Anthropometric and physiologic assessment in sleep apnoea patients regarding body fat distribution

Background: Obstructive sleep apnoea (OSA) is characterised by repeated episodes of pauses in breathing during sleep due to obstruction of the upper airway that result in transient hypoxaemia, sleep fragmentation and long-term cardiovascular disease. The most common risk factors for OSA include: obesity, age over 50 and neck circumference of more than 41 cm for females and more than 43 cm in males. Sleep apnoea is more common in men than in women. The aim of the conducted research was to evaluate relations between the anthropometric features connected with adipose tissue distribution and the severity of OSA. Materials and methods: The study was carried out on 180 patients (144 males and 36 females) diagnosed with OSA syndrome. The standard sleep parameters obtained from night polysomnography as well as skin-fat fold thickness and neck circumference and waist-to-hip ratio were analysed. Statistical analysis was performed using STATISTICA 10. Results: It was stated that anthropometric parameters connected with the accu­mulation of adipose tissue in upper body were significantly related to severity of OSA in males (p ≤ 0.05). Body mass index (BMI) was significantly correlated with severity of OSA in females (p ≤ 0.05). Conclusions: In males, there is a connection between the severity of OSA, BMI and a higher accumulation of adipose tissue in upper part of the body measured by neck circumference and shoulder thickness of skin-fat folds, whereas in females only by BMI

Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions

Cyclic vomiting syndrome (CVS) is characterized by severe episodic emesis in adults and children. Cannabinoid hyperemesis syndrome is an increasingly recognized CVS‐like illness that has been associated with chronic cannabis use. There are significant gaps in our understanding of the pathophysiology, clinical features, comorbidities, and effective management options of CVS. Recommendations for treating CVS are based on limited clinical data, as no placebo‐controlled, randomized trials have yet been conducted. Diseases associated with CVS, including migraine, mitochondrial disorders, autonomic dysfunction, and psychiatric comorbidities, provide clues about pathophysiologic mechanisms and suggest potential therapies. We review our current understanding of CVS and propose future research directions with the aim of developing effective therapy. Establishing a multicenter, standardized registry of CVS patients could drive research on multiple fronts including developing CVS‐specific outcome measures to broaden our understanding of clinical profiles, to serve as treatment end points in clinical trials, and to provide a platform for patient recruitment for randomized clinical trials. Such a robust database would also facilitate conduct of research that aims to determine the underlying pathophysiological mechanisms and genetic basis for CVS, as well as identifying potential biomarkers for the disorder. Soliciting government and industry support is crucial to establishing the necessary infrastructure and achieving these goals. Patient advocacy groups such as the Cyclic Vomiting Syndrome Association (CVSA), which partner with clinicians and researchers to disseminate new information, to promote ongoing interactions between patients, their families, clinicians, investigators, to support ongoing CVS research and education, must be an integral part of this endeavor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/1/nmo13607.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/2/nmo13607_am.pd

Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome

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.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/1/nmo13606_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/2/nmo13606.pd

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association

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.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/1/nmo13604.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/2/nmo13604_am.pd

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting

Background Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort‐ with nausea/vomiting‐predominant disease. Methods Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate‐severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [ PAGI ‐ SYM ] score ≥3) vs none‐mild ( PAGI ‐ SYM  < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. Key Results Upper abdominal pain was moderate‐severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate‐severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate‐severe pain (P ≤ 0.008). Factors associated with moderate‐severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. Conclusions & Inferences Moderate‐severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97520/1/nmo12091.pd

Management of cyclic vomiting syndrome in adults: Evidence review

BackgroundThis evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults.MethodsWe followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant?ResultsWe found very low‐quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co‐morbid conditions and complementary therapies.ConclusionsThis evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/1/nmo13605.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/2/nmo13605_am.pd

Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes

BackgroundIn studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients.MethodsQuestionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and followâ up differences between diabetes subtypes.Key ResultsAt baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p â ¤ 0.05). On followâ up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p â ¤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life.Conclusions & InferencesBaseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.This study defined similarities and differences in gastroparesis severity, healthcare utilization, psychological function, and quality of life in patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gastroparesis. At baseline enrollment, T1DM patients had higher hemoglobin A1c levels and more severe emptying delays, but the severity of GI symptoms was similar to those of patients with T2DM and gastroparesis. After 48 weeks of followâ up, gastroparesis symptom scores significantly decreased in T2DM patients but not in T1DM patients despite increased use of prokinetic, acid suppressant, anxiolytic, and gastric electrical stimulation therapy in the T1DM group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122408/1/nmo12800.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122408/2/nmo12800_am.pd

Association of low numbers of CD 206‐positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis

Background There is increasing evidence for specific cellular changes in the stomach of patients with diabetic ( DG ) and idiopathic ( IG ) gastroparesis. The most significant findings are loss of interstitial cells of Cajal ( ICC ), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD 206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD 206+ and i NOS + cells. To investigate associations between cellular phenotypes and ICC . Methods Full thickness gastric body biopsies were obtained from non‐diabetic controls (C), diabetic controls ( DC ), DG , and IG patients. Sections were labeled for CD 45, CD 206, Kit, i NOS , and putative human macrophage markers ( HAM 56, CD 68, and EMR 1). Immunoreactive cells were quantified from the circular muscle layer. Key Results Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD 206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between i NOS + cells and ICC in the DC group, but not the other groups. CD 68 and HAM 56 reliably labeled the same cell populations, but EMR 1 labeled other cell types. Conclusions & Inferences Depletion of ICC and correlation with changes in CD 206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD 206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages. Loss of interstitial cells of Cajal and an immune cell infiltrate have been identified in the gastric smooth muscle of patients with gastroparesis. This study reports a correlation between ICC numbers and CD206‐positive, alternatively activated M2 macrophage numbers in the gastric body of patients with diabetes (Panels B, D), but not in non‐diabetic controls (A) or idiopathic gastroparesis (C). Thus, CD206‐positive macrophages may play a cytoprotective role in the stomach of diabetic patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108285/1/nmo12389-sup-0001-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108285/2/nmo12389.pd

Diabetic and idiopathic gastroparesis is associated with loss of CD206‐positive macrophages in the gastric antrum

BackgroundAnimal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis.MethodsFull thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti‐inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index.ResultsBoth diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti‐inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206‐positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04).ConclusionLoss of antral CD206‐positive anti‐inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.Animal studies have highlighted an important role of macrophages in development of delayed gastric emptying. However, their role in human gastroparesis is unclear. Upon assessment of full thickness gastric antrum biopsies, both diabetic and idiopathic gastroparesis patients showed a loss of CD206‐positive anti‐inflammatory macrophages as compared to controls. This correlated with loss of ICC suggesting a role of innate immune cells in pathophysiology of human gastroparesis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137212/1/nmo13018.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137212/2/nmo13018_am.pd

Developmental regulation of mitochondrial apoptosis by c-Myc governs age- and tissue-specific sensitivity to cancer therapeutics

It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage. While expression of the apoptotic protein machinery is nearly absent by adulthood, in young tissues its expression is driven by c-Myc, linking developmental growth to cell death. These differences may explain why pediatric cancer patients have a higher risk of developing treatment-associated toxicities