<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pilonidal disease and can you explain it in depth? [/INST] Pilonidal disease is a type of skin infection which typically occurs as a cyst between the cheeks of the buttocks and often at the upper end. Symptoms may include pain, swelling, and redness. There may also be drainage of fluid, but rarely a fever.Risk factors include obesity, family history, prolonged sitting, greater amounts of hair, and not enough exercise. The underlying mechanism is believed to involve a mechanical process. The lesions may contain hair and skin debris. Diagnosis is based on symptoms and examination.If there is infection, treatment is generally by incision and drainage just off the midline. Shaving the area and laser hair removal may prevent recurrence. More extensive surgery may be required if the disease recurs. Antibiotics are usually not needed. Without treatment the condition may remain long term.About 3 per 10,000 people per year are affected, and it occurs more often in males than females. Young adults are most commonly affected. The term "pilonidal" means "nest of hair". The condition was first described in 1833.

Signs and symptoms
Pilonidal cysts are itchy and often very painful, and typically occur between the ages of 15 and 35.  Although usually found near the coccyx, the condition can also affect the navel, armpit, the cheek, or the genital region, though these locations are much rarer.
Signs and symptoms may include:
Intermittent pain/discomfort or swelling above the anus or near the tailbone
Opaque yellow (purulent) or bloody discharge from the tailbone area
Unexpected moisture in the tailbone region
Discomfort sitting on the tailbone, doing sit-ups or riding a bicycle—any activities that roll over the tailbone areaSome people with a pilonidal cyst will be asymptomatic.

Pilonidal sinus
Pilonidal sinus (PNS): is a sinus tract, or small channel, that may originate from the source of infection and open to the surface of the skin. Material from the cyst drains through the pilonidal sinus.  A pilonidal cyst is usually painful, but with draining the patient might not feel pain.

Causes
One proposed cause of pilonidal cysts is ingrown hair, although hairs found in pilonidal sinus tracts may originate from the head. Excessive sitting is thought to predispose people to the condition, as sitting increases pressure on the coccygeal region. Trauma is not believed to cause a pilonidal cyst; however, such an event may result in inflammation of an existing cyst; there are cases where this can occur months after a localized injury to the area. Some researchers have proposed that pilonidal cysts may be caused by a congenital pilonidal dimple. Excessive sweating can also contribute to the formation of a pilonidal cyst: moisture can fill a stretched hair follicle, which helps create a low-oxygen environment that promotes the growth of anaerobic bacteria, often found in pilonidal cysts. The presence of bacteria and low oxygen levels hamper wound healing and exacerbate a forming pilonidal cyst.

Differential diagnosis
A pilonidal cyst can resemble a dermoid cyst, a kind of teratoma (germ cell tumor).  In particular, a pilonidal cyst in the gluteal cleft can resemble a sacrococcygeal teratoma.  Correct diagnosis is important because all teratomas require consultation with an oncologist and complete surgical excision, if possible without any spillage.

Treatment
If there is infection, treatment is generally by incision and drainage just off the midline. Following five simple rules has been known to prevent recurring inflammations for some people and avoid the surgery: 1. Avoiding chairs and car seats that put pressure on coccyx; 2. Being of normal weight, preferably with low BMI; 3. Keeping the area clean; 4. Keeping the area dry by wearing exclusively cotton garments; 5. Keeping the area completely hair free, for example by regularly using an IPL hair removal device.The evidence for elective treatment of pilonidal sinus disease is poor. The most commonly performed surgery is for the pilonidal sinus complex to be surgically excised with the wound often left open to heal. Post-surgical wound packing may be necessary, and packing typically must be replaced daily for 4 to 8 weeks. In some cases, two years may be required for complete granulation to occur.  Sometimes the cyst is resolved via surgical marsupialization.Surgeons can also excise the sinus and repair with a reconstructive flap technique, such as a "cleft lift" procedure or Z-plasty, usually done under general anesthetic. This approach is especially useful for complicated or recurring pilonidal disease, leaves little scar tissue and flattens the region between the buttocks, reducing the risk of recurrence.  This approach typically results in a more rapid recovery than the traditional surgery, however there are fewer surgeons trained in the cleft lift procedure and it consequently may not be as accessible to patients, depending on their location. Meta-analysis shows recurrence rates were lower in open healing than with primary closure (RR 0.60, 95% CI 0.42 to 0.87), at the expense of healing time. Pilonidal cysts can recur, and do so more frequently if the surgical wound is sutured in the midline, as opposed to away from the midline, which obliterates the natal cleft and removes the focus of shearing stress. An incision lateral to the intergluteal cleft is therefore preferred, especially given the poor healing of midline incisions in this region </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pterygium and can you explain it in depth? [/INST] Pterygium (plural pterygia or pterygiums) refers to any wing-like triangular membrane occurring in the neck, eyes, knees, elbows, ankles or digits.The term comes from the Greek word pterygion meaning "wing".

Types
Popliteal pterygium syndrome, a congenital condition affecting the face, limbs, or genitalia but named after the wing-like structural anomaly behind the knee
Pterygium (eye) or surfers eye, a growth on the cornea of the eye
Pterygium colli or webbed neck,  a congenital skin fold of the neck down to the shoulders
Pterygium inversum unguis or ventral pterygium, adherence of the distal portion of the nailbed to the ventral surface of the nail plate
Pterygium unguis or dorsal pterygium, scarring between the proximal nail fold and matrix

Pterygium of the eye
A pterygium reduces the vision in several ways:

Distortion of the corneal optics.  This begins usually when the pterygium is greater than 2mm from the corneal edge (limbus).
Disruption of the tear film.  The tear film is the first lens in the eye </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Glaucoma and can you explain it in depth? [/INST] Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye remains open, with less common types including closed-angle (narrow angle, acute congestive) glaucoma and normal-tension glaucoma. Open-angle glaucoma develops slowly over time and there is no pain. Peripheral vision may begin to decrease, followed by central vision, resulting in blindness if not treated. Closed-angle glaucoma can present gradually or suddenly. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye, and nausea. Vision loss from glaucoma, once it has occurred, is permanent. Eyes affected by glaucoma are referred to as being glaucomatous.
Risk factors for glaucoma include increasing age, high pressure in the eye, a family history of glaucoma, and use of steroid medication. For eye pressures, a value of 21 mmHg or 2.8 kPa above atmospheric pressure (760 mmHg) is often used, with higher pressures leading to a greater risk. However, some may have high eye pressure for years and never develop damage. Conversely, optic nerve damage may occur with normal pressure, known as normal-tension glaucoma. The mechanism of open-angle glaucoma is believed to be the slow exit of aqueous humor through the trabecular meshwork, while in closed-angle glaucoma the iris blocks the trabecular meshwork. Diagnosis is achieved by performing a dilated eye examination. Often, the optic nerve shows an abnormal amount of cupping.If treated early, it is possible to slow or stop the progression of disease with medication, laser treatment, or surgery. The goal of these treatments is to decrease eye pressure. A number of different classes of glaucoma medication are available. Laser treatments may be effective in both open-angle and closed-angle glaucoma. A number of types of glaucoma surgeries may be used in people who do not respond sufficiently to other measures. Treatment of closed-angle glaucoma is a medical emergency.About 70 million people have glaucoma globally, with about two million patients in the United States. It is the leading cause of blindness in African Americans. It occurs more commonly among older people, and closed-angle glaucoma is more common in women. Glaucoma has been called the "silent thief of sight", because the loss of vision usually occurs slowly over a long period of time. Worldwide, glaucoma is the second-leading cause of blindness after cataracts. Cataracts caused 51% of blindness in 2010, while glaucoma caused 8%. The word "glaucoma" is from the Ancient Greek glaukos, which means "shimmering." In English, the word was used as early as 1587 but did not become commonly used until after 1850, when the development of the ophthalmoscope allowed doctors to see the optic nerve damage.

Signs and symptoms
As open-angle glaucoma is usually painless with no symptoms early in the disease process, screening through regular eye exams is important. The only signs are gradually progressive visual field loss and optic nerve changes (increased cup-to-disc ratio on fundoscopic examination).
About 10% of people with closed angles present with acute angle closure characterized by sudden ocular pain, seeing halos around lights, red eye, very high intraocular pressure (>30 mmHg (4.0 kPa)), nausea and vomiting, suddenly decreased vision, and a fixed, mid-dilated pupil. It is also associated with an oval pupil in some cases. Acute angle closure is an emergency.
Opaque specks may occur in the lens in glaucoma, known as glaukomflecken.

Causes
Ocular hypertension (increased pressure within the eye) is the most important risk factor for glaucoma, but only about 50% of people with primary open-angle glaucoma actually have elevated ocular pressure. Ocular hypertension—an intraocular pressure above the traditional threshold of 21 mmHg (2.8 kPa) or even above 24 mmHg (3.2 kPa)—is not necessarily a pathological condition, but it increases the risk of developing glaucoma. One study found a conversion rate of 18% within five years, meaning fewer than one in five people with elevated intraocular pressure will develop glaucomatous visual field loss over that period of time. It is a matter of debate whether every person with an elevated intraocular pressure should receive glaucoma therapy; currently, most ophthalmologists favor treatment of those with additional risk factors.Open-angle glaucoma accounts for 90% of glaucoma cases in the United States. Closed-angle glaucoma accounts for fewer than 10% of glaucoma cases in the United States, but as many as half of glaucoma cases in other nations (particularly East Asian countries).

Dietary
No clear evidence indicates that vitamin deficiencies cause glaucoma in humans. As such, oral vitamin supplementation is not a recommended treatment. Caffeine increases intraocular pressure in those with glaucoma, but does not appear to affect normal individuals.

Ethnicity
Many people of East Asian descent are prone to developing angle closure glaucoma because of shallower anterior chamber depths, with the majority of cases of glaucoma in this population consisting of some form of angle closure. Higher rates of glaucoma have also been reported for Inuit populations, compared to White populations, in Canada and Greenland.

Genetics
Positive family history is a risk factor for glaucoma. The relative risk of having primary open-angle glaucoma (POAG) is increased about two- to four-fold for people who have a sibling with glaucoma. Glaucoma, particularly primary open-angle glaucoma, is associated with mutations in several genes, including MYOC, ASB10, WDR36, NTF4, TBK1, and RPGRIP1, although most cases of glaucoma do not involve these genetic mutations. Normal-tension glaucoma, which comprises one-third of POAG, is also associated with genetic mutations (including OPA1 and OPTN genes).Various rare congenital/genetic eye malformations are associated with glaucoma. Occasionally, failure of the normal third-trimester gestational atrophy of the hyaloid canal and the tunica vasculosa lentis is associated with other anomalies. Angle closure-induced ocular hypertension and glaucomatous optic neuropathy may also occur with these anomalies and has been modelled in mice.

Other
Other factors can cause glaucoma, known as "secondary glaucoma", including prolonged use of steroids (steroid-induced glaucoma); conditions that severely restrict blood flow to the eye, such as severe diabetic retinopathy and central retinal vein occlusion (neovascular glaucoma); ocular trauma (angle-recession glaucoma); and inflammation of the middle layer of the pigmented vascular eye structure (uveitis), known as uveitic glaucoma.

Pathophysiology
The underlying cause of open-angle glaucoma remains unclear. Several theories exist on its exact etiology. However, the major risk factor for most glaucomas and the focus of treatment is increased intraocular pressure. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary processes of the eye, and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary processes into the posterior chamber, bounded posteriorly by the lens and the zonules of Zinn, and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea.
From here, the trabecular meshwork drains aqueous humor via the scleral venous sinus (Schlemms canal) into scleral plexuses and general blood circulation.In open/wide-angle glaucoma, flow is reduced through the trabecular meshwork, due to the degeneration and obstruction of the trabecular meshwork, whose original function is to absorb the aqueous humor. Loss of aqueous humor absorption leads to increased resistance and thus a chronic, painless buildup of pressure in the eye.In close/narrow-angle, the iridocorneal angle is completely closed because of forward displacement of the final roll and root of the iris against the cornea, resulting in the inability of the aqueous fluid to flow from the posterior to the anterior chamber and then out of the trabecular network. This accumulation of aqueous humor causes an acute increase in pressure and pain.
Degeneration of axons of the retinal ganglion cells (the optic nerve) is a hallmark of glaucoma. The inconsistent relationship of glaucomatous optic neuropathy with increased intraocular pressure has provoked hypotheses and studies on anatomic structure, eye development, nerve compression trauma, optic nerve blood flow, excitatory neurotransmitter, trophic factor, retinal ganglion cell/axon degeneration, glial support cell, immune system, aging mechanisms of neuron loss, and severing of the nerve fibers at the scleral edge.

Diagnosis
Screening for glaucoma is usually performed as part of a standard eye examination performed by optometrists and ophthalmologists. Testing for glaucoma includes measurements of the intraocular pressure using tonometry, anterior chamber angle examination or gonioscopy as well as examination of the optic nerve to discern visible damage, changes in the cup-to-disc ratio, rim appearance and vascular change. A formal visual field test is performed. The retinal nerve fiber layer can be assessed with imaging techniques such as optical coherence tomography, scanning laser polarimetry or scanning laser ophthalmoscopy (Heidelberg retinal tomogram). Visual field loss is the most specific sign of the condition, though it occurs later in the course of the disease.As all methods of tonometry are sensitive to corneal thickness, methods such as Goldmann tonometry may be augmented with pachymetry to measure the central corneal thickness (CCT). A thicker cornea can result in a pressure reading higher than the true pressure but a thinner cornea can produce a pressure reading lower than the true pressure.Because pressure-measurement error can be caused by more than just CCT (such as by corneal hydration or elastic properties), it is impossible to adjust pressure measurements based only on CCT measurements. The frequency-doubling illusion can also be used to detect glaucoma with the use of a frequency-doubling technology perimeter.Examination for glaucoma is assessed with attention given to gender, race, history of drug use, refraction, inheritance and family history.
Glaucoma has been classified into specific types:

Primary glaucoma and its variants
Primary glaucoma (H40.1-H40.2)

Primary open-angle glaucoma, also known as chronic open-angle glaucoma, chronic simple glaucoma, glaucoma simplexHigh-tension glaucoma
Low-tension glaucomaPrimary angle closure glaucoma, also known as primary closed-angle glaucoma, narrow-angle glaucoma, pupil-block glaucoma, acute congestive glaucomaAcute angle closure glaucoma (aka AACG)
Chronic angle closure glaucoma
Intermittent angle closure glaucoma
Superimposed on chronic open-angle closure glaucoma ("combined mechanism" – uncommon)Variants of primary glaucoma

Pigmentary glaucoma
Exfoliation glaucoma, also known as pseudoexfoliative glaucoma or glaucoma capsulare
Primary juvenile glaucomaPrimary angle closure glaucoma is caused by contact between the iris and trabecular meshwork, which in turn obstructs outflow of the aqueous humor from the eye. This contact between iris and trabecular meshwork (TM) may gradually damage the function of the meshwork until it fails to keep pace with aqueous production, and the pressure rises. In over half of all cases, prolonged contact between iris and TM causes the formation of synechiae (effectively "scars").
These cause permanent obstruction of aqueous outflow. In some cases, pressure may rapidly build up in the eye, causing pain and redness (symptomatic, or so-called "acute" angle closure). In this situation, the vision may become blurred, and halos may be seen around bright lights. Accompanying symptoms may include a headache and vomiting.
Diagnosis is made from physical signs and symptoms: pupils mid-dilated and unresponsive to light, cornea edematous (cloudy), reduced vision, redness, and pain. However, the majority of cases are asymptomatic. Prior to the very severe loss of vision, these cases can only be identified by examination, generally by an eye care professional.
Once any symptoms have been controlled, the first line (and often definitive) treatment is laser iridotomy. This may be performed using either Nd:YAG or argon lasers, or in some cases by conventional incisional surgery. The goal of treatment is to reverse and prevent contact between the iris and trabecular meshwork. In early to moderately advanced cases, iridotomy is successful in opening the angle in around 75% of cases. In the other 25%, laser iridoplasty, medication (pilocarpine) or incisional surgery may be required.
Primary open-angle glaucoma is when optic nerve damage results in a progressive loss of the visual field. This is associated with increased pressure in the eye. Not all people with primary open-angle glaucoma have eye pressure that is elevated beyond normal, but decreasing the eye pressure further has been shown to stop progression even in these cases.
The increased pressure is caused by trabecular meshwork blockage. Because the microscopic passageways are blocked, the pressure builds up in the eye and causes imperceptible very gradual vision loss. Peripheral vision is affected first, but eventually the entire vision will be lost if not treated.
Diagnosis is made by looking for cupping of the optic nerve. Prostaglandin agonists work by opening uveoscleral passageways. Beta-blockers, such as timolol, work by decreasing aqueous formation. Carbonic anhydrase inhibitors decrease bicarbonate formation from ciliary processes in the eye, thus decreasing the formation of aqueous humor. Parasympathetic analogs are drugs that work on the trabecular outflow by opening up the passageway and constricting the pupil. Alpha 2 agonists (brimonidine, apraclonidine) both decrease fluid production (via inhibition of AC) and increase drainage.

Developmental glaucoma
Developmental glaucoma (Q15.0)

Primary congenital glaucoma
Infantile glaucoma
Glaucoma associated with hereditary or familial diseases

Secondary glaucoma
Secondary glaucoma (H40.3-H40.6)

Inflammatory glaucomaUveitis of all types
Fuchs heterochromic iridocyclitisPhacogenic glaucomaAngle-closure glaucoma with mature cataract
Phacoanaphylactic glaucoma secondary to rupture of lens capsule
Phacolytic glaucoma due to phacotoxic meshwork blockage
Subluxation of lensGlaucoma secondary to intraocular hemorrhageHyphema
Hemolytic glaucoma, also known as erythroclastic glaucomaTraumatic glaucomaAngle recession glaucoma: Traumatic recession on anterior chamber angle
Postsurgical glaucomaAphakic pupillary block
Ciliary block glaucomaNeovascular glaucoma (see below for more details)
Drug-induced glaucomaCorticosteroid induced glaucoma
Alpha-chymotrypsin glaucoma. Postoperative ocular hypertension from use of alpha chymotrypsin.Glaucoma of miscellaneous originAssociated with intraocular tumors
Associated with retinal detachments
Secondary to severe chemical burns of the eye
Associated with essential iris atrophy
Toxic glaucomaNeovascular glaucoma, an uncommon type of glaucoma, is difficult or nearly impossible to treat, and is often caused by proliferative diabetic retinopathy (PDR) or central retinal vein occlusion (CRVO). It may also be triggered by other conditions that result in ischemia of the retina or ciliary body. Individuals with poor blood flow to the eye are highly at risk for this condition.
Neovascular glaucoma results when new, abnormal vessels begin developing in the angle of the eye that begin blocking the drainage. People with such condition begin to rapidly lose their eyesight. Sometimes, the disease appears very rapidly, especially after cataract surgery procedures. A new treatment for this disease, as first reported by Kahook and colleagues, involves the use of a novel group of medications known as anti-VEGF agents. These injectable medications can lead to a dramatic decrease in new vessel formation and, if injected early enough in the disease process, may lead to normalization of intraocular pressure. Currently, there are no high-quality controlled trials demonstrating a beneficial effect of anti-VEGF treatments in lowering IOP in people with neovascular glaucoma.Toxic glaucoma is open-angle glaucoma with an unexplained significant rise of intraocular pressure following unknown pathogenesis. Intraocular pressure can sometimes reach 80 mmHg (11 kPa). It characteristically manifests as ciliary body inflammation and massive trabecular oedema that sometimes extends to Schlemms canal. This condition is differentiated from malignant glaucoma by the presence of a deep and clear anterior chamber and a lack of aqueous misdirection. Also, the corneal appearance is not as hazy. A reduction in visual acuity can occur followed neuroretinal breakdown.
Associated factors include inflammation, drugs, trauma and intraocular surgery, including cataract surgery and vitrectomy procedures. Gede Pardianto (2005) reported on four patients who had toxic glaucoma. One of them underwent phacoemulsification with small particle nucleus drops. Some cases can be resolved with some medication, vitrectomy procedures or trabeculectomy. Valving procedures can give some relief, but further research is required.

Absolute glaucoma
Absolute glaucoma (H44.5) is the end stage of all types of glaucoma. The eye has no vision, absence of pupillary light reflex and pupillary response, and has a stony appearance. Severe pain is present in the eye. The treatment of absolute glaucoma is a destructive procedure like cyclocryoapplication, cyclophotocoagulation, or injection of 99% alcohol.

Types
Glaucoma is an umbrella term for eye conditions that damage the optic nerve and that can lead to a loss of vision. The main cause of damage to the optic nerve is intraocular pressure (IOP), excessive fluid pressure within the eye, which can be caused by factors such as blockage of drainage ducts and narrowing or closure of the angle between the iris and cornea.
Glaucoma is primarily categorized as either open-angle or closed-angle (or angle-closure). In open-angle glaucoma, the iris meets the cornea normally, allowing the fluid from inside the eye to drain, thus relieving the internal pressure. When this angle is narrowed or closed, pressure increases over time, causing damage to the optic nerve and leading to blindness.
Primary open-angle glaucoma (also called primary or chronic glaucoma) involves the slow clogging of drainage canals resulting in increased eye pressure, which causes progressive optic nerve damage. This manifests as a gradual loss of the visual field, starting with a loss of peripheral vision, but eventually all vision will be lost if the condition is not treated. This is the most common type of glaucoma, accounting for 90% of cases in the United States, but is less prevalent in Asian countries. Onset is slow and painless, and loss of vision is gradual and irreversible.
With narrow-angle glaucoma (also called closed-angle glaucoma), the iris bows forward, narrowing the angle that drains the eye, increasing pressure within the eye. If untreated, it can lead to the medical emergency of angle-closure glaucoma.
With angle-closure glaucoma (also called closed-angle, primary angle-closure or acute glaucoma), the iris bows forward and causes physical contact between the iris and trabecular meshwork, which blocks the outflow of aqueous humor from within the eye. This contact may gradually damage the draining function of the meshwork until it fails to keep pace with aqueous production, and the intraocular pressure rises. The onset of symptoms is sudden and causes pain and other noticeable symptoms, and the condition is treated as a medical emergency. Unlike open-angle glaucoma, angle-closure glaucoma is a result of the closing of the angle between the iris and cornea. This tends to occur in the farsighted, who have smaller anterior chambers, making physical contact between the iris and trabecular meshwork more likely. A variety of tests may be performed to detect those at risk of angle-closure glaucoma.Normal-tension glaucoma (NTG, also called low-tension or normal-pressure glaucoma) is a condition in which the optic nerve is damaged although intraocular pressure (IOP) is in the normal range (12 to 22 mmHg (1.6 to 2.9 kPa)). Individuals with a family history of NTG, those of Japanese ancestry, those with a history of systemic heart disease and those with Flammer syndrome are at an elevated risk of developing NTG. The cause of NTG is unknown.
Secondary glaucoma refers to any case in which another disease, trauma, drug or procedure causes increased eye pressure, resulting in optic nerve damage and vision loss, which may be mild or severe. This may be the result of an eye injury, inflammation, a tumor or advanced cases of cataracts or diabetes. It can also be caused by certain drugs such as steroids. Treatment depends on whether the condition is identified as open-angle or angle-closure glaucoma.
With pseudoexfoliation glaucoma (also known as PEX or exfoliation glaucoma) the pressure results from the accumulation of microscopic granular protein fibers, which can block normal drainage of the aqueous humor. PEX is prevalent in Scandinavia, primarily in those over 70, and more commonly in women.
Pigmentary glaucoma (also known as pigmentary dispersion syndrome) is caused by pigment cells sloughing off from the back of the iris and floating around in the aqueous humor. Over time, these pigment cells can accumulate in the anterior chamber and begin to clog the trabecular meshwork. It is a rare condition that occurs mostly among white males in their mid-20s to 40s, most of whom are nearsighted.
Primary juvenile glaucoma is a neonate or juvenile abnormality in which ocular hypertension is evident at birth or shortly thereafter and is caused by abnormalities in the anterior chamber angle development that blocks the outflow of the aqueous humor.
Uveitic glaucoma is caused by uveitis, the swelling and inflammation of the uvea, the middle layer of the eye. The uvea provides most of the blood supply to the retina. Increased eye pressure can result from the inflammation itself or from the steroids used to treat it.

Visual field defects in glaucoma
In glaucoma visual field defects result from damage to the retinal nerve fiber layer. Field defects are seen mainly in primary open angle glaucoma. Because of the unique anatomy of the RNFL, many noticeable patterns are seen in the visual field. Most of the early glaucomatous changes are seen within the central visual field, mainly in Bjerrums area, 10-20° from fixation.Following are the common glaucomatous field defects:

Generalized depression: Generalized depression is seen in early stages of glaucoma and many other conditions. Mild constriction of central and peripheral visual field due to isopter contraction comes under generalized depression. If all the isopters show similar depression to the same point, it is then called a contraction of visual field. Relative paracentral scotomas are the areas where smaller and dimmer targets are not visualized by the patient. Larger and brighter targets can be seen. Small paracentral depressions, mainly superonasal are seen in normal tension glaucoma (NTG). The generalized depression of the entire field may be seen in cataract also.
Baring of blind spot: "Baring of blind spot" means exclusion of blind spot from the central field due to inward curve of the outer boundary of 30° central field. It is only an early non-specific visual field change, without much diagnostic value in glaucoma.
Small wing-shaped Paracentral scotoma: Small wing-shaped Paracentral scotoma within Bjerrums area is the earliest clinically significant field defect seen in glaucoma. It may also be associated with nasal steps. Scotoma may be seen above or below the blind spot.
Siedels sickle-shaped scotoma: Paracentral scotoma joins with the blind spot to form the Seidel sign.
Arcuate or Bjerrums scotoma:  It is formed at later stages of glaucoma by extension of Seidels scotoma in an area either above or below the fixation point to reach the horizontal line. Peripheral breakthrough may occur due to damage of nerve fibers.
Ring or Double arcuate scotoma: Two arcuate scotomas join to form a Ring or Double arcuate scotoma. This defect is seen in advanced stages of glaucoma.
Roennes central nasal step: It is created when two arcuate scotomas run in different arcs to form a right angled defect. This is also seen in advanced stages of glaucoma.
Peripheral field defects: Peripheral field defects may occur in early or late stages of glaucoma. Roennes peripheral nasal steps occur due to contraction of peripheral isopter.
Tubular vision:  Since macular fibers are the most resistant to glaucomatous damage, the central vision remains unaffected until end stages of glaucoma. Tubular vision or Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision. It is seen in the end stages of glaucoma. Retinitis pigmentosa is another disease that causes tubular vision.
Temporal island of vision: It is also seen in end stages of glaucoma. The temporal islands lie outside of the central 24 to 30° visual field, so it may not be visible with standard central field measurements done in glaucoma.

Screening
The United States Preventive Services Task Force stated, as of 2013, that there was insufficient evidence to recommend for or against screening for glaucoma. Therefore, there is no national screening program in the US. Screening, however, is recommended starting at age 40 by the American Academy of Ophthalmology.There is a glaucoma screening program in the UK. Those at risk are advised to have a dilated eye examination at least once a year.

Treatment
The modern goals of glaucoma management are to avoid glaucomatous damage and nerve damage, and preserve visual field and total quality of life for patients, with minimal side-effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although intraocular pressure (IOP) is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment. A review of people with primary open-angle glaucoma and ocular hypertension concluded that medical IOP-lowering treatment slowed down the progression of visual field loss.Vascular flow and neurodegenerative theories of glaucomatous optic neuropathy have prompted studies on various neuroprotective therapeutic strategies, including nutritional compounds, some of which may be regarded by clinicians as safe for use now, while others are on trial. Mental stress is also considered as consequence and cause of vision loss which means that stress management training, autogenic training and other techniques to cope with stress can be helpful.

Medication
Intraocular pressure can be lowered with medication, usually eye drops. Several classes of medications are used to treat glaucoma, with several medications in each class. By reducing pressure, eye drops also help to lower the risk of sight loss. Latanoprost, for example, seems to halve this risk.Each of these medicines may have local and systemic side effects. Wiping the eye with an absorbent pad after the administration of eye drops may result in fewer adverse effects, like the growth of eyelashes and hyperpigmentation in the eyelid. Initially, glaucoma drops may reasonably be started in either one or in both eyes.The possible neuroprotective effects of various topical and systemic medications are also being investigated.
Prostaglandin analogs, such as latanoprost, bimatoprost and travoprost, increase uveoscleral outflow of aqueous humor. Bimatoprost also increases trabecular outflow.
Topical beta-adrenergic receptor antagonists, such as timolol, levobunolol, and betaxolol, decrease aqueous humor production by the epithelium of the ciliary body.
Alpha2-adrenergic agonists, such as brimonidine and apraclonidine, work by a dual mechanism, decreasing aqueous humor production and increasing uveoscleral outflow.
Less-selective alpha agonists, such as epinephrine, decrease aqueous humor production through vasoconstriction of ciliary body blood vessels, useful only in open-angle glaucoma. Epinephrines mydriatic effect, however, renders it unsuitable for closed-angle glaucoma due to further narrowing of the uveoscleral outflow (i.e. further closure of trabecular meshwork, which is responsible for absorption of aqueous humor).
Miotic agents (parasympathomimetics), such as pilocarpine, work by contraction of the ciliary muscle, opening the trabecular meshwork and allowing increased outflow of the aqueous humour. Echothiophate, an acetylcholinesterase inhibitor, is used in chronic glaucoma.
Carbonic anhydrase inhibitors, such as dorzolamide, brinzolamide, and acetazolamide, lower secretion of aqueous humor by inhibiting carbonic anhydrase in the ciliary body.

Adherence
Poor compliance with medications and follow-up visits is a major reason for vision loss in glaucoma patients. A 2003 study of patients in an HMO found half failed to fill their prescriptions the first time, and one-quarter failed to refill their prescriptions a second time. Patient education and communication must be ongoing to sustain successful treatment plans for this lifelong disease with no early symptoms.
Adherence to medication protocol can be confusing and expensive; if side effects occur, the patient must be willing either to tolerate them or to communicate with the treating physician to improve the drug regimen. Initially, glaucoma drops may reasonably be started in either one or in both eyes.

Laser
Argon laser trabeculoplasty (ALT) may be used to treat open-angle glaucoma, but this is a temporary solution, not a cure. A 50-μm argon laser spot is aimed at the trabecular meshwork to stimulate the opening of the mesh to allow more outflow of aqueous fluid. Usually, half of the angle is treated at a time. Traditional laser trabeculoplasty uses a thermal argon laser in an argon laser trabeculoplasty procedure.
Nd:YAG laser peripheral iridotomy (LPI) may be used in patients susceptible to or affected by angle closure glaucoma or pigment dispersion syndrome. During laser iridotomy, laser energy is used to make a small, full-thickness opening in the iris to equalize the pressure between the front and back of the iris, thus correcting any abnormal bulging of the iris. In people with narrow angles, this can uncover the trabecular meshwork. In some cases of intermittent or short-term angle closure, this may lower the eye pressure. Laser iridotomy reduces the risk of developing an attack of acute angle closure. In most cases, it also reduces the risk of developing chronic angle closure or of adhesions of the iris to the trabecular meshwork.
Diode laser cycloablation lowers IOP by reducing aqueous secretion by destroying secretory ciliary epithelium.

Surgery
Both laser and conventional surgeries are performed to treat glaucoma. Surgery is the primary therapy for those with congenital glaucoma. Generally, these operations are a temporary solution, as there is not yet a cure for glaucoma.

Canaloplasty
Canaloplasty is a nonpenetrating procedure using microcatheter technology. To perform a canaloplasty, an incision is made into the eye to gain access to the Schlemms canal in a similar fashion to a viscocanalostomy. A microcatheter will circumnavigate the canal around the iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material called viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened.
By opening the canal, the pressure inside the eye may be relieved, although the reason is unclear, since the canal (of Schlemm) does not have any significant fluid resistance in glaucoma or healthy eyes. Long-term results are not available.

Trabeculectomy
The most common conventional surgery performed for glaucoma is the trabeculectomy. Here, a partial thickness flap is made in the scleral wall of the eye, and a window opening is made under the flap to remove a portion of the trabecular meshwork. The scleral flap is then sutured loosely back in place to allow fluid to flow out of the eye through this opening, resulting in lowered intraocular pressure and the formation of a bleb or fluid bubble on the surface of the eye.
Scarring can occur around or over the flap opening, causing it to become less effective or lose effectiveness altogether. Traditionally, chemotherapeutic adjuvants, such as mitomycin C (MMC) or 5-fluorouracil (5-FU), are applied with soaked sponges on the wound bed to prevent filtering blebs from scarring by inhibiting fibroblast proliferation. Contemporary alternatives to prevent the scarring of the meshwork opening include the sole or combinative implementation of nonchemotherapeutic adjuvants such as the Ologen collagen matrix, which has been clinically shown to increase the success rates of surgical treatment.Collagen matrix prevents scarring by randomizing and modulating fibroblast proliferation in addition to mechanically preventing wound contraction and adhesion.

Glaucoma drainage implants
The first glaucoma drainage implant was developed in 1966. Since then, several types of implants have followed on from the original: the Baerveldt tube shunt, or the valved implants, such as the Ahmed glaucoma valve implant or the ExPress Mini Shunt and the later generation pressure ridge Molteno implants. These are indicated for glaucoma patients not responding to maximal medical therapy, with previous failed guarded filtering surgery (trabeculectomy). The flow tube is inserted into the anterior chamber of the eye, and the plate is implanted underneath the conjunctiva to allow a flow of aqueous fluid out of the eye into a chamber called a bleb.

The first-generation Molteno and other nonvalved implants sometimes require the ligation of the tube until the bleb formed is mildly fibrosed and water-tight. This is done to reduce postoperative hypotony—sudden drops in postoperative intraocular pressure.
Valved implants, such as the Ahmed glaucoma valve, attempt to control postoperative hypotony by using a mechanical valve.
Ab interno implants, such as the Xen Gel Stent, are transscleral implants by an ab interno procedure to channel aqueous humor into the non-dissected Tenons space, creating a subconjunctival drainage area similar to a bleb. The implants are transscleral and different from other ab interno implants that do not create a transscleral drainage, such as iStent, CyPass, or Hydrus.The ongoing scarring over the conjunctival dissipation segment of the shunt may become too thick for the aqueous humor to filter through. This may require preventive measures using antifibrotic medications, such as 5-fluorouracil or mitomycin-C (during the procedure), or other nonantifibrotic medication methods, such as collagen matrix implant, or biodegradable spacer, or later on create a necessity for revision surgery with the sole or combinative use of donor patch grafts or collagen matrix implant. And for glaucomatous painful blind eye and some cases of glaucoma, cyclocryotherapy for ciliary body ablation could be considered to be performed.

Laser-assisted nonpenetrating deep sclerectomy
The most common surgical approach currently used for the treatment of glaucoma is trabeculectomy, in which the sclera is punctured to alleviate intraocular pressure.
Nonpenetrating deep sclerectomy (NPDS) surgery is a similar, but modified, procedure, in which instead of puncturing the scleral bed and trabecular meshwork under a scleral flap, a second deep scleral flap is created, excised, with further procedures of deroofing the Schlemms canal, upon which, percolation of liquid from the inner eye is achieved and thus alleviating intraocular pressure, without penetrating the eye. NPDS is demonstrated to have significantly fewer side effects than trabeculectomy. However, NPDS is performed manually and requires higher level of skills that may be assisted with instruments.   In order to prevent wound adhesion after deep scleral excision and to maintain good filtering results, NPDS as with other non-penetrating procedures is sometimes performed with a variety of biocompatible spacers or devices, such as the Aquaflow collagen wick, ologen Collagen Matrix, or Xenoplast glaucoma implant.Laser-assisted NPDS is performed with the use of a CO2 laser system. The laser-based system is self-terminating once the required scleral thickness and adequate drainage of the intraocular fluid have been achieved. This self-regulation effect is achieved as the CO2 laser essentially stops ablating as soon as it comes in contact with the intraocular percolated liquid, which occurs as soon as the laser reaches the optimal residual intact layer thickness.

Lens extraction
For people with chronic closed-angle glaucoma, lens extraction can relieve the block created by the pupil and help regulate the intraocular pressure.

Prognosis
In open-angle glaucoma, the typical progression from normal vision to complete blindness takes about 25 years to 70 years without treatment, depending on the method of estimation used. The intraocular pressure can also have an effect, with higher pressures reducing the time until blindness.

Epidemiology
As of 2010, there were 44.7 million people in the world with open angle glaucoma. The same year, there were 2.8 million people in the United States with open angle glaucoma. By 2020, the prevalence is projected to increase to 58.6 million worldwide and 3.4 million in the United States.Both internationally and in the United States, glaucoma is the second-leading cause of blindness. Globally, cataracts are a more common cause. Glaucoma is also the leading cause of blindness in African Americans, who have higher rates of primary open-angle glaucoma. Bilateral vision loss can negatively affect mobility and interfere with driving.A meta-analysis published in 2009 found that people with primary open angle glaucoma do not have increased mortality rates, or increased risk of cardiovascular death.

History
The association of elevated intraocular pressure (IOP) and glaucoma was first described by Englishman Richard Banister in 1622: "...that the Eye be grown more solid and hard, then naturally it should be...". Angle-closure glaucoma was treated with cataract extraction by John Collins Warren in Boston as early as 1806. The invention of the ophthalmoscope by Hermann Helmholtz in 1851 enabled ophthalmologists for the first time to identify the pathological hallmark of glaucoma, the excavation of the optic nerve head due to retinal ganglion cell loss. The first reliable instrument to measure intraocular pressure was invented by Norwegian ophthalmologist Hjalmar August Schiøtz in 1905. About half a century later, Hans Goldmann in Berne, Switzerland, developed his applanation tonometer which still today - despite numerous new innovations in diagnostics - is considered the gold standard of determining this crucial pathogenic factor. In the late 20th century, further pathomechanisms beyond elevated IOP were discovered and became the subject of research like insufficient blood supply – often associated with low or irregular blood pressure – to the retina and optic nerve head. The first drug to reduce IOP, pilocarpine, was introduced in the 1870s; other major innovations in pharmacological glaucoma therapy were the introduction of beta blocker eye drops in the 1970s and of prostaglandin analogues and topical (locally administered) carbonic anhydrase inhibitors in the mid-1990s.. Early surgical techniques like iridectomy and fistulating methods have recently been supplemented by less invasive procedures like small implants, a range of options now widely called MIGS (micro-invasive glaucoma surgery).

Etymology
The word "glaucoma" comes from the Ancient Greek γλαύκωμα, a derivative of γλαυκóς, which commonly described the color of eyes which were not dark (i.e. blue, green, light gray). Eyes described as γλαυκóς due to disease might have had a gray cataract in the Hippocratic era, or, in the early Common Era, the greenish pupillary hue sometimes seen in angle-closure glaucoma.

Research
Eye drops vs. other treatments
The TAGS randomised controlled trial investigated if eye drops or trabeculectomy is more effective in treating advanced primary open-angle glaucoma. After two years researchers found that vision and quality of life are similar in both treatments. At the same time eye pressure was lower in people who underwent surgery and in the long-run surgery is more cost-effective.The LiGHT trial compared the effectiveness of eye drops and selective laser trabeculoplasty for open angle glaucoma. Both contributed to a similar quality of life but most people undergoing laser treatment were able to stop using eye drops. Laser trabeculoplasty was also shown to be more cost-effective.

Rho kinase inhibitors
Rho kinase inhibitors, such as ripasudil, work by inhibition of the actin cytoskeleton, resulting in the morphological changes in the trabecular meshwork and increased aqueous outflow </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Adolescent idiopathic scoliosis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Medulloblastoma and can you explain it in depth? [/INST] Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa.The brain is divided into two main parts, the larger cerebrum on top and the smaller cerebellum below towards the back. They are separated by a membrane called the tentorium. Tumors that originate in the cerebellum or the surrounding region below the tentorium are, therefore, called infratentorial.
Historically medulloblastomas have been classified as a primitive neuroectodermal tumor (PNET), but it is now known that medulloblastoma is distinct from supratentorial PNETs and they are no longer considered similar entities.Medulloblastomas are invasive, rapidly growing tumors that, unlike most brain tumors, spread through the cerebrospinal fluid and frequently metastasize to different locations along the surface of the brain and spinal cord. Metastasis all the way down to the cauda equina at the base of the spinal cord is termed "drop metastasis".
The cumulative relative survival rate for all age groups and histology follow-up was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively, with children doing better than adults.

Signs and symptoms
Signs and symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle and tumors are usually present for 1 to 5 months before diagnosis is made. The child typically becomes listless, with repeated episodes of vomiting, and a morning headache, which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon after, the child will develop a stumbling gait, truncal ataxia, frequent falls, diplopia, papilledema, and sixth cranial nerve palsy. Positional vertigo and nystagmus are also frequent, and facial sensory loss or motor weakness may be present. Decerebrate attacks appear late in the disease.
Extraneural metastasis to the rest of the body is rare, and when it occurs, it is in the setting of relapse, more commonly in the era prior to routine chemotherapy.

Pathogenesis
Medulloblastomas are usually found in the vicinity of the fourth ventricle, between the brainstem and the cerebellum.  Tumors with similar appearance and characteristics originate in other parts of the brain, but they are not identical to medulloblastoma.Although medulloblastomas are thought to originate from immature or embryonal cells at their earliest stage of development, the cell of origin depends on the subgroup of medulloblastoma.  WNT tumors originate from the lower rhombic lip of the brainstem, while SHH tumors originate from the external granular layer.Currently, medulloblastomas are thought to arise from cerebellar stem cells that have been prevented from dividing and differentiating into their normal cell types. This accounts for the histologic variants seen on biopsy. Both perivascular pseudorosette and Homer Wright pseudorosette formations are highly characteristic of medulloblastomas and are seen in up to half of cases. The classic rosette with tumor cells around a central lumen can be seen.In the past, medulloblastoma was classified using histology, but recent integrated genomic studies have revealed that medulloblastoma is composed of four distinct molecular and clinical variants termed WNT/β-catenin, Sonic Hedgehog, Group 3, and Group 4.  Of these subgroups, WNT patients have an excellent prognosis and group 3 patients have a poor prognosis. Also, a subgroup-specific alternative splicing further confirms the existence of distinct subgroups and highlights the transcriptional heterogeneity between subgroups.  Amplification of the Sonic Hedgehog pathway is the best characterized subgroup, with 25% of human tumors having mutations in Patched, Sufu (Suppressor of Fused Homolog), Smoothened, or other genes in this pathway. Medulloblastomas are also seen in Gorlin syndrome as well as Turcot syndrome. Recurrent mutations in the genes CTNNB1, PTCH1, MLL2, SMARCA4, DDX3X, CTDNEP1, KDM6A, and TBR1 were identified in individuals with medulloblastoma. Additional pathways disrupted in some medulloblastomas include MYC, Notch, BMP, and TGF-β signaling pathways.

Diagnosis
The tumor is distinctive on T1- and T2-weighted MRI with heterogeneous enhancement and a typical location adjacent to and extension into the fourth ventricle. Histologically, the tumor is solid, pink-gray in color, and is well circumscribed. The tumor is very cellular, with high mitotic activity, little cytoplasm, and a tendency to form clusters and rosettes.
The Chang staging system can be used in making the diagnosis [1].
Correct diagnosis of medulloblastoma may require ruling out atypical teratoid rhabdoid tumor.

Treatment
Treatment begins with maximal surgical removal of the tumor. The addition of radiation to the entire neuraxis and chemotherapy may increase the disease-free survival. Some evidence indicates that proton beam irradiation reduces the impact of radiation on the cochlear and cardiovascular areas and reduces the cognitive late effects of cranial irradiation.
This combination may permit a 5-year survival in more than 80% of cases. The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if the child is less than 3 years old, degree of resection is inadequate, or if any CSF, spinal, supratentorial, or systemic spread occurs. Dementia after radiotherapy and chemotherapy is a common outcome appearing two to four years following treatment. Side effects from radiation treatment can include cognitive impairment, psychiatric illness, bone growth retardation, hearing loss, and endocrine disruption. Increased intracranial pressure may be controlled with corticosteroids or a ventriculoperitoneal shunt. A new approach to monitor tumor development and treatment response by liquid biopsy is promising, but remains challenging.

Chemotherapy
Chemotherapy is often used as part of treatment. Evidence of benefit, however, is not clear as of 2013. A few different chemotherapeutic regimens for medulloblastoma are used; most involve a combination of lomustine, cisplatin, carboplatin, vincristine, or cyclophosphamide. In younger patients (less than 3–4 years of age), chemotherapy can delay, or in some cases possibly even eliminate, the need for radiotherapy. However, both chemotherapy and radiotherapy often have long-term toxicity effects, including delays in physical and cognitive development, higher risk of second cancers, and increased cardiac disease risks.

Outcomes
Array-based karyotyping of 260 medulloblastomas resulted in the following clinical subgroups based on cytogenetic profiles:
Poor prognosis: gain of 6q or amplification of MYC or MYCN
Intermediate: gain of 17q or an i(17q) without gain of 6q or amplification of MYC or MYCN
Excellent prognosis: 6q and 17q balanced or 6q deletionTranscriptional profiling shows the existence of four main subgroups (Wnt, Shh, Group 3, and Group 4).
Very good prognosis: WNT group, CTNNB1 mutation
Infants good prognosis, others intermediate: SHH group, PTCH1/SMO/SUFU mutation, GLI2 amplification, or MYCN amplification
Poor prognosis: Group 3, MYC amplification, photoreceptor/GABAergic gene expression
Intermediate prognosis: Group 4, gene expression of neuronal/glutamatergic, CDK6 amplification, MYCN amplification

Survival
The historical cumulative relative survival rate for all age groups and histology follow-up was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively. Patients diagnosed with a medulloblastoma or PNET are 50 times more likely to die than a matched member of the general population.
The most recent population-based (SEER) 5-year relative survival rates are 69% overall: 72% in children (1–9 years) and 67% in adults (20+ years). The 20-year survival rate is 51% in children. Children and adults have different survival profiles, with adults faring worse than children only after the fourth year after diagnosis (after controlling for increased background mortality). Before the fourth year, survival probabilities are nearly identical. Long-term sequelae of standard treatment include hypothalamic-pituitary and thyroid dysfunction and intellectual impairment. The hormonal and intellectual deficits created by these therapies causes significant impairment of the survivors.In current clinical studies, the patients are divided into low-, standard- and high-risk groups:

Depending on the study, healing rates of up to 100% are achieved in the low-risk group (usually WNT-activated). The current efforts are therefore moving in the direction of reducing the intensity of the therapy and thus the negative long-term consequences while confirming the high healing rates.
In the HIT-SIOP PNET 4 study, in which 340 children and adolescents of the standard-risk group between the ages of four and 21 from several European countries participated, the 5-year survival rate was between 85% and 87% depending on the randomization. Around 78% of the patients remained without relapse for 5 years and are therefore considered to be cured. After a relapse, the prognosis was very poor. Despite intensive treatment, only four of 66 patients were still alive 5 years after a relapse.
A US study involved 161 patients between the ages of three and 21 with a high-risk profile. Depending on the randomization, half of the patients additionally received carboplatin daily during the radiation. The 5-year survival rate of patients with carboplatin was 82%, those without 68% </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Normal pressure hydrocephalus and can you explain it in depth? [/INST] Normal-pressure hydrocephalus (NPH), also called malresorptive hydrocephalus, is a form of communicating hydrocephalus in which excess cerebrospinal fluid (CSF) occurs in the ventricles, and with normal or slightly elevated cerebrospinal fluid pressure. As the fluid builds up, it causes the ventricles to enlarge and the pressure inside the head to increase, compressing surrounding brain tissue and leading to neurological complications. The disease presents in a classic triad of symptoms, which are memory impairment, urinary frequency, and balance problens/gait deviations (note: this diagnosis method is obsolete). The disease was first described by Salomón Hakim and Adams in 1965.The treatment is surgical placement of a ventriculoperitoneal shunt to drain excess CSF into the lining of the abdomen where the CSF will eventually be absorbed. NPH is often misdiagnosed as other conditions including Parkinsons disease (due to gait) or Alzheimers disease (due to cognitive dysfunction).

Signs and symptoms
NPH exhibits a classic triad of clinical findings (known as the Adams triad or Hakims triad). The triad consists of walking difficulty, reduced attention span, and urinary frequency or incontinence. The triad is considered obsolete for diagnosis purposes and newer guidelines are available.Gait deviations are present in nearly all patients and usually the first symptom. This is caused by expansion of the lateral ventricles to impinge on the corticospinal tract motor fibers. The typical gait abnormality in NPH is a broad-based, slow, short-stepped, "stuck to the floor", or "magnetic" movement. The gait abnormalities in NPH may bear resemblance to a gait associated with Parkinsons disease. The gait deviation can be classified as mild, marked, or severe: "marked" is when the patient has difficulty walking because of considerable instability; "severe" is when it is not possible for the patient to walk without aids (such as a cane or a wheeled walker).Dementia presents as progressive cognitive impairment which is present in 60% of patients at time of treatment. This is caused by distortions predominantly at the frontal lobe and the subcortex. Initial deficits involve planning, organization, attention, and concentration. Further deficits include difficulty managing finances, taking medications, driving, keeping track of appointments, daytime sleeping, short-term memory impairments, and psychomotor slowing. Late stage features include apathy, reduced drive, slowed thinking, and reduced speech.
Urinary incontinence appears late in the illness, and is present in 50% of patients at time of treatment. Urinary dysfunction begins as increased frequency often at night, and progresses to urge incontinence and permanent incontinence.

Pathogenesis
Every day, the body makes roughly 600–700 ml of CSF, and about the same amount is reabsorbed into the bloodstream. Hydrocephalus is due to an imbalance between the amount of fluid produced and its absorption rate. Enlarged ventricles put increased pressure on the adjacent cortical tissue and cause myriad effects in the patient, including distortion of the fibers in the corona radiata. This leads to an increase in intracranial pressure (ICP). The ICP gradually falls, but still remains slightly elevated, and the CSF pressure reaches a high normal level of 150 to 200 mm H2O. Measurements of ICP, therefore, are not usually elevated. Because of this, patients do not exhibit the classic signs that accompany increased intracranial pressure such as headache, nausea, vomiting, or altered consciousness, although some studies have shown pressure elevations to occur intermittently.The exact pathogenesis is unknown, but consensus on some mechanisms include:
An imbalance exists between production and resorption of CSF.
The resistance to CSF outflow is often elevated.
The disease is not caused by overproduction of CSF or obstruction of CSF flow at the ventricles.The syndrome is often divided into two groups, primary (also called idiopathic) and secondary, based on cause. The underlying etiology of primary NPH has not yet been identified. Primary NPH affects adults age 40 years or older, most commonly affecting the elderly. Secondary NPH can affect persons of any age and occurs due to conditions such as subarachnoid hemorrhage, meningitis, brain surgery, brain radiation, or traumatic brain injury.

Diagnosis
Patients with suspected NPH should have typical symptoms in addition to ventricular enlargement on neuroimaging. The international evidenced-based diagnostic criteria for primary NPH are:
Gradual onset after age 40 years, symptoms duration of ≥ 3–6 months, clinical evidence of gait or balance impairment, and impairment of cognition or urinary incontinence
Imaging from magnetic resonance imaging (MRI) or computed tomography (CT) is needed to demonstrate enlarged ventricles and no macroscopic obstruction to cerebrospinal fluid flow.  Imaging should show an enlargement to at least one of the temporal horns of lateral ventricles, and impingement against the falx cerebri resulting in a callosal angle ≤ 90° on the coronal view, showing evidence of altered brain water content, or normal active flow (which is referred to as "flow void") at the cerebral aqueduct and fourth ventricle.MRI scans are the preferred imaging. The distinction between normal and enlarged ventricular size by cerebral atrophy is difficult to ascertain. Up to 80% of cases are unrecognized and untreated due to difficulty of diagnosis. Imaging should also reveal the absence of any cerebral mass lesions or any signs of obstructions. Although all patients with NPH have enlarged ventricles, not all elderly patients with enlarged ventricles have primary NPH. Cerebral atrophy can cause enlarged ventricles, as well, and is referred to as hydrocephalus ex vacuo.
The Miller Fisher test  involves a high-volume lumbar puncture (LP) with removal of 30–50 ml of CSF. Gait and cognitive function are typically tested just before and within 2–3 hours after the LP to assess for signs of symptomatic improvement. The CSF infusion test and the lumbar test are similar tests to Miller Fisher test. The tests have a positive predictive value over 90%, but a negative predictive value less than 50%. The LP should show normal or mildly elevated CSF pressure. CSF should have normal cell contents, glucose levels, and protein levels.

Treatment
Ventriculoperitoneal shunts
For suspected cases of NPH, CSF shunting is the first-line treatment. The most common type used to treat NPH is ventriculoperitoneal (VP) shunts, which drain CSF fluid to the peritoneal cavity. Adjustable valves allow fine-tuning of CSF drainage </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Abdominal aortic aneurysm and can you explain it in depth? [/INST] Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. They usually cause no symptoms, except during rupture. Occasionally, abdominal, back, or leg pain may occur. Large aneurysms can sometimes be felt by pushing on the abdomen. Rupture may result in pain in the abdomen or back, low blood pressure, or loss of consciousness, and often results in death.AAAs occur most commonly in those over 50 years old, in men, and among those with a family history. Additional risk factors include smoking, high blood pressure, and other heart or blood vessel diseases. Genetic conditions with an increased risk include Marfan syndrome and Ehlers–Danlos syndrome. AAAs are the most common form of aortic aneurysm. About 85% occur below the kidneys with the rest either at the level of or above the kidneys. In the United States, screening with abdominal ultrasound is recommended for males between 65 and 75 years of age with a history of smoking. In the United Kingdom and Sweden, screening all men over 65 is recommended. Once an aneurysm is found, further ultrasounds are typically done on a regular basis.Abstinence from cigarette smoking is the single best way to prevent the disease. Other methods of prevention include treating high blood pressure, treating high blood cholesterol, and avoiding being overweight. Surgery is usually recommended when the diameter of an AAA grows to >5.5 cm in males and >5.0 cm in females. Other reasons for repair include the presence of symptoms and a rapid increase in size, defined as more than one centimeter per year. Repair may be either by open surgery or endovascular aneurysm repair (EVAR). As compared to open surgery, EVAR has a lower risk of death in the short term and a shorter hospital stay, but may not always be an option. There does not appear to be a difference in longer-term outcomes between the two. Repeat procedures are more common with EVAR.AAAs affect 2-8% of males over the age of 65. They are five times more common in men. In those with an aneurysm less than 5.5 cm, the risk of rupture in the next year is below 1%. Among those with an aneurysm between 5.5 and 7 cm, the risk is about 10%, while for those with an aneurysm greater than 7 cm the risk is about 33%. Mortality if ruptured is 85% to 90%. During 2013, aortic aneurysms resulted in 168,200 deaths, up from 100,000 in 1990. In the United States AAAs resulted in between 10,000 and 18,000 deaths in 2009.

Signs and symptoms
The vast majority of aneurysms are asymptomatic. However, as the abdominal aorta expands and/or ruptures, the aneurysm may become painful and lead to pulsating sensations in the abdomen or pain in the chest, lower back, legs, or scrotum.

Complications
The complications include rupture, peripheral embolization, acute aortic occlusion, and aortocaval (between the aorta and inferior vena cava) or aortoduodenal (between the aorta and the duodenum) fistulae. On physical examination, a palpable and pulsatile abdominal mass can be noted. Bruits can be present in case of renal or visceral arterial stenosis.The signs and symptoms of a ruptured AAA may include severe pain in the lower back, flank, abdomen or groin. A mass that pulses with the heart beat may also be felt. The bleeding can lead to a hypovolemic shock with low blood pressure and a fast heart rate, which may cause fainting. The mortality of AAA rupture is as high as 90 percent. 65 to 75 percent of patients die before they arrive at the hospital and up to 90 percent die before they reach the operating room. The bleeding can be retroperitoneal or into the abdominal cavity. Rupture can also create a connection between the aorta and intestine or inferior vena cava. Flank ecchymosis (appearance of a bruise) is a sign of retroperitoneal bleeding and is also called Grey Turners sign.

Causes
The exact causes of the degenerative process remain unclear. There are, however, some hypotheses and well-defined risk factors.
Tobacco smoking: More than 90% of people who develop an AAA have smoked at some point in their lives.
Alcohol and hypertension: The inflammation caused by prolonged use of alcohol and hypertensive effects from abdominal edema which leads to hemorrhoids, esophageal varices, and other conditions, is also considered a long-term cause of AAA.
Genetic influences: The influence of genetic factors is high. AAA is four to six times more common in male siblings of known patients, with a risk of 20–30%. The high familial prevalence rate is most notable in male individuals. There are many hypotheses about the exact genetic disorder that could cause higher incidence of AAA among male members of the affected families. Some presumed that the influence of alpha 1-antitrypsin deficiency could be crucial, while other experimental works favored the hypothesis of X-linked mutation, which would explain the lower incidence in heterozygous females. Other hypotheses of genetic causes have also been formulated. Connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome, have also been strongly associated with AAA. Both relapsing polychondritis and pseudoxanthoma elasticum may cause abdominal aortic aneurysm.
Atherosclerosis: The AAA was long considered to be caused by atherosclerosis, because the walls of the AAA frequently carry an atherosclerotic burden. However, this hypothesis cannot be used to explain the initial defect and the development of occlusion, which is observed in the process.
Other causes of the development of AAA include: infection, trauma, arteritis, and cystic medial necrosis.

Pathophysiology
The most striking histopathological changes of the aneurysmatic aorta are seen in the tunica media and intima layers. These changes include the accumulation of lipids in foam cells, extracellular free cholesterol crystals, calcifications, thrombosis, and ulcerations and ruptures of the layers. Adventitial inflammatory infiltrate is present.
However, the degradation of the tunica media by means of a proteolytic process seems to be the basic pathophysiologic mechanism of AAA development. Some researchers report increased expression and activity of matrix metalloproteinases in individuals with AAA. This leads to elimination of elastin from the media, rendering the aortic wall more susceptible to the influence of blood pressure. Other reports have suggested the serine protease granzyme B may contribute to aortic aneurysm rupture through the cleavage of decorin, leading to disrupted collagen organization and reduced tensile strength of the adventitia. There is also a reduced amount of vasa vasorum in the abdominal aorta (compared to the thoracic aorta); consequently, the tunica media must rely mostly on diffusion for nutrition, which makes it more susceptible to damage.Hemodynamics affect the development of AAA, which has a predilection for the infrarenal aorta. The histological structure and mechanical characteristics of the infrarenal aorta differ from those of the thoracic aorta. The diameter decreases from the root to the aortic bifurcation, and the wall of the infrarenal aorta also contains a lesser proportion of elastin. The mechanical tension in the abdominal aortic wall is therefore higher than in the thoracic aortic wall. The elasticity and distensibility also decline with age, which can result in gradual dilatation of the segment. Higher intraluminal pressure in patients with arterial hypertension markedly contributes to the progression of the pathological process. Suitable hemodynamic conditions may be linked to specific intraluminal thrombus (ILT) patterns along the aortic lumen, which in turn may affect AAAs development.

Diagnosis
An abdominal aortic aneurysm is usually diagnosed by physical exam, abdominal ultrasound, or CT scan. Plain abdominal radiographs may show the outline of an aneurysm when its walls are calcified. However, the outline will be visible by X-ray in less than half of all aneurysms. Ultrasonography is used to screen for aneurysms and to determine their size if present. Additionally, free peritoneal fluid can be detected. It is noninvasive and sensitive, but the presence of bowel gas or obesity may limit its usefulness. CT scan has nearly 100% sensitivity for an aneurysm and is also useful in preoperative planning, detailing the anatomy and possibility for endovascular repair. In the case of suspected rupture, it can also reliably detect retroperitoneal fluid. Alternative less often used methods for visualization of an aneurysm include MRI and angiography.An aneurysm ruptures if the mechanical stress (tension per area) exceeds the local wall strength; consequently, peak wall stress (PWS) and peak wall rupture risk (PWRR) have been found to be more reliable parameters than diameter to assess AAA rupture risk. Medical software allows computing these rupture risk indices from standard clinical CT data and provides a patient-specific AAA rupture risk diagnosis. This type of biomechanical approach has been shown to accurately predict the location of AAA rupture.

Classification
Abdominal aortic aneurysms are commonly divided according to their size and symptomatology. An aneurysm is usually defined as an outer aortic diameter over 3 cm (normal diameter of the aorta is around 2 cm), or more than 50% of normal diameter. If the outer diameter exceeds 5.5 cm, the aneurysm is considered to be large.
Ruptured AAA should be suspected in any person older than 60 who experiences collapse, unexplained low blood pressure, or sudden-onset back or abdominal pain. Abdominal pain, shock, and a pulsatile mass is only present in a minority of cases. Although an unstable person with a known aneurysm may undergo surgery without further imaging, the diagnosis will usually be confirmed using CT or ultrasound scanning.The suprarenal aorta normally measures about 0.5 cm larger than the infrarenal aorta.

Differential diagnosis
Aortic aneurysm rupture may be mistaken for the pain of kidney stones, or muscle related back pain.

Prevention
Smoking cessation
Treatment of hypertension

Screening
The U.S. Preventive Services Task Force (USPSTF) recommends a single screening abdominal ultrasound for abdominal aortic aneurysm in males age 65 to 75 years who have a history of smoking. Among this group who does not smoke, screening may be selective. It is unclear if screening is useful in women who have smoked and the USPSTF recommend against screening in women who have never smoked.In the United Kingdom the NHS AAA Screening Programme invites men in England for screening during the year they turn 65. Men over 65 can contact the programme to arrange to be screened.In Sweden one time screening is recommended in all males over 65 years of age. This has been found to decrease the risk of death from AAA by 42% with a number needed to screen of just over 200. In those with a close relative diagnosed with an aortic aneurysm, Swedish guidelines recommend an ultrasound at around 60 years of age.Australia has no guideline on screening.Repeat ultrasounds should be carried out in those who have an aortic size greater than 3.0 cm. In those whose aorta is between 3.0 and 3.9 cm this should be every three years, if between 4.0 and 4.4 cm every two years, and if between 4.5 and 5.4 cm every year.

Management
The treatment options for asymptomatic AAA are conservative management, surveillance with a view to eventual repair, and immediate repair. Two modes of repair are available for an AAA: open aneurysm repair, and endovascular aneurysm repair (EVAR). An intervention is often recommended if the aneurysm grows more than 1 cm per year or it is bigger than 5.5 cm. Repair is also indicated for symptomatic aneurysms. Ten years after open AAA repair, the overall survival rate was 59%. Mycotic abdominal aorta aneurysm (MAAA) is a rare and life-threatening condition. Because of its rarity, there is a lack of adequately powered studies and consensus on its treatment and follow up. A management protocol on the management of mycotic abdominal aortic aneurysm was recently published in the Annals of Vascular Surgery by Premnath et al.

Conservative
Conservative management is indicated in people where repair carries a high risk of mortality and in patients where repair is unlikely to improve life expectancy. The mainstay of the conservative treatment is smoking cessation.Surveillance is indicated in small asymptomatic aneurysms (less than 5.5 cm) where the risk of repair exceeds the risk of rupture. As an AAA grows in diameter, the risk of rupture increases. Surveillance until an aneurysm has reached a diameter of 5.5 cm has not been shown to have a higher risk as compared to early intervention.

Medication
No medical therapy has been found to be effective at decreasing the growth rate or rupture rate of asymptomatic AAAs. Blood pressure and lipids should, however, be treated per usual.

Surgery
The threshold for repair varies slightly from individual to individual, depending on the balance of risks and benefits when considering repair versus ongoing surveillance. The size of an individuals native aorta may influence this, along with the presence of comorbidities that increase operative risk or decrease life expectancy. Evidence, however, does not usually support repair if the size is less than 5.5 cm.

Open repair
Open repair is indicated in young patients as an elective procedure, or in growing or large, symptomatic or ruptured aneurysms. The aorta must be clamped during the repair, denying blood to the abdominal organs and sections of the spinal cord; this can cause a range of complications. As it is essential to perform the critical part of the operation quickly, the incision is typically made large enough to facilitate the fastest repair. Recovery after open AAA surgery takes significant time. The minimums are a few days in intensive care, a week total in the hospital and a few months before full recovery.

Endovascular repair
Endovascular repair first became practical in the 1990s and although it is now an established alternative to open repair, its role is yet to be clearly defined. It is generally indicated in older, high-risk patients or patients unfit for open repair. However, endovascular repair is feasible for only a portion of AAAs, depending on the morphology of the aneurysm. The main advantages over open repair are that there is less peri-operative mortality, less time in intensive care, less time in hospital overall and earlier return to normal activity. Disadvantages of endovascular repair include a requirement for more frequent ongoing hospital reviews and a higher chance of further required procedures. According to the latest studies, the EVAR procedure does not offer any benefit for overall survival or health-related quality of life compared to open surgery, although aneurysm-related mortality is lower. In patients unfit for open repair, EVAR plus conservative management was associated with no benefit, more complications, subsequent procedures and higher costs compared to conservative management alone. Endovascular treatment for paraanastomotic aneurysms after aortobiiliac reconstruction is also a possibility. A 2017 Cochrane review found tentative evidence of no difference in outcomes between endovascular and open repair of ruptured AAA in the first month.

Rupture
In those with aortic rupture of the AAA, treatment is immediate surgical repair. There appear to be benefits to allowing permissive hypotension and limiting the use of intravenous fluids during transport to the operating room.

Prognosis
Although the current standard of determining rupture risk is based on maximum diameter, it is known that smaller AAAs that fall below this threshold (diameter<5.5 cm) may also rupture, and larger AAAs (diameter>5.5 cm) may remain stable. In one report, it was shown that 10–24% of ruptured AAAs were less than 5 cm in diameter. It has also been reported that of 473 non-repaired AAAs examined from autopsy reports, there were 118 cases of rupture, 13% of which were less than 5 cm in diameter. This study also showed that 60% of the AAAs greater than 5 cm (including 54% of those AAAs between 7.1 and 10 cm) never experienced rupture. Vorp et al. later deduced from the findings of Darling et al. that if the maximum diameter criterion were followed for the 473 subjects, only 7% (34/473) of cases would have died from rupture prior to surgical intervention as the diameter was less than 5 cm, with 25% (116/473) of cases possibly undergoing unnecessary surgery since these AAAs may never have ruptured.Alternative methods of rupture assessment have been recently reported. The majority of these approaches involve the numerical analysis of AAAs using the common engineering technique of the finite element method (FEM) to determine the wall stress distributions. Recent reports have shown that these stress distributions have been shown to correlate to the overall geometry of the AAA rather than solely to the maximum diameter. It is also known that wall stress alone does not completely govern failure as an AAA will usually rupture when the wall stress exceeds the wall strength. In light of this, rupture assessment may be more accurate if both the patient-specific wall stress is coupled together with patient-specific wall strength. A noninvasive method of determining patient-dependent wall strength was recently reported, with more traditional approaches to strength determination via tensile testing performed by other researchers in the field. Some of the more recently proposed AAA rupture-risk assessment methods include: AAA wall stress; AAA expansion rate; degree of asymmetry; presence of intraluminal thrombus (ILT); a rupture potential index (RPI); a finite element analysis rupture index (FEARI); biomechanical factors coupled with computer analysis; growth of ILT; geometrical parameters of the AAA; and also a method of determining AAA growth and rupture based on mathematical models.The postoperative mortality for an already ruptured AAA has slowly decreased over several decades but remains higher than 40%. However, if the AAA is surgically repaired before rupture, the postoperative mortality rate is substantially lower, approximately 1-6%.

Epidemiology
The occurrence of AAA varies by ethnicity. In the United Kingdom, the rate of AAA in Caucasian men older than 65 years is about 4.7%, while in Asian men it is 0.45%. It is also less common in individuals of African, and Hispanic heritage. They occur four times more often in men than in women.There are at least 13,000 deaths yearly in the U.S. secondary to AAA rupture. The peak number of new cases per year among males is around 70 years of age, and the percentage of males affected over 60 years is 2–6%. The frequency is much higher in smokers than in non-smokers (8:1), and the risk decreases slowly after smoking cessation. In the U.S., the incidence of AAA is 2–4% in the adult population.Rupture of the AAA occurs in 1–3% of men aged 65 or more, for whom the mortality rate is 70–95%.

History
The first historical records about AAA are from Ancient Rome in the 2nd century AD, when Greek surgeon Antyllus tried to treat the AAA with proximal and distal ligature, central incision and removal of thrombotic material from the aneurysm.
However, attempts to treat the AAA surgically were unsuccessful until 1923. In that year, Rudolph Matas (who also proposed the concept of endoaneurysmorrhaphy), performed the first successful aortic ligation on a human. Other methods that were successful in treating the AAA included wrapping the aorta with polyethene cellophane, which induced fibrosis and restricted the growth of the aneurysm. Endovascular aneurysm repair was first performed in the late 1980s and has been widely adopted in the subsequent decades. Endovascular repair was first used for treating a ruptured aneurysm in Nottingham in 1994.

Society and culture
Theoretical physicist Albert Einstein underwent an operation for an abdominal aortic aneurysm in 1949 that was performed by Rudolph Nissen, who wrapped the aorta with polyethene cellophane. Einsteins aneurysm ruptured on April 13, 1955. He declined surgery, saying, "I want to go when I want. It is tasteless to prolong life artificially. I have done my share, it is time to go. I will do it elegantly." He died five days later at age 76.Actress Lucille Ball died April 26, 1989, from an abdominal aortic aneurysm. At the time of her death, she was in Cedars-Sinai Medical Center recovering from emergency surgery performed just six days earlier because of a dissecting aortic aneurysm near her heart. Ball was at increased risk as she had been a heavy smoker for decades.Musician Conway Twitty died in June 1993 from an abdominal aortic aneurysm at the age of 59, two months before the release of what would be his final studio album, Final Touches.Actor George C. Scott died in 1999 from a ruptured abdominal aortic aneurysm at age 71.In 2001, former presidential candidate Bob Dole underwent surgery for an abdominal aortic aneurysm in which a team led by vascular surgeon Kenneth Ouriel inserted a stent graft:
Ouriel said that the team inserted a Y-shaped tube through an incision in Doles leg and placed it inside the weakened portion of the aorta. The aneurysm will eventually contract around the stent, which will remain in place for the rest of Doles life.
— Associated Press
Actor Robert Jacks, who played Leatherface in Texas Chainsaw Massacre: The Next Generation, died from an abdominal aneurysm on August 8, 2001, one day shy of his 42nd birthday. His father also died from the same cause when Jacks was a child.
Actor Tommy Ford died of abdominal aneurysm in October 2016 at 52 years old.Gary Gygax, co-creator of Dungeons and Dragons, died in 2008 from an abdominal aortic aneurysm at the age of 69.

Research
Risk assessment
There have been many calls for alternative approaches to rupture risk assessment over the past number of years, with many believing that a biomechanics-based approach may be more suitable than the current diameter approach. Numerical modeling is a valuable tool to researchers allowing approximate wall stresses to be calculated, thus revealing the rupture potential of a particular aneurysm. Experimental models are required to validate these numerical results and provide a further insight into the biomechanical behavior of the AAA. In vivo, AAAs exhibit a varying range of material strengths from localised weak hypoxic regions to much stronger regions and areas of calcifications.Finding ways to predict future AAA growth is seen as a research priority.

Experimental models
Experimental models can now be manufactured using a novel technique involving the injection-moulding lost-wax manufacturing process to create patient-specific anatomically correct AAA replicas. Work has also focused on developing more realistic material analogues to those in vivo, and recently a novel range of silicone-rubbers was created allowing the varying material properties of the AAA to be more accurately represented. These rubber models can also be used in a variety of experimental situations, from stress analysis using the photoelastic method New endovascular devices are being developed that are able to treat more complex and tortuous anatomies.

Prevention and treatment
An animal study showed that removing a single protein prevents early damage in blood vessels from triggering a later-stage, complications. By eliminating the gene for a signaling protein called cyclophilin A (CypA) from a strain of mice, researchers were able to provide complete protection against abdominal aortic aneurysm.Other recent research identified Granzyme B (GZMB) (a protein-degrading enzyme) to be a potential target in the treatment of abdominal aortic aneurysms </s>