Studies have shown that about 75%-80% of Parkinson’s disease patients who receive levodopa treatment will gradually develop sports complications after 3-5 years. Parkinson’s motor complications are divided into motor fluctuations and dyskinesias, each of which is subdivided into multiple manifestations. Clinical manifestations of end-of-dose phenomenon: The maintenance time of levodopa is gradually shortened from the first few hours, generally less than 4h, and the time is usually shortened to 1-2h. Causes: Dopaminergic neuron function declines, and the improvement of symptoms is more dependent on exogenous levodopa; levodopa half-life is shortened &.lt.4h; dopaminergic receptor sensitivity decreases. Add COMT inhibitor or MAO-B inhibitor to reduce the elimination of levodopa and prolong its action time; add long-acting dopamine receptor agonists (DAs) or switch to dopamine agonists; reduce compound levodopa For a single dose, increase the number of doses; for early end-of-dose phenomena (especially at night), controlled-release tablets can be used instead. Note: MAO-B inhibitor rasagiline can shorten the “off” period, but the efficacy of selegiline is not certain; add COMT inhibitor (entocapone is more effective than tocapone) to avoid abnormal movement It is necessary to reduce the dose of compound levodopa by 20%~30%; because the receptor agonist has a slow onset, it is recommended to maintain the dose of compound levodopa until the symptoms improve, and then gradually reduce the dose of relapsed levodopa ( It can be reduced by 19%~25%); due to the incomplete absorption of controlled-release tablets in the gastrointestinal tract, the dosage should be increased by 20%~30% when switching to controlled-release tablets. Delayed or no “open” phenomenon Clinical manifestations: After taking levodopa, there may be no improvement in the patient’s symptoms, or the effect may be significantly delayed. Causes: High protein in food interferes with the absorption of levodopa; weakened gastrointestinal motility and insufficient gastric motility; decreased gastric acid secretion. To promote the absorption of levodopa as the principle: increase the crude fiber content in the diet or use laxatives to relieve constipation; choose levodopa preparations to be taken 1h before meals or 1.5h after meals, take a low-protein diet, or recommend only dinner High-protein foods. ”Switch” phenomenon Clinical manifestations: The movable “on” state and the non-movable “off” state switch mutually, which has nothing to do with the dose of levodopa and plasma drug concentration, and it is unpredictable. Cause: It is currently believed that the phenomenon of “on one off” is related to the desensitization of dopamine receptors, and the clinical treatment effect is not good. Add COMT inhibitor; add dopa receptor agonist, or switch to dopa receptor agonist; low protein diet: the central nervous system dopamine storage capacity of patients with advanced PD is reduced, and the dopamine transported into the brain is only slightly reduced It will lead to the occurrence of the “off” period, so it is recommended that only dinner with a protein diet; consider continuous levodopa treatment; if necessary, deep brain electrical stimulation surgery can be performed.
MDS is characterized by the increased apoptosis of hematopoietic precursor cells in the ineffective hematopoietic bone marrow, the decrease of peripheral blood whole blood cells, and the transformation of acute myeloid leukemia. So far, the treatment methods are still limited, and the patient’s age and comorbidities need to be considered. Patients in the group generally receive chemotherapy. What kind of drugs are generally used for chemotherapy? 1. DNA methyltransferase inhibitors The principle of DNA methyltransferase inhibitors in the treatment of MDS is to reverse the epigenetic silencing caused by hypermethylation and re-expression of silenced genes. Methyltransferase inhibitors inhibit methyltransferase by being incorporated into DNA, and its onset time is about several cell replication cycles. Currently, two demethylation drugs (5-azacytidine and decitabine) have been approved for the treatment of MDS. Their mechanism of action is concentration-dependent, inducing cytotoxicity at high concentrations, and demethylation at low concentrations. The 7-day medication method of 5AC (75mg/m2 per day, subcutaneous injection, 7 consecutive days, a course of treatment every 28d) is very effective for the treatment of MDS. Decitabine (15mg/m3, intravenously administered once every 8 hours for 3 consecutive days), the mortality rate of patients treated with decitabine is 10%. The difference in mortality between the two suggests that the 3-day intravenous infusion regimen of decitabine may be more toxic than the 5-azacytidine regimen. 2. Histone deacetylase inhibitors are used to treat MDS in clinical studies. 30% of patients have achieved treatment response, most of which are hematological improvements, but the effect seems to be better for patients in the low-risk group. 3. Farnesyltransferase inhibitor can inhibit the RAS proto-oncogene, and the most common side effect is bone marrow suppression. 4. Arsenic trioxide combined with low-dose thalidomide (100mg per day) has an effective rate of 25% in patients with low and high-risk MDS. Toxic reactions include neutropenia and thrombocytopenia. Fever, fatigue, and electrolyte disturbances, prolonged QTc interval. The clinical study of the combination of ATO and other drugs (such as cytarabine) for the treatment of high-risk MDS is currently underway. 5. The use of thalidomide for immunosuppressive drugs is 100-400 mg per day, which is effective in only 13% of patients. Although increasing the dose can increase the efficacy, the usual regimen is lenalidomide 10 mg/d, or 25 mg/d, orally 21 day. Every 28 days is a cycle, but the toxicity increases and it cannot be tolerated by the patient. The biological activity of Lelidomide is better than that of Thalidomide, and its neurotoxicity is significantly lower than that of Thalidomide. It is especially effective for patients with chromosome 5q anomaly (del5q). Only 19% of patients maintained a median time of non-reliant blood transfusion efficacy of 2.2 years. In short, patients with MDS have limited response to conventional chemotherapy, and high-dose chemotherapy is not easy to bear. Patients usually die from complications such as infection and bleeding. Low-intensity chemotherapy is difficult for patients to achieve long-term survival. Although hematopoietic stem cell transplantation is a cure, it is only Suitable for some patients, so people are always looking for better treatments.
General term for purpura skin and mucous membrane color change after bleeding. The clinical manifestations are bleeding points, purpura, and ecchymosis. They generally do not rise above the skin surface. They can only bulge slightly in allergic purpura. They begin to be purplish red, and the color does not fade. Afterwards, they gradually become lighter and fade to yellow after about two weeks. . Treatment of allergic purpura: 1. Identify and remove the incentives to avoid suspicious related foods and drugs; remove the infected lesions, and apply antibiotics appropriately. 2. Rest in bed to facilitate the resolution of skin purpura and reduce its recurrence. 3. Those with simple skin type can be treated with antihistamines, butadiene, calcium gluconate, increased dose of vitamin C 3-5 grams, or glycyrrhizin. 4. For patients with allergic purpura or arthritis purpura with severe skin damage, moderate doses of corticosteroids or immunosuppressive agents may be given. Commonly used prednisone 0.5-1mg/kg/d, orally once a day, or an equivalent amount of dexamethasone or methylprednisolone intravenously drip daily, after the condition improves, change the prednisone orally, and gradually reduce the amount to stop medicine. The course of treatment is generally 1 to 2 weeks, kidney type can be extended as appropriate. Hormones are often ineffective for kidney type and cannot prevent relapse. Renal patients can be treated with immunosuppressive agents such as cyclophosphamide, azathioprine, and tripterygium wilfordii for a period of 2 to 3 months. Combination therapy with hormones and immunosuppressants can also be used. 5. For patients with purpuric nephritis, anticoagulant drugs such as dipyridamole (Pan Sheng Ding), heparin or low-molecular-weight heparin calcium can also be used, and Chinese medicine Zhikang capsules can also be used. 6, symptomatic treatment of joint swelling and pain can be taken orally aspirin (not for patients with intestinal bleeding); abdominal pain can be injected 654-2; gastrointestinal bleeding can be treated with omeprazole, cimetidine, etc. Limit diet when necessary; those with intussusception, intestinal obstruction, and hemorrhage should consider surgical treatment. 7. Treatment of traditional Chinese medicine The treatment plan of traditional Chinese medicine is aimed at the category of typhus. The wind and heat or damp heat attacks the blood and blood, causing heat to hurt the veins, making the blood not follow the meridian, overflowing outside the pulse, and staying in Caused by skin. Treatment should be based on the principles of wind-relief, heat-clearing, cooling blood and removing blood stasis.
Immunotherapy is called the fourth treatment method of cancer in addition to surgery, chemotherapy, and radiotherapy. It is also called the treatment method closest to the cure of cancer. It does not directly kill cancer cells, but helps the immune system. Fight cancer. So, how does immunotherapy help the immune system fight cancer cells? What other immunotherapy has benefited mankind? Before answering these questions, let’s take a look at how the normal immune system works. Under human health, immune cells require two important steps to clear cancer cells. The first step is identification and the second step is elimination. In an intact immune system, the immune cells first need to identify some surface features of the tumor cells, just as the police use various clues to lock the criminal suspect (tumor cell), and after the interrogation and the support of various evidences, he is determined to be true criminal. Determining criminals is just a small step. The important thing is to eradicate or educate them to rehabilitate. However, in the second step of elimination in the immune system, the tumor cells have no chance of being corrected, and once found, they are eliminated immediately. Since the body’s own immune function can remove these cells that are harmful to itself, how can tumor cells survive or even evolve into cancer? Look at the fight between cancer and the immune system, and you will understand. In the struggle between the enemy and the enemy, the bad guys will not obediently wait for us to get rid of it, and so will the tumor cells. When removing tumor cells, as long as there is a problem in one of the steps of identification and elimination, they will promote their crazy growth. Obviously, they seized this opportunity. Some of the tumor cells fled when the immune system was weak during the struggle, and cunningly they would pretend to be “good people” and let the immune cells pass them by. Some more cunning tumor cells will also send various signals to immune cells, so as to confuse our “policemen”, and can not destroy them when they are recognized as bad people. In order to survive, these tumor cells that escaped to the roots like the saplings took root in the body to continuously absorb nutrients, and at the same time used different strategies to suppress the body’s immune system so that it could not normally kill the tumor cells, so that in all stages of the anti-tumor immune response Survived. Their growth process can be called “those who can’t kill me will eventually make me stronger”. In the game between tumor cells and the human immune system, the immune system temporarily prevails, which promotes the growth of tumor cells, which in turn suppresses the immune system, which is the immunosuppression of cancer. Scientists have adopted a variety of treatments or drugs in response to the characteristics of cancer immunosuppression to try to enhance autoimmunity and break cancer suppression. These methods are collectively referred to as immunotherapy. It can help the body create an effective cellular army to fight cancer and break its own cancer suppression. So what are the specific immunotherapy? 1. Tumor vaccines, like flu vaccines, therapeutic tumor vaccines can alert the immune system to monitor dangerous intruders, but it does not prepare the immune system to attack potential bad people (pathogens), but helps key immune cells recognize that Unique cancer cells that exist in the human body. After the tumor vaccine enters the human body, it activates its own immune system, uses tumor cells or tumor antigens to induce the body’s specific cellular and humoral immune responses, enhances the body’s ability to fight cancer, and prevents the growth, spread, and recurrence of the tumor to achieve clearance. Or the purpose of controlling the tumor. 2. Cellular immunotherapy. Tumor cell immunotherapy, also known as tumor biotherapy, is to import the treated autologous or allogeneic immune cells or immune molecules into the patient’s body, restore and enhance the tumor patient’s own immune monitoring and tumor killing function, and effectively kill The tumor cells remaining in the patient’s body after surgery, radiotherapy and chemotherapy can be eliminated to achieve the purpose of treating tumors, preventing recurrence and improving the quality of life. The processed autologous or allogeneic immune cells or immune molecules have the dual effects of breaking immune tolerance, activating and enhancing the body’s immune capacity, and taking into account both treatment and health care. The chimeric antigen receptor T cell (CAR-T) therapy proposed in 1989 has achieved stable results in the treatment of hematological tumors such as acute leukemia and non-Hodgkin’s lymphoma. 3. Immune checkpoint suppression As mentioned earlier, some of the tumor cells will release signals to the police (immune system) to confuse the police and let them go. Immune checkpoint suppression drugs are specifically aimed at this type of tumor cells to solve their deceptive effects and allow the police to work efficiently again. Immunization checkpoints currently on the market
On the outpatient clinic on Wednesday afternoon, a patient’s family came to consult her uncle in Jilin. Her uncle had liver transplantation because of liver cirrhosis and liver cancer. Now, the tumor recurs and the cancerous nodules are full of liver. Almost tried various treatment methods, and also tried different kinds of molecular targeted drugs. This time, I want to know whether HAIC is suitable (HAIC is a method of continuous hepatic artery infusion chemotherapy), or whether there are other treatment methods. Facing family members who refuse to give up, can the doctor give any “hope” when the condition is so late? In addition to nutrition, support, and symptomatic treatment, is there any substantive treatment that will enable patients to reach their end of life in “hope”? In the late stages of malignant tumors, often miracle immunotherapy can be used in patients with tumor recurrence after liver transplantation? This question is really not a simple “can” or “can’t” answer. After organ transplantation, an anti-“rejection” reaction must be performed, and the patient’s body must develop “immune” tolerance before accepting this foreign transplanted organ. In this process, T cells are the protagonist. This T cell has a temperament and has a positive side and a lazy side. If it is more active, it will attack abnormal things, such as transplanted organs like “outsiders”; malignant tumors with uncontrolled growth; normal cells that are “dragged” by the virus, and so on. If it is lazy, it will open one eye to the other, and will not attack. The effect of T cell temperament lies in the information it receives. The so-called “survival of the fittest” is also true in the cell world. There is no PD1 protein on the surface of T cells. However, if there is a tumor or graft induced stimulation, PD1 protein will be produced. To some extent, the tumor is also a heterologous molecule, and its survival also has a set of logic. Once the PDL1 ligand protein on the surface of the tumor cell binds to the PD1 protein on the surface of the T cell, the T cell releases the tumor cell and does not attack the tumor. cell. “It’s also an evil to let go of a bad person.” Because PD1 binds to PDL1, T cells let go of tumor cells, and they enter into “programmed death” instead. Tumor cells can escape and proliferate, and the progeny of this tumor cell inherit this ability, and they will be able to continually avoid attacks and grow stronger. Now, humans have discovered this pattern and produced a drug called PD1 inhibitor and PDL1 inhibitor. These drugs are given intravenously and infused every 2-3 weeks. These “monoclonal antibody” drugs will actively approach T cells in the blood circulation, blocking PD1 on the surface of T cells or PDL1 on the surface of tumor cells. This process is a bit like the practice of “putting matches in other people’s locks”. In this way, the PD1 protein on the surface of the T cell and the PDL1 protein on the surface of the tumor cell will not stick together. When the T cell encounters the “alien molecule” of the tumor cell, it will attack it and record the characteristics of the tumor. Passed to the next generation of T cells to produce an attack memory, the daughter T cells will attack the daughter tumor cells. Therefore, once the PD1 inhibitor drug is effective, even a late stage tumor or a “melanoma” with a very high degree of malignancy can obtain a miraculous effect. However, this kind of “reversing the heavens and changing lives” is slightly worse, and the consequences are serious. Humans have not completely unlocked the “book of heaven”. For immunotherapy, there are many codes waiting to be unlocked one by one. For example, if an PD1 inhibitor is used after organ transplantation, it may induce the body to produce an immune rejection reaction, leading to failure of the transplanted organ, or even a severe acute rejection reaction, which is life-threatening. With regard to the recurrence of liver cancer after liver transplantation, the question of whether PD1 inhibitors can be used. The first person to eat crabs was Andreas Varkaris and his colleagues. They were in the American Journal of GASTROENTEROLOGY The reader sent a letter to report a case of liver cancer patients treated during 2014-2016. In the case where other methods have not worked, I tried the “Pabolizumab” monoclonal antibody, which is called K medicine. At the same time lowered “tacrolimus”
Currently, tumor immunotherapy is recognized as the “fourth model beyond surgery, radiotherapy, and chemotherapy.” “Science” magazine ranked it as the top ten scientific breakthrough in the year as early as 2013. Immunotherapy is a kind of tumor biological therapy, which has many types and different mechanisms. We usually say that PD1/PDL1 is just one of many immunotherapy, and it is also the most popular one at present. Immunotherapy classification: 1. Monoclonal antibody checkpoint inhibitors include PD-1/PD-L1 inhibitors (O drugs, K drugs, T drugs, etc.), anti-CTLA-4 specific monoclonal antibodies (such as Ipil MAb). 2. Cell therapy includes the famous chimeric antigen receptor T cell immunotherapy (CAR-T), as well as the biological therapy mentioned in the Wei Zexi incident, autologous dendritic cells (DC) stimulate CIK cells (DC-CIK Cells) and so on. 3. Cancer vaccines such as cervical cancer vaccines. Today’s immunotherapy refers specifically to immune checkpoint inhibitors. Is frailty an absolute contraindication to immunotherapy? Frailty is a very broad term. From a professional point of view, there are many specific indicators for the actual pre-medication evaluation. Including indicators of age, indicators of physical condition, indicators of organ function, imaging examinations, etc. The immune checkpoint inhibitor PD1/PDL1 is not absolutely safe, non-toxic and harmless. On the contrary, these drugs also have various adverse reactions. To this end, the Chinese Society of Clinical Oncology (CSCO) has developed guidelines for toxicity management related to immune checkpoint inhibitors. Its toxicity includes immune-related adverse events, infusion reactions, and possible off-target reactions. According to the CSCO guidelines, elderly patients can use immunotherapy (category 2A evidence). At present, most foreign immunotherapy clinical trials do not have a clear age limit. Elderly patients (≥65 years old) participating in clinical trials account for 35-50% of the total population, most of whom are 65-75 years old. Patient enrollment data is lacking. A retrospective study by ASCO in 2018 showed that the age spectrum of patients aged <70 compared with patients ≥70 years old had similar immunotherapy toxicity profiles. Another retrospective study compared the efficacy of PD1/PDL1 treatment for patients with advanced non-small cell lung cancer of different ages, and found that patients ≥80 years old had lower progression-free survival or overall survival than other age groups. Therefore, in terms of age, immunotherapy for the elderly under the age of 75 is not absolutely contraindicated, and the elderly over the age of 80 should be cautious when using it. Only after comprehensive evaluation can they consider whether to use it. The “physical weakness” is a professional assessment method for cancer patients by ECOG physical condition score, 0-1 is good physical strength, and physical performance is worse than 2 points. In the immunotherapy CheckMate171 study, 98 patients with ECOG performance scores ≥ 2 received nivolumab, and the incidence of grade 3-4 treatment-related adverse events was 2%, with safe control. However, considering that the benefit of immunotherapy for patients with poor general conditions is limited, it is recommended to use immunotherapy drugs with caution.
Lupus is a systemic disease. It often causes kidney problems, known as lupus nephritis (LN). LN brings higher mortality and disability rates. & nbsp. & nbsp. The study found that about 50-70% of patients in clinical will have LN, and among them, 81.6% of women are between 14 and 44 years old. So what are the risk factors for LN and how to treat it? Let’s understand it together. What are the risk factors for lupus nephritis? Clinical manifestations of anti-dsDNA antibody titers of young men with high anti-snRNP positive lupus nephritis at the onset of high SLE disease activity. The most common signs of kidney damage in LN are hematuria and proteinuria. Some patients had an increase in blood creatinine at the beginning. Generally speaking, an increase in blood creatinine indicates a decline in kidney function, that is, a decrease in glomerular filtration rate (GFR). There are many early manifestations. Fever, arthralgia and facial erythema are the most common early symptoms of the disease. Some patients are asymptomatic early, but proteinuria or hematuria may also occur. With the involvement of the kidneys, edema, hypertension, renal insufficiency and even uremia will appear later. Pathological classification and treatment of lupus nephritis The ISN / RPS2003 classification system divides LN into 6 different types: mild mesangial LN (type I): mesangial proliferative LN (type II): focal hyperplastic LN ( Type III): diffuse hyperplastic LN (Type IV) membranous LN (Type V) severe sclerosis LN (Type VI) Ⅰ (slight mesangial type), type Ⅱ (mesenchymal hyperplasia) lesions are often reversible, and the prognosis is good Intensive immunosuppressive therapy is not necessary, and treatment needs to refer to the involvement of the external organs of the kidney to select the intensity of treatment. Type Ⅲ (focal hyperplasia) and Ⅳ (diffuse hyperplasia) are common and severe lesions of LN, and clinically often given active immunosuppressive therapy. Type Ⅴ (membrane type) is a special type. Since the risk of kidney damage is less than that of proliferative lupus nephritis, the immunosuppressive treatment plan of type Ⅴ LN is guided by the severity of proteinuria. For patients with proteinuria or conservative treatment of proteinuria in the range of nephropathy, immunosuppressive therapy should be upgraded, and calcineurin inhibitors (tacrolimus or cyclosporin A) are better. Type Ⅵ (progressive sclerosis type) due to chronic and irreversible pathological manifestations, glomerular sclerosis, renal tubular atrophy, interstitial fibrosis, and arteriosclerosis, it is necessary to decide whether to use immunosuppressive agents based on extrarenal lupus activity. It mainly deals with the complications of chronic kidney disease and initiates renal replacement therapy. & nbsp. Although the application of hormones and immunosuppressants greatly improves the prognosis of LN, there are still many difficulties in the process of applying hormones and immunosuppressants: some patients have poor treatment with hormones and immunosuppressants; Serious side effects, such as severe infection, impaired sexual function and cardiocerebrovascular comorbidity, are difficult to avoid; the recurrence rate is high. In the process of LN treatment, integrated Chinese and Western medicine treatment is used to play the role of traditional Chinese medicine, which can effectively improve the therapeutic effect on LN, reduce the toxic and side effects of hormones and immunosuppressants, and prevent the recurrence of the disease.
In a study on alcohol intake with PDE-5 inhibitors, 45.5% of the middle-aged and older men enrolled used PDE-5 inhibitors with alcohol for recreational purposes. Compared with men in the control group, the drinking group showed significantly higher complications, including headache (23.6% vs. 7.3%) and facial flushing (69.6% vs. 12.4%). The results show that, in the normal male population without sexual dysfunction, alcohol abuse when taking PDE-5 inhibitors may also cause serious complications, including chest discomfort and dizziness. Therefore, when men take small blue tablets, they should Avoid drinking alcohol. In addition, there are a few points to note: high-fat foods will also affect the absorption of drugs and reduce their effectiveness; after taking a meal, the effect will be relatively slow; after taking the drug, you ca n’t “sit and wait for the effect”, and the corresponding stimulation is needed; The initial effect is not satisfactory, it is normal, about 40% of men have taken multiple times to accumulate medication experience, and some studies have shown that the best results are generally achieved after taking 8 times; in addition, if you are taking any dosage form of nitrate drugs , Do not take PDE-5 inhibitors.