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Arteriosclerosis, Thrombosis, and... Mar 2020The aortic wall is composed of highly dynamic cell populations and extracellular matrix. In response to changes in the biomechanical environment, aortic cells and... (Review)
Review
The aortic wall is composed of highly dynamic cell populations and extracellular matrix. In response to changes in the biomechanical environment, aortic cells and extracellular matrix modulate their structure and functions to increase aortic wall strength and meet the hemodynamic demand. Compromise in the structural and functional integrity of aortic components leads to aortic degeneration, biomechanical failure, and the development of aortic aneurysms and dissections (AAD). A better understanding of the molecular pathogenesis of AAD will facilitate the development of effective medications to treat these conditions. Here, we summarize recent findings on AAD published in . In this issue, we focus on the dynamics of aortic cells and extracellular matrix in AAD; in the next issue, we will focus on the role of signaling pathways in AAD.
Topics: Aortic Dissection; Animals; Aorta; Aortic Aneurysm; Dilatation, Pathologic; Endothelial Cells; Extracellular Matrix; Fibroblasts; Hemodynamics; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Vascular Remodeling
PubMed: 32101472
DOI: 10.1161/ATVBAHA.120.313991 -
Gastroenterology Sep 2023Belching, bloating, and abdominal distention are all highly prevalent gastrointestinal symptoms and account for some of the most common reasons for patient visits to... (Review)
Review
DESCRIPTION
Belching, bloating, and abdominal distention are all highly prevalent gastrointestinal symptoms and account for some of the most common reasons for patient visits to outpatient gastroenterology practices. These symptoms are often debilitating, affecting patients' quality of life, and contributing to work absenteeism. Belching and bloating differ in their pathophysiology, diagnosis, and management, and there is limited evidence available for their various treatments. Therefore, the purpose of this American Gastroenterological Association (AGA) Clinical Practice Update is to provide best practice advice based on both controlled trials and observational data for clinicians covering clinical features, diagnostics, and management considerations that include dietary, gut-directed behavioral, and drug therapies.
METHODS
This Expert Review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. These best practice advice statements were drawn from a review of the published literature based on clinical trials, the more robust observational studies, and from expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Clinical history and physical examination findings and impedance pH monitoring can help to differentiate between gastric and supragastric belching. BEST PRACTICE ADVICE 2: Treatment options for supragastric belching may include brain-gut behavioral therapies, either separately or in combination, such as cognitive behavioral therapy, diaphragmatic breathing, speech therapy, and central neuromodulators. BEST PRACTICE ADVICE 3: Rome IV criteria should be used to diagnose primary abdominal bloating and distention. BEST PRACTICE ADVICE 4: Carbohydrate enzyme deficiencies may be ruled out with dietary restriction and/or breath testing. In a small subset of at-risk patients, small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth. BEST PRACTICE ADVICE 5: Serologic testing may rule out celiac disease in patients with bloating and, if serologies are positive, a small bowel biopsy should be done to confirm the diagnosis. A gastroenterology dietitian should be part of the multidisciplinary approach to care for patients with celiac disease and nonceliac gluten sensitivity. BEST PRACTICE ADVICE 6: Abdominal imaging and upper endoscopy should be ordered in patients with alarm features, recent worsening symptoms, or an abnormal physical examination only. BEST PRACTICE ADVICE 7: Gastric emptying studies should not be ordered routinely for bloating and distention, but may be considered if nausea and vomiting are present. Whole gut motility and radiopaque transit studies should not be ordered unless other additional and treatment-refractory lower gastrointestinal symptoms exist to warrant testing for neuromyopathic disorders. BEST PRACTICE ADVICE 8: In patients with abdominal bloating and distention thought to be related to constipation or difficult evacuation, anorectal physiology testing is suggested to rule out a pelvic floor disorder. BEST PRACTICE ADVICE 9: When dietary modifications are needed (eg, low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet), a gastroenterology dietitian should preferably monitor treatment. BEST PRACTICE ADVICE 10: Probiotics should not be used to treat abdominal bloating and distention. BEST PRACTICE ADVICE 11: Biofeedback therapy may be effective for bloating and distention when a pelvic floor disorder is identified. BEST PRACTICE ADVICE 12: Central neuromodulators (eg, antidepressants) are used to treat bloating and abdominal distention by reducing visceral hypersensitivity, raising sensation threshold, and improving psychological comorbidities. BEST PRACTICE ADVICE 13: Medications used to treat constipation should be considered for treating bloating if constipation symptoms are present. BEST PRACTICE ADVICE 14: Psychological therapies, such as hypnotherapy, cognitive behavioral therapy, and other brain-gut behavior therapies may be used to treat patients with bloating and distention. BEST PRACTICE 15: Diaphragmatic breathing and central neuromodulators are used to treat abdominophrenic dyssynergia.
Topics: Female; Humans; United States; Eructation; Celiac Disease; Pelvic Floor Disorders; Quality of Life; Constipation; Flatulence; Dilatation, Pathologic
PubMed: 37452811
DOI: 10.1053/j.gastro.2023.04.039 -
Circulation Research Jan 2021Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease...
RATIONALE
Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease remains untested. The current study detected eosinophil accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting eosinophil participation in this aortic disease.
OBJECTIVE
To test whether and how eosinophils affect AAA growth.
METHODS AND RESULTS
Population-based randomized clinically controlled screening trials revealed higher blood eosinophil count in 579 male patients with AAA than in 5063 non-AAA control (0.236±0.182 versus 0.211±0.154, 10/L, <0.001). Univariate (odds ratio, 1.381, <0.001) and multivariate (odds ratio, 1.237, =0.031) logistic regression analyses indicated that increased blood eosinophil count in patients with AAA served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected eosinophil accumulation and eosinophil cationic protein expression in human and murine AAA lesions. Results showed that eosinophil deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell loss using angiotensin-II perfusion-induced AAA in and eosinophil-deficient ΔdblGATA mice. Eosinophil deficiency increased lesion chemokine expression, muted lesion expression of IL (interleukin) 4 and eosinophil-associated-ribonuclease-1 (mEar1 [mouse EOS-associated-ribonuclease-1], human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, eosinophil-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11bLy6C monocytes, and increased CD11bLy6C monocytes. mEar1 treatment or adoptive transfer of eosinophil from wild-type and mice, but not eosinophil from mice, blocked AAA growth in ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for eosinophil IL4 and mEar1 in blocking NF-κB (nuclear factor-κB) activation in macrophages, smooth muscle cells, and endothelial cells.
CONCLUSIONS
Eosinophils play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.
Topics: Adoptive Transfer; Aged; Angiotensin II; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cells, Cultured; Dilatation, Pathologic; Disease Models, Animal; Eosinophils; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-4; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout, ApoE; Monocytes; NF-kappa B; Phenotype; Ribonucleases; Vascular Remodeling; Mice
PubMed: 33153394
DOI: 10.1161/CIRCRESAHA.120.318182 -
The New England Journal of Medicine Jan 2022Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation.
METHODS
We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death.
RESULTS
Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60).
CONCLUSIONS
Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).
Topics: Aged; Cardiac Valve Annuloplasty; Dilatation, Pathologic; Disease Progression; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Male; Mitral Valve; Mitral Valve Insufficiency; Pacemaker, Artificial; Postoperative Complications; Quality of Life; Reoperation; Survival Analysis; Tricuspid Valve; Tricuspid Valve Insufficiency
PubMed: 34767705
DOI: 10.1056/NEJMoa2115961 -
Circulation Research Mar 2022Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic...
BACKGROUND
Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF.
METHODS
First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice.
RESULTS
In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling.
CONCLUSIONS
In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Creatine Kinase; Creatine Kinase, Mitochondrial Form; Energy Metabolism; Heart Failure; Humans; Hypertrophy, Left Ventricular; Mice; Myocardium; Reactive Oxygen Species; Ventricular Remodeling
PubMed: 35109669
DOI: 10.1161/CIRCRESAHA.121.319648 -
The British Journal of Radiology Sep 2021Cholangitis refers to inflammation of the bile ducts with or without accompanying infection. When intermittent or persistent inflammation lasts 6 months or more, the... (Review)
Review
Cholangitis refers to inflammation of the bile ducts with or without accompanying infection. When intermittent or persistent inflammation lasts 6 months or more, the condition is classified as chronic cholangitis. Otherwise, it is considered an acute cholangitis. Cholangitis can also be classified according to the inciting agent, complete mechanical obstruction, which is the leading cause of acute cholangitis, longstanding partial mechanical blockage, or immune-mediated bile duct damage that results in chronic cholangitis.The work-up for cholangitis is based upon medical history, clinical presentation, and initial laboratory tests. Whereas ultrasound is the first-line imaging modality used to identify bile duct dilatation in patients with colicky abdominal pain, cross-sectional imaging is preferable when symptoms cannot be primarily localised to the hepatobiliary system. CT is very useful in oncologic, trauma, or postoperative patients. Otherwise, magnetic resonance cholangiopancreatography is the method of choice to diagnose acute and chronic biliary disorders, providing an excellent anatomic overview and, if gadoxetic acid is injected, simultaneously delivering morphological and functional information about the hepatobiliary system. If brush cytology, biopsy, assessment of the prepapillary common bile duct, stricture dilatation, or stenting is necessary, then endoscopic ultrasound and/or retrograde cholangiography are performed. Finally, when the pathologic duct is inaccessible from the duodenum or stomach, percutaneous transhepatic cholangiography is an option. The pace of the work-up depends upon the severity of cholestasis on presentation. Whereas sepsis, hypotension, and/or Charcot's triad warrant immediate investigation and management, chronic cholestasis can be electively evaluated.This overview article will cover the common cholangitides, emphasising our clinical experience with the chronic cholestatic liver diseases.
Topics: Bile Ducts; Cholangitis; Diagnostic Imaging; Humans
PubMed: 34233488
DOI: 10.1259/bjr.20210417 -
Pediatric Nephrology (Berlin, Germany) Oct 2023This review provides updated knowledge on the long-term outcomes among children with antenatally diagnosed urinary tract dilatation (UTD), previously often referred to... (Review)
Review
This review provides updated knowledge on the long-term outcomes among children with antenatally diagnosed urinary tract dilatation (UTD), previously often referred to as antenatal hydronephrosis. Different definitions of UTD exist, which makes comparison between studies and generalized conclusions difficult. Roughly, one-third of antenatally diagnosed UTD, defined as a renal pelvis anterior posterior diameter (APD) of ≥ 4 mm in the second trimester and/or ≥ 7 mm in the third trimester, will resolve before birth, another third will resolve within the first years of life, and in the remaining cases, UTD will persist or a congenital abnormality (CAKUT) will be diagnosed postnatally. The risk of a postnatal CAKUT diagnosis increases with the degree of prenatal and postnatal dilatation, except for vesicoureteral reflux (VUR), which cannot be predicted from the degree of UTD. Urinary tract infections (UTIs) occur in 7-14% of children with UTD during the first years of life. The risk of UTI is higher in children with traditional risk factors for UTI, such as dilated VUR, hydroureteronephrosis, female gender, and intact foreskin. Continuous antibiotic prophylaxis may be considered in selected patients during the first years of life. In long-term follow-ups, permanent kidney damage is diagnosed in approximately 40% of children with moderate or severe UTD, but hypertension, proteinuria, and/or reduced eGFR are uncommon (0-5%). In children with mild UTD, the long-term outcome is excellent, and these children should not be subjected to unnecessary examinations and/or follow-up.
Topics: Child; Humans; Female; Pregnancy; Dilatation; Vesico-Ureteral Reflux; Hydronephrosis; Urinary Tract Infections; Dilatation, Pathologic; Kidney Pelvis; Urinary Tract
PubMed: 36920569
DOI: 10.1007/s00467-023-05907-z -
Journal of Refractive Surgery... Dec 2021
Topics: Corneal Surgery, Laser; Corneal Topography; Dilatation, Pathologic; Humans
PubMed: 34914561
DOI: 10.3928/1081597X-20211025-01 -
Forensic Science, Medicine, and... Jun 2023Following a witnessed lethal lightning strike of an adult male who was standing outside in a storm, numerous Lichtenberg figures were identified upon external...
Following a witnessed lethal lightning strike of an adult male who was standing outside in a storm, numerous Lichtenberg figures were identified upon external examination of the body. Sectioning across multiple areas of linear erythema in the figures showed no subcutaneous hemorrhage. This was later confirmed on histology which showed only subtle dermal capillary dilatation with no interstitial hemorrhage or inflammation in these areas. The only areas of interstitial hemorrhage were present in adjacent scattered punctate burns from arcing. The documented resolution of Lichtenberg figures within hours would be more in keeping with temporary functional capillary dilatation, shown in this case, rather than with tissue alteration by interstitial hemorrhage or inflammation.
Topics: Adult; Humans; Male; Skin; Lightning Injuries; Dilatation, Pathologic; Inflammation; Hemorrhage
PubMed: 37046062
DOI: 10.1007/s12024-023-00612-7