bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression Profile During the Repair Process in a Rat Calvarial Bone Critical Size Defect
Authors: Clifford John L , Yang Ruoting , Bowman Phillip D , Bynum James A , Wenke Joseph C , Hammamieh Rasha
Published: June 2021

Bone is a complex tissue, providing support and protection while also adapting to the body's mechanical needs. In response to injury or fracture, bone has a significant capability for self‐repair and regeneration that requires the regulated expression of diverse families of genes that coordinate complex interactions among various cell types. Studies on bone non‐union have led to the critical size defect (CSD) theory, which states that as bone defects increase in size, a point will be reached where bone union will not occur and the bone will not heal spontaneously during the lifetime of the animal. CSDs fail to heal and regenerate bone, while noncritical defects produce an acceptable repair after bone loss. To improve outcome following significant bone loss we sought to identify genes differentially expressed between an 8 mm (CSD) and 4 mm (non‐CSD) size defects in a rat calvarial bone defect model. Rat whole genome microarrays were used to measure gene expression over the course of bone healing, and analysis of differentially expressed genes (DEGs) with Cytoscape® software revealed multiple temporal patterns of fold differences for DEGs. The patterns indicated that greatest number of differences occur at the earliest time point post‐injury (day 1), and starting at day 7 and continuing through day 21. Gene ontology and functional classification of genes altered in expression between the CSD and non‐CSD was conducted using Ingenuity Pathway Analysis software®. During the earliest (day 1,3) and later (day 14,21) times post injury, multiple DEGs and gene networks related to cell death and survival, cancer, connective tissue development and function, DNA Replication/recombination/repair, skeletal and muscular system development and function, and others, were identified. At the early time points TGF‐β1 and VEGFα signaling pathways are down modulated in CSD relative to non‐CSD include. Pathways that regulate movement of lymphocytes and activation of antigen presenting cells, as well as NFk‐B signaling, are upregulated at later times post‐ injury in CSD compared to non‐CSD. We conclude that genes and signaling pathways that promote healing and tissue homeostasis are suppressed in the CSD, in favor of activation of pro‐inflammatory signaling.

Disclaimer: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.

Support or Funding Information

This work was supported by funding from the United States Army Medical Research and Material Command Combat Casualty Care and Clinical and Rehabilitative Medicine Research Programs
Modulations of calcium in adipose tissue by TRPC1: a key player in obesity
Authors: Schaar Anne , Krout Danielle , Roemmich James N , Claycombe‐Larson Kate J , Singh Brij B
Published: June 2021

The disruption of metabolic homeostasis, the regulation of energy the body extracts, stores and uses, leads to excess adipose tissue accumulation and the onset of obesity. White adipose tissue (WAT) is a metabolically dynamic endocrine organ responsible for maintaining metabolic homeostasis through mitochondrion function and the secretion of cytokines. A key modulator of glucose and lipid metabolism is the WAT secreted cytokine adiponectin, however, the regulation of it is not fully known. Transient Receptor Potential Canonical (TRPC) channels are a major class of Ca2+ permeable channels found in key metabolic tissues (hypothalamus, adipocytes, and skeletal muscle). Fluctuations in intracellular Ca2+ are due to the release of Ca2+ stores from the endoplasmic reticulum (ER) that initiates store‐operated Ca2+ entry (SOCE) mechanism, or by direct Ca2+ entry from the extracellular space upon membrane depolarization. Within our work, we provide evidence that Ca2+ entry into the cell, especially upon store‐depletion, plays an important role in WAT functionality and subsequently metabolic regulation. It was found that mice deficient in the Ca2+ channel TRPC1−/− have significantly increased adipose deposition without an increase in overall weight as compared to control. When investigating WAT, the reduced Ca2+ influx due to a loss of TRPC1 results in a decline in mitochondria function. Further, TRPC1−/− mice were found to have reduced serum adiponectin levels along with a reduction in the downstream enzymes adiponectin regulates necessary for lipid metabolism. Combined, these results indicate that TRPC1 may have an important role in the regulation of metabolic homeostasis and the onset of obesity through the regulation of WAT.

Support or Funding Information

This work was supported by the National Institutes of Health awarded to B.B.S (DE017102; DE024300; GM113123), by ND EPSCoR through National Science Foundation (IIA‐1355466) awarded to A.S., and from the USDA Agricultural Research Service Project #3062‐51000‐052‐00D awarded to K.C.
Nuclear Blebbing Solely as a Function of Chromatin Compaction State
Authors: Liu Patrick Z. , Stephens Andrew D. , Banigan Edward J. , Almassalha Luay , Backman Vadim , Adams Stephen A. , Goldman Robert D. , Marko John F.
Published: June 2021

The nucleus houses the genome and is critical for regulating its functional organization. Classically, in mammalian nuclei, the compact, transcriptionally silent heterochromatin is docked to the lamina network at the periphery, thereby providing mechanical support to the nucleus. In many human diseases, such as progeria, cancers, and muscular dystrophies, nuclear morphology becomes severely altered and demonstrates blebbing as a result of impaired nuclear rigidity stemming from disruptions to chromatin compaction and lamina content. To elucidate chromatin's individual role in contributing to the formation of pathologically misshapen nuclei, we show that decompacting chromatin via histone deacetylase inhibitor (HDACi) treatment alone is sufficient to induce nuclear blebbing. Through immunofluorescence imaging via confocal microscopy, we demonstrate that treating mouse embryonic fibroblasts with HDACi decompacts chromatin, relocates euchromatin to the periphery, and causes blebbing independent of disruptions to the lamina or actin network. Moreover, the divalent ion magnesium is known to compact chromatin. In accordance with this, we found that increasing extracellular magnesium chloride concentrations rescues nuclear blebbing in a dose‐dependent manner, restores heterochromatin signal at the periphery, and significantly increases the heterochromatin signal histone H3 lysine 27 tri‐methyl. Moreover, nuclear morphology in HeLa cells expressing progerin, a mutated form of lamin A present in progeria that causes severe nuclear deformities, was also rescued via magnesium chloride treatment. Thus, nuclear blebbing can both be induced and suppressed through solely altering chromatin compaction states. Similarly, a pathological phenotype that stems from a lamina mutation can be rescued through the same chromatin mechanism, thereby suggesting a significant role of chromatin in disease and providing a potential therapeutic target.

Support or Funding Information

J. F. M. is supported by NSF Grants DMR‐1206868 and MCB‐1022117 and by NIH Grants GM105847 and CA193419.
Longitudinal study of the human gastrointestinal microbiota following fecal microbiota transplant (FMT) for Clostridium difficile infections
Authors: Joseph Oluyemisi D , Thompson Sharon V , Bogner Anna , Martin Daniel , Farrell John J , Swanson Kelly S , Holscher Hannah D
Published: June 2021

Background

Clostridium difficile infection (CDI) is a nosocomial infection known to be the most crucial antecedent of healthcare‐associated diarrhea. Fecal microbiota transplant (FMT) has emerged as a successful treatment method when standard antibiotic therapy is ineffective for refractory CDI. However, our understanding is limited regarding the longitudinal differences in the gastrointestinal (GI) microbiota between patients with a successful or failed FMT.

Objective

We aimed to investigate the microbial structure and predictive metagenome functional content of FMT patients over a 90‐day period, and to determine if these outcomes differed in patients with a successful or failed procedure over time.

Methods

Patient microbiome samples were assessed prior to FMT (n=8), and at 30 (n=4) and 90 days (n=4) post treatment. Treatment failure was defined as ≥3 episodes of diarrhea/day or, within 30 days, retreatment with antibiotics or FMT. Metagenome functional potential was predicted using PICRUSt (v. 1.0.0). PICRUSt data and relative abundances of microbial taxa were then analyzed using LEFSe (v. 1.0), a Linear Discriminant Analysis model which evaluated discriminant features using a Kruskall‐Wallis test for FMT status (success/fail) followed by Wilcoxon test for pairwise comparisons between timepoints (baseline/30‐d/90‐d).

Results

Across timepoints, relative abundance of Fusobacteriaceae was significantly higher among patients with a failed FMT (p=0.015), and Enterococcaceae (p=0.020) and an unclassified family of Lactobacillales (p=0.023) were significantly greater in patients with a successful FMT. At the genus level, relative abundance of Lactococcus (p=0.027) and Fusobacterium (p=0.007) were higher in patients with failed FMT over time. Metagenome functional potential analyses revealed that enzymes related to steroid hormone and glycosphingolipid synthesis and glycosaminoglycan degradation were significantly higher in participants with a failed FMT over time.

Conclusions

The use of innovative bioinformatic tools in the present study permits identification of key differences in microbial community structures and functional gene potential between participants with a successful or failed FMT procedure across a 90‐day period. Differences in steroid hormone synthesis, glucocorticoid in particular, has been linked to increased mortality of CDI patients. An increase in the synthesis and metabolism of glycoconjugates have also been associated with an increase in the pathogenicity of microbes such as C. difficile. More research is required to determine if the gut microbial structure of patients with CDI can be used to predict if FMT is the best route for treatment.

Support or Funding Information

Partial funding for this study was provided by the USDA National Institute of Food and Agriculture, Hatch project ILLU 538 384.
Assessment of Dietary Intervention Compliance of Subjects Participating in an Ongoing Randomized Controlled Trial
Authors: Dietrich Jessica R , Kaczmarek Jennifer L , Reeser Ginger E , Khan Naiman A , Holscher Hannah D
Published: June 2021

Background

When conducting human subject research, outcomes vitally depend upon how well participants follow instructions provided by the research team. Assessing compliance to interventions enables participant classification as per protocol or intention to treat for outcome assessments. It also provides insight into participant characteristics that may be related to study compliance, with relevance to future dietary intervention studies.

Objective

Herein we aimed to determine overall self‐reported compliance of study participants to a dietary intervention during an ongoing randomized, controlled trial. Our secondary objectives were to determine whether factors such as age, sex, income, or education are related to study compliance.

Methods

All study participants were counseled to consume the entire study meal daily throughout a 12‐week intervention. Daily compliance records were provided throughout the study. Participants were instructed to indicate the percentage of the meal consumed each day. Consumption was computed on a per‐week basis for each participant. Statistical analyses was performed in SAS 9.4, accepting a p‐value of 0.05 as statistically significant. A general linear mixed model was created for each demographic variable using compliance as the outcome measure and including week of the study as a repeated measure predictor. Week was included in order to examine not only what variables were associated with compliance, but also how compliance changed over the duration of the study.

Results

The average overall consumption of the control group (n=31) was 87%, and the average overall consumption of the intervention group (n=27) was 90%. The average meal consumption for females was 86% (n=36) and 92% (n=22) for males. The analysis of the entire participant pool (n=58) showed no significant relationships between meal compliance and group, age, sex, income, or education level.

Conclusion

These results reveal that overall study compliance is high with no differences between groups or over time. Even when other variables such as age, sex, income, and education were considered, there still were no significant associations with compliance, nor did compliance decrease significantly over the course of the study.

Support or Funding Information

Partial funding for this study was provided by the Hass Avocado Board and the USDA National Institute of Food and Agriculture, Hatch project ILLU 538 384.
Self‐reported diabetes status moderates the association between food insecurity and body mass index
Authors: Liu Yibin , Remley Daniel T. , Zhang Yumin , Eicher‐Miller Heather A.
Published: June 2021

Food insecurity is associated with reduced consumption of fruits, vegetables, dairy, and lower levels of micronutrients. These dietary patterns are linked to the development of chronic diseases. Few studies have explored disease factors that impact the relationship of food insecurity with obesity. The purpose of this study was to investigate the role of self‐reported diabetes status in moderating the association between food insecurity and body mass index (BMI) among Indiana food pantry users aged 21 – 80 y (n = 285). Food pantry users that speak and read English were recruited from eight rural and low income counties in Indiana. Participants were interviewed for individual and household characteristics, household food security status (US Household Food Security Survey Module), and measured for height and weight to determine BMI. Results from adjusted multiple linear regression model showed that marginal food‐secure adults had an estimated 8.2 kg/m2 higher BMI (P = 0.03), low food‐secure adults had an estimated 9.3 kg/m2 higher BMI (P = 0.008), and very low food‐secure adults had an estimated 6.6 kg/m2 higher BMI (P = 0.06), compared with high food‐secure adult BMI. There was a significant interaction between food security status and self‐reported diabetes status. Among adults with self‐reported diabetes, BMI was significantly higher in marginal and low food‐secure groups (P = 0.03, P = 0.007), compared with the high food‐secure group. Among adults without diabetes, BMI in marginal, low, and very low food‐secure groups was not significantly different from the high food‐secure group (P = 0.59, P = 0.55, P = 0.42). Results of this study suggest that overweight and obesity are more prevalent among diabetic food pantry clients in marginal and low food‐secure groups. Food pantries may serve diabetic clients in marginal and low food secure groups by supporting provision of appropriate foods for these clients and allowing client choice along with offering nutrition education to improve self‐sufficiency and enable healthy, high‐quality, and appropriate food selection.

Support or Funding Information

This project is supported by the Agriculture and Food Research Initiative competitive grant no. 2013‐69004‐20401 of the USDA National Institute of Food and Agriculture.
Not all silver nanoparticles are equal: Effect of functionalization on K homeostasis in human red blood cells
Authors: Alla Praveen Kumar , Lauf Peter K , Sizemore Ioana , Paluri Arathi S.L , Yaklic Jerome , Adragna Norma C
Published: June 2021

Although silver nanoparticles (AgNPs) are one of the most frequently used nanomaterials (NMs) in industrial and biomedical applications, their toxicity and interaction with blood components, such as erythrocytes, has been insufficiently investigated. Here, we report on the effect of AgNPs at the level of cellular function, and particularly on ion transport in human red blood cells (HRBCs). These AgNPs were size‐selected, concentrated and purified by tangential flow filtration before HRBC exposure. Two methods of synthesis were used for the functionalization of AgNPs, Creighton and Lee‐Meisel. HRBCs were obtained from adult donors at a blood bank, expired or fresh or further stored refrigerated in the laboratory for variable lengths of time, and from fresh or stored refrigerated cord blood. Rubidium, used as a K congener to measure K influx, and the K concentration were determined in the presence and absence of several concentrations (0–150 μg/mL) of negatively charged, spherical 10 nm AgNPs at different time points (0–60 min). Our findings indicate that Creighton AgNPs, independently of the source and in a time‐ and dose‐dependent manner, inhibited Rb influx by ~ 80 % (p < 0.001, n=7) and depleted the cells of K by more than 90 % (p < 0.0001, n = 7), although interindividual differences were observed. In comparison to the Creighton, Lee‐Meisel AgNPs caused a maximum Rb inhibition of ~ 50 % and K loss of ~ 15 % with larger interindividual variability than Creighton AgNPs, albeit in a small sample. The loss of K from HRBCs was entirely accounted for by an increase in K concentration in the extracellular medium. These findings indicate that functionalization of AgNPs has a significant effect on HRBC K homeostasis. Further studies are required to identify the mechanisms underlying the observed changes in HRBC ionic composition.

Support or Funding Information

Funded by NSF
Brain Microvascular Endothelial Cell Activation and Barrier Disruption in a Mouse Model of Psychological Resilience
Authors: Cefalu Lindsay M , Bieniek Gerald E , Cain Roiseann M , Ho Dao H
Published: June 2021

Psychological resilience, as measured by the ability of an individual to overcome the development of psychological disorders following exposure to stressful or traumatic events, varies significantly from individual to individual. The mechanisms underlying this variability among individuals have not been fully elucidated. A key factor in the development and progression of psychological disorders such as depression, schizophrenia, and post‐traumatic stress disorder is disruption of the blood brain barrier, thus we hypothesized that the function of brain microvascular endothelial cells (BMECs) of resilient individuals are more resistant to disruption by endothelial cell activators (ethanol (EtOH), corticosterone (CORT), and lipopolysaccharide (LPS)), compared to non‐resilient individuals. We used Electric Cell‐substrate Impedance Signaling (ECIS) technology (Applied BioPhysics, Troy, NY) to measure transendothelial electrical resistance (TEER) of cultured BMECs of the resilient C57BL6 mouse (BMECC57BL6), and the non‐resilient BalbC mouse (BMECBalbC). BMECs were plated at a density of 4.8 × 104 cells/cm2, and allowed to establish a monolayer for 48 hours. BMECs were then treated with either EtOH (0, 1, 10, 25, 50, or 100 mM), CORT (0, 10, 100 or 1000 ng/ml), or LPS derived from E. coli (0, 1, 10, or 100 ng/ml). TEER was continuously recorded for an additional 24 hours. Barrier function (Rb), membrane capacitance (Cm), and constraint on current flow beneath the cells (α) were derived via ECIS mathematical modeling. We found that at baseline, BMECC57BL6 had significantly lower Rb (1.31±0.14 versus 2.64±0.43 Ωcm2, p = 0.009, n = 4) and α (6.13±0.33 versus 7.56±0.53 Ω0.5cm, p = 0.009, n = 4), and significantly higher Cm (2.65±1.19 versus 1.28±0.012 μF/cm2, p = 0.007, n = 4) when compared to BMECBalbC. Contrary to our hypothesis, the effect of EtOH, CORT, or LPS on these baseline parameters did not significantly differ between the two types of BMEC. These findings indicate that variability in psychological resilience among individuals may be associated with functional differences in BMECs, an important component of the blood brain barrier.

Support or Funding Information

The views expressed in this presentation are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the U.S. government.
Pre-operative proteinuria, postoperative acute kidney injury and mortality
Authors: Chang Chun-Yu , Chien Yung-Jiun , Kao Ming-Chang , Lin Han-Yu , Chen Yu-Long , Wu Meng-Yu
Published: June 2021

OBJECTIVE

To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up.

BACKGROUND

Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting.

METHODS

We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated.

RESULTS

Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+.

CONCLUSION

Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients.

PROSPERO REGISTRATION

CRD42020190065.
Feasibility of 24-h blood pressure telemonitoring in community pharmacies: the TEMPLAR project
Authors: Omboni Stefano , Ballatore Tommaso , Rizzi Franco , Tomassini Fernanda , Campolo Luca , Panzeri Edoardo
Published: June 2021

Objectives:

Low-quality ambulatory blood pressure monitoring (ABPM) due to recurring artifacts may limit its clinical value. We evaluated the features and impact on BP control and patient management of ABPMs performed in Italian community pharmacies, according to their quality.

Methods:

Twenty-four-hour ABPMs were obtained by a clinically validated, automated upper arm device and uploaded on a certified web-based telemedicine platform (www.tholomeus.net). The system automatically evaluated the quality of the recording according to current guidelines. In case of poor ABPM quality, the pharmacist was prompted to repeat the test. All the ABPMs were labeled as valid or invalid. Demographic and clinical characteristics of the patients and BP control were compared between the two groups.

Results:

A total of 45 232 ABPMs were obtained in as many patients through 812 pharmacies (87.7% recordings were valid). Factors significantly associated with a better ABPM quality were younger age, use of antihypertensive medications, presence of at least one cardiovascular risk factor, concomitant disease or treatment, a test performed in the coldest months, and residence in the cooler northern regions of the country. The 24-h and daytime ambulatory BP level and the prevalence of ambulatory hypertension and white-coat hypertension were higher, and the prevalence of masked hypertension lower in patients with valid recordings. High odds of obtaining a valid recording were observed in patients repeating the ABPM.

Conclusion:

Ambulatory BP telemonitoring is feasible in community pharmacies as long as potential predictors of unsuccessful outcomes are taken into account and adequately managed.
Wedge-Shaped Pars Plana Sclerotomies: Is It Still an Actuality in the Era of Microincision Vitrectomy?
Authors: Caporossi Tomaso , Governatori Lorenzo , Baldascino Antonio , Savastano Alfonso , De Vico Umberto , Rizzo Stanislao
Published: June 2021

Purpose:

To describe and evaluate the effectiveness of wedge-shaped sclerotomies to close 25-gauge and 23-gauge transconjunctival pars plana vitrectomies.

Materials and Methods:

This prospective, consecutive, interventional study examined 50 eyes of 50 patients who underwent 25-gauge and 23-gauge vitrectomy with wedge-shaped sclerotomies.

Results:

The number of eyes requiring a wedge shape for sclerotomy closure and sclerotomies requiring sutures was collected. Three eyes had hypotony on Day 1. No statistically significant difference was observed between preoperative intraocular pressure and postoperative intraocular pressure on Days 15 and 30. No postoperative complications were observed during the follow-up period.

Conclusion:

The wedge-shaped sclerotomy is a simple, fast, and effective technique that does not require extra surgical materials and could be applied to microincision vitrectomy.
Association between sleep disturbance and multidimensional frailty assessed by Frailty Index in hospitalized cirrhosis
Authors: Hui Yangyang , Xu Lin , Wang Xiaoyu , Feng Hongjuan , Yu Zihan , Li Chaoqun , Mao Lihong , Fan Xiaofei , Wang Bangmao , Chen Xin , Sun Chao
Published: June 2021

Objectives

Both sleep disturbance and frailty are common in patients with cirrhosis, but their correlation remains elusive. We aimed to investigate whether dysregulated sleep [as estimated by Pittsburgh Sleep Quality Index (PSQI)] is independently associated with frailty and their relationship in distinct subgroups.

Methods

In total 105 adult cirrhotic patients were recruited. The frailty phenotype was identified by a self-reported scale (Frailty Index) which demonstrates good validity and moderate performance based on our previous publication. Patients were categorized into frailty and nonfrailty groups according to a cut-point of 0.38 by Frailty Index. Multiple linear regression was performed to determine independent factors associated with frailty.

Results

The median PSQI was 6.0 in the entire cohort and sleep disturbance was observed in 61 patients with cirrhosis (58.1%). Poor sleepers had a significantly higher Frailty Index than that in good sleepers (0.11 vs. 0.08; P = 0.025). In univariate analysis, PSQI score was markedly associated with the Frailty Index (β = 0.012; 95% CI, 0.006–0.018; P < 0.001), and remained significantly associated with frailty phenotype in multivariate adjustment (β = 0.010; 95% CI, 0.004–0.015; P = 0.001). The escalating PSQI scores were more prominent in frail patients, with female gender or aged 65 years and over.

Conclusions

Poor sleep quality is strongly associated with frailty in patients with cirrhosis. Given that sleep disturbance is modifiable, our data suggest that efficient interventions to mitigate frailty should incorporate strategies by reversing sleep dysfunction in cirrhotics with poor sleep quality.
False positive pharmacologic myocardial perfusion SPECT study in the setting of a left bundle branch block
Authors: Nguyen Thuy D. , Lin David , Hernandez Pampaloni Miguel
Published: June 2021

We herein report a case of a false positive vasodilatory pharmacologic SPECT stress test in the setting of a left bundle branch block (LBBB). While this is more commonly seen with exercise stress testing, it can also occur with pharmacologic stress testing. In our SPECT exam, we illustrate the commonly mistaken septal/anteroseptal perfusion defects in those patients with a LBBB. PET stress testing may be more reliable for patients with LBBB.
75SeHCAT whole body retention for unexplained chronic diarrhoea based on early first whole body counting
Authors: Soares Sara , Heraghty Neil , Gulliver Nick , Peters Adrien Michael
Published: June 2021

Background

There are many protocol variations in the whole-body 75SeHCAT retention test [whole-body retention (WBR)] for investigation of bile acid diarrhoea. The time between capsule consumption and first count, however, is widely taken, without debate, to be 3 h. In the Covid-19 era, it is desirable to limit the time patients spend in the department. We, therefore, questioned the need for a 3 h interval between capsule administration and the initial count.

Methods

Using an uncollimated gamma camera, whole-body counting was performed at 5, 30 and 180 min after capsule ingestion in 24 patients with chronic diarrhoea. Geometric mean was taken of counts acquired from posterior and anterior projections. WBR was expressed as the ratio of 7 day-to-initial whole-body counts (%) to give WBR5, WBR30 and WBR180. A small meal was given at 60 min after capsule ingestion.

Results

There was a close correlation between WBR30 and WBR180 (y = 1.0x − 0.29%; r = 0.99). For WBR180 values of <15% (lower limit of normal), there was close agreement between WBR30 and WBR180 (bias 0.03%; precision 0.7%). WBR5 overestimated WBR180. However, cWBR5, obtained by multiplication of WBR5 by 0.75, also correlated closely with WBR180 (y = 1.2x − 4.5%; r = 0.97), and there was close agreement between cWBR5 and WBR180 for WBR180 values <15% (bias 0.08%, precision 1.3%).

Conclusion

The first whole-body count in the 75SeHCAT test can be undertaken at 30 min postcapsule without loss of accuracy, or even 5 min if only subnormal values are considered relevant. No food is required after capsule consumption.
Pancreas transplantation
Authors: Vistoli Fabio , Kauffmann Emanuele F. , Boggi Ugo
Published: June 2021

Purpose of review

To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference.

Recent findings

During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.

The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.

Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK.

COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference.
The Effect of Perioperative Blood Transfusion on Long-Term Survival Outcomes After Surgery for Pancreatic Ductal Adenocarcinoma
Authors: Ye Linda , Livingston Edward H. , Myers Bethany , Hines O. Joe
Published: June 2021

Objective

To evaluate survival outcomes associated with perioperative allogeneic red blood cell transfusion (RBCT) in patients with pancreatic ductal adenocarcinoma undergoing surgery.

Methods

PubMed, Embase, Cochrane, and Web of Science Core Collection were queried for English-language articles until May 28, 2020. Studies evaluating long-term outcomes of RBCT compared with no transfusion in adults with pancreatic ductal adenocarcinoma undergoing pancreatectomy were included. E-value sensitivity analysis assessed the potential for unmeasured confounders to overcome these findings.

Results

Of 4379 citations, 5 retrospective cohort studies were included. Three studies reported shorter recurrence-free survival by 1 to 5 months with RBCT. Two studies found shorter disease-specific survival by 5 to 13 months with RBCT. Overall survival was reduced by 5 to 7 months with RBCT in 3 studies. All multivariable findings associated with RBCT could be readily overcome unmeasured confounding on sensitivity analysis. Confounding in baseline characteristics resulted in high risk of bias.

Conclusions

Imprecision, unmeasured confounding, small effect sizes, and overall low quality of the available literature result in uncertainty regarding the effect of transfusion on recurrence-free survival, disease-specific survival, and overall survival in patients undergoing surgery for pancreatic cancer. Randomized trials are needed to determine if there is a causal relationship between transfusion and survival after pancreatic resection.
The Nursing Professional Development Role in Fostering Professional Development, Leadership, and Academic Progression for New Graduate Registered Nurses
Authors: Shinners Jean , Africa Larissa , Meyer Donna
Published: June 2021

As the new graduate nurse transitions from academia to practice, they commit to lifelong learning to enhance their professional and personal growth. This article provides a comparison between bachelor of science in nursing and associate degree nursing nurses who participated in a multisite national nurse residency program between 2015 and 2019 in areas of professional development, leadership, and academic progression during their initial 3 years of practice. It also provides nursing professional development practitioners with strategies from two national experts to support new graduate nurses during early practice.
Evaluation of Pain in the Pediatric Emergency Department and the Request of Analgesia
Authors: Bergeron Jennifer , Bailey Benoit
Published: June 2021

Objectives

To determine the acute pain level associated with request for analgesia by children and their parents in the pediatric emergency department (ED) when pain was assessed by verbal numeric scale (VNS), visual analog scale (VAS), and verbal rating scale (VRS).

Methods

A secondary analysis of a prospective cohort study using a sample of children aged 8 to 17 presenting to the ED with acute pain. Patients and their parents were asked to quantify the child's pain on the VNS, VAS, and VRS. Scores for patients and parents who answered “yes” to the request of analgesia were compared with those responding “no.”

Results

A total of 202 patients aged 12.2 ± 2.6 years were enrolled. The median levels of pain associated with a request of analgesia and no request for analgesia by the patient were: 6.0 (4.0–7.4) and 5.0 (3.0–6.0) (Δ 1.0; 95% confidence interval [CI], 0.5–2.0) for the VNS; 5.7 (3.9–7.2) and 4.3 (2.6–5.8) (Δ 1.3; 95% CI, 0.6–1.9) for the VAS; and 2.0 (2.0–2.0) and 2.0 (1.0–2.0) (Δ 0.0; 95% CI, 0.0–0.0) for the VRS.

Conclusions

Children who requested analgesia had higher pain scores on the VNS and the VAS, than those who did not request analgesia. No difference was demonstrated with the VRS. The pain scores between the analgesia request categories could overlap. This suggests that children seen in the ED should be asked if they want analgesia to decrease their acute pain.
Therapeutic Risk Management for Violence: Chain Analysis of Other-directed Violent Ideation and Behavior
Authors: Borges Lauren M. , Barnes Sean M. , Nazem Sarra , Gerard Georgia R. , McGarity Suzanne , Clark Kaily , Matarazzo Bridget B. , Bahraini Nazanin H. , Wortzel Hal S.
Published: June 2021

Violence risk assessment is a requisite component of mental health treatment. Adhering to standards of care and ethical and legal requirements necessitates a cogent process for conducting, and then documenting, other-directed violence (ODV) risk screening, assessment, and management. In this 5-part series, we describe a model for achieving therapeutic risk management of the potentially violent patient, with essential elements involving: clinical interview augmented by structured screening or assessment tools; risk stratification in terms of temporality and severity; chain analysis to intervene on the functions of ODV ideation and behavior; and a personalized safety plan to mitigate/manage risk. In this fourth column of the series, we describe chain analysis as a critical tool for assessing and intervening on ODV ideation and behavior. We identify the pathways of reinforcement that can cause ODV to persist, and how to navigate potential barriers to completing ODV chains. Using a case example, we demonstrate how to apply chain analysis to ODV ideation and behavior and offer interventional strategies that can be used to disrupt the chain and ultimately reduce the risk for violence.
Commentary: Diagnostic Challenges in Evaluating Adolescents
Authors: Garakani Amir
Published: June 2021

Three cases presented in this issue highlight diagnostic challenges in evaluating adolescents, in particular those with a constellation of symptoms that includes hallucinations. These cases raise the question of the accuracy of patient reports and the importance of further exploring symptoms before rushing to a diagnosis or treatment. The first case involved an 18-year-old female patient with Cotard syndrome. She had the syndrome’s typical delusions and hallucinations, but her case was unusual because this syndrome is more common in adults and usually involves prominent mood symptoms. The second case involved a 14-year-old girl with depressive symptoms, suicidal ideas, and auditory and visual hallucinations, as well as sexually predatory behavior. This case was unusual in that girls and women are less commonly sexual predators although such behavior is more common among survivors of sexual abuse, as was the case with this patient. The authors believe that the patient’s “hallucinations” were more likely related to posttraumatic stress disorder and dissociation. The third case involved a 16-year-old girl diagnosed with schizophrenia and treated with antipsychotics based merely on her report of “visions” of demons but absent any auditory hallucinations, delusions, or thought disorder. The authors, consulting on the case, identified more prominent depression, anxiety, and trauma-related symptoms as a result of school bullying and concluded that the patient did not have schizophrenia. Only the patient in the first of these 3 cases actually met the criteria for a psychotic disorder and warranted medication treatment. These cases highlight the importance of a full differential diagnosis in evaluating adolescent patients presenting with what appear to be psychotic symptoms to avoid the harm that can occur in terms of stigma and unnecessary treatment with the risk of side effects from antipsychotic medications when an incorrect diagnosis is made.
Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus
Authors: Guardigni Viola , Toschi Alice , Badia Lorenzo , Rosselli Del Turco Elena , Salsi Eleonora , Cristini Francesco , Sighinolfi Laura , Fabbri Gabriele , Massari Marco , Cuomo Gianluca , Viale Pierluigi , Verucchi Gabriella
Published: June 2021

Objectives:

Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population.

Design:

We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017.

Methods:

We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer.

Results:

During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/μl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline.

Conclusion:

Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.
Safety Profile and Predictors of Aesthetic Outcomes After Prepectoral Breast Reconstruction With Meshed Acellular Dermal Matrix
Authors: Belmonte Briana M. , Campbell Chris A.
Published: June 2021

Introduction

Prepectoral acellular dermal matrix (ADM)-assisted breast reconstruction has demonstrated improved pain scores, faster return to full range of motion, and an appropriate postoperative safety profile when compared with cohorts with submuscular implant placement; however, there are limited data on aesthetic outcomes. Basic science biointegration research has previously demonstrated faster ADM incorporation with fenestrated compared with confluent ADM. We report the safety profile of anterior support meshed ADM prepectoral breast reconstruction and analyze predictive factors for aesthetic outcomes after gel implant placement.

Methods

All consecutive immediate staged prepectoral expander–to–implant breast reconstructions with more than 6 months of follow-up were compared with a partially submuscular cohort for demographics, comorbidities, and postoperative complications. All patients 1 to 3.5 years after gel implant placement were evaluated for the impact of clinical characteristics on aesthetic outcomes.

Results

Two hundred twenty-four prepectoral tissue expander placements were compared with 535 partially submuscular tissue expanders with no significant differences in demographics. There was increased wound dehiscence repaired in clinic and insignificantly decreased seromas with prepectoral expander placement. One hundred sixty breasts were reconstructed with gel implants, and 12 underwent autologous reconstruction during the conduct of the study. The remaining 21 patients were continuing expansion, and 3 succumbed to disease progression. Regression analysis of 86 breast reconstructions showed that a body mass index of greater than 30, fat grafting, and highly cohesive anatomic implants decreased rippling, whereas radiation increased capsular contracture (P < 0.05).

Conclusions

Prepectoral meshed ADM breast reconstruction has an equivalent safety profile to partially submuscular ADM-assisted reconstruction and early aesthetic ratings comparable with other published accounts of implant-based reconstruction. Radiated skin envelopes carry higher capsular contracture rates. Thin patients have a higher risk of visible rippling, whereas fat grafting and higher cohesivity implants are associated with less rippling.
Cost Analysis and National Trends in the Treatment of Dupuytren Contracture Comparing Collagenase Injection, Needle Fasciotomy, and Open Fasciectomy Procedures
Authors: Jain Abhishek , Tarabishy Sami , Carter Jordan , Gonzalez Gilberto , Herrera Fernando A.
Published: June 2021

Background

Dupuytren contracture (DC) is a common disorder characterized by progressive fibrosis of palmar fascia. This study analyzed cost trends of 3 common treatments for DC: fasciotomy, fasciectomy, and collagenase injection (CI)/cord manipulation.

Methods

The Vizient Clinical Data/Resource Manager electronic database was reviewed for all procedures for the treatment of DC at participating hospitals in the United States (US) from October 1, 2015, to September 1, 2019. Cases were placed into 1 of 3 categories: (1) CI, (2) needle fasciotomy (NF), and (3) open fasciectomy (OF). Total and direct costs were averaged for each procedure and compared nationally and regionally. Temporal trends and specific market share were analyzed. One-tailed t test and Pearson correlation analysis was performed (P < 0.05 and r > 0.9 or r < −0.9 was considered significant).

Results

A total of 22,974 total cases were identified. A total of 16,966 OF, 3962 NF, and 2046 CI were performed. There was a nearly a 4-fold increase in number of procedures to treat DC from 2015 to 2018. Market share percentage of each procedure stayed relatively similar over time. However, market share percentage differed between procedures. Needle fasciotomy had the lowest market share percentage approximately 7%. Collagenase injection had the highest average cost at US $4453.66 and was significantly higher than OF at US $3394.90 and NF at US $2010.75. Cost and distribution of procedures were further analyzed by geographic regions. In 2018, 32% of procedures performed were in the Northeastern US, 29% in the Midwestern US, 23% in the Southern US, and 16% in the Western US. Total number of Dupuytren procedures increased more than 300% in all regions across the US from 2015 to 2018. In every region, NF was the lowest cost intervention. Cost of OF and CI varied between regions and was often the most expensive intervention.

Conclusions

Treatment of DCs with NF seems to be the least costly treatment option. Needle fasciotomy seems to be the least commonly performed procedure. Regional data show variations in the cost of OF and CI. However, OF has the majority market share nationally and regionally. Although the cost of these procedures seems to vary regionally, the type of procedures being performed seem to be similar across regions.
Analysis of Pediatric Dog Bite Injuries at a Level 1 Trauma Center Over 10 Years
Authors: Reuter Muñoz Katherine D. , Powell Lauren E. , Andersen Emily S. , Nye Anthony D. , Powers Jeremy M. , Rhodes Jennifer , Pozez Andrea L.
Published: June 2021

Background

Dog bite injuries cause significant preventable patient morbidity and health care expenditure in children. This study aimed to characterize the patient and healthcare burden related to pediatric dog bite injuries at a level 1 trauma center.

Methods

This is a retrospective review of 356 pediatric patients who presented to Virginia Commonwealth University Pediatric Emergency Department between July 2007 and August 2017 after sustaining dog bite injuries. Demographic information, injury details, management, outcomes, and financial information were analyzed.

Results

Most pediatric dog bite injuries afflicted male children (55.6%), ages 6 to 12 years (45.7%), by a household dog (36.2%). The most common offending breed was a pit bull or pit bull mix (53.0%). Infants and grade schoolers were more likely to sustain bites to the head/face (P = 0.001). Usual management consisted of primary repair (75.9%), whereas approximately 25% of the patients required advanced reconstructive techniques. Most patients healed uneventfully, but prolonged antibiotics, additional wound care, or procedures were necessary in 8.4% of the patients. Hospital charges per patient averaged US $8830.70 and tended to be higher in the younger age groups. Insurance status was statistically associated with use of conscious sedation, surgical consult placement, and surgical repair.

Conclusions

Although most pediatric dog bite injuries in this study healed uneventfully from primary management in the emergency department, 25% required additional interventions. Furthermore, patient care for these injuries was associated with significant but potentially avoidable personal and financial burden to families. Our data reflect a need for safety education on animal care, behavior, and interaction.