User:Pattkait/sandbox

Inuit section edited out:

Inuit populations
The Inuit population is often cited as an example of a population thriving on a long term low-carbohydrate, fat-based diet in the form of their traditional Inuit cuisine.However, their diet has not been proven to cause a prolonged state of ketosis. Inuit consume calories from carbohydrates from the glycogen found in raw meats as well as available plant matter such as mosses and lichens which may be above the carbohydrate allotment to achieve consistent ketosis. It has also been proposed that the high prevalence of Carnitine palmitoyltransferase I (CPT1A) deficiency among the Inuit may contribute to lower ketone levels as the mutation prevents normal ketone production due to impaired transport of fatty acids across the mitochondrial membrane. CPT1A deficiency is an autosomal recessive allele, predisposing homozygotes to dangerous hypoketotic hypoglycemia during fasting, infant death, hepatomegaly, and hypoglycemia, however heterozygote carriers may have a selective advantage in extreme cold environments due to shunting of free fatty acids to brown fat for thermogenesis

Classification
There are different types of neurogenic bladder depending on the underlying cause.

Uninhibited
Uninhibited bladder is usually due to damage to the brain from a stroke or tumor. This can cause reduced sensation of bladder fullness, lower capacity bladder and incontinence but does not lead to high bladder pressures that can cause incontinence.

Spastic
In spastic neurogenic bladder (also known as upper motor neuron, or hyper-reflexive bladder), the muscles of the bladder detrusor and sphincter do not work together and are usually tightly contracted at the same time. This can cause high pressures in the bladder and damage the kidneys. The bladder volume is usually low due to increased muscle tone of the detrusor. Spastic neurogenic bladder is usually caused by damage to the spinal cord above T10.

Flaccid
In flaccid (also known as lower motor neuron or hypotonic) bladder, the muscles of the bladder lose ability to contract normally. This can cause the inability to void urine even if the bladder is full and cause a large bladder capacity. The internal urinary spincter is intact, however urinary incontinence is common. This is caused from damage to the peripheral nerves.

Mixed
Mixed type of neurogenic bladder can cause a combination of the above presentations. In mixed type A, the detrusor is flaccid but the spincter is overactive. This causes a large, low pressure bladder and inability to void although not as much risk for kidney damage as a spastic bladder. Mixed type B is characterized by a flaccid external spinchter and a spastic bladder causing problems with incontinence.

Detruser hyperactivity with impaired bladder contractility
10.1155/2012/816274

CAuses
Damage or diseases of the central, peripheral, and autonomic nervous systems may result in neurogenic bladder dysfunction.

Complications
Utilizing various treatments and strategies reduce commplication rate dramatically. Kidney disease secondary to neurogenic bladder used to be the leading cause of death in people with spinal cord injury, accounting for 80% of SCI mortality. In comparison, today accounts for 3%. Bladder symptoms and management have a huge impact on quality of life.

Individuals with spina bifida, SCI, high burden of spinal cord disease, transverse myelitis, and men with MS make up the group with the highest risk of complications. Complications include damage to the upper urinary system (kidneys), ckd, nephrolithiasis

10.1016/j.ucl.2017.04.003.

Manack et al. [3] examined insurance and pharmacy claims of nearly 60,000 patients with neurogenic bladder over a 4-year period and found a 29–36% rate of lower urinary tract infections, 9–14% rate of urinary retention, and a 6–11% rate of urinary tract obstructions. Upper urinary tract infections were noted in 1.4–2.2% of the neurogenic bladder cohort, and serious systemic illnesses were also diagnosed in this group including septicemia in 2.6–4.7% and acute renal failure in 0.8–2.2%. Neurogenic bladder patients averaged 16 office and 0.5 emergency room visits per year, approximately a third of them leading to hospitalization.

Neurogenic bladder with detrusor overactivity may cause incontinence, which not only leads to embarrassment, depression and social isolation but also may lead to skin decubiti, urethral erosions, and upper urinary tract damage [5].

Pathophysiology
Normal micturition involves passive, low pressure filling of the bladder during the urine storage phase while voiding requires coordination of detrusor contraction with internal and external urinary sphincter relaxation. This micturition process is controlled by the central nervous system, which coordinates the sympathetic and parasympathetic nervous system activation with the somatic nervous system to ensure normal micturition with urinary continence Usually there is balanced opposing input to the bladder and the spincter muscles. This is controlled by a specific part of the brain called the PMC. The PMC is responsible for mediating a coordinated mechanism of bladder storage and bladder emptying through organizing the interaction between the PMC, the sacral micturition center, and the cerebral cortex. When the PMC is interrupted, the normal opposing relationship between the detrusor and the internal/external sphincter is lost. disrupted transmission between the PMC and neurons in the sacral spinal cord prevent the PMC from resulting detrusor compliance during storage and coordinating bladder and sphincter activity during voiding. Over the long term, this can result in permanent changes to detrusor function and elasticity, leading to upper tract damage due to high pressures rogressive upper urinary tract damage due to chronic, excessive detrusor pressures.

Evaluation
Laboratory evaluation of neurogenic bladder patients should include urinalysis, urine culture and sensitivity, serum BUN/creatinine, and creatinine clearance [13]. Post-void residual (PVR) urine volume involves transurethral catheterization to measure residual urine volume in the bladder immediately after voiding to determine the ability of the bladder to empty completely. PVR determination should always be performed after discontinuing Foley catheterization or before instituting intermittent catheterization as part of a bladder retraining program.

Epidemiology

Neurogenic bladder dysfunction may complicate a variety of neurologic conditions. In the United States, neurogenic bladder affects 40–90% of persons with multiple sclerosis, 37–72% of those with Parkinsonism, and 15% of those with stroke [2]. Detrusor hyperreflexia is seen in 50–90% of persons with multiple sclerosis, while another 20–30% have detrusor areflexia. There are more than 200,000 persons with spinal cord injuries, and 70–84% of these individuals have at least some degree of bladder dysfunction [3]. Bladder dysfunction is also common in spina bifida, which affects approximately 1 per 1000 live births. Vesicoureteral reflux may occur in up to 40% of children with spina bifida by age 5, and up to 61% of young adults with spina bifida experience urinary incontinence [4]. Less common causes of neurogenic bladder include diabetes mellitus with autonomic neuropathy, pelvic surgery sequelae, and cauda equina syndrome due to lumbar spine pathology.

Sarcopenia drafting
preferential reduction in type II fibers Changes in satellite cell activation (muscle stem cells) Low anabolic hormones Insulin resistance Low Akt/mTOR activity in muscle Attenuated response to exercise

sarcopenia/cachexia articles
Fry, C. S., Drummond, M. J., Glynn, E. L., Dickinson, J. M., Gundermann, D. M., Timmerman, K. L., … Rasmussen, B. B. 2011. Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skeletal Muscle 2011. 1(1), 11.

Jatoi A, Ritter HL, Dueck A, et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9). Lung Cancer 2010; 68(2):234–239.

Jewell, J. L., & Guan, K.-L. Nutrient signaling to mTOR and cell growth. Trends in Biochemical Sciences 2013; 38(5), 233–242. Lenk, K., Schuler, G., & Adams, V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. Journal of Cachexia, Sarcopenia and Muscle 2010; 1(1), 9–21.

Li, H., Malhotra, S., & Kumar, A. Nuclear factor-kappa B signaling in skeletal muscle atrophy. Journal of Molecular Medicine 2008; 86(10), 1113–1126.

Penna, F., Ballarò, R., Beltrà, M., De Lucia, S., García Castillo, L., & Costelli, P. The skeletal muscle as an active player against cancer cachexia. Frontiers in Physiology 2019; 10.

Peterson, S. J., & Mozer, M. Differentiating sarcopenia and cachexia among patients with cancer. Nutrition in Clinical Practice 2017; 32(1), 30–39.

Porporato, P. E. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis 2016; 5(2), e200–e200.

Sadeghi, M., Keshavarz-Fathi, M., Baracos, V., Arends, J., Mahmoudi, M., & Rezaei, N. Cancer cachexia: Diagnosis, assessment, and treatment. Critical Reviews in Oncology/Hematology 2018; 127, 91–104.

Shum, A., Polly, P. Cancer cachexia: molecular targets and pathways for diagnosis and drug intervention. Endocrine, Metabolic & Immune Disorders-Drug Targets 2012; 12(3), 247–259.

Tuca, A., Jimenez-Fonseca, P., & Gascón, P. Clinical evaluation and optimal management of cancer cachexia. Critical Reviews in Oncology/Hematology 2013; 88(3), 625–636.

Edited out of sarcopenia
quote = In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people.

RESULTS: A total of seven randomized controlled trials were included, in which 147 older adults received HMB intervention and 140 were assigned to control groups. The meta-analysis showed greater muscle mass gain in the intervention groups compared with the control groups (standard mean difference=0.352kg; 95% confidence interval: 0.11, 0.594; Z value=2.85; P=0.004). There were no significant fat mass changes between intervention and control groups (standard mean difference=-0.08kg; 95% confidence interval: -0.32, 0.159; Z value=0.66; P=0.511). CONCLUSION: Beta-hydroxy-beta-methylbutyrate supplementation contributed to preservation of muscle mass in older adults. HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors. Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults.

In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013).

tudies suggest dietary protein and leucine or its metabolite b-hydroxy b-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. ... These have identified the leucine metabolite β-hydroxy β-methylbutyrate (HMB) as a potent stimulator of protein synthesis as well as an inhibitor of protein breakdown in the extreme case of cachexia.65, 72, 76, 77, 78, 79, 80, 81, 82, 83, 84 A growing body of evidence suggests HMB may help slow, or even reverse, the muscle loss experienced in sarcopenia and improve measures of muscle strength.44, 65, 72, 76, 77, 78, 79, 80, 81, 82, 83, 84 However, dietary leucine does not provide a large amount of HMB: only a small portion, as little as 5%, of catabolized leucine is metabolized into HMB.85 Thus, although dietary leucine itself can lead to a modest stimulation of protein synthesis by producing a small amount of HMB, direct ingestion of HMB more potently affects such signaling, resulting in demonstrable muscle mass accretion.71, 80 Indeed, a vast number of studies have found that supplementation of HMB to the diet may reverse some of the muscle loss seen in sarcopenia and in hypercatabolic disease.65, 72, 83, 86, 87 The overall treatment of muscle atrophy should include dietary supplementation with HMB, although the optimal dosage for each condition is still under investigation.68 ... Figure 4: Treatments for sarcopenia. It is currently recommended that patients at risk of or suffering from sarcopenia consume a diet high in protein, engage in resistance exercise, and take supplements of the leucine metabolite HMB.

There are a number of nutrition products on the market that are touted to improve sports performance. HMB appears to be the most promising and to have clinical applications to improve muscle mass and function. Continued research using this nutraceutical to prevent and/or improve malnutrition in the setting of muscle wasting is warranted.

This includes β-hydroxy β-methylbutyrate (HMB), a metabolite of leucine which is sold as a dietary supplement, which has demonstrated efficacy in preventing the loss of muscle mass in individuals with sarcopenia. A growing body of evidence supports the efficacy of HMB as a treatment for reducing, or even reversing, the loss of muscle mass, muscle function, and muscle strength in hypercatabolic disease states such as cancer cachexia;  consequently,  it is recommended that both the prevention and treatment of sarcopenia and muscle wasting in general include supplementation with HMB, regular resistance exercise, and consumption of a high-protein diet. Based upon a meta-analysis in 2015, HMB supplementation appears to be useful as a treatment for preserving lean muscle mass in older adults. More research is needed to determine the precise effects of HMB on muscle strength and function in this age group.

Edited out of cachexia article
Symptoms of cancer cachexia include progressive weight loss and depletion of host reserves of adipose tissue and skeletal muscle. Cachexia should be suspected if involuntary weight loss of greater than 5% of premorbid weight occurs within a six-month period. Traditional treatment approaches, such as appetite stimulants, 5-HT3 antagonists, nutrient supplementation, and COX-2 inhibitor, have failed to demonstrate success in reversing the metabolic abnormalities seen in cancer cachexia.

Those suffering from the eating disorder anorexia nervosa appear to have high plasma levels of ghrelin. Ghrelin levels are also high in patients who have cancer-induced cachexia.

Cachexia is also associated with advanced stages of chronic kidney disease, cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia, HIV/AIDS,tuberculosis, multiple system atrophy, mercury poisoning, Crohn's disease, Celiac disease untreated type 1 diabetes mellitus as well as other systemic diseases.

It is a positive risk factor for death, meaning if the person has cachexia, the chance of death from the underlying condition is increased dramatically. It can be a sign of various underlying disorders; when a patient presents with cachexia, a doctor will generally consider the possibility of adverse drug reactions, cancer, metabolic acidosis, certain infectious diseases (e.g., tuberculosis, AIDS), chronic pancreatitis and some autoimmune disorders. Cachexia physically weakens patients to a state of immobility stemming from loss of appetite, asthenia and anemia, and response to standard treatment is usually poor. Cachexia includes sarcopenia as a part of its pathology.

HMB edited out from cachexia page
It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013). }}  consequently, it is recommended that both the prevention and treatment of muscle wasting conditions include supplementation with HMB, regular resistance exercise and consumption of a high-protein diet.

Diagnosis
Diagnostic guidelines and criteria have only recently been proposed despite the prevalence of cachexia. Diagnostic criteria and they have shifted over time as understanding of cachexia as a complex syndrome evolved resulting in multiple different criteria proposed. Despite the varying and changing criteria, the primary features of cachexia include progressive depletion of muscle and fat mass; reduced oral intake due to anorexia and treatment‐related side effects; abnormal metabolism of carbohydrate, protein, and fat; and reduced quality of life or increased physical impairment.(10.1177/0884533616680354

Historically, body weight and weight changes were used as the primary metrics of cachexia including low BMI, involuntary weight loss of >10%, or >5% in 6 months in the setting of concurrent illness.(10.21037/apm.2018.08.07). However, using weight alone may not identify many patients as it is affected by edema, tumor mass and the high prevalence of obesity in the general population. It also does not take into account changes in body composition, especially loss of lean body mass.

In the attempt to include a broader evaluation of the burden of cachexia, diagnostic criteria using assessments of laboratory metrics and symptoms in addition to weight have been proposed. This criteria included weight loss of at least 5% in 12 months or low BMI <22 kg/m2 with 3 of 5 of the following features: decreased muscle strength, fatigue, anorexia, low fat‐free mass index, or abnormal biochemistry (increased inflammatory markers [CRP, interleukin‐6], anemia [hemoglobin <12 g/dL], low serum albumin [<3.2 g/dL]).78- fearon?- 2007

Laboratory markers are often used in evaluation of patients with cachexia including albumin, prealbumin, CRP, or hemoglobin. However, laboratory metrics used and cut-off values are not standardized across different guidelines and diagnostic criteria. Acute phase reactants ((IL)-6, IL-1b, tumor necrosis factor-a, IL-8, interferon-g) are sometimes measured but correlate poorly with outcomes. Currently, there are no biomarkers to identify precachectic patients with cancer who may progress to further stages. (differentiating, palliative care) Loumaye

In the effort to better classify cachexia severity, several scoring systems have been proposed including the Cachexia Staging Score (CSS) and CASCO. The CSS takes into account weight loss, subjective reporting of muscle function, performance status, appetite loss, and laboratory changes to categorize patients into non-cachexia, pre-cachexia, cachexia and refractory cachexia. The Cachexia SCOre (CASCO) is another validated score that includes evaluation of body weight loss and composition, inflammation/metabolic disturbances/immunosuppression, physical performance, anorexia, and quality of life. (palliative)

Evaluation of changes in body composition is limited by the difficulty in measuring muscle mass and health in a non-invasive and cost-effective way. Imaging with quantification of muscle mass has been investigated including bioelectrical impedance analysis (BIA) (49), computed tomography (CT) imaging analysis (50), and dual-energy X-ray absorptiometry (DXA) and MRI but are not widely used.

10.1358/dot.2016.52.9.2545017

Biomarkers of cancer cachexia. Loumaye A et al. Clin Biochem. (2017)

Home / Vol 8, No 1 (January 2019) / Measuring cachexia—diagnostic criteria

In the United States, cachexia from any disease is estimated to affect >5 million people.8 Among patients with cancer, approximately 50% will lose weight throughout treatment. However, the incidence of weight loss upon diagnosis varies by tumor site. The highest prevalence of weight loss and cachexia has been observed in patients presenting with solid tumors, specifically gastric, pancreatic, lung, colorectal, and head and neck.68 One‐third of patients will lose >5% of precancer body weight.83 Up to 80% of patients with advanced cancer may be diagnosed with cancer cachexia.79 By the last 1–2 weeks of life, the prevalence of weight loss has been documented as high as 86%.87,88

Ketosis Pathophysiology drafting
Ketones are primarily produced from free fatty acids in the mitochondria of hepatocytes. The production of ketones is strongly regulated by insulin and an absolute or relative lack of insulin underlies the pathophysiology of ketoacidosis (cite). Insulin is a potent inhibitor of fatty acid release, so insulin deficiency can cause an uncontrolled release of fatty acids from adipose tissue. Insulin deficiency can also enhance ketone production and inhibit peripheral use of ketones. (oster) This can occur during states of complete insulin deficiency (untreated diabetes) or relative insulin deficiency due to increased glucagon and counterregulatory hormones (starvation, heavy chronic alcohol use).

Ketones circulate in the blood and act as a metabolic fuel as well as signalling molecules (cite). The rate of ketone production is carefully regulated by multiple hormones.

Fatty acids can be released from adipose tissue by adipokine signaling of high glucagon and epinephrine levels and low insulin levels. High glucagon and low insulin correspond to times of low glucose availability such as fasting.[13]

Useful papers
Reaven G. Insulin resistance, cardiovascular disease, and the metabolic syndrome. Diabetes. Care. 27(4),1011–1012 (2004).

Meng Y, Bai H, Wang S et al. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: A systematic review and meta-analysis of randomized controlled trials. Diabetes. Res. Clin. Pract. 131,124–131 (2017).

Sainsbury E, Kizirian NV, Partridge SR, Gill T, Colagiuri S, Gibson AA. Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2018;139:239–252CrossRefPubMed

https://care.diabetesjournals.org/content/42/Supplement_1/S46