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Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g. methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given.
A systematic review of antineutrophil cytoplasmic antibody (ANCA) positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.
Treatment involves medications to suppress the immune system, including prednisone and cyclophosphamide. In some cases, methotrexate or leflunomide may be helpful. Some patients have also noticed a remission phase when a four-dose infusion of rituximab is used before the leflunomide treatment is begun. Therapy results in remissions or cures in 90% of cases. Untreated, the disease is fatal in most cases. The most serious associated conditions generally involve the kidneys and gastrointestinal tract. A fatal course usually involves gastrointestinal bleeding, infection, myocardial infarction, and/or kidney failure.
In case of remission, about 60% experience relapse within five years. In cases caused by hepatitis B virus, however, recurrence rate is only around 6%.
Treatment consists of immunoglobulin replacement therapy, which replenishes Ig subtypes that the person lack. This treatment is given at frequent intervals for life, and is thought to help reduce bacterial infections and boost immune function. Before therapy begins, plasma donations are tested for known blood-borne pathogens, then pooled and processed to obtain concentrated IgG samples. Infusions can be administered in three different forms: intravenously (IVIg):, subcutaneously (SCIg), and intramuscularly (IMIg).
The administration of intravenous immunoglobulins requires the insertion of a cannula or needle in a vein, usually in the arms or hands. Because highly concentrated product is used, IVIg infusions take place every 3 to 4 weeks. Subcutaneous infusions slowly release the Ig serum underneath the skin, again through a needle, and takes place every week. Intramuscular infusions are no longer widely used, as they can be painful and are more likely to cause reactions.
People often experience adverse side effects to immunoglobulin infusions, including:
- swelling at the insertion site (common in SCIG)
- chills
- headache
- nausea (common in IVIG)
- fatigue (common in IVIG)
- muscle aches and pain, or joint pain
- fever (common in IVIG and rare in SCIG)
- hives (rare)
- thrombotic events (rare)
- aseptic meningitis (rare, more common in people with SLE)
- anaphylactic shock (very rare)
In addition to Ig replacement therapy, treatment may also involve immune suppressants, to control autoimmune symptoms of the disease, and high dose steroids like corticosteroids. In some cases, antibiotics are used to fight chronic lung disease resulting from CVID. The outlook for people varies greatly depending on their level of lung and other organ damage prior to diagnosis and treatment.
Vasculitis secondary to connective tissue disorders. Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçet's disease, and other connective tissue disorders.
Vasculitis secondary to viral infection. Usually due to hepatitis B and C, HIV, cytomegalovirus, Epstein-Barr virus, and Parvo B19 virus.
Uveitis is typically treated with glucocorticoid steroids, either as topical eye drops (prednisolone acetate) or as oral therapy. Prior to the administration of corticosteroids, corneal ulcers must be ruled out. This is typically done using a fluoresence dye test. In addition to corticosteroids, topical cycloplegics, such as atropine or homatropine, may be used. Successful treatment of active uveitis increases T-regulatory cells in the eye, which likely contributes to disease regression.
In some cases an injection of posterior subtenon triamcinolone acetate may also be given to reduce the swelling of the eye.
Antimetabolite medications, such as methotrexate are often used for recalcitrant or more aggressive cases of uveitis. Experimental treatments with Infliximab or other anti-TNF infusions may prove helpful.
The anti-diabetic drug metformin is reported to inhibit the process that causes the inflammation in uveitis.
In the case of herpetic uveitis, anti-viral medications, such as valaciclovir or aciclovir, may be administered to treat the causative viral infection.
Polyarteritis nodosa, also known as panarteritis nodosa, periarteritis nodosa, Kussmaul disease, Kussmaul-Maier disease or PAN, is a systemic vasculitis of small- or medium-sized muscular arteries, typically involving renal and visceral vessels but sparing the pulmonary circulation. Polyarteritis nodosa may present in infants. In polyarteritis nodosa, small aneurysms are strung like the beads of a rosary, therefore making "rosary sign" an important diagnostic feature of the vasculitis.
With treatment, five-year survival is 80%; without treatment, five-year survival is 13%. Death is often a consequence of kidney failure, myocardial infarction, or stroke.
Steroids are mostly used for short term and quick use. The use provides improvement, but should not be considered a long term plan. Physicians would normally prescribe steroids after a biopsy and after further analysis has been completed.
Treatment is first with many different high-dose steroids, namely glucocorticoids. Then, if symptoms do not improve additional immunosuppression such as cyclophosphamide are added to decrease the immune system's attack on the body's own tissues. Cerebral vasculitis is a very rare condition that is difficult to diagnose, and as a result there are significant variations in the way it is diagnosed and treated.
Treatment also involves central nervous system penetrating chemotherapy. Options include intrathecal, intraventricular, and systemic chemotherapy. These must penetrate the blood-brain barrier in order to be effective. Sometimes mixing multiple forms of treatment with chemotherapy seems to be the best route. For example, some significant improvement has been shown as a result of cranial radiation treatment preceding a brief course of intrathecal chemotherapy. Although this is an effective treatment to do, penetrating the blood-brain barrier can cause side effects due to the toxicity in the nervous system. These would include dizziness, confusion, and changes in mental status. Another form could be the use of pharmaceuticals, which have all shown positive results for treatment but should always be consulted with a physician to asses risks.
The prognosis is generally good for those who receive prompt diagnosis and treatment, but serious complication including cataracts, glaucoma, band keratopathy, macular edema and permanent vision loss may result if left untreated. The type of uveitis, as well as its severity, duration, and responsiveness to treatment or any associated illnesses, all factor into the outlook.
The following types of CVID have been identified, and correspond to mutations in different gene segments.
Breast implant-associated ALCL is a recently recognized lymphoma and definitive management and therapy is under evaluation. However, it appears that removal of the implant, and resection of the capsule around the implant as well as evaluation by medical and surgical oncologists are cornerstones. Still under evaluation is the extent of capsulectomy: partial versus complete capsulectomy; similarly it is not defined the significance of replacement of the implant in the affected breast, or the removal of contralateral implant. Similarly, the value of radiation therapy and chemotherapy are under evaluation.
Currently, there is a drug, LDK378, undergoing Phase III clinical trials at Vanderbilt University that targets ALK positive small cell lung cancer, and has showed clinical promise in its previous clinical trials. Because approximately 70% of ALCL neoplasms are also ALK positive, there is hope that similar highly selective and potent ALK inhibitors may be used in the future to treat ALK positive cases of ALCL.
Most patients with T-cell prolymphocytic leukemia require immediate treatment.
T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), etoposide, bleomycin (VAPEC-B).
Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.
Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.
Cerebral vasculitis or central nervous system vasculitis (sometimes the word angiitis is used instead of "vasculitis") is vasculitis (inflammation of the blood vessel wall) involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels (capillaries), medium-size blood vessels (arterioles and venules), or large blood vessels (arteries and veins). If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die. It may produce a wide range of neurological symptoms, such as headache, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to coma and herniation. Some of its signs and symptoms may resemble multiple sclerosis. 10% have associated bleeding in the brain.
Multiagent chemotherapy is recommended, but the preferred regimen is controversial, as is consolidative radiotherapy.
Treatment consists of Anti-VEGF drugs like Lucentis or intravitreal steroid implant (Ozurdex) and Pan-Retinal Laser Photocoagulation usually. Underlying conditions also require treatment. Non-Ischemic CRVO has better visual prognosis than Ischemic CRVO.
A systematic review studied the effectiveness of the anti-VEGF drugs ranibizumab and pagatanib sodium for patients suffering from non-ischemic CRVO. Though there was a limited sample size, participants in both treatment groups showed improved visual acuity over 6 month periods, with no safety concerns.
There is no specific treatment for rubella; however, management is a matter of responding to symptoms to diminish discomfort. Treatment of newborn babies is focused on management of the complications. Congenital heart defects and cataracts can be corrected by direct surgery.
Management for ocular congenital rubella syndrome (CRS) is similar to that for age-related macular degeneration, including counseling, regular monitoring, and the provision of low vision devices, if required.
If caught early, the neovascularization can be reversed with prompt pan retinal photocoagulation (PRP), or injection of anti-VEGF medications with subsequent PRP. The injection blocks the direct effect of VEGF and acts more quickly but will wear off in about 6 weeks. PRP has a slower onset of action but can last permanently. Once the neovascularization has been longstanding, the new vessels recruit fibrous tissue, and as this forms and contracts, the angle can be permanently damaged, and will not respond to treatment. If this occurs, then surgical intervention is required to reduce the pressure (such as a glaucoma drainage implant)
The goal of antiretroviral use during pregnancy is to reduce the risk of transmission of HIV from mother to child. It is important to choose medications that are safe for the mother and the fetus and which are effective at decreasing the total viral load. Some studies have shown an increase in stillbirths, preterm delivery, and delayed fetal growth in women using high doses of antiretroviral drugs during pregnancy. However, the overall benefits of ART are believed to outweigh the risks and all women are encouraged to use ART for the duration of their pregnancy.
Due to physiological changes in the body during pregnancy, it may be necessary to alter the dosing of medications so that they remain effective. Generally, the dose or the frequency of dosing are increased to account for these changes.
The recommended ART regimen for HIV-positive pregnant women consists of drugs from 4 different classes of medications listed below. In the United States, the favored regimen is a three-drug regimen where the first two drugs are NRTIs and the third is either a protease inhibitor, an integrase inhibitor, or an NNRTI.
- Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the "backbone" of ART and 2 medications are generally used in combination. Due to its known safety profile and extensive use in pregnant patients, zidovudine-lamivudine (ZDV/3TC) is the preferred choice as the NRTI backbone. Zidovudine may worsen anemia, so patients with anemia are advised to use an alternative agent. For women who are coinfected with Hepatitis B, tenofovir with either emtricitabine or lamivudine is the preferred NRTI backbone. NRTI use may cause lactic acidosis in some women, so it is important to monitor patients for this complication. Deaths from lactic acidosis and liver failure have been associated with the use of two NRTIs, stavudine and didanosine (Zerit and Videx, respectively); therefore, combinations involving these drugs should be avoided in pregnancy.
- Protease inhibitors (PIs) have been studied extensively in pregnancy and are therefore the preferred third drug in the regimen. Atazanavir-ritonavir and darunavir-ritonavir are two of the most common PIs used during pregnancy. There is conflicting data regarding their association with preterm births, so women who are at a high risk for premature delivery are advised not to use PIs. Some PIs have been associated with hyperglycemia but is unclear whether they add to the risk of developing gestational diabetes. Some PIs have been noted to cause hyperbilirubinemia and nausea, so these side effects should be monitored for closely.
- Integrase inhibitors (IIs) are generally the third drug in the regimen when a PI cannot be used. They rapidly reduce the viral load and for this reason, they are often used in women who are diagnosed with HIV late in the pregnancy. Raltegravir is the most common II used.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs), the most popular being efavirenz and nevirapine, may be used during pregnancy. However, there are significant toxicities associated with their use, making them a less desirable option.
- Efavirenz (brand name Sustiva, and a component of the combination drug Atripla) is classified as a category D drug by the US Food and Drug Administration indicating there are risks associated with its use during pregnancy. In a study analyzing the use of the drug in pregnant women, 2.3% of births were associated with birth defects. However, a systematic review of the safety of efavirenz use in humans during the first trimester found no increase in birth defects among women using the drug. Given the uncertain potential for risk the U.S. DHHS recommends against using efavirenz in the first trimester of pregnancy or in women who may become pregnant. They instead recommend a protease inhibitor based regimen with lopinavir or atazanavir. However, to simplify regimens and provide a uniform recommendation for HIV-infected individuals during pregnancy, the WHO continues to recommend efavirenz as a first line agent for HIV positive women. Women using efavirenz prior to their pregnancy may continue with the drug as it is more dangerous to stop or change medications during pregnancy because this can result in improper control of the viral load.
- Nevirapine (trade name Viramune) increases the risk of very serious liver damage in women with CD4 counts greater than 250 cells/mm . It is generally avoided in pregnant women. Women taking nevirapine safely prior to pregnancy may continue with the medication because nevirapine-related liver damage has not been seen in women previously using the medication.
In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. There is not enough evidence to support the use of herbal medicines. There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.
Currently no effective treatment exists for kernicterus. Future therapies may include neuroregeneration. A handful of patients have undergone deep brain stimulation, and experienced some benefit. Drugs such as baclofen, clonazepam, and artane are often used to manage movement disorders associated with kernicterus. Proton pump inhibitors are also used to help with reflux. Cochlear implants and hearing aids have also been known to improve the hearing loss that can come with kernicterus (auditory neuropathy - ANSD).
Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes," of antiretroviral agents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analog reverse transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include protease inhibitors (PI) are used if the above regimen loses effectiveness.
The World Health Organization and United States recommends antiretrovirals in people of all ages including pregnant women as soon as the diagnosis is made regardless of CD4 count. Once treatment is begun it is recommended that it is continued without breaks or "holidays". Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria treatment is effective in more than 95% of people during the first year.
Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death. In the developing world treatment also improves physical and mental health. With treatment there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include poor access to medical care, inadequate social supports, mental illness and drug abuse. The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence. Even though cost is an important issue with some medications, 47% of those who needed them were taking them in low and middle income countries as of 2010 and the rate of adherence is similar in low-income and high-income countries.
Specific adverse events are related to the antiretroviral agent taken. Some relatively common adverse events include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus, especially with protease inhibitors. Other common symptoms include diarrhea, and an increased risk of cardiovascular disease. Newer recommended treatments are associated with fewer adverse effects. Certain medications may be associated with birth defects and therefore may be unsuitable for women hoping to have children.
Treatment recommendations for children are somewhat different from those for adults. The World Health Organization recommends treating all children less than 5 years of age; children above 5 are treated like adults. The United States guidelines recommend treating all children less than 12 months of age and all those with HIV RNA counts greater than 100,000 copies/mL between one year and five years of age.
To overcome imatinib resistance and to increase responsiveness to TK inhibitors, four novel agents were later developed. The first, dasatinib, blocks several further oncogenic proteins, in addition to more potent inhibition of the BCR-ABL protein, and was initially approved in 2007 by the US FDA to treat CML in patients who were either resistant to or intolerant of imatinib. A second new TK inhibitor, nilotinib, was also approved by the FDA for the same indication. In 2010, nilotinib and dasatinib were also approved for first-line therapy, making three drugs in this class available for treatment of newly diagnosed CML. In 2012, Radotinib joined the class of novel agents in the inhibition of the BCR-ABL protein and was approved in South Korea for patients resistant to or intolerant of imatinib. Bosutinib received US FDA and EU European Medicines Agency approval on September 4, 2012 and 27 March 2013 respectively for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
Neither the combination of antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes.
When rhesus macaques were given interferon-α2b and ribavirin and exposed to MERS, they developed less pneumonia than control animals. Five critically ill people with MERS in Saudi Arabia with ARDS and on ventilators were given interferon-α2b and ribavirin but all ended up dying of the disease. The treatment was started late in their disease (a mean of 19 days after hospital admission) and they had already failed trials of steroids so it remains to be seen whether it may have benefit earlier in the course of disease. Another proposed therapy is inhibition of viral protease or kinase enzymes. Researchers are investigating a number of ways to combat the outbreak of Middle East respiratory syndrome coronavirus, including using interferon, chloroquine, chlorpromazine, loperamide, and lopinavir, as well as other agents such as mycophenolic acid and camostat.
While capable of producing significantly improved responses compared with the action of imatinib, neither dasatinib nor nilotinib could overcome drug resistance caused by one particular mutation found to occur in the structure of BCR-ABL known as the T315I mutation (i.e. where the 315th amino acid is mutated from a threonine residue to an isoleucine residue). Two approaches were developed to the treatment of CML as a result:
In 2007, Chemgenex released results of an open-label Phase 2/3 study (CGX-635-CML-202) that investigated the use of a non BCR-ABL targeted agent omacetaxine, administered subcutaneously (under the skin) in patients who had failed with imatinib and exhibited T315I kinase domain mutation. This is a study which is ongoing through 2014. In September 2012, the FDA approved omacetaxine for the treatment of CML in the case of resistance to other chemotherapeutic agents.
Independently, ARIAD pharmaceuticals, adapting the chemical structures from first and second-generation TK inhibitors, arrived at a new pan-BCR-ABL inhibitor which showed (for the first time) efficacy against T315I, as well as all other known mutations of the oncoprotein. The drug, ponatinib, gained FDA approval in December 2012 for treatment of patients with resistant or intolerant CML. Just as with second generation TK inhibitors, early approval is being sought to extend the use of ponatinib to newly diagnosed CML also.