Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours.

The Landscape of Resource Utilization After Resuscitation of 22-, 23-, and 24-Weeks' Gestation Infants.

OBJECTIVE: To compare estimated healthcare resources needed to care for 22 through 24 weeks' gestation infants. STUDY DESIGN: This multicenter, retrospective cohort study included 1505 live in-born and out-born infants 22 through 24 weeks' gestational age at delivery from 6 pediatric tertiary care hospitals from 2011 through 2020. Median neonatal intensive care unit (NICU) length of stay (LOS) for each gestational age was used as a proxy for hospital resource utilization, and the number of comorbidities and medical technology use for each infant were used as estimates of future medical care needs. Data were analyzed using Kruskal-Wallis with Nemenyi's posthoc test and Fisher's exact test. RESULTS: Of the identified newborns, 22-week infants had shorter median LOS than their 23- and 24-week counterparts due to low survival rates. There was no significant difference in LOS for surviving 22-week infants compared with surviving 23-week infants. Surviving 22-week infants had similar proportions of comorbidities and medical technology use as 23-week infants. CONCLUSIONS: Compared with 23- and 24-week infants, 22-week infants did not use a disproportionate amount of hospital resources. Twenty-two-week infants should not be excluded from resuscitation based on concern for increased hospital care and medical technology requirements. As overall resuscitation efforts and survival rates increase for 22-week infants, future research will be needed to assess the evolution of these results.

Frailty in the prediction of delirium in the intensive care unit: A secondary analysis of the Deli study.

BACKGROUND: Delirium is an acute disorder of attention and cognition with an incidence of up to 70% in the adult intensive care setting. Due to the association with significantly increased morbidity and mortality, it is important to identify who is at the greatest risk of an acute episode of delirium while being cared for in the intensive care. The objective of this study was to determine the ability of the cumulative deficit frailty index and clinical frailty scale to predict an acute episode of delirium among adults admitted to the intensive care. METHODS: This study is a secondary analysis of the Deli intervention study, a hybrid stepped-wedge cluster randomized controlled trial to assess the effectiveness of a nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to the four adult intensive care units in the south-west of Sydney, Australia. Important predictors of delirium were identified using a bootstrap approach and the absolute risks, based on the cumulative deficit frailty index and the clinical frailty scale are presented. RESULTS: During the 10-mth data collection period (May 2019 and February 2020) 2566 patients were included in the study. Both the cumulative deficit frailty index and the clinical frailty scale on admission, plus age, sex, and APACHE III (AP III) score were able to discriminate between patients who did and did not experience an acute episode of delirium while in the intensive care, with AUC of 0.701 and 0.703 (moderate discriminatory ability), respectively. The addition of a frailty index to a prediction model based on age, sex, and APACHE III score, resulted in net reclassified of risk. Nomograms to individualize the absolute risk of delirium using these predictors are also presented. CONCLUSION: We have been able to show that both the cumulative deficits frailty index and clinical frailty scale predict an acute episode of delirium among adults admitted to intensive care.

Physician Perceptions on Quality of Life and Resuscitation Preferences for Extremely Early Newborns.

OBJECTIVE: The study aimed to explore physician views on whether extremely early newborns will have an acceptable quality of life (QOL), and if these views are associated with physician resuscitation preferences. STUDY DESIGN: We performed a cross-sectional survey of neonatologists and maternal fetal medicine (MFM) attendings, fellows, and residents at four U.S. medical centers exploring physician views on future QOL of extremely early newborns and physician resuscitation preferences. Mixed-effects logistic regression models examined association of perceived QOL and resuscitation preferences when adjusting for specialty, level of training, gender, and experience with ex-premature infants. RESULTS: A total of 254 of 544 (47%) physicians were responded. A minority of physicians had interacted with surviving extremely early newborns when they were ≥3 years old (23% of physicians in pediatrics/neonatology and 6% in obstetrics/MFM). The majority of physicians did not believe an extremely early newborn would have an acceptable QOL at the earliest gestational ages (11% at 22 and 23% at 23 weeks). The majority of physicians (73%) believed that having an extremely preterm infant would have negative effects on the family's QOL. Mixed-effects logistic regression models (odds ratio [OR], 95% confidence interval [CI]) revealed that physicians who believed infants would have an acceptable QOL were less likely to offer comfort care only at 22 (OR: 0.19, 95% CI: 0.05-0.65, p < 0.01) and 23 weeks (OR: 0.24, 95% CI: 0.07-0.78, p < 0.02). They were also more likely to offer active treatment only at 24 weeks (OR: 9.66, 95% CI: 2.56-38.87, p < 0.01) and 25 weeks (OR: 19.51, 95% CI: 3.33-126.72, p < 0.01). CONCLUSION: Physician views of extremely early newborns' future QOL correlated with self-reported resuscitation preferences. Residents and obstetric physicians reported more pessimistic views on QOL. KEY POINTS: · Views of QOL varied by specialty and level of training.. · Contact with former extremely early newborns was limited.. · QOL views were associated with preferred resuscitation practices..

A nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to intensive care: A stepped-wedge cluster randomised trial.

BACKGROUND: Delirium is an acute change in behaviour, characterised by a fluctuating course, inattention, and disorganised thinking. For critically ill adults in the intensive care, the incidence of delirium has been reported to be at least 30% and is associated with both short-term and long-term complications, longer hospital stay, increased risk of mortality, and long-term cognitive problems. AIM: The objective of this study was to determine the effectiveness of a nurse-led delirium-prevention protocol in reducing the incidence and duration of delirium among adults admitted to intensive care. METHODS: A hybrid stepped-wedge cluster randomised controlled trial was conducted to assess the effectiveness of the implementation and dissemination of the nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to the four adults intensive care units in the southwest of Sydney, Australia. RESULTS: Between May 2019 and February 2020, over a 10-month period, 2618 admissions, among 2566 patients, were included in the study. After an initial 3-month baseline period, each month there was a random crossover to the nurse-led intervention in one of the four intensive care units, and by the 7th month of the trial, all units were exposed to the intervention for at least 3 months. The incidence of acute delirium was observed to be 10.7% (95% confidence interval [CI] = 9.1-12.4%), compared to 14.1% (95% CI = 12.2-16.2%) during the preintervention (baseline) period (adjusted rate ratio [adjRR] = 0.78, 95% CI = 0.57-1.08, p = 0.134). The average delirium-free-days for these preintervention and postintervention periods were 4.1 days (95% CI = 3.9-4.3) and 4.4 days (95% CI = 4.2-4.5), respectively (adjusted difference = 0.24 days [95% CI = -0.12 to 0.60], p = 0.199). CONCLUSION: Following the introduction of a nurse-led, nonpharmacological intervention to reduce the burden of delirium, among adults admitted to intensive care, we observed no statistically significant decrease in the incidence of delirium or the duration of delirium.

Frailty, delirium and hospital mortality of older adults admitted to intensive care: the Delirium (Deli) in ICU study.

BACKGROUND: Clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of patients, an acute episode of delirium is also common, but its relationship to frailty and increased risk of mortality has not been extensively explored. Therefore, the aim of this study was to explore the relationship between clinical frailty, delirium and hospital mortality of older adults admitted to intensive care. METHODS: This study is part of a Delirium in Intensive Care (Deli) Study. During the initial 6-month baseline period, clinical frailty status on admission to intensive care, among adults aged 50 years or more; acute episodes of delirium; and the outcomes of intensive care and hospital stay were explored. RESULTS: During the 6-month baseline period, 997 patients, aged 50 years or more, were included in this study. The average age was 71 years (IQR, 63-79); 55% were male (n = 537). Among these patients, 39.2% (95% CI 36.1-42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% (n = 127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted rate ratio (adjRR) = 1.71, 95% confidence interval (CI) 1.20-2.43, p = 0.003), had a longer hospital stay (2.6 days, 95% CI 1-7 days, p = 0.009) and had a higher risk of hospital mortality (19% versus 7%, adjRR = 2.54, 95% CI 1.72-3.75, p < 0.001), when compared to non-frail patients. Patients who were frail and experienced an acute episode of delirium in the intensive care had a 35% rate of hospital mortality versus 10% among non-frail patients who also experienced delirium in the ICU. CONCLUSION: Frailty and delirium significantly increase the risk of hospital mortality. Therefore, it is important to identify patients who are frail and institute measures to reduce the risk of adverse events in the ICU such as delirium and, importantly, to discuss these issues in an open and empathetic way with the patient and their families.

Euploid rates among oocyte donors: is there an optimal age for donation?

PURPOSE: To examine cycle blastocyst euploid rates among age subgroups of oocyte donors. METHODS: Retrospective cohort analysis of ova donation in vitro fertilization cycles (OD-IVF) for which trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) by array comparative genomic hybridization (aCGH) or next generation gene sequencing (NGS) was employed between January 2015 and December 2018 in a single high-volume fertility center. RESULTS: Compared to oocyte donors age 26-30, oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates (80 [66.7, 87.5]%, vs. 75 [62.5, 87.5]%, median [IQR], p = 0.07), blastocyst formation rates (66.7 [50, 75]%, vs. 62.5 [52, 75]%, p = 0.55), and number of retrieved oocytes (29 [23, 37] vs. 27 [20, 35], p = 0.18). Age of oocyte donor from 18 to 34 was not correlated with cycle blastocyst euploid rate. CONCLUSION: Oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates, blastocyst formation rates, and number of retrieved oocytes compared to donors age 26-30. There was no correlation between cycle blastocyst euploid rates and age of the oocyte donor from 18 to 34 years. Given the lack of significant age-related change in cycle blastocyst euploid rates, our data support existing practices which do not favor a specific age subgroup of young oocyte donors.

Delirium in intensive care: A stepped-wedge cluster randomised controlled trial for a nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to the intensive care unit (protocol).

BACKGROUND: Delirium is an acute disorder of attention and cognition with the highest rates among adults receiving intensive care. An acute episode of delirium is associated with morbidity and mortality, as well as a significant psychological sequela. Importantly, an increasing body of evidence supports the benefit of nonpharmacological, nurse-led interventions to reduce the incidence and duration of delirium among adults cared for in the intensive care unit (ICU). OBJECTIVES: This study will evaluate the impact of a nursing-led delirium prevention protocol that is aimed at reducing the incidence and duration of delirium among adults admitted to the ICU. The delirium prevention nursing protocol specifically targets risk factors for delirium. STUDY PLAN: A stepped-wedge cluster randomised controlled trial approach will be used to assess the effectiveness of the nurse-led intervention, in four adult ICUs across the South Western Sydney Local Health District (SWS-LHD), over a 12-month period. The primary outcomes of interest are (i) the incidence of delirium before and after the implementation of the nurse-led intervention and (ii) the number of delirium-free days during an ICU stay, before and after the implementation of the nurse-led intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): (ACTRN12618000411246p).

Evidence for the effectiveness of chlorhexidine bathing and health care-associated infections among adult intensive care patients: a trial sequential meta-analysis.

BACKGROUND: Health care associated infections (HAI) among adults admitted to the intensive care unit (ICU) have been shown to increase length of stay, the cost of care, and in some cases increased the risk of hospital death (Kaye et al., J Am Geriatr Soc 62:306-11, 2014; Roberts et al., Med Care 48:1026-35, 2010; Warren et al., Crit Care Med 34:2084-9, 2006; Zimlichman et al., JAMA Intern Med 173:2039-46, 2013). Daily bathing with chlorhexidine gluconate (CHG) has been shown to decrease the risk of infection in the ICU (Loveday et al., J Hosp Infect 86:S1-S70, 2014). However, due to varying quality of published studies, and varying estimates of effectiveness, CHG bathing is not universally practiced. As a result, current opinion of the merit of CHG bathing to reduce hospital acquired infections in the ICU, is divergent, suggesting a state of 'clinical equipoise'. This trial sequential meta-analysis aims to explore the current status of evidence for the effectiveness of chlorhexidine (CHG) bathing, in adult intensive care patients, to reduce hospital acquired infections, and address the question: do we need more trials? METHODS: A systematic literature search was undertaken to identify trials assessing the effectiveness of chlorhexidine bathing to reduce risk of infection, among adult intensive care patients. With particular focus on: (1) Blood stream infections (BSI); (2) Central Line Associated Blood Stream Infections (CLABSI); (3) Multi-Resistant Drug Organism (MRDO); (4) Ventilator Associated Pneumonia; and, Catheter Associated Urinary Tract Infections (CAUTI). Only randomised-control or cluster randomised cross-over trials, were include in our analysis. A Trial Sequential Analysis (TSA) was used to describe the current status of evidence for the effectiveness of chlorhexidine (CHG) bathing, in adult intensive care patients, to reduce hospital acquired infections. RESULTS: Five trials were included in our final analysis - two trials were individual patient randomised-controlled, and the remaining cluster-randomised-crossover trials. Daily bathing with CHG was estimated to reduce BSI in the ICU by approximately 29% (Der-Simonian and Laird, Random-Effects. (DL-RE) Incidence Rate Ratio (IRR) = 0.71, 95% confidence interval (CI) 0.51, 0.98); reduce CLABSI in the ICU by approximately 40% (DL-RE IRR = 0.60, 95% CI 0.34, 1.04); reduce MDRO in the ICU by approximately 18% (DL-RE IRR = 0.82, 95% CI 0.69, 0.98); no effect in reducing VAP in the ICU (DL-RE IRR = 1.33, 95% CI 0.81, 2.18); and, no effect in reducing CAUTI in the ICU (DL-RE IRR = 0.77, 95% CI 0.52, 1.15). Upper (superiority) monitoring boundaries from TSA were not crossed for all five specific infections in the ICU. CONCLUSION: Routine bathing with CHG does not occur in the ICU setting, and TSA suggests that more trials are needed to address the current state of 'clinical equipoise'. Ideally these studies would be conducted among a diverse group of ICU patients, and to the highest standard to ensure generalisability of results.

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT.

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid (18F-FTHA) and glucose analog 18F-fluorodeoxyglucose (18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol (18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant ( P = .1) and distribution volume ( P = .1), significantly higher 18F-FDG myocardial influx rate constant ( P = 4×10-8), and significantly lower 18F-FTHA myocardial influx rate constant ( P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant ( P = 5×10-6) and distribution volume ( P = 3×10-8), significantly higher 18F-FDG myocardial influx rate constant ( P = 3×10-8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011-2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.

A Telemedicine-Based Intervention Reduces the Frequency and Severity of COPD Exacerbation Symptoms: A Randomized, Controlled Trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may not recognize worsening symptoms that require intensification of therapy. They may also be reluctant to contact a healthcare provider for minor worsening of symptoms. A telemedicine application for daily symptom reporting may reduce these barriers and improve patient outcomes. MATERIALS AND METHODS: Patients hospitalized for a COPD exacerbation within the past year or using supplemental O2 were approached for participation. Patients received optimal COPD care and were given a telecommunication device for symptom reporting. Initial symptom scores were obtained while patients were in their usual state of health. Patients were randomly assigned to an intervention group or a control group (usual medical care). The control group patients were instructed to seek medical care if their condition worsened. The intervention group symptom scores were assessed by a computer algorithm and compared with initial values. Scores 1 or more points above the initial score generated an "alert," and patients were reviewed by a nurse and referred to a physician who prescribed treatment. RESULTS: Eighty-six patients were screened; 79 met entry criteria and were randomized (intervention group, n=39; control group, n=40). Twelve patients submitted five or fewer symptom reports (5 intervention; 7 control) and were excluded from the analysis. Daily peak flow and dyspnea scores improved only in the intervention group. There were no differences in hospitalization and mortality rates between groups. No serious adverse events were reported. CONCLUSIONS: A telemedicine-based symptom reporting program facilitated early treatment of symptoms and improved lung function and functional status.

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women.

AIMS/HYPOTHESIS: The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk. METHODS: We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis. RESULTS: LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.) CONCLUSIONS/INTERPRETATION: LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.

Sex hormone-binding globulin and risk of clinical diabetes in American black, Hispanic, and Asian/Pacific Islander postmenopausal women.

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations. METHODS: We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians). RESULTS: Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09-0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10-0.38) for blacks; RR, 0.17 (95% CI, 0.05-0.57) for Hispanics; and 0.13 (95% CI, 0.03-0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07-0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14-0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RR(per SD) = 0.42, 95% CI, 0.34-0.51; past users: RR(per SD) = 0.53;, 95% CI, 0.37-0.77; current users: RR(per SD) = 0.57; 95% CI, 0.46-0.69; P-interaction = 0.10). CONCLUSIONS: In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance.

Faculty and applicant perceptions of virtual interviews on subspecialty fellowship match in obstetrics and gynecology.

BACKGROUND: In response to COVID-19, the AAMC recommended that hospitals conduct interviews in a virtual setting. OBJECTIVE: To evaluate whether fellowship video conference interviews (VCIs) are an acceptable alternative to in-person interviews from both the applicant and program perspectives. METHODS: Applicants and faculty from a single academic institution with five OBGYN subspecialty fellowship programs were invited to complete surveys regarding their experience using VCIs during the 2020 interview season. Survey responses used a 5-point Likert scale (strongly disagree to strongly agree). Comparative analyses between faculty and applicants responses to survey questions were performed with two-tailed Student's t-tests. RESULTS: 45 faculty members and 131 applicants received the survey. Response rate for faculty members and applicants was 95.6% (n = 43) and 46.6% (n = 61), respectively. Faculty and applicants agreed that the VCIs allowed them to accurately represent themselves (83.7% vs. 88.6%, p = 0.48). Most applicants (62.3%, n = 38) reported a fundamental understanding of the fellowship's culture. The majority of applicants (77.1%, n = 47) and faculty (72.1%, n = 31) agreed that they were able to develop connections during the virtual interview (p = 0.77). Faculty and applicants stated that VCIs assisted them in determining whether the candidate or program, respectively, was a good fit (83.7% vs. 67.2%, p = 0.98). CONCLUSIONS: The VCI fellowship recruitment process allowed OBGYN fellowship applicants and programs to accurately represent themselves compared to in-person interviews. Most applicants and faculty were able to develop relationships over the virtual platform. Although not explicitly assessed, it is possible that the virtual interviews can achieve a suitable match between applicant and program across all OBGYN subspecialty fellowships. The VCI process may be a long-term resolution to minimize both the financial burden and time commitment presented by traditional in-person interviews. Follow-up studies should assess the performance of the virtually selected fellows compared to those selected in previous years using traditional in-person interviews.

Common variations in the genes encoding C-reactive protein, tumor necrosis factor-alpha, and interleukin-6, and the risk of clinical diabetes in the Women's Health Initiative Observational Study.

BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. METHODS: To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. RESULTS: After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). CONCLUSIONS: We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.

In vivo positron emission tomography imaging with [¹¹C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons.

PURPOSE: Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [(11)C]ABP688, a positron emission tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [(11)C]ABP688 in nonhuman primates is essential. METHODS: Test-retest studies were performed in baboons (Papio anubis) to compare modeling approaches and determine the optimal reference region. The mGluR5-specific antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) was then used in test-block studies, in which ligand binding was measured before and after MTEP administration. Test/block data were analyzed both by calculating changes in binding and using a graphical approach, which allowed estimation of both MTEP occupancy and nonspecific binding. RESULTS: Test-retest results, which have not been previously reported for [(11)C]ABP688, indicated that [(11)C]ABP688 variability is low using an unconstrained two-tissue compartment model. The most appropriate, though not ideal, reference region was found to be the gray matter of the cerebellum. Using these optimal modeling techniques on the test/block data, about 90% occupancy was estimated by the graphical approach. CONCLUSION: These studies are the first to demonstrate the specificity of [(11)C]ABP688 for mGluR5 with in vivo PET in nonhuman primates. The results indicate that, in baboons, occupancy of mGluR5 is detectable by in vivo PET, a useful finding for proceeding to human studies, or performing further baboon studies, quantifying the in vivo occupancy of novel therapeutics targeting mGluR5.

Single-dose intramuscular methotrexate for treatment of cervical ectopic pregnancy: A case report.

INTRODUCTION: Cervical ectopic pregnancy (CEP) is a rare but potentially life-threatening phenomenon, and conclusive management guidelines have not been elucidated. Patients undergoing assisted reproductive technologies (ART) are at increased risk of CEP and noninvasive, fertility-sparing treatments are necessary for this population. This case report demonstrates the safety and efficacy of a single dose of intramuscular methotrexate for CEP in early gestation. CASE DESCRIPTION: A 45-year-old patient (G3P0030) presenting with painless vaginal bleeding was found to have CEP on transvaginal ultrasound at 5 weeks and 1 day of gestation after undergoing day-5 frozen embryo transfer. She was given one 50 mg/m2 dose of intramuscular methotrexate and she remained in a stable condition while being observed in the hospital. Her beta-hCG level decreased 38.2% between day 4 and day 7 after treatment and returned to nonpregnancy levels by day 28. DISCUSSION: A single dose of intramuscular methotrexate is an effective, noninvasive, fertility-sparing method of treatment for CEP in patients who are early in gestation and hemodynamically stable. This is a recommended option, especially for those undergoing fertility treatment. Further studies need to be performed to formulate national guidelines regarding the treatment of CEP.

Availability of Fertility Preservation Information on the Websites of U.S. News and World Report Top-Ranked Pediatric Cancer Programs.

Purpose: To evaluate the availability of fertility preservation (FP) services and educational resources on the websites of top-ranked U.S. pediatric cancer programs. Methods: Cross-sectional survey of information and resources related to FP on websites from top-ranked pediatric cancer programs according to the 2018-2019 U.S.-News & World Report (USNWR) ranking. Factors that predicted the website availability of FP information or a fertility team were analyzed, as was availability in Spanish and for specific groups by sex and puberty status. As a surrogate marker of comprehensive oncological services, the availability of resources for psychological support was compared to FP. Results: A fertility team was referenced on the website of 36% of programs, but only 32% provided FP educational resources for patients. Among them, 100%, 93.8%, 93.8%, and 68.8% provided specific information for postpubertal females, prepubertal females, postpubertal males, and prepubertal males, respectively. The majority (93.8%) did not provide information in Spanish. The ranking on USNWR (p < 0.05) and patient volume (p < 0.05) positively correlated with the availability of FP information and fertility team on the program's website. Information regarding psychological support was provided more often than information regarding FP (96% vs. 32%, p < 0.05). Conclusion: The majority of the top-ranked pediatric cancer programs in the United States do not list FP resources or a fertility team on their website. The lack of resources is particularly concerning for the Spanish-speaking population, as well as for prepubertal males. This may be potentially hindering access to FP and contributing to health care disparities.

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass.

Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL's predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. METHODS: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. RESULTS: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occurred between uNGAL values of neonates with AKI and those without AKI. Odds ratios at each time point significantly exceeded unity, peaking at 10 h post-operatively (3.48 (1.58, 8.71)). Between 4 and 16 h post-operatively, uNGAL discriminated AKI from no-AKI, with a sensitivity of 0.63 (0.49, 0.75) and a specificity of 0.68 (0.62, 0.74) at a cut-off value of 100 ng/mL. CONCLUSION: After 4 h until 16 h post-operatively, elevated uNGAL is associated with AKI in neonates receiving CPB during cardiac surgery; however, this relationship is more complex than in older children.