Energy expenditure during nutritional rehabilitation: a scoping review to investigate hypermetabolism in individuals with anorexia nervosa.

BACKGROUND: Weight gain and nutritional rehabilitation are essential first steps to achieve medical stabilization in anorexia nervosa, and frequent resistance to weight gain requires patients to consume high kilocalorie loads. Adaptive hypometabolism is common when patients begin treatment, and rebound hypermetabolism is suspected to be a significant barrier to weight gain. The aim of this review was to summarize existing data describing metabolic changes in anorexia nervosa during weight restoration. The reported findings challenge current hypotheses of weight gain resistance and highlight key areas for future research. METHODS: Using scoping review guidelines, three databases were searched for studies investigating metabolic changes in anorexia nervosa before and after renourishment. Two reviewers systematically screened the titles and abstracts of 447 articles, and full-text versions of 106 studies were assessed for eligibility. A total of 36 studies were included for review. Data regarding the study description, sample population (including age, weight, BMI, duration of treatment, and caloric intake), and metabolic variable descriptions were extracted. RESULTS: Female patients with anorexia nervosa from studies across 13 countries were included. Across the studies, average BMI increased from 13.7 kg/m2 at admission to 17.57 kg/m2. Patients presented to treatment with clinically reduced energy expenditure levels. After varying levels of nutritional rehabilitation and weight restoration, measured energy expenditure increased significantly in 76% of the studies. Energy expenditure values at the second timepoint increased to the standard range for normal weight female teenagers and adults. Despite these increases, the studies do not indicate the presence of a hypermetabolic state during renourishment. Additionally, all studies including both measured and predicted energy expenditure reported that predicted energy expenditure overestimated measured values. CONCLUSION: This study provides a detailed evaluation of the literature investigating energy expenditure and metabolic rate in patients with anorexia nervosa before and following a period of renourishment. The findings from this review identify important gaps in the current beliefs of energy expenditure in anorexia nervosa and highlight a need for further exploration of metabolic alterations during weight restoration.

Nutritional rehabilitation and weight restoration are two primary goals of anorexia nervosa treatment that pose significant physiological and psychological challenges for patients. Patients often require high caloric loads to continue an adequate weight gain trajectory, but the underlying cause of weight gain resistance remains unknown. We completed a scoping review of research into energy expenditure and metabolic rate during treatment. Our search identified 447 relevant articles from academic databases, and 106 were deemed eligible after screening. We extracted data, including sample characteristics, kilocalorie intake, energy expenditure, and treatment information, from 36 studies. When individuals arrived for treatment, their energy expenditure was lower than that of individuals without an eating disorder due to the prolonged state of nutrient deprivation. After varying amounts of time and kilocalorie intake, most studies reported significant increases in energy expenditure. However, energy expenditure after a period of renourishment did not indicate an overactive metabolism (i.e., "hypermetabolism"). Funders should consider supporting exploration of additional factors that may be functioning as barriers to weight gain during treatment, in pursuit of making treatment more efficient and long-lasting. Additionally, future research describing metabolism in anorexia nervosa should provide more consistent methodologies, robust statical testing, and comprehensive reporting of dietary intake.

Long-Term Epidural Patching Outcomes and Predictors of Benefit in Patients With Suspected CSF Leak Nonconforming to ICHD-3 Criteria.

BACKGROUND AND OBJECTIVES: Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. METHODS: We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. RESULTS: The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. DISCUSSION: Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

Diagnosis and Treatment of Spontaneous Intracranial Hypotension: Role of Epidural Blood Patching.

Purpose of Review: This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. Recent Findings: SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. Summary: SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Topological state-space estimation of functional human brain networks.

We introduce an innovative, data-driven topological data analysis (TDA) technique for estimating the state spaces of dynamically changing functional human brain networks at rest. Our method utilizes the Wasserstein distance to measure topological differences, enabling the clustering of brain networks into distinct topological states. This technique outperforms the commonly used k-means clustering in identifying brain network state spaces by effectively incorporating the temporal dynamics of the data without the need for explicit model specification. We further investigate the genetic underpinnings of these topological features using a twin study design, examining the heritability of such state changes. Our findings suggest that the topology of brain networks, particularly in their dynamic state changes, may hold significant hidden genetic information.

Impact of Spinal CSF Leaks on Quality of Life and Mental Health and Long-Term Reversal by Surgical Closure.

Background and Objectives: Spontaneous intracranial hypotension (SIH) caused by a spinal CSF leak is a multisymptom syndrome, which can dramatically affect physical and mental health. However, systematic data on health-related quality of life (HRQoL) and mental health are scarce. We hypothesized that surgical treatment leads to significant and sustained improvements in HRQoL and mental health in patients with SIH. Methods: In this single-center cohort study, we prospectively collected HRQoL and mental health data in patients undergoing surgical closure of a spinal CSF leak from September 2020 to November 2022. EuroQoL (EQ-5D-5L), including the health state index (EQ-Index) and the visual analog scale (EQ-VAS), measured HRQoL. The 21-item version of the Depression Anxiety Stress Scales (DASS-21) measured symptoms of mental health. Follow-ups were performed 3 and 6 months postoperatively. Primary outcome was the change in EQ-Index, EQ-VAS, and DASS-21 subscales. Secondary outcome was the impact of baseline depression symptoms on HRQoL outcomes following surgery. Results: Seventy-four patients were included. EQ-VAS improved from 40 (interquartile range [IQR] 30-60) preoperatively to 70 (IQR 55-85) at 3 months and to 72 (IQR 60-88) at 6 months postoperatively (p < 0.001, respectively). EQ-Index increased from 0.683 (IQR 0.374-0.799) to 0.877 (0.740-0.943) at 3 months and to 0.907 (0.780-0.956) at 6 months postoperatively (p < 0.001, respectively). Depression, anxiety, and stress significantly improved after surgery. Preoperative depressive symptoms did not affect the HRQoL outcome. Discussion: The severe impact of a spinal CSF leak on HRQoL and mental health significantly improved after closure of the leak. Higher levels of depressive symptoms do not predict worse outcomes and should not discourage invasive treatment. Further systematic evaluation of outcomes, with special regard to quality of life, is needed, as it allows a comparison of symptom burden between SIH and more familiar diseases as well as a comparison of different treatment modalities in future studies.

Intestinal energy harvest is associated with post-bariatric surgery weight loss.

Background/Objectives: Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity; however, a significant subset of patients does not achieve expected weight loss or have substantial weight recurrence over time. The intestinal energy harvest is a potential determinant of varying weight loss outcomes, but with limited exploration. We assess the relationships between diet, intestinal energy harvest, and weight outcomes over 24 months in individuals who have undergone MBS. Subjects/Methods: Calorie absorption was assessed with bomb calorimetry and dietary questionnaires before and after MBS. Within a total of 67 patients, fecal energy density was measured in 67, 56, 60, 67, 44, 47 samples at 0, 1, 6, 12, 18, and 24 months, respectively. Multivariate regression was developed to identify potential weight loss predictors, and random forest algorithms were employed to forecast weight results based on intestinal energy harvest. Results: Intestinal energy harvest enhanced the predictability of patient weight loss outcomes with random forest models. A notable difference in relative fecal energy content was observed between patients experiencing optimal and sub-optimal weight loss (p<0.01). Prior to MBS, an increased energy content in feces (indicating less energy absorption) is associated with greater weight loss after the operation. Associations between diet and energy harvest were insignificant. Conclusion: MBS changes energy harvest capacity post-surgery. A higher relative fecal energy content (lower energy absorption) at one month correlates with better weight loss outcomes at 6M, 12M, 18M and 24M post-MBS. Findings may guide the development of diagnostic tools and treatment guidelines for patients at risk of suboptimal weight loss outcomes. CLINICAL TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03065426).

Progressive superficial siderosis despite complete remission of intracranial hypotension symptoms following epidural patching: Case report.

Spontaneous intracranial hypotension (SIH) commonly results from ventral spinal cerebrospinal fluid (CSF) leaks and epidural patches are advocated as first-line treatment. Complications such as superficial siderosis can arise but have previously been reported only in the context of long-term persistent, ongoing, CSF leak and SIH. We report a case of a patient with SIH from a ventral spinal CSF leak that was treated with epidural patching and experienced complete resolution of SIH. Four years later SIH symptoms recurred, and brain magnetic resonance imaging unexpectedly showed the interval accumulation of hemosiderin pigmentation on the cerebellum and brainstem during the period when the patient was without symptoms of SIH. This case uniquely demonstrates the progression of superficial siderosis despite the apparent resolution of SIH. Our findings suggest two divergent pathophysiological outcomes from spinal ventral dural tear: (1) CSF loss causing SIH; and (2) persistent low-level bleeding arising from the spinal dural tear leading to superficial siderosis. These divergent pathophysiologies had a discordant response to epidural patching. Epidural patching successfully treated the SIH but did not prevent the progression of superficial siderosis, indicating that some patients may require more than epidural patching despite symptom resolution. This case highlights the need for post-treatment monitoring protocols in patients with ventral spinal CSF leaks and SIH and raises important questions about the adequacy of epidural patching in certain SIH cases arising from ventral spinal CSF leak.

Gut microbiota are differentially correlated with blood pressure status in African American collegiate athletes: A pilot study.

Hypertension (HTN) is common among athletes and the most recent epidemiologic data reports that cardiovascular (CV) sudden death is significantly greater in African Americans (AAs). Gut microbial dysbiosis (a poorly diverse stool microbial profile) has been associated with HTN in sedentary people but microbial characteristics of athletes with HTN are unknown. Our purpose was to differentiate microbiome characteristics associated with BP status in AA collegiate athletes. Thirty AA collegiate athletes were stratified by normal BP (systolic BP (SBP) ≤130 mmHg; n = 15) and HTN (SBP ≥130 mmHg; n = 15). 16S rRNA gene sequencing was performed on stool samples to identify microbes at the genus level. We did not observe any significant differences in alpha diversity, but beta diversity was different between groups. Principal coordinate analysis was significantly different (PERMANOVA, p < 0.05, R = 0.235) between groups. Spearman rank correlations showed a significant (p < 0.05) correlation between systolic BP and abundances for Adlercreutzia (R = 0.64), Coprococcus (R = 0.49), Granulicatella (R = 0.63), and Veillonella (R = 0.41). Gut microbial characteristics were associated with differentially abundant microbial genus' and BP status. These results will direct future studies to define the functions of these microbes associated with BP in athletes.

Racial Microaggressions and Anti-Racism: A Review of the Literature with Implications for School-Based Interventions and School Psychologists.

Many racial-ethnic minoritized individuals are repeatedly exposed to subtle actions reflecting racial slights, termed racial microaggressions (RMAs), which are associated with adjustment problems in early adult and adult populations. Early adolescence represents a unique developmental period when minoritized youth begin their racial-ethnic identity exploration and are subjected to stereotypes and prejudice, thereby making them vulnerable to RMAs. Based upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, a systematic literature search, screening and review of RMA literature focusing on high schoolers and younger youth was conducted and yielded 54 publications. This paper reviewed the publications and identified gaps in the field such as the need for systematic research on early adolescents including the frequency and severity of RMAs and the important contributions of peers, parents and teachers for RMA victims, and the need for more evidence-based programming for middle schoolers. Findings suggest that developing school-based microaggression anti-racism programs is clearly needed for minoritized and White youth.

Mechanism of chronic iatrogenic CSF leak following dural puncture-ventral dural leak: case report.

BACKGROUND: Postdural puncture headache has been traditionally viewed as benign, self-limited, and highly responsive to epidural blood patching (EBP) when needed. A growing body of data from patients experiencing unintended dural puncture (UDP) in the setting of attempted labor epidural placement suggests a minority of patients will have more severe and persistent symptoms. However, the mechanisms accounting for the failure of EBP following dural puncture remain obscure. An understanding of these potential mechanisms is critical to guide management decisions in the face of severe and persistent cerebrospinal fluid (CSF) leak. CASE PRESENTATION: We report the case of a peripartum patient who developed a severe and persistent CSF leak unresponsive to multiple EBPs following a UDP during epidural catheter placement for labor analgesia. Lumbar MRI revealed a ventral rather than dorsal epidural fluid collection suggesting that the needle had crossed the thecal sac and punctured the ventral dura, creating a puncture site not readily accessible to blood injected in the dorsal epidural space. The location of this persistent ventral dural defect was confirmed with digital subtraction myelography, permitting a transdural surgical exploration and repair of the ventral dura with resolution of the severe intracranial hypotension. CONCLUSIONS: A ventral rather than dorsal dural puncture is one mechanism that may contribute to both severe and persistent spinal CSF leak with resulting intracranial hypotension following a UDP.

Giardia Antagonizes Beneficial Functions of Indigenous and Therapeutic Intestinal Bacteria during Malnutrition.

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

Eating disorders: are gut microbiota to blame?

Gut microbiota could be involved in weight regulation and impact brain function via the gut-brain axis. Moreover, gut microbiota may impact the development of eating disorders (EDs) since they are characterized by weight-related concerns and symptoms and may represent a therapeutic target if future research can establish a causal link.

A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.

BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.

Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer.

Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate that bariatric surgery reduces TNBC risk, while evidence is limited or conflicted for weight loss via low-fat diet (LFD) or calorie restriction (CR). Using a murine model of obesity-driven TNBC, we compared the antitumor effects of vertical sleeve gastrectomy (VSG) with LFD, chronic CR, and intermittent CR. Each intervention generated weight and fat loss and suppressed tumor growth relative to obese mice (greatest suppression with CR). VSG and CR regimens exerted both similar and unique effects, as assessed using multiomics approaches, in reversing obesity-associated transcript, epigenetics, secretome, and microbiota changes and restoring antitumor immunity. Thus, in a murine model of TNBC, bariatric surgery and CR each reverse obesity-driven tumor growth via shared and distinct antitumor mechanisms, and CR is superior to VSG in reversing obesity's procancer effects.

Postoperative opioid prescribing patients with diabetes: Opportunities for personalized pain management.

BACKGROUND: Opioids are commonly prescribed for postoperative pain, but may lead to prolonged use and addiction. Diabetes impairs nerve function, complicates pain management, and makes opioid prescribing particularly challenging. METHODS: This retrospective observational study included a cohort of postoperative patients from a multisite academic health system to assess the relationship between diabetes, pain, and prolonged opioid use (POU), 2008-2019. POU was defined as a new opioid prescription 3-6 months after discharge. The odds that a patient had POU was assessed using multivariate logistic regression controlling for patient factors (e.g., demographic and clinical factors, as well as prior pain and opiate use). FINDINGS: A total of 43,654 patients were included, 12.4% with diabetes. Patients with diabetes had higher preoperative pain scores (2.1 vs 1.9, p<0.001) and lower opioid naïve rates (58.7% vs 68.6%, p<0.001). Following surgery, patients with diabetes had higher rates of POU (17.7% vs 12.7%, p<0.001) despite receiving similar opioid prescriptions at discharge. Patients with Type I diabetes were more likely to have POU compared to other patients (Odds Ratio [OR]: 2.22; 95% Confidence Interval [CI]:1.69-2.90 and OR:1.44, CI: 1.33-1.56, respectively). INTERPRETATION: In conclusion, surgical patients with diabetes are at increased risk for POU even after controlling for likely covariates, yet they receive similar postoperative opiate therapy. The results suggest a more tailored approach to diabetic postoperative pain management is warranted.

Gut Microbial Changes Following Fecal Microbiota Transplantation for D-Lactic Acidosis in Two Children.

D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA.

Prediction of opioid-related outcomes in a medicaid surgical population: Evidence to guide postoperative opiate therapy and monitoring.

BACKGROUND: Treatment of surgical pain is a common reason for opioid prescriptions. Being able to predict which patients are at risk for opioid abuse, dependence, and overdose (opioid-related adverse outcomes [OR-AE]) could help physicians make safer prescription decisions. We aimed to develop a machine-learning algorithm to predict the risk of OR-AE following surgery using Medicaid data with external validation across states. METHODS: Five machine learning models were developed and validated across seven US states (90-10 data split). The model output was the risk of OR-AE 6-months following surgery. The models were evaluated using standard metrics and area under the receiver operating characteristic curve (AUC) was used for model comparison. We assessed calibration for the top performing model and generated bootstrap estimations for standard deviations. Decision curves were generated for the top-performing model and logistic regression. RESULTS: We evaluated 96,974 surgical patients aged 15 and 64. During the 6-month period following surgery, 10,464 (10.8%) patients had an OR-AE. Outcome rates were significantly higher for patients with depression (17.5%), diabetes (13.1%) or obesity (11.1%). The random forest model achieved the best predictive performance (AUC: 0.877; F1-score: 0.57; recall: 0.69; precision:0.48). An opioid disorder diagnosis prior to surgery was the most important feature for the model, which was well calibrated and had good discrimination. CONCLUSIONS: A machine learning models to predict risk of OR-AE following surgery performed well in external validation. This work could be used to assist pain management following surgery for Medicaid beneficiaries and supports a precision medicine approach to opioid prescribing.

Erratum to 'successful epidural fibrin glue patch to treat intracranial hypotension in a patient with bacteraemia and malignancy' [BJAOpen 4 (2022) 100091].

[This corrects the article DOI: 10.1016/j.bjao.2022.100091.].

An extensive ß1-adrenergic receptor gene signaling network regulates molecular remodeling in dilated cardiomyopathies.

We investigated the extent, biologic characterization, phenotypic specificity, and possible regulation of a ß1-adrenergic receptor-linked (ß1-AR-linked) gene signaling network (ß1-GSN) involved in left ventricular (LV) eccentric pathologic remodeling. A 430-member ß1-GSN was identified by mRNA expression in transgenic mice overexpressing human ß1-ARs or from literature curation, which exhibited opposite directional behavior in interventricular septum endomyocardial biopsies taken from patients with beta-blocker-treated, reverse remodeled dilated cardiomyopathies. With reverse remodeling, the major biologic categories and percentage of the dominant directional change were as follows: metabolic (19.3%, 81% upregulated); gene regulation (14.9%, 78% upregulated); extracellular matrix/fibrosis (9.1%, 92% downregulated); and cell homeostasis (13.3%, 60% upregulated). Regarding the comparison of ß1-GSN categories with expression from 19,243 nonnetwork genes, phenotypic selection for major ß1-GSN categories was exhibited for LV end systolic volume (contractility measure), ejection fraction (remodeling index), and pulmonary wedge pressure (wall tension surrogate), beginning at 3 months and persisting to study completion at 12 months. In addition, 121 lncRNAs were identified as possibly involved in cis-acting regulation of ß1-GSN members. We conclude that an extensive 430-member gene network downstream from the ß1-AR is involved in pathologic ventricular remodeling, with metabolic genes as the most prevalent category.