Development of a Risk Stratification Model for Pre-liver-Transplant Screening Colonoscopy.

BACKGROUND AND AIMS: Colonoscopies are routinely obtained before liver transplantation, although their utility is a highly debated topic in the literature. We aimed to determine the risk factors in patients with decompensated cirrhosis (DC) for post-colonoscopy complications (PCC). MATERIALS AND METHODS: We performed a single-center retrospective study of patients with DC undergoing colonoscopy as part of their pre-liver-transplant evaluation. The primary composite outcome was defined as a complication occurring within 30 days of the colonoscopy. Complications included acute renal failure, new or worsening ascites or hepatic encephalopathy, gastrointestinal bleeding, or any cardiopulmonary or infectious complication. Logistic regression analysis was utilized to derive a risk score in predicting the primary composite outcome. RESULTS: The strongest predictors of post-colonoscopy complication were MELD-Na ≥21 [aOR 4.0026 ( P =0.0050)] and history of any infection in the 30 days before colonoscopy [aOR 8.4345 ( P =0.0093)]. The area under the receiver operating characteristic curve of the final model was 0.78. The predicted risk of any complication at the lowest quartile was 16.2% to 39.4%, and the observed risk was 30.6% (95% CI: 15.5-45.6%), while the predicted risk at the highest quartile was 71.9% to 97.1%, and the observed risk was 81.3% (95% CI: 67.7-95%). CONCLUSION: In this cohort of patients with DC undergoing colonoscopy for pre-liver-transplant evaluation, a history of ascites, spontaneous bacterial peritonitis, and MELD-Na were found to be predictive of PCC. This risk score may help to predict PCC in patients with DC undergoing a pre-transplant colonoscopy. External validation is recommended.

Proposed dietary recommendations for iron overload: a guide for physician practice.

PURPOSE OF REVIEW: Iron overload disorders such as hemochromatosis involve unregulated absorption of dietary iron, leading to excessive iron accumulation in multiple organs. Phlebotomy is the standard of care for removal of excess iron, but dietary modification is not standardized in practice. The purpose of this article is to help standardize hemochromatosis diet counseling based on commonly asked patient questions. RECENT FINDINGS: The clinical benefit regarding dietary modification in iron overload patients is limited due to lack of large clinical trials, but preliminary results are promising. Recent studies suggest diet modification could reduce iron burden in hemochromatosis patients resulting in less annual phlebotomy as supported through small patient studies, concepts of physiology, and animal studies. SUMMARY: This article is a guide for physicians to counsel hemochromatosis patients based on commonly asked questions such as foods to avoid, foods to consume, use of alcohol, and use of supplements. The goal of this guide is to help standardize hemochromatosis diet counseling to reduce phlebotomy amount in patients. Standardization of diet counseling could help facilitate future patient studies to analyze the clinical significance.

Preoperative echocardiography as a prognostic tool for liver transplant in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) presents with a hypertrophied left ventricle (LV). It is often associated with LV outflow tract obstruction (LVOTO) and a risk for sudden death. This study aimed to describe outcomes of patients with HCM who underwent liver transplant (LT). METHODS: A retrospective review was conducted for patients diagnosed with HCM undergoing LT. Patient characteristics, preoperative echocardiography results, HCM risk of sudden cardiac death prediction model score, and 5-year mortality were examined. A univariable Cox proportional hazards model was used to evaluate the association between risk factors and 5-year mortality. All tests were two-sided with the alpha level set at .05. RESULTS: Twenty-nine patients were included in the analysis. Six patients (21%) had a perioperative cardiopulmonary complication. The 5-year survival rate was 61% (95% CI, 45-82). The analyzed risk factors showed that 5-year post-LT survival was significantly predicted by maximal LV outflow tract gradient at rest > 60 mmHg (hazard ratio, 1.04 [95% CI, 1.01-1.06]). CONCLUSIONS: Preoperative LV outflow tract resting gradient > 60 mmHg was associated with 5-year post-LT mortality. The results suggest the severity of LVOTO identified by echocardiography is a prognostic tool for patients with HCM after LT.

Abnormal findings on abdominopelvic cross-sectional imaging in patients with microscopic colitis: a retrospective, multicenter study.

OBJECTIVES: Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS: This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS: 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS: Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Incidentalomas are associated with an increase in liver transplantation in patients with cirrhosis: a single-center retrospective study.

BACKGROUND: Incidentalomas, defined as incidental findings on imaging, are a growing concern. Our aim was to determine the impact and outcomes of extrahepatic incidentalomas on liver transplantation. METHODS: Patients at a large liver transplant center, who had an initial MRI for hepatocellular carcinoma screening between January 2004 and March 2020 were identified. Clinical data were collected retrospectively. Survival analysis, utilizing Kaplan Meier estimates and Cox proportional hazards regression analysis, was utilized to determine factors associated with liver transplantation. RESULTS: 720 patients were included. NASH (24.9%), HCV (22.1%) and alcohol (20.6%) were the most common causes of cirrhosis. 79.7% of patients had an extrahepatic incidentaloma. Older age and having received a liver transplant by the end of the study were associated with an incidentaloma. MELD was not associated with the presence of an incidentaloma. On univariate Cox proportional hazards regression, male sex, history of moderate alcohol use, smoking history, MELD, and incidentalomas were predictors of liver transplantation. On multivariate analysis, only MELD and the presence of an incidentaloma were found to be significant. Discovery of an incidentaloma was associated with a 30% increase in the risk of liver transplantation. Median time to transplantation did not differ based on the presence on an incidentaloma. Patients with cirrhosis from alcohol or HCV had a significantly shorter median time to transplantation than those with NASH. Renal and pancreatic lesions comprised 91% of all incidentalomas. CONCLUSIONS: In this single-center retrospective study, extrahepatic incidentalomas were common in patients with cirrhosis. The finding of an incidentaloma was associated with a higher risk of liver transplantation despite a similar median time to transplantation if no incidentaloma was discovered.

Lymphocytic Esophagitis: Assessing Risk Factors and Clinical Outcomes.

BACKGROUND: Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited. AIM: To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis. METHODS: This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed. RESULTS: Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02-1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4-4.9, p = 0.001), statin use (2.2, 95% CI 1.2-4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08-5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54-12.8, p = 0.0001). CONCLUSIONS: Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy.

Creation of a score to predict risk of high conscious sedation requirements in patients undergoing endoscopy.

BACKGROUND AND AIMS: The administration of intravenous conscious sedation to patients undergoing GI endoscopy carries a risk of cardiopulmonary adverse events. Our study aim was to create a score that stratifies the risk of occurrence of either high-dose conscious sedation requirements or a failed procedure. METHODS: Patients receiving endoscopy via endoscopist-directed conscious sedation were included. The primary outcome was occurrence of sedation failure, which was defined as one of the following: (1) high-dose sedation, (2) the need for benzodiazepine/narcotic reversal agents, (3) nurse-documented poor patient tolerance to the procedure, or (4) aborted procedure. High-dose sedation was defined as >10 mg of midazolam and/or >200 µg of fentanyl or the meperidine equivalent. Patients with sedation failure (n = 488) were matched to controls (n = 976) without a sedation failure by endoscopist and endoscopy date. RESULTS: Significant associations with sedation failure were identified for age, sex, nonclonazepam benzodiazepine use, opioid use, and procedure type (EGD, colonoscopy, or both). Based on these 5 variables, we created the high conscious sedation requirements (HCSR) score, which predicted the risk of sedation failure with an area under the curve of 0.70. Compared with the patients with a risk score of 0, risk of a sedation failure was highest for patients with a score ≥3.5 (odds ratio, 17.31; P = 2 × 10-14). Estimated area under the curve of the HCSR score was 0.68 (95% confidence interval, 0.63-0.72) in a validation series of 250 cases and 250 controls. CONCLUSIONS: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy.

Diagnosis and Management of Genetic Iron Overload Disorders.

Iron overload disorders lead to excess iron deposition in the body, which can occur as a result of genetic or secondary causes. Genetic iron overload, referred to as hereditary hemochromatosis, may present as a common autosomal recessive mutation or as one of several uncommon mutations. Secondary iron overload may result from frequent blood transfusions, exogenous iron intake, or certain hematological diseases such as dyserythropoietic syndrome or chronic hemolytic anemia. Iron overload may be asymptomatic, or may present with significant diseases of the liver, heart, endocrine glands, joints, or other organs. If treated appropriately prior to end-organ damage, life expectancy has been shown to be similar compared to matched populations. Alongside clinical assessment, diagnostic studies involve blood tests, imaging, and in some cases liver biopsy. The mainstay of therapy is periodic phlebotomy, although oral chelation is an option for selected patients.

Serum Electrolyte Levels and Outcomes in Patients Hospitalized with Hepatic Encephalopathy.

INTRODUCTION AND AIMS: Serum electrolyte derangements are common in patients with decompensated cirrhosis hospitalized for hepatic encephalopathy. There are limited data describing the association between electrolyte levels and outcomes in hepatic encephalopathy. We assessed the association between initial serum electrolyte values and outcomes in patients with hepatic encephalopathy. MATERIAL AND METHODS: A total of 385 consecutive patients hospitalized with encephalopathy were included in the study. Baseline electrolyte levels (sodium, potassium, chloride, bicarbonate, calcium and phosphorus) were measured at the time of admission and assessed for association with outcomes, which included survival, admission to the intensive care unit, requirement for mechanical ventilation, and length of hospital stay. P-values ≤ 0.0083 were considered significant after adjustment for multiple testing. RESULTS: In unadjusted analysis, significant associations were identified regarding both bicarbonate and phosphorus (admission to intensive care unit), and calcium (mechanical ventilation); however these findings weakened and no longer approached statistical significance when adjusting for confounding variables. No other significant associations between serum electrolyte measurements and outcomes were observed. CONCLUSIONS: Our findings suggest that in patients hospitalized with encephalopathy, serum electrolyte measurements are not strong predictors of patient outcome.

Abnormal Liver Enzymes.

Abnormal liver enzymes are frequently encountered in primary care offices and hospitals and may be caused by a wide variety of conditions, from mild and nonspecific to well-defined and life-threatening. Terms such as "abnormal liver chemistries" or "abnormal liver enzymes," also referred to as transaminitis, should be reserved to describe inflammatory processes characterized by elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Although interchangeably used with abnormal liver enzymes, abnormal liver function tests specifically denote a loss of synthetic functions usually evaluated by serum albumin and prothrombin time. We discuss the entities that most commonly cause abnormal liver enzymes, specific patterns of enzyme abnormalities, diagnostic modalities, and the clinical scenarios that warrant referral to a hepatologist.

Update on the Diagnosis and Treatment of Cholangiocarcinoma.

PURPOSE OF REVIEW: Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates. RECENT FINDINGS: Cholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease. This article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center.

INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 - 1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. CONCLUSIONS: In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Colonoscopy bowel preparation quality improvement for patients with decompensated cirrhosis undergoing evaluation for liver transplantation.

BACKGROUND/AIMS: Inadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education. METHODS: A total of 121 patients undergoing evaluation at our institution prior to implementation of the quality improvement initiative and 91 patients undergoing evaluation after implementation were included. The initiative was an educational intervention via a 6-minute colonoscopy and split-prep bowel preparation educational video during the initial liver transplantation evaluation visit for all patients with scheduled colonoscopy. RESULTS: Inadequate bowel preparation was observed in 36 patients (29.8%) in the pre-intervention period compared to 29 patients (31.9%) in the post-intervention period. This corresponded to a lack of a significant difference in both single-variable analysis and multivariable analysis. Of note, there was a significantly higher rate of inadequate bowel preparation as ascites worsened (P=.028). CONCLUSION: Patient educational video failed to improve bowel preparations in patients undergoing colonoscopy with decompensated cirrhosis.

Patent foramen ovale in liver transplant recipients does not negatively impact short-term outcomes.

AIM: Patent foramen ovale (PFO) is a common atrial septal defect that is largely asymptomatic and often undiagnosed. The impact of a PFO in patients undergoing liver transplantation (LT) is unknown. OBJECTIVE: Assess the impact of PFO and physiologic intrapulmonary shunt (IPS) on the perioperative outcomes of patients who underwent LT. METHODS: We performed a retrospective, intention-to-treat analysis of patients with PFO and controls without PFO who underwent LT at Mayo Clinic in Florida between 2008 and 2013. Patients with physiologic IPS were also analyzed. The cohorts were compared for baseline characteristics, length of stay in the intensive care unit (ICU), postoperative oxygen requirements, 30-d cerebrovascular accidents, and mortality. RESULTS: Of the 935 patients who underwent LT, 10.4% had proven PFO by pre-LT echocardiogram. Control patients (n = 101) were statistically older than PFO and IPS (n = 56) patients, but similar in sex, BMI, Model for End-stage Liver Disease score, American Society of Anesthesiologist score, and left ventricular ejection fraction. PFO and IPS patients had similar length of stay in the ICU, mechanical ventilation times, post-LT oxygen requirements, and 30-d mortality compared to controls. Subgroup analysis showed similar outcomes for large PFO and IPS patients to controls. CONCLUSIONS: The presence of PFO did not have a negative impact on perioperative LT outcomes.

Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis.

PURPOSE: Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction. METHODS: In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') > 15, and 3) global longitudinal strain (GLS) < 18. Multivariable logistic regression was utilized to identify predictors of cardiac dysfunction. RESULTS: 582 patients (median age 57 years, 61.2% male) were included. The frequency of LVEF < 55%, E/e' > 15 and GLS < 18 was 9.0% (52/580), 9.6% (51/534) and 20.2% (25/124), respectively. In multivariable analysis, non-White race, age, and hypertension were associated with E/e' > 15. No specific HFE genetic mutation was associated with LVEF < 55%. A history of myocardial infarction was strongly associated with both LVEF < 55% and E/e' > 15. In patients with LVEF ≥ 55%, the C282Y/H63D genetic mutation was associated with reduced likelihood of E/e' > 15, p = 0.024. Patients with C282Y/H63D had a higher frequency of myocardial infarction. Smoking and alcohol use were significantly associated with GLS < 18 in unadjusted analysis. CONCLUSION: We found the traditional risk factors of male sex, and history of myocardial infarction or heart failure, were associated with a reduced LVEF, irrespective of the underlying HFE genetic mutation. Patients with a C282Y/H63D genetic mutation had a higher frequency of myocardial infarction, yet this mutation was associated with reduced odds of diastolic dysfunction compared to other genetic mutations in patients with a normal LVEF.

Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. METHODS: We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. RESULTS: Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. CONCLUSIONS: Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.

Brain state transition analysis using ultra-fast fMRI differentiates MCI from cognitively normal controls.

Purpose: Conventional resting-state fMRI studies indicate that many cortical and subcortical regions have altered function in Alzheimer's disease (AD) but the nature of this alteration has remained unclear. Ultrafast fMRIs with sub-second acquisition times have the potential to improve signal contrast and enable advanced analyses to understand temporal interactions between brain regions as opposed to spatial interactions. In this work, we leverage such fast fMRI acquisitions from Alzheimer's disease Neuroimaging Initiative to understand temporal differences in the interactions between resting-state networks in 55 older adults with mild cognitive impairment (MCI) and 50 cognitively normal healthy controls. Methods: We used a sliding window approach followed by k-means clustering. At each window, we computed connectivity i.e., correlations within and across the regions of the default mode, salience, dorsal attention, and frontoparietal network. Visual and somatosensory networks were excluded due to their lack of association with AD. Using the Davies-Bouldin index, we identified clusters of windows with distinct connectivity patterns, also referred to as brain states. The fMRI time courses were converted into time courses depicting brain state transition. From these state time course, we calculated the dwell time for each state i.e., how long a participant spent in each state. We determined how likely a participant transitioned between brain states. Both metrics were compared between MCI participants and controls using a false discovery rate correction of multiple comparisons at a threshold of. 0.05. Results: We identified 8 distinct brain states representing connectivity within and between the resting state networks. We identified three transitions that were different between controls and MCI, all involving transitions in connectivity between frontoparietal, dorsal attention, and default mode networks (p<0.04). Conclusion: We show that ultra-fast fMRI paired with dynamic functional connectivity analysis allows us to capture temporal transitions between brain states. Most changes were associated with transitions between the frontoparietal and dorsal attention networks connectivity and their interaction with the default mode network. Although future work needs to validate these findings, the brain networks identified in our work are known to interact with each other and play an important role in cognitive function and memory impairment in AD.

Activation of noradrenergic locus coeruleus and social behavior network nuclei varies with duration of male midshipman advertisement calls.

Vocal courtship is vital to the reproductive success of many vertebrates and is therefore a highly-motivated behavioral state. Catecholamines have been shown to play an essential role in the expression and maintenance of motivated vocal behavior, such as the coordination of vocal-motor output in songbirds. However, it is not well-understood if this relationship applies to anamniote vocal species. Using the plainfin midshipman fish model, we tested whether specific catecholaminergic (i.e., dopaminergic and noradrenergic) nuclei and nodes of the social behavior network (SBN) are differentially activated in vocally courting (humming) versus non-humming males. Herein, we demonstrate that tyrosine hydroxylase immunoreactive (TH-ir) neuron number in the noradrenergic locus coeruleus (LC) and induction of cFos (an immediate early gene product and proxy for neural activation) in the preoptic area differentiated humming from non-humming males. Furthermore, we found relationships between activation of the LC and SBN nuclei with the total amount of time that males spent humming, further reinforcing a role for these specific brain regions in the production of motivated reproductive-related vocalizations. Finally, we found that patterns of functional connectivity between catecholaminergic nuclei and nodes of the SBN differed between humming and non-humming males, supporting the notion that adaptive behaviors (such as the expression of advertisement hums) emerge from the interactions between various catecholaminergic nuclei and the SBN.

Increased rates of spinal fusion surgery in patients with hereditary hemochromatosis: a five-year propensity matched cohort analysis.

OBJECT: Spinal arthropathy is associated with hereditary hemochromatosis and has been linked to calcium pyrophosphate dehydrate crystal deposition (CPPD) which resembles ankylosing spondylitis on radiograph, yet lacks clinical findings of inflammatory spinal arthritis. The aim of our study was to assess the use of spinal surgery and its outcomes in the US inpatient population with hereditary hemochromatosis from 2012 to 2016 by using the US Nationwide Inpatient Sample (NIS) database. METHODS: The observational retrospective cohort study uses the NIS 2012 to 2016. All patients with hereditary hemochromatosis were included using International Classification of Diseases 9th and 10th revisions, Clinical Modification codes. The cohort was stratified according to having undergone spinal surgery and substratified by the type of surgery. The primary outcome was determining the use of spinal surgery in patients with hereditary hemochromatosis. Secondary outcomes were determining length of hospital stay and total hospital charges and costs. RESULTS: A total of 39 780 patients with hereditary hemochromatosis were identified and propensity matched to nonhereditary hemochromatosis controls. The mean patient age was 61 years, and 65% were females. For the primary outcome patients with hereditary hemochromatosis underwent significantly more spinal fusion surgery compared to patients without hereditary hemochromatosis odds of 2.13 (P = 0.05). While there was no difference in mean LOS, or costs, patients with hereditary hemochromatosis had higher hospital charges. CONCLUSION: Hereditary hemochromatosis is associated with higher odds of spinal fusion. It is a major complication not improved by phlebotomy, and there are currently no therapies to prevent this joint disease.