Persius/hicric huggingface dataset:
Major or mild neurocognitive disorder due to Parkinson's disease

# Overview
Cognitive impairment and dementia can occur in the PD but in some ways its different from Alzheimer disease. Language dysfunction and memory deficit is less prominent while executive and visuospatial dysfunction is more prominent in PD. Parkinsons diseases memory deficits are in the area of retrieval of learned information. Aphasia, apraxia and sever memory loss are uncommon in PD.

# Major or Mild Neurocognitive Disorder Due to Parkinson's Disease
Cognitive impairment and dementia can occur in the PD but in some ways its different from Alzheimer disease. Language dysfunction and memory deficit is less prominent while executive and visuospatial dysfunction is more prominent in PD. Parkinsons diseases memory deficits are in the area of retrieval of learned information. Aphasia, apraxia and sever memory loss are uncommon in PD.

# Epidemiology and Demographics
The prevalence of major or mild neurocognitive disorder due to parkinson's disease is:
75,000 per 100,000 (75%) major neurocognitive disorder.
27,000 per 100,000 (27%) mild neurocognitive disorder.

# Risk Factors
Risk factors for developing Cognitive impairment and dementia in Parkinson disease are: Duration of PD, severity of the disease, age of onset >60 years, old age, presence of rapid eye movement sleep behavior disorder, autonomic dysfunction, gait problem and hyposmia.

# Differential Diagnosis
the differential diagnosis for PDD includes:
- Alzheimer disease
- Dementia with Lewy bodies
- Multiple system atrophy
- Corticobasal degeneration
- Progressive supranuclear palsy
- vascular parkinsonism
Natural orifice translumenal endoscopic surgery (NOTES) overview
For the WikiPatient page for this topic, click here
Synonyms and keywords: Natural orifice translumenal endoscopic surgery, Single incision laparoscopic surgery, Minimally invasive surgery, Transanal endoscopic microsurgery, Natural orifice surgery consortium for assessment and research, Society of american gastrointestinal and endoscopic surgeons.

# Natural Orifice Translumenal Endoscopic Surgery (NOTES) Overview
Natural orifice translumenal endoscopic surgery (NOTES) is an experimental surgical technique whereby "scarless" abdominal and thoracic operations can be performed. A diagnostic or therapeutic procedures can be performed by getting access to the peritoneal cavity or the thoracic cavity through a hollow viscous . NOTES involves passing surgical instruments and a tiny camera through a natural orifice (mouth, urethra, anus, etc.), then the procedure can be performed through an internal incision in the hollow viscous (stomach, vagina, colon, etc.) thus avoiding scars and external incisions through the skin, muscles, and nerves . The patients recover more quickly and experience less pain (visceral pain only instead of visceral and somatic pain) and better cosmesis. The postoperative complications such as wound infections and hernias are significantly reduced .
Animal models and cadavers have been used to demonstrate that NOTES procedures are safe and feasible. Some of the NOTES applications are abdominal cavity screening, internal organs biopsy, appendectomy, cholecystectomy, tubal ligation, gastrojejunostomy, partial hysterectomy, oophorectomy, colorectal resection and trans-esophageal myotomy.
NOTES describes going beyond the margins of a lumen (hollow organ). The word translumenal could be spelled as "transluminal". Analogies are found with nomen, foramen or abdomen which build the corresponding adjective form with an "i" (nominal, foraminal, abdominal) instead of "e".
Paroxysmal AV Block Natural History, Complications and Prognosis

# Overview
Natural history most commonly includes recurrent unexplained syncope and presyncope. Complications such as sudden cardian death or indefinite periods of asystole may arise. Prognosis of intrinsic paroxysmal AV block is more dire than extrinsic idiopathic paroxysmal AV block or extrinsic vagal paroxysmal AV block.

# Natural History, Complications, and Prognosis

## Natural History
- Paroxysmal AV Block is a poorly defined entity.
- The symptoms of paroxysmal AV block can develop at any age (with some studies suggesting a predominance in older individuals) and presents with symptoms such as recurrent unexplained syncope and presyncope, which further manifests on an ECG as intermittent and progressively increasing periods of asystole.

## Complications
- Common complications of paroxysmal AV Block include asystole, complete AV Block and sudden cardiac death.
- Complications that can develop as a result of theophylline therapy are  nausea, vomiting, abdominal pain, irritability, hallucinations, arrhythmias, acute lung injury and seizures.
- Complications that can develop as a result of cardiac pacing are procedural, component or biophysical interface related. These include hemothroax, pneumothorax,acute thromboembolism, arrhythmia, pericarditis, device battery failure, pulse generator circuit failure, wound dehiscence, erosion, pain and infection.

## Prognosis
- Given the presence of an innate structural defect, there is an increase risk of progression to complete AV Block in patients with intrinsic AV block. Sparse literature suggest some correlation between length of asystole and increased severity.
- Given that extrinsic vagally mediated AV block is not associated with an innate conduction defect (seen in intrinsic paroxysmal AV block) and is at the level of the AV node, it is considered benign. 
- Given the absence of structural heart disease, the paroxysmal nature of the episodes and the low probability of progression into more severe forms of AV block, extrinsic idiopathic paroxysmal AV block has a good prognosis.
The patient has hyperkalemia requiring a conservative management

# The patient does not have a life threatening hyperkalemia, and can be managed conservatively as follows

## Restrict exogenous potassium intake.

## Stop any medication that can cause or worsen hyperkalemia.
- Amiloride
- ACEI
- Amino acids
- ARB
- Azole
- Cyclosporine
- Digoxin
- Heparin
- NSAID
- Spironolactone
- Succinylcholine
- Tacrolimus
- Triamterene
- Trimethoprim
- Pentamidine

## Search for a possible etiology.

### Life-Threatening Causes
Life-threatening causes include conditions which result in death or permanent disability within 24 hours if left untreated.
- Acute renal failure
- Adrenal insufficiency
- Diabetic ketoacidosis
- Large IV doses of calcium chloride or calcium gluconate
- Massive hemolysis
- Metabolic acidosis
- Rapid tissue necrosis
- Rhabdomyolysis
- Tumor lysis syndrome

### Common Causes
- Pseudohyperkalemia
- Renal insufficiency
- Adrenal insufficiency
- Medications: ACE inhibitors, angiotensin receptor blockers, amiloride, spironolactone, NSAIDS, ciclosporin, tacrolimus, trimethoprim, pentamidine, succinylcholine
- Renal tubular acidosis type 4
- Iatrogenic
- Diabetic ketoacidosis
A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers

# Official Title
An adaptive, phase I, randomized, placebo-controlled, sponsor-unblinded, multiple ascending dose study to investigate the safety, tolerability and pharmacokinetics of intravenous CSL112 in healthy volunteers

# Objectives
- To measure the biomarkers of cholesterol movement following a single and multiple infusions of CSL-112 in healthy subjects.
- To evaluate role of CSL-112 in decreasing cholesterol-loaded plaques that contribute to cardiovascular disease.

# Sponsor
CSL Limited

# Timeline
The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.

# Study Description
The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.

# Eligibility Criteria

## Inclusion Criteria
- Healthy individual
- Age: 18-55 year old
- Weight  5 kg
- BMI between 18-42 kg/m2

## Exclusion Criteria
- Clinically significant medical condition or disease
- Abnormal lab test result
- History of alcohol or other substance abuse

# Outcomes

## Primary Outcomes
Safety and tolerability defined as rate of clinically-associated adverse events that occur within 14 days of CSL112 infusion.

## Secondary Outcomes
Evaluation of lipoprotein pharmacokinetics during a time frame of 10 days following CSL112 infusion and measurement of plasma levels of lipoprotein.

# Publications

## Results
- Infusions of CSL-112 caused immediate and profound elevation in all the biomarkers of cholesterol transport, including preBeta1-HDL and global cholesterol efflux as measured by activity of ATP-binding cassette transporter (ABCA1) cells.
- Serum preBeta1-HDL elevation was up to 20-fold.
- The infusion of CSL112 caused a dose-dependent increase of all biomarkers.  Levels were consistent in magnitude and time course following the first and last infusions.
- Serum preBeta1-HDL and cholesterol efflux capacity peaked after infusion and returned to baseline at 24 hour while there was a 72 hour sustained response for serum HDL following its peak at 24-48 hours after infusion.
- Multiple infusions of CSL112 cause a greater efflux of cholesterol from tissues to HDL when compared with a single infusion.
- There were no observed changes in the baseline of other lipoproteins.

## Conclusion
Single and multiple infusions of CSL-112 in healthy subjects rapidly initiates the reverse cholesterol transport, and this is beneficial in rapidly lowering the risk of recurrent cardiovascular events following acute coronary syndromes.
Bannayan-Riley-Ruvalcaba syndrome epidemiology and demographics

# Overview
The incidence of Bannayan-Riley-Ruvalcaba syndrome is approximately 1 per 200,000 individuals worldwide. Bannayan-Riley-Ruvalcaba syndrome commonly affects individuals of younger age.

# Epidemiology and Demographics

## Incidence
- The incidence of Bannayan-Riley-Ruvalcaba syndrome is approximately 1 per 200,000 individuals worldwide.

## Prevalence
- The prevalence of PTEN mutations Bannayan-Riley-Ruvalcaba syndrome is approximately 65%.

## Age
- Bannayan-Riley-Ruvalcaba syndrome commonly affects individuals of younger age.
- The median age for Bannayan-Riley-Ruvalcaba syndrome diagnosis is as young as five years
European society of cardiology guidelines classification scheme

# Overview
The European Society of Cardiology (ESC) represents more than 50,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the impact of cardiovascular disease in Europe.
The ESC achieves a variety of scientific and educational activities including the coordination of clinical practice guidelines, education courses and initiatives, pan-European surveys on specific disease areas. It also organizes the ESC Annual Congress, which is the largest medical meeting in Europe.
The ESC is comprised of 3 Councils, 5 Associations, 19 Working Groups and 50 National Cardiac Societies. The administrative headquarters of the ESC, based at the European Heart House, is situated in the South of France, in the area of Sophia Antipolis that is between Nice and Cannes.

# Classes of Recommendations
- Class I: Evidence and/or general agreement that a given diagnostic procedure or treatment is beneficial, useful, and effective.
- Class II: Conflicting evidence and/or a divergence of opinion about the usefulness or efficacy of the treatment or procedure.
- Class IIa: Weight of evidence or opinion is in favour of usefulness or efficacy.
- Class IIb: Usefulness or efficacy is less well established by evidence or opinion.
- Class III: Evidence or general agreement that the treatment or procedure is not useful or effective and, in some cases, may be harmful.

# Level of Evidence
- Level of Evidence: A Data derived from multiple randomized clinical trials or meta-analyses.
- Level of Evidence: B Data derived from a single randomized clinical trial or large non-randomized studies.
- Level of Evidence: C Consensus of opinion of the experts and/or small studies, retrospective studies, and registries.

# Source
- ESC official website
Le Dain Commission of Inquiry into the Non-Medical Use of Drugs
The Commission of Inquiry into the Non-Medical Use of Drugs, often referred to as the Le Dain Commission after its chair Dean Gerald Le Dain, was a Canadian government commission that was begun in 1969 and completed its work in 1972. The final report recommended that cannabis be removed from the Narcotic Control Act and that the provinces implement controls on possession and cultivation, similar to those governing the use of alcohol. The report also recommended that the federal government conduct further research to monitor and evaluate changes in the extent and patterns of the use of cannabis and other drugs, and to explore possible consequences to health, and personal and social behaviour, resulting from the controlled legal distribution of cannabis.
A total of 365 submissions were presented at the hearings and an additional 50 were forwarded to the Commission's office. About 12,000 people attended and participated in these hearings which included testimony from a number of prominent individuals including John Lennon on December 22, 1969 in Montreal.
Although the report was widely praised for its thoroughness and thoughtfullness, its conclusions were largely ignored by the federal government.
The heart in gastrointestinal, hepatobilier & pancreatic tumors

# Overview

# Histopathological Changes
Image courtesy of Professor Peter Anderson DVM PhD and published with permission  PEIR, University of Alabama at Birmingham, Department of Pathology
- HEART: Colon Cancer Metastasis: Note massive infiltration of right ventricle and atrium.
- HEART: Metastatic Carcinoma: Micro med mag H&E, a small metastasis in myocardium, stomach is primary
- HEART: Sinus Node Fibrosis: Micro low mag trichrome, a nice photo to illustrate this lesion in 67yo Female with resected colon carcinoma metastases, infectious complications and arrhythmia
- HEART: Marantic endocarditis in a patient with pancreas cancer
- HEART: Thrombotic Nonbacterial Endocarditis: Gross natural color close-up well shown vegetations on all three cusps of aortic valve. A case of carcinoma of tail of pancreas
- HEART: Thrombotic Nonbacterial Endocarditis: Gross natural color close-up large vegetations on anterior and posterior leaflets of mitral valve. A case of carcinoma of tail of pancreas
Torcetrapib Associated with Higher CV Event Rates in ILLUMINATE
November 4, 2007 By Scott P. Williams 
Orlando, FL: The results of the ILLUMINATE trial suggest that patients with a history of cardiovascular disease (CVD) who are treated with torcetrapib face an increased risk of death and cardiac events.  Importantly, the increased risk of adverse events may be mediated by off target toxicity due to a rise in aldosterone and blood pressure in patients treated with torcetrapib.  The results were announced today at the American Heart Associations Scientific Sessions.
The research team hypothesized that torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, would decrease the risk of clinical cardiovascular events by lowering the patients LDL cholesterol level and raising their HDL cholesterol levels.  To test this hypothesis the researchers conducted a prospective, randomized, multi-center, double-blind clinical trial.  Men and women spanning the ages of 45 to 75 years old were eligible to participate in the trial if they displayed symptoms of CVD (MI, stroke, ACS, UA, PVD, cardiac revascularization) 30 days to 5 years prior to enrollment.  Diabetic patients without prior CVD were also eligible for the study.  Upon the completion of 4 to 10 weeks of lifestyle counseling treatment with atorvastatin (as necessary) to reach an LDL cholesterol level of less than 100 mg per deciliter, patients were randomized to receive either atorvastatin and 60 mg torcetrapib (n=7533) or atorvastatin and placebo (n=7534).  The median follow up for both groups of patients was 550 days.
The primary endpoint of ILLUMINATE was the occurrence of a major cardiovascular event, which was defined as any of the following: death from coronary heart disease, nonfatal MI, stroke, and hospitalization for UA.  Secondary endpoints were the time to occurrence of each individual component of the primary endpoint, the time to all cause death, and change in HDL and LDL cholesterol levels.
A 72.1% increase in HDL cholesterol and a 24.9% decrease in LDL cholesterol, as compared with baseline, was observed among patients treated with torcetrapib (p<0.001).  On the other hand, a 5.4 mm Hg increase in systolic blood pressure, increases in serum bicarbonate, aldosterone, and sodium, and a decrease in serum potassium were all observed among patients treated with torcetrapib (p<0.001).
With respect clinical events, treatment with torcetrapib was associated with an increased risk of major cardiovascular events (6.2% vs. 5.0%, HR 1.25, p = 0.001).
Dr Philip Barter, principal investigator of the study indicated that the HDL formed by the drug appears to be functional, and that the increase in aldosterone levels is most likely responsible for the adverse outcomes.  Importantly, other CETP inhibitors do not appear to have the same off target toxicity, and the class of agents may still be of benefit.
Clopidogrel dosing and role of genetics: ELEVATE-TIMI 56 trial

# Overview
The results of the ELEVATE-TIMI 56 trial were recently presented in AHA November 2011 held at Orlando, Florida. The multicentric randomized double blinded trial was able to show that increasing the maintenance doses of clopidogrel to 225 mg daily in CYP2C19 heterozygotes patients with stable cardiovascular diseases, were able to cause similar levels of platelet reactivity as seen with the standard 75-mg dose in non-carriers. However, in patients who were homozygotes for CYP2C19 genes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.

# ELEVATE-TIMI 56 trial 
- Hypothesis - To assess whether increasing the dose of clopidogrel to 300 mg / day rather than the standard 75 mg / day maintenance dose improves outcomes in patients with loss-of-function CYP2C19 genotypes.
- Study design - Multicenter, randomized, double-blind trial
- Duration of study - 1 years
- Intervention - Maintenance doses of clopidogrel for 4 treatment periods, (each treatment period lasted 14 days). 247 noncarriers received 75 and 150 mg daily of clopidogrel (2 periods each), and 86 carriers (80 heterozygotes, 6 homozygotes) received 75, 150, 225, and 300 mg daily.
- Primary end point - Platelet function test results and adverse events.
- Conclusions - Increasing the maintenance doses of clopidogrel to 225 mg daily in CYP2C19 heterozygotes patients with stable cardiovascular diseases, were able to cause similar levels of platelet reactivity as seen with the standard 75-mg dose in non-carriers. However, in patients who were homozygotes for CYP2C19 genes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.
Critical illness-related corticosteroid insufficiency overview

# Overview
Critical illness-related corticosteroid insufficiency (CIRCI) is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.
The hypothalamic-pituitary-adrenal axis (HPA axis), in which the hypothalamus and pituitary gland control adrenal secretions,  undergoes profound changes during critical illness. Both very high and very low levels of cortisol have been linked to a poor outcome in intensive care patients. It has been suggested that high levels could represent severe stress, whereas low levels are due to blunted cortisol production and response.
CIRCI can be suspected in patients with low blood pressure (low blood pressure) despite resuscitation with intravenous fluids and vasopressor drugs. The Surviving Sepsis Campaign guidelines advocate intravenous hydrocortisone only in adults with septic shock and refractory hypotension. The exact definition of this condition, the best ways to test for corticoid insufficiency in critically ill patients, and the therapeutic use of (usually low doses) of corticosteroids remains a subject of debate.
Electrocardiographic findings in right ventricular hypertrophy

# Overview
The general electrocardiographic findings of right ventricular hypertrophy include right axis deviation, an R/S ratio > 1 in V1, and the presence of P pulmonale.

# Summary of EKG Criteria for RVH
- Right axis deviation of +90 degrees or more
- The R wave in V1 is 7 mm or more in height
- RV1 + SV5 or SV6 = 10 mm or more
- R/S ratio in V1 = 1.0 or more
- S/R ratio in V6 = 1.0 or more
- Late intrinsicoid deflection in V1 (0.035+)
- Incomplete RBBB pattern
- ST T strain pattern in 2,3,aVF
- P pulmonale or P congenitale
- S1 S2 S3 pattern in children

# Differential Diagnosis of R>S in V1
- RVH
- Posterior MI
- WPW
- HCM (septal hypertrophy)
- Kulbertus' block (septal fascicular block)
- Duchennes Muscular Dystrophy
- Normal variant
- V4r may be a more useful and reliable than lead V1 in that it often reveals an r>s while v1 remains normal
- An incomplete right bundle branch block in the right precordial chest leads may signal the development of RVH
- In the limb leads right axis deviation develops and at times prominent Q waves simulating an IMI appear in leads 2,3, and aVF.
- In children an S1 S2 S3 pattern (i.e. an S wave deeper than R in all 3 standard leads) is a reliable index of RVH
- RV strain can be seen in leads V1 and V2 but also in leads 2,3, aVF

# Electrocardiographic Examples of RVH
- Right ventricular hypertrophy
- Right ventricular hypertrohpy, the R wave > the S wave in V1
High triglyceride natural history, prognosis and complications

# Overview

# Unclear Association of Hypertriglyceridemia with Atherosclerosis and Cardiovascular Events
It remains unclear if there is an independent association between hypertriglyceridemia and adverse cardiovascular outcomes .  The ascertainment of any independent association between hypertriglyceridemia and clinical outcomes is confounded by the fact that hypertriglyceridemia is associated with so many atherosclerotic risk factors including obesity, diabetes and insulin resistance, metabolic syndrome, the presence of other dyslipidemias associated themselves both with high triglycerides and atherosclerosis (e.g. mixed hyperlipidemia, low HDL (hypoalphalipoproteinemia), Familial dysbetalipoproteinemia (type III hyperlipoproteinemia), etc.),  high levels of small, dense LDL and finally  high levels of apolipoprotein B (apoB).
For example, the relationship among hypertriglyceridemia, atherosclerosis, and apoB is complex. Specifically, those forms of hypertriglyceridemia associated with high levels of apoB, but not those associated with low levels of apoB, are associated with atherosclerosis.

# Pancreatitis
Hypertriglyceridemia can be associated with pancreatitis when the triglyceride levels are markedly elevated (i.e. when the triglyceride concentration is greater, and often very much greater, than 1000 mg/dl or 12 mmol/l).

# Acute Treatment of Pancreatitis Due to Hypertriglyceridemia
- The patient should be treated with apheresis (specifically therapeutic plasma exchange) if the following are present:
- Triglyceride level is > 1000 mg/dl
- Lipase level is > 3 times the upper limit of normal
- Lactic acidosis
- Hypocalcemia
The patient should be treated with intravenous insulin at 0.1 to 0.3 units/kg/day to maintain glucose of 150 to 200 if the following are present:
- The patient cannot tolerate apheresis
- Apheresis is not available,
- Serum glucose >500 mg/dL
- The insulin should be discontinued when the triglyceride level drops to below 500 mg/dl
Secondary prevention of hypertriglyeride induced pancreatitis consists of a low-carbohydrate diet and gemfibrozil 600 mg PO BID.

# Xanthoma