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.

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.

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.

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.

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.

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.

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.

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.

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.].

Preoperative Versus Perioperative Risk Factors for Delayed Pain and Opioid Cessation After Total Joint Arthroplasty: A Prospective Cohort Study.

INTRODUCTION: The evolution of pre- versus postoperative risk factors remains unknown in the development of persistent postoperative pain and opioid use. We identified preoperative versus comprehensive perioperative models of delayed pain and opioid cessation after total joint arthroplasty including time-varying postoperative changes in emotional distress. We hypothesized that time-varying longitudinal measures of postoperative psychological distress, as well as pre- and postoperative use of opioids would be the most significant risk factors for both outcomes. METHODS: A prospective cohort of 188 patients undergoing total hip or knee arthroplasty at Stanford Hospital completed baseline pain, opioid use, and emotional distress assessments. After surgery, a modified Brief Pain Inventory was assessed daily for 3 months, weekly thereafter up to 6 months, and monthly thereafter up to 1 year. Emotional distress and pain catastrophizing were assessed weekly to 6 months, then monthly thereafter. Stepwise multivariate time-varying Cox regression modeled preoperative variables alone, followed by all perioperative variables (before and after surgery) with time to postoperative opioid and pain cessation. RESULTS: The median time to opioid and pain cessation was 54 and 152 days, respectively. Preoperative total daily oral morphine equivalent use (hazard ratio-HR 0.97; 95% confidence interval-CI 0.96-0.98) was significantly associated with delayed postoperative opioid cessation in the perioperative model. In contrast, time-varying postoperative factors: elevated PROMIS (Patient-Reported Outcomes Measurement Information System) depression scores (HR 0.92; 95% CI 0.87-0.98), and higher Pain Catastrophizing Scale scores (HR 0.85; 95% CI 0.75-0.97) were independently associated with delayed postoperative pain resolution in the perioperative model. CONCLUSIONS: These findings highlight preoperative opioid use as a key determinant of delayed postoperative opioid cessation, while postoperative elevations in depressive symptoms and pain catastrophizing are associated with persistent pain after total joint arthroplasty providing the rationale for continued risk stratification before and after surgery to identify patients at highest risk for these distinct outcomes. Interventions targeting these perioperative risk factors may prevent prolonged postoperative pain and opioid use.

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.

Longer-Term Weight Loss Outcomes Are Not Primarily Driven by Diet Following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Metabolic and bariatric surgery (MBS) is the most effective long-term treatment for Class III obesity. Reduced dietary intake is considered a behavioral driver of post-surgical weight loss, but limited data have examined this association. Therefore, this study examined prospective, longitudinal relationships between dietary intake and weight loss over 24 months following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Relationships between weight loss and dietary intake were examined using a validated 24-h dietary recall method. Associations between total energy/macronutrient intake and weight loss outcomes were assessed at 12-, 18-, and 24-months following MBS, defining patients as "responders" and "suboptimal responders". Consistent with previous literature, 12-month responders and suboptimal responders showed significant associations between weight loss and energy (p = 0.018), protein (p = 0.002), and total fat intake (p = 0.005). However, this study also revealed that many of these associations are no longer significant 24 months post-MBS (p > 0.05), despite consistent weight loss trends. This study suggests a short-term signal between these dietary factors and weight loss outcomes 12 months post-MBS; however, this signal does not persist beyond 12 months. These results are essential for interpreting and designing clinical studies measuring long-term post-surgical weight loss outcomes.

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.