioperative approach, utilization of novel pulmonary vascular disease-targeted therapy, adequate perioperative optimization, and thoughtful selection of anesthetic technique seems to be a potential strategy to at least maintain similar perioperative outcomes among higher- and lower-risk patients with PAH undergoing NCS.

Outcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted.Patients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results-Medicare database were evaluated for racial trends in clinical myeloma-defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS).Among 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006-2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P.001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P.001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P.01). Better OS was noted among patients who had higher median incomes.The current results indicate that there have been significant changes in the management of patients with MM over time and provide an in-depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710-21. © 2018 American Cancer Society.

Background Over 40% of women undergoing breast screening have mammographically dense breasts. Elevated mammographic breast density (MBD) is an established breast cancer risk factor and is known to mask tumors within the dense tissue. However, the association of MBD with high risk benign breast disease (BBD) is unknown. Method We analyzed data for 3400 women diagnosed with pathologically confirmed BBD in the Mayo Clinic BBD cohort from 1985–2001, with a clinical MBD measure (either parenchymal pattern (PP) or Breast Imaging Reporting and Data Systems (BI-RADS) density) and expert pathology review. Risk factor information was collected from medical records and questionnaires. MBD was dichotomized as dense (PP classification P2 or DY, or BI-RADS classification c or d) or non-dense (PP classification N1 or P1, or BI-RADS classification a or b). Associations of clinical and histologic characteristics with MBD were examined using logistic regression analysis to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results Of 3400 women in the study, 2163 (64%) had dense breasts. Adjusting for age and body mass index (BMI), there were positive associations of dense breasts with use of hormone therapy (HT), lack of lobular involution, presence of atypical lobular hyperplasia (ALH), histologic fibrosis, columnar cell hyperplasia/flat epithelia atypia (CCH/FEA), sclerosing adenosis (SA), cyst, usual ductal hyperplasia, and calcifications. In fully adjusted multivariate models, HT (1.3, 95% CI 1.1–1.5), ALH (1.5, 95% CI 1.0–2.2), lack of lobular involution (OR 1.6, 95% CI 1.2–2.1, compared to complete involution), fibrosis (OR 2.2, 95% CI 1.9–2.6) and CCH/FEA (OR 1.3, 95% CI 1.0–1.6) remained significantly associated with high MBD. Conclusion Our findings support an association between high risk BBD and high MBD, suggesting that risks associated with the latter may act early in breast carcinogenesis. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0922-6) contains supplementary material, which is available to authorized users.

Purpose The aim of this study was to explore the association of an elevated modified shock index (MSI) in sepsis and myocardial dysfunction. Methods This single center exploratory retrospective cohort study was conducted at Mayo Clinic from 2011 to 2014. It includes adults admitted to the medical intensive care unit with severe sepsis or septic shock. The time MSI > 1.3, area under the curve, in the first 6 h was assessed using logistic regression for primary outcomes of myocardial dysfunction and depression and secondary outcomes including mortality and SOFA score. Results Overall 578 individuals met inclusion criteria, 169 (29%) developed myocardial dysfunction and 23 (4%) myocardial depression. Adjusted for age, gender, Charlson score, and baseline APACHE 3 score, area MSI > 1.3 was associated with increased odds of myocardial dysfunction (OR 1.10, 95% CI 1.00–1.21; p = 0.058) and depression (OR 1.28, 95% CI 1.07–1.53; p = 0.007). Associations were also seen with ICU mortality (OR 1.17, 95% CI 1.04–1.32; p = 0.011), hospital mortality (OR 1.13, 95% CI 1.02–1.25; p = 0.025) and SOFA score. Conclusion Elevated modified shock index during early sepsis is associated with the development of myocardial dysfunction and depression, SOFA score and mortality.

Diabetes mellitus (DM) has a bidirectional association with pancreatic cancer (PaC); however, its effect on clinical outcomes has not been thoroughly evaluated. We analyzed these data in a large sample of PaC subjects who had undergone surgical resection.Subjects enrolled in the Mayo Clinic Pancreatic Cancer SPORE registry from 2000 to 2010 who had resection with curative intent were identified (n=488). Tumor size, cancer stage, and postoperative median survival were evaluated. Median survivals were compared with Kaplan-Meier curves and Cox proportional hazards regression modeling.A total of 275 (56%) subjects had DM before surgery. DM subjects had larger tumors compared with those without DM (3.6 cm vs. 3.3, P=0.002), even after controlling for covariates including age, body mass index, and tumor grade. Cancer stage at the time of surgery was not affected by DM status (P=0.575). Preoperative DM was not associated with an increased risk of death using a multivariable survival analysis (hazard ratio 1.06, 95% confidence interval 0.81-1.38, P=0.676). The median survival following cancer resection was similar between subjects with and without DM (24 vs. 26 months, P=0.610). In addition, postoperative survival was similar on the basis of the duration of DM (new-onset vs. long-standing) and prior use of antidiabetic treatments in diabetic subjects.PaC subjects with DM have larger tumors than nondiabetic subjects. Despite this observation, preoperative DM does not negatively impact the cancer stage at the time of surgery or postoperative survival. Thus, the effect of DM on tumor size is either overshadowed by early metastatic spread of the cancer or is mitigated by the tumor resection.

Over one million American women have a benign breast biopsy annually. Sclerosing adenosis (SA) is a common, but poorly understood benign breast lesion demonstrating increased numbers of distorted lobules accompanied by stromal fibrosis. Few studies of its association with breast cancer have been conducted, with contradictory results. We studied SA in the Mayo Benign Breast Disease (BBD) Cohort, which includes women who had benign biopsies at Mayo-Rochester 1967–2001. Breast cancer risk in defined subsets was assessed using standardized incidence ratios (SIRs), relative to the Iowa Surveillance, Epidemiology, and End Results registry. This BBD cohort of 13,434 women was followed for a median of 15.7 years. SA was present in 3,733 women (27.8 %) who demonstrated an SIR for breast cancer of 2.10 (95 % CI 1.91–2.30) versus an SIR of 1.52 (95 % CI 1.42–1.63) for the 9,701 women without SA. SA was present in 62.4 % of biopsies with proliferative disease without atypia and 55.1 % of biopsies with atypical hyperplasia. The presence of SA stratified risk in subsets of women defined by age, involution status, and family history. However, SA does not further stratify risk in women diagnosed with other forms of proliferative breast disease, either with or without atypia. SA is a common proliferative lesion of the breast which, as a single feature, conveys an approximate doubling of breast cancer risk. Its role in breast carcinogenesis remains undefined; its presence may aid in risk prediction for women after a breast biopsy.