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An ideal bone substituting material should be bone-mimicking in terms of mechanical properties, present a precisely controlled and fully interconnected porous structure, and degrade ...in the human body to allow for full regeneration of large bony defects. However, simultaneously satisfying all these three requirements has so far been highly challenging. Here we present topologically ordered porous magnesium (WE43) scaffolds based on the diamond unit cell that were fabricated by selective laser melting (SLM) and satisfy all the requirements. We studied the in vitro biodegradation behavior (up to 4 weeks), mechanical properties and biocompatibility of the developed scaffolds. The mechanical properties of the AM porous WE43 (E = 700–800 MPa) scaffolds were found to fall into the range of the values reported for trabecular bone even after 4 weeks of biodegradation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), electrochemical tests and µCT revealed a unique biodegradation mechanism that started with uniform corrosion, followed by localized corrosion, particularly in the center of the scaffolds. Biocompatibility tests performed up to 72 h showed level 0 cytotoxicity (according to ISO 10993-5 and -12), except for one time point (i.e., 24 h). Intimate contact between cells (MG-63) and the scaffolds was also observed in SEM images. The study shows for the first time that AM of porous Mg may provide distinct possibilities to adjust biodegradation profile through topological design and open up unprecedented opportunities to develop multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects.
The ideal biomaterials for bone tissue regeneration should be bone-mimicking in terms of mechanical properties, present a fully interconnected porous structure, and exhibit a specific biodegradation behavior to enable full regeneration of bony defects. Recent advances in additive manufacturing have resulted in biomaterials that satisfy the first two requirements but simultaneously satisfying the third requirement has proven challenging so far. Here we present additively manufactured porous magnesium structures that have the potential to satisfy all above-mentioned requirements. Even after 4 weeks of biodegradation, the mechanical properties of the porous structures were found to be within those reported for native bone. Moreover, our comprehensive electrochemical, mechanical, topological, and biological study revealed a unique biodegradation behavior and the limited cytotoxicity of the developed biomaterials.
Cyclic vomiting syndrome (CVS) in children is characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. In the absence of robust data, the treatment of CVS remains ...largely empiric starting with the 2008 NASPGHAN Consensus Statement recommendations of cyproheptadine for children < 5 years of age and amitriptyline for those ≥ 5 years with propranolol serving as the second-line agent. Comprehensive management begins with lifestyle alterations, and extends to medications, supplements, and stress reduction therapies. Standard drug therapy is organized by the four phases of the illness: (1)
interictal
(preventative medications and mitochondrial supplements), (2)
prodromal
(abortive agents), (3)
vomiting
(fluids/energy substrates, antiemetics, analgesics, and sedatives) and (4)
recovery
(supportive care and nutrition). Because the response to treatment is heterogeneous, clinicians often trial several different preventative strategies including NK1 antagonists, cautious titration of amitriptyline to higher doses, anticonvulsants, Ca
2+
-channel blockers, and other TCA antidepressants. When the child remains refractory to treatment, reconsideration of possible missed diagnoses and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities (especially anxiety), specific subphenotype, and when available, genotype. For hospital intervention, IV fluids with 10% dextrose, antiemetics, and analgesics can lessen symptoms while effective sedation in some instances can truncate severe episodes.
Conclusion
: Although management of CVS remains challenging to the clinician, approaches based upon recent literature and accumulated experience with subgroups of patients has led to improved treatment of the refractory and hospitalized patient.
What is Known:
•
Cyclic vomiting syndrome is a complex disorder that remains challenging to manage.
•
Previous therapy has been guided by the NASPGHAN Consensus Statement of 2008.
What is New:
•
New prophylactic approaches include NK1 antagonists and higher dosages of amitriptyline.
•
Strategies based upon comorbidities and subphenotype are helpful in refractory patients.
The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence‐based guidelines on the management of CVS in adults, which was sponsored by the ...American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly recommends that adults with moderate‐to‐severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first‐line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L‐carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well‐being and patient care outcomes.
ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is an immune‐mediated chronic inflammatory disorder triggered by food antigen(s). A 6‐food elimination diet (SFED) excluding cow's milk, soy, ...wheat, egg, peanuts/tree nuts, and seafood has been shown to induce remission in a majority of children with EoE. The goal of the present study was to identify specific food antigens responsible for eosinophilic esophageal inflammation in children with EoE who had achieved histological remission with the SFED.
Patients and Methods:
In this analysis, we retrospectively analyzed children with EoE who completed subsequent single‐food reintroductions that led to identification of foods causing disease recurrence. Repeat upper endoscopy with biopsies was performed after single‐food introductions. Recurrence of esophageal eosinophilia following a food reintroduction identified that food antigen as a cause of EoE.
Results:
A total of 36/46 (25 M/11F) children who were initially successfully treated with SFED completed this trial; the mean age was 7.6 ± 4.3 years. The most common foods identified were 25 to cow's milk (74%), 8 to wheat (26%), 4 to eggs (17%), 3 to soy (10%), and 1 to peanut (6%). Milk was 8 times more likely to cause EoE compared with wheat, the next most common food (95% confidence interval 2.41–26.62, P = 0.0007).
Conclusions:
Serial single‐food reintroductions following induction of histological remission with the SFED can lead to the identification of specific causal food antigen(s) in EoE. Cow's milk was the most common food identified in subjects with EoE treated with SFED. A subset of children with EoE may develop tolerance to their food sensitivities while on the SFED.
Cyclic vomiting syndrome (CVS) is a chronic disorder of gut-brain interaction characterized by recurrent disabling episodes of nausea, vomiting, and abdominal pain. CVS affects both children and ...adults with a prevalence of approximately 2% in the United States. CVS is more common in female individuals and affects all races. The pathophysiology of CVS is unknown and a combination of genetic, environmental, autonomic, and neurohormonal factors is believed to play a role. CVS is also closely associated with migraine headaches and likely have a shared pathophysiology. The diagnosis of CVS is based on the Rome criteria, and minimal recommended testing includes an upper endoscopy and imaging studies of the abdomen. CVS is frequently associated with anxiety, depression, and autonomic dysfunction. Patients with CVS commonly use cannabis therapeutically for symptom relief. By contrast, cannabinoid hyperemesis syndrome is believed to be a subset of CVS with chronic heavy cannabis use leading to hyperemesis. Due to the recalcitrant nature of the illness, patients often visit the emergency department and are hospitalized for acute CVS flares. Guidelines on the management of CVS recommend a biopsychosocial approach. Prophylactic therapy consists of tricyclic antidepressants (amitriptyline), antiepileptics (topiramate), and aprepitant in refractory patients. Abortive therapy consists of triptans, antiemetics (ondansetron), and sedation. Treatment of comorbid conditions is extremely important to improve overall patient outcomes. CVS has a significant negative impact on patients, families, and the healthcare system, and future research to understand its pathophysiology and develop targeted therapies is needed.
ABSTRACT
Cyclic vomiting syndrome (CVS) is a disorder noted for its unique intensity of vomiting, repeated emergency department visits and hospitalizations, and reduced quality of life. It is often ...misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. Because no accepted approach to management has been established, the task force was charged to develop a report on diagnosis and treatment of CVS based upon a review of the medical literature and expert opinion. The key issues addressed were the diagnostic criteria, the appropriate evaluation, the prophylactic therapy, and the therapy of acute attacks. The recommended diagnostic approach is to avoid “shotgun” testing and instead to use a strategy of targeted testing that varies with the presence of 4 red flags: abdominal signs (eg, bilious vomiting, tenderness), triggering events (eg, fasting, high protein meal), abnormal neurological examination (eg, altered mental status, papilledema), and progressive worsening or a changing pattern of vomiting episodes. Therapeutic recommendations include lifestyle changes, prophylactic therapy (eg, cyproheptadine in children 5 years or younger and amitriptyline for those older than 5), and acute therapy (eg, 5‐hydroxytryptamine receptor agonists, termed triptans herein, as abortive therapy, and 10% dextrose and ondansetron for those requiring intravenous hydration). This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the diagnosis and treatment of CVS in children and adolescents.
Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the ...recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called “compulsive hot water bathing” has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow‐up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder.
Objectives/Background
Cyclic vomiting syndrome (CVS) is a disabling disorder of gut–brain interaction manifested by stereotypical and severe episodes of nausea and vomiting. Prevalence data indicate ...that CVS affects 1–2% of children and there has been a recent dramatic rise in diagnosed adults.
Methods
This narrative review summarizes relevant literature pertaining to pediatric and adult CVS and provides a guide to management based on extensive clinical experience.
Results
More timely diagnosis is facilitated by an expert consensus diagnostic approach and limited testing. Some diagnostic tests of exclusion remain essential. These include an upper gastrointestinal (GI) contrast study to exclude intestinal malrotation and basic laboratory screening. An abdominal ultrasound is recommended to exclude renal hydronephrosis in children and biliary disease in adults. Exclusion of metabolic/genetic conditions is warranted in those with specific warning signs, presentation in infants/toddler age, and in those with refractory disease. In the absence of chronic GI symptoms, referral to a GI specialist for upper endoscopy is generally not necessary in children but recommended in adults. A large subset termed migraine‐equivalent CVS display strong clinical and genetic features of migraine. A unifying pathophysiologic core concept involves neuronal hyperexcitability and aberrant central modulation of autonomic signals. This is coupled with multiple susceptibility factors including mitochondrial dysfunction/cellular energy deficits, a hyper‐responsive hypothalamic–pituitary–adrenal axis and many comorbidities that increase vulnerability to triggering events. CVS episodes are frequently triggered by stressors and intercurrent illnesses. Lifestyle and non‐pharmacological interventions thus play a pivotal role in successful management. Pharmacological therapies are categorized into abortive, supportive/rescue, and prophylactic treatments. The majority respond particularly well to migraine‐focused treatment strategies.
Conclusion
Despite improved characterization and understanding, CVS remains classified as a functional disorder of brain–gut interaction that is often disjointly managed by generalists and subspecialists. Early recognition, evaluation, and management will facilitate care and improve outcomes. Further research into its natural history with common progression to migraine headaches, neuroendocrine mechanisms, and the pathophysiologic relation to migraine diathesis is much needed.
Background:
Cyclic vomiting syndrome (CVS) is a disabling condition frequently refractory to pharmacologic therapy. The aim of this study was to evaluate the effects of noninvasive, auricular ...percutaneous electrical nerve field stimulation (PENFS) as prophylactic therapy for pediatric CVS.
Methods:
Children 8–18 years with drug‐refractory CVS were prospectively enrolled from a tertiary care CVS clinic. Subjects received 6 consecutive weeks of PENFS. CVS severity was quantified by episode frequency and duration score (range 0–25) at baseline and at extended follow‐up (4–6 months after end of therapy). Response was classified as ≥50% improvement in either frequency or duration of attacks at extended follow‐up. Subjects also completed validated surveys of nausea, disability, and global response.
Results:
Thirty subjects completed the study. Median (interquartile range, IQR) age was 10.5 (8.5–15.5) years; 60% were female. At follow‐up, 80% met criteria for treatment response with a median (IQR) response duration of 113 (61–182) days. The frequency‐duration score improved from baseline median (IQR) 12.0 (9.0–16.0) to 3.0 (1.0–6.0) at follow‐up, P < 0.0001. Median (IQR) nausea and disability scores decreased from baseline to week 6: 2.1 (1.3–2.7) to 0.9 (0–1.6), P = 0.003 and 47.5 (41.0–53.0) to 38.0 (16.0–51.0), P = 0.001, respectively. At end of therapy, 66% and 55% patients reported global response of at least “moderately better” and “a good deal better,” respectively. There were no serious side effects.
Conclusions:
This study suggests long‐term benefits of PENFS for children with CVS. PENFS improves several disabling aspects of CVS, including episode frequency, duration, and functional disability.
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