Association between dextrose-containing maintenance fluids and phosphorus supplementation during total parenteral nutrition initiation in adult patients who were hospitalized: A retrospective cohort study.

BACKGROUND: Use of dextrose-containing maintenance fluids prior to parenteral nutrition (PN) initiation is speculated to reduce the risk for refeeding syndrome. We aimed to assess if the use of dextrose vs nondextrose maintenance fluids before PN initiation changes electrolyte supplementation requirements and shifts during initiation. METHODS: This retrospective cohort study included patients who received nothing by mouth but received maintenance fluids ≥72 h before PN. The major end point was phosphorus supplementation over 48 h following nutrition initiation. Minor end point included other electrolyte supplementation, changes in electrolyte levels, time to discharge, and goal kilocalories per day. RESULTS: Fifty-three patients between August 1, 2019, and August 26, 2020, met criteria for analysis; 60% (n = 32) used a dextrose and 40% (n = 21) used a nondextrose maintenance fluid. Baseline characteristics were similar between fluid groups except for body mass index (25.1 dextrose vs 27.5 kg/m2 nondextrose), sex (43.8% female vs 52.4% male), and severe malnutrition (46.9% vs 28.6%), respectively. Phosphorus (52.5 vs 50 mmol; P = 0.33) and magnesium (24 vs 22 g; P = 0.63) supplementation 48 h following nutrition initiation were similar between groups; however, potassium supplementation was lower in the dextrose group (165.0 vs 208.7 mEq; P = 0.01). No difference was observed between groups for time to discharge following nutrition initiation or time to goal kilocalories per day. After controlling for patients who were malnourished between fluid groups using linear regression, phosphorus repletion differences remained nonsignificant. CONCLUSION: This study did not detect a difference in phosphorus supplementation between groups, even after controlling for patients who were malnourished.

Comparison of CRISPR/Cas and Argonaute for nucleic acid tests.

Guided, programmable, and target-activated nucleases, exemplified by Cas in the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system and Argonaute (Ago), are emerging as a new generation of nucleic acid tests (NATs). A specific approach for comparison of these two nucleases side by side in terms of similarities, differences, and complementarities is instrumental for the sensible design of novel NATs.

An innovative program to provide methodological mentoring and to foster the development of robust research teams for K awardees: RAMP Mentors.

Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.

Findings in Stillbirths Associated with Placental Disease.

OBJECTIVE: Placental disease is a leading cause of stillbirth. Our purpose was to characterize stillbirths associated with placental disease. STUDY DESIGN: The Stillbirth Collaborative Research Network conducted a prospective, case-control study of stillbirths and live births from 2006 to 2008. This analysis includes 512 stillbirths with cause of death assignment and a comparison group of live births. We compared exposures between women with stillbirth due to placental disease and those due to other causes as well as between women with term (≥ 37 weeks) stillbirth due to placental disease and term live births. RESULTS: A total of 121 (23.6%) out of 512 stillbirths had a probable or possible cause of death due to placental disease by Initial Causes of Fetal Death. Characteristics were similar between stillbirths due to placental disease and other stillbirths. When comparing term live births to stillbirths due to placental disease, women with non-Hispanic black race, Hispanic ethnicity, lack of insurance, or who were born outside of the United States had higher odds of stillbirth due to placental disease. Nulliparity and antenatal bleeding also increased risk of stillbirth due to placental disease. CONCLUSION: Multiple discrete exposures were associated with stillbirth caused by placental disease. The relationship between these factors and utility of surveillance warrants further study.

Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases.

Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.

Heparin-induced anaphylactoid reaction associated with heparin-induced thrombocytopenia in the ED.

Although rare, heparin-induced anaphylactic and anaphylactoid reactions have been previously described in the literature. We present a case of a patient who presented to the emergency department with dyspnea and was subsequently diagnosed with an acute pulmonary venous thromboembolism. Shortly after being started on intravenous unfractionated heparin, she developed sudden cardiovascular collapse leading to a cardiopulmonary arrest. She was successfully resuscitated and, after further diagnostic evaluation, was found to have developed a heparin-induced anaphylactoid reaction.

Beyond responsible conduct: taking responsibility for the responsible conduct of others.

A unique Responsible Conduct of Research (RCR) course was created for Ph.D., M.D., and M.D./Ph.D. postdoctoral fellows and junior faculty at Northwestern University, some of whom had prior RCR training and some of whom did not. The unique feature of the course is its dual focus on learning the core elements of RCR and preparing participants for being responsible for guiding and monitoring RCR behaviors of others. These more advanced but still junior scientists are at a key junction where they are beginning to mentor and supervise others. A second unique element is a required conversation on at least two RCR topics with their current mentors, with a short written report, modeling explicit conversations about RCR prospectively. Overall response has been very positive with a high level of engagement. Formal and informal evaluation feedback reveals how participants see the value of the course and how it has shaped how they intend to guide others in the future. An important goal of the course is to also position high quality RCR and RCR training within the research environment, not just the classroom.

Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats.

We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague-Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [3H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naïve group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user.