RU2339044C1 - Method of estimation of patient condition - Google Patents

Abstract

FIELD: medicine; traumatology.

SUBSTANCE: blood from the patient is taken; carry out the analysis in blood serum and bracing of fluctuations of an immunologic indicator in any chosen time interval during observation over the patientis carried out. In blood serum a caption of a staphylococcal antitoxin is defined, estimate its level is estimated and if titre is in limits from 0.5 to 2.0 AE/ml the prediction of a current of traumatic illness or the postoperative period consider as favorable. If the titre is higher 2.0 AE/ml - prognosticate possibility of inflammatory process or its exacerbation. If the titre below 0.5 AE/ml it specifies in oppression of immune system and probability of a neoplasm in an osteal tissue. Thus if the titre tends in dynamics of inspection to augmentation from 0.5 to 2.0 AE/ml a condition of the patient also co-ordinate to inflammatory process.

EFFECT: diagnostics of inflammatory processes on early terms and the exact information on pathological process.

2 tbl, 8 ex

Description

The invention relates to medicine, namely to traumatology and orthopedics, and can be used to diagnose and predict the condition of the patient in the post-traumatic and postoperative period with the development of the inflammatory process, as well as, in particular, in the differential diagnosis of neoplasms in bone tissue.

A known method for predicting the development of osteomyelitis, characterized in that the concentration of magnesium, copper, zinc, calcium, chlorides, thyroid stimulating hormone and acid phosphatase activity is determined in the patient's blood serum. Then calculate by the formula the percentage deviation of each indicator from the established medians of the regional normal indicators taken as control values. When detecting cumulative changes: an increase in magnesium by more than 3%, copper - more than 5%, zinc - more than 3%, and activity of acid phosphatase - more than 15% and a decrease in calcium by more than 5%, chlorides - more than 5% and thyroid-stimulating hormone - more than 10%, consider the prognosis of osteomyelitis to be unfavorable (RF Patent No. 2279081, class G01N 33/49, 33/573, 33/78, 33/84. Publish. June 27, 2006 Bull. No. 18).

The disadvantages of this method are the large time and economic costs of determining in blood serum numerous indicators, the complexity of the interpretation of the results.

There is also a method for diagnosing a chronic nonspecific inflammatory process by clinical examination of patients, in which quantitative determination of serum immunoglobulin levels of classes A, M, J is carried out by the method of radial immunodiffusion in gel in dynamics, followed by an assessment of the individual dynamics of the content of serum immunoglobulins during the exacerbation period. Then, an analysis of the state of the immunological background relative to the levels of serum immunoglobulins recorded in the patient in the phase of remission of the disease is carried out (RF Patent No. 2007723, class C01N 33/53. Publ. 15.02.94 Bul. No. 3).

The disadvantage of this method is the duration of the study, the need for multiple blood sampling to establish reliable indicators characterizing a certain condition of the patient.

Closest to the proposed in its technical essence is a method for assessing the patient’s condition, including blood sampling, analysis of blood serum and fixing the fluctuations of immunological parameters in any selected period of time during the period of their activity (RF Patent No. 2103692, CL G01N 33/53, 33 / 50, 33/68. Published on January 27, 1998, Bull. No. 3).

The disadvantage of this method is that this method cannot give a differentiated answer about the bone pathology of the patient, and treatment tactics depend on it.

The task to be solved by the claimed method is aimed at prompt and economical, taking into account individual characteristics of patients, prognosis and diagnosis of the inflammatory process in traumatologic and orthopedic patients, as well as the possibility of differential diagnosis of the inflammatory process from neoplasm in bone tissue.

This problem is solved by the fact that in the method for assessing the patient’s condition, including blood sampling, analysis in blood serum and fixing the fluctuations of the immunological indicator at any selected time interval during the observation of the patient, titers of staphylococcal antitoxin are determined in blood serum, their level is estimated, and if the titer is in the range from 0.5 to 2.0 AU / ml, then the prognosis of the course of a traumatic disease or postoperative period is considered favorable; if the titer is higher than 2.0 AU / ml, the possibility of an inflammatory process or its exacerbation is predicted; and if the titer is below 0.5 AU / ml, then this indicates an inhibition of the immune system and the likelihood of neoplasm in the bone tissue. Moreover, if the titer in the dynamics of the survey tends to increase from 0.5 to 2.0 AU / ml, then the patient’s condition is also linked to the inflammatory process.

The determination of staphylococcal antitoxin titer in blood serum in case of purulent-inflammatory complications in traumatologic and orthopedic patients is not accidental, since the authors of the invention obtained data from a bacteriological study of purulent, separated from 2002 to 2005, showing that 1302 Staphylococcus spp strains were isolated , which amounted to 66.7% of the total number of identified microorganisms and demonstrated the predominance of gram-positive coccal flora in the etiological structure of purulent-inflammatory complications th with a predominance of Staphylococcus aureus (70.28%).

When examining 248 practically healthy people (primary donors), it was found that all people have staphylococcal antitoxin in their blood in an amount that is almost constant for each person. The average annual staphylococcal antitoxin was determined, which is 1.06 + 0.017 AU / ml (normal) with minimal fluctuations depending on age, gender, seasonal changes of the year, which can be neglected. Studies have shown that in 93.55% of practically healthy people (outside the infection), staphylococcal antitoxin titer values ranged from 0.5 to 2.0 antitoxic units (AE / ml). The highest titer of staphylococcal antitoxin in healthy people was in the range of 2.5-3 AU / ml, but such titers, unrelated to a clear infection, are extremely rare at the time of the examination (in 2.42% of cases). Staphylococcal infections transferred do not create long-term immunity. Low titers of staphylococcal antitoxin were found in 4.03% of cases.

The inventors have experimentally found that if the titer of staphylococcal antitoxin is in the range from 0.5 to 2.0 AU / ml, then the prognosis of the course of a traumatic disease or postoperative period can be considered favorable; if the titer is higher than 2.0 AU / ml (for example, 3.0 AU / ml, 4 AE / ml or more), the possibility of developing an inflammatory process or an exacerbation of a chronic inflammatory process is predicted, even without visible clinical signs; titers below 0.5 AU / ml (e.g. 0.25 AU / ml, 0.125 AU / ml, 0.0625 AU / ml) indicate inhibition of the immune system. If the titer in the dynamics of the survey tends to increase from 0.5 to 2.0 AU / ml, then the patient’s condition is also linked to the inflammatory process. Of particular note is the differential diagnosis of bone tissue pathology. If the radiological diagnosis of bone tissue pathology is difficult, at high titers of staphylococcal antitoxin (as shown above), the inflammatory process (hematogenous osteomyelitis of a non-helpless form or the development of deep foci of staphylococcal infection in soft tissues) is diagnosed, and in the presence of low titers, the presence of a tumor process can be assumed.

The technical result consists in early diagnosis of the inflammatory process in trauma and orthopedic patients, expanding the scope of the method, in particular, in the differential diagnosis of inflammatory processes from neoplasms in bone tissue, increasing diagnostic efficiency by using differentiation of diagnostic criteria for inflammatory processes and processes associated with neoplasms musculoskeletal system.

The claimed essential features are not known from the prior art. The proposed method has passed clinical trials.

The method is as follows. To determine the titer of staphylococcal antitoxin (TCA), the following ingredients are required: blood serum of the patient in the amount of 0.6-1.0 ml, standard staphylococcal toxin with known Lh (Lizes haemolitica of the toxin is its amount in ml, which, being associated with 1 AE serum, will cause almost complete, by +++, rabbit erythrocyte hemolysis), rabbit erythrocytes. In the reaction to determine the antitoxin in the blood, its ability to neutralize the property of the toxin to hemolize rabbit erythrocytes is used.

Before setting the reaction, serum is inactivated by heating at 56 ° C for 20-30 minutes to break down the proteins of the complement system, then it is diluted with physiological saline to the initial dilution of 1: 5, and then titrated according to a short scheme (table 1). All serum dilutions are prepared in a volume of 1 ml. For convenience, physiological saline in the desired volume is preferably added to the tubes in advance.

Table 1 The scheme of titration of serums for determination of staphylococcal antitoxin in the range of 0.5-6 AU / ml No. of tubes The blood serum of the subject, ml Fiz. solution, ml Transfer Intelligence. serum Stafilok. toxin, ml Amount AE / ml Lh / 5 Lh / 10 0 1 ml - From 1st 1: 5 - 1 ml 0.5 one 0.6 whole whey 2,4 In the zero and in the 2nd 1 ml 1: 5 1 ml - one 2 1 ml of the 1st 1,0 In the 3rd 1 ml 1:10 1 ml - 2 3 1 ml of the 2nd 0.5 In the 4th 0.5 ml 1:15 1 ml - 3 four 0.5 ml of the 3rd 0.5 - 1:30 1 ml - 6

The standard staphylococcal toxin is reacted in a dilution of Lh / 5 and Lh / 10, and, if necessary, Lh / 20 and Lh / 40, based on the Lh of the available toxin. The toxin was diluted with physiological saline (0.9%) and added in an amount of 1 ml of the desired Lh to all tubes except the control sera.

When setting up the reaction, controls are necessary for each ingredient used in the reaction:

1. Control of the test serum: a) test tube with 0.2 ml of undiluted non-inactivated serum with 1.8 ml of physiological saline and b) test tube with 0.2 ml of undiluted inactivated serum with 1.8 ml of saline.

2. Control of rabbit erythrocytes: test tube with 2 ml of physiological saline and 2 drops of prepared red blood cells.

3. Toxin control: a) test tube with 1 ml of Lh / 5 toxin and 1 ml of physiological saline and b) test tube with 1 ml of Lh / 10 and 1 ml of physiological saline.

The total volume of ingredients in each tube (in the experimental and control) is 2 ml.

Then, 1-2 drops of prepared red blood cells are added to all test tubes (experimental and control) and the contents of the tubes are thoroughly mixed.

To prepare rabbit erythrocytes participating in the reaction, 9 ml of blood is taken from the rabbit's ear vein into a test tube with 1 ml of a 5% solution of trisubstituted sodium citrate and mixed thoroughly. In this form, red blood cells can be stored at + 4 ° C for 1-2 weeks. Before setting up the reaction, red blood cells are washed three times by centrifugation in physiological saline to obtain a clear, colorless supernatant, which is aspirated, and red blood cells are diluted based on the initial volume of 1: 3.

The test tube rack is placed in a thermostat at 37 ° C for one hour, then incubated for 1 hour at room temperature and the reaction result is noted.

The absence of hemolysis is indicated by a minus (-), partial hemolysis by one, two and three crosses (+, ++, +++). Complete hemolysis is indicated by four crosses (++++). The dilution is taken as the serum titer, which, in a mixture with a standard dose of toxin (Lh / 5), gives a delay of hemolysis by two crosses ++.

The convenient and short breeding scheme of the test sera was used to determine the normal and elevated toxin content from 0.5 to 6 AU, which is typical for most people. However, with a staph infection, titers can be significantly higher. If there is still no hemolysis in the fourth test tube, a reaction with a higher dilution of sera must be performed.

In the case when it is radiologically difficult to identify the signs that are most characteristic of various tumor and inflammatory processes in bone tissue, a staphylococcal antitoxin titer determination scheme is used, covering a wider range of values (table 2). In this case, all dilutions of the test serum are prepared in a volume of 0.5 ml and 0.5 ml of the standard staphylococcal toxin of the desired Lh is added, and an additional control of the toxin Lh / 20 and Lh / 40 is added. The total volume of ingredients in each tube is 1 ml.

table 2 Modification of the serum titration scheme to determine the staphylococcal antitoxin titer (range from 0.125 to 20 AU / ml) No. of tubes The blood serum of the subject, ml Fiz. solution, ml Pour out Intelligence. serum Staphylococcus aureus. toxin Lh Amount AE / ml one. from 4th - 0.5 - - 1: 5 1/40 0.125 2. from 4th - 0.5 - - 1: 5 1/20 0.25 3. from 4th - 0.5 - - 1: 5 1/10 0.5 four. undeveloped. 0.6 2,4 - 1: 5 1/5 1,0 5. out of 4 - 1,0 1,0 - 1:10 1/5 2.0 6. out of 5 - 0.5 0.25 - 1:15 1/5 3.0 7. out of 5 - 0.5 0.5 - 1:20 1/5 4.0 8. out of 6 - 0.25 0.25 - 1:30 1/5 6.0 9. from the 7th - 0.5 0.5 - 1:40 1/5 8.0 10. out of 5 - 0.1 0.4 - 1:50 1/5 10.0 eleven. out of 5 - 0.1 0.5 0.1 1:50 1/5 12.0 12. out of 5th -0.1 0.6 0.2 1:70 1/5 14.0 13. out of 9th - 0.5 0.5 0.5 1:80 1/5 16,0 fourteen. out of 5 - 0.1 0.8 0.4 1:90 1/5 18.0 fifteen. out of 5 - 0.1 0.9 0.5 1: 100 1/5 20,0

When examining a patient in dynamics, low titers may also have diagnostic value. For example, if during the first examination the patient had a titer of 0.5 AU / ml, and after a week rose to 2 AE / ml (without vaccination), then the patient's condition can be associated with the inflammatory process of staphylococcal etiology. It should be noted that the depletion, general weakness of the body caused by the underlying disease or traumatic operations, leads to a reactive state, delay the production of antibodies in cases of known infection (fistulous forms of staphylococcal osteomyelitis and suppuration of deep open wounds caused by staphylococcal infection, were accompanied by an increase in antitoxin titer in the blood 59.2% of patients).

Example 1. Patient S., 24 years old. He was admitted to the hospital in February 2000 with a diagnosis of an open fracture of both bones in the middle third of the right lower leg with displacement of fragments, in the wound fracture area 2.0 × 1.0 cm. Upon receipt, the initial surgical treatment of the wound and osteosynthesis by Ilizarov apparatus were performed.

Clinical blood tests are normal. The staphylococcal antitoxin titer was equal to 1.0 AU / ml and remained unchanged until the end of the patient's stay in the clinic. Postoperative therapy was carried out by generally accepted methods. After the operation period was uneventful, the wound healed by first intention. The patient was discharged on the 12th day in satisfactory condition with recommendations to come for control after 1.5 months.

Example 2. Patient T., 33 years old. He was admitted to the clinic in August 2003 with a diagnosis of pseudarthrosis, post-traumatic defect, chronic osteomyelitis of the upper third of the left femur in the acute stage, purulent fistula, contracture of the left knee joint. Condition after resection of the false joint, osteosynthesis according to Ilizarov. On examination: the axis of the leg is correct, shortening by 6 cm due to a defect of the femur, there is a fistula along the lateral outer surface of the left thigh, and the support ability is impaired. On radiographs after fistulography, the fistula passes through the soft tissues, forming a large “depot”, then penetrates the bone (fracture site), the structure is changed in the proximal femur. Coalescence is doubtful.

The staphylococcal antitoxin titer was 4.5 AU / ml. In bacteriological examination of the separated fistula, St. aureus.

Operation - fistulonecrosecvestrectomy, flushing drainage.

The staphylococcal antitoxin titer continues to remain high - 4.5 AU / ml. In the postoperative period, 2 fistulas were formed. The second operation was performed - necrectomy, muscle plastic, a circular circular bandage with a window was applied. Antibacterial therapy with meropenem was carried out. There has been an improvement in the patient's condition. The staphylococcal antitoxin titer began to decrease to 3 AU / ml. The patient was discharged from the hospital for outpatient treatment at the place of residence in satisfactory condition with recommendations to walk with crutches without loading the left limb.

Example 3. Patient E., 36 years old. Was admitted to the clinic in September 2006 for conservative treatment with a diagnosis of bilateral dysplastic coxarthrosis of the III degree, shortening of the left lower limb by 2 cm. Sick since childhood. In 2003, an operation was performed: arthrodesis of the left hip joint. Arthrodesis did not take place. Complaints of pain in the right hip joint, lameness, limitation of movements in it.

The staphylococcal antitoxin titer was 4.5 AU / ml.

Conservative treatment with non-steroidal drugs and physiotherapy were performed. There has been an improvement in the patient's condition. The patient was discharged from the hospital with recommendations for total endoprosthetics of the right hip joint.

Example 4. Patient 3., 18 years old. He was admitted to the clinic in December 2003 with a diagnosis of a suspected tumor of the right thigh or osteomyelitis. Complaints of recurring pain in the right thigh, the presence of an oval seal.

Sick since February 2001, when after a fall the right thigh was bruised. An X-ray examination of the bone pathology was not detected, but in the next few months, a lump appeared in the lower third of the right thigh. A biopsy was done: no cancerous, atypical cells were found (according to the patient). The patient was referred to SarnIIITO for a consultation. Conservative treatment, antibacterial therapy were carried out, an X-ray examination was performed in dynamics. Body temperature did not rise. Recent radiographs show destructive changes in the bone. The patient was hospitalized to clarify the diagnosis with suspected chronic osteomyelitis of the right thigh in the lower third.

The staphylococcal antitoxin titer was 4.5 AU / ml.

Further, the results of computed tomography of the femur confirmed that the patient has chronic sclerosing osteomyelitis Garre. The patient was operated on: pathological soft tissues were removed, sequestrectomy was performed. The inflammatory process is histologically confirmed. During bacteriological examination, St. aureus.

Example 5. Patient S., 10 years old. He was admitted to the clinic in December 2006 with a diagnosis of a tumor of the right tibia. Sick since November 2006, when during the flu, the temperature rose sharply to 40 ° C, there was pain, redness and swelling in the right ankle joint. The diagnosis was made: complication of the joint after the flu. A course of antibiotic therapy. There was a temporary improvement in the patient's condition, and then pain, redness in the ankle joint reappeared. On radiographs of the right lower limb in the ankle joint in the growth area of the tibia, a tumor formation of 1 × 0.5 cm is determined.The patient was hospitalized in the Saratov Regional Children's Hospital, and then transferred to SarNIIITO for further examination, to clarify the diagnosis and develop tactics for further treatment.

The staphylococcal antitoxin titer was 2.5 AU / ml.

With palpation of the ankle joint, the seal is not determined, there is no pain. An X-ray examination determined the destruction site in the area of the distal metaepiphysis of the right tibia adjacent to the growth zone 1 × 1 cm. The surrounding bone tissue is sclerotic, the adjacent part of the growth zone is expanded, has fuzzy contours. On the inner part of the tibial bone surface, a focus of enlightenment is determined - a zone of pathological reconstruction.

Given the anamnesis, x-ray picture and clinical tests, there is more evidence to support the inflammatory process. An edge resection was made along the anterior surface of the tibia in the distal region. Purulent contents of a dark green color were found. During bacteriological examination, St. aureus. Histological and cytological studies confirmed the inflammatory process.

Example 6. Patient B., 58 years old. Was admitted to the clinic in January 2006 with a diagnosis of a tumor of L ₃ -L ₄ vertebrae of the lumbar spine. When examining the lumbar region, swelling is determined. Complaints of pain in the lumbar spine, problems with urination, stool, decreased muscle strength in the legs. The onset of pain is associated with hypothermia. Sick lying. On radiographs, there is an uneven contour of the L ₃ -L ₄ vertebrae, the absence of an intervertebral disc, the presence of leaks. When studying the data of computed tomography, there was an impression of tuberculous spondylitis with leaks. However, after consultation with a phthisioorthopedist, district phthisiatrician, and after negative analyzes, the specific nature of spondylitis was ruled out. The staphylococcal antitoxin titer was 8 AU / ml. According to the analysis, a significant increase in the titer of staphylococcal antitoxin is noted. Massive antibacterial therapy (Fortum intravenously) was given. There was an improvement in the patient's condition, the pain syndrome was significantly reduced, the patient rises from bed. On the control radiograph positive dynamics was noted - ossification in the anterior regions of the vertebral bodies. The patient was discharged from the hospital with recommendations to wear a corset, control at the SarnIIITO clinic. Final diagnosis: osteomyelitis L ₃ -L ₄ .

Example 7. Patient K., 72 years old. He was admitted in November 2006 with a diagnosis of giant cell tumor of the left thigh. Complaints of pain, limited range of motion in the left knee joint, impaired support. In 1995, there was a fracture of the middle third of the left femur. Operation: osteosynthesis of the left thigh with a rod, then the rod migrated and in 1996 a larger diameter rod was reinstalled. For ten years there were no complaints from the patient, but in the spring of 2005 a pronounced pain syndrome appeared in the left knee joint. Conservative treatment did not work. There was a restriction of movements, night pains began to disturb. The patient moves on crutches, there is varus deformity of the bones of the left lower limb, hypotrophy of the muscles of the thigh and lower leg, swelling of the knee joint, sharp pain during palpation in the popliteal region, a soft-tissue tumor formation 10 × 6 × 4.5 cm in size is palpated. Hospitalized for examination and determination treatment tactics.

The staphylococcal antitoxin titer was 0.125 AU / ml.

On radiographs of the left femur, an overgrown fracture in the lower third of the femur is determined, the condition after surgery (intramedullary osteosynthesis). In the area of the medial condyle, a large, structureless formation is determined, without clear external contours.

Considering the anamnesis and clinical and radiological data, the diagnosis was established: a giant cell tumor of the lower third of the left thigh with a lytic form with signs of malignancy, pain, the condition after osteosynthesis of the left thigh with a rod. Histological and cytological studies performed after endoprosthetics of the left knee joint confirmed the diagnosis.

Example 8. Patient L., 13 years old. Was admitted to the hospital in June 1999 two weeks after a car accident with a diagnosis of traumatic amputation of the right lower limb, fracture of the forearm bones on the right and a scalped wound 16.0 × 4.5 cm on the outer surface, a wound size 3.0 × 1.5 see in the ankle of the left tibia on the outer surface, concussion. In the sacral region there are two pressure sores 6.0 × 4.5 cm in size, suppuration of all wound surfaces. Polyantibiotic-resistant St. was isolated from the wound aureus.

The staphylococcal antitoxin titer was 0.75 AU / ml.

In the treatment of purulent wounds, ozone therapy and a 1% solution of poviargol were used. The titer of staphylococcal antitoxin at the beginning of treatment increased to 1.5 AU / ml, then to 2.5 AE / ml. With the improvement of the patient's condition in the process of wound cleansing, the titer of staphylococcal antitoxin began to decrease and at the end of treatment was equal to 1.0 AU / ml. The inflammatory process has been stopped. Complete epithelialization of wounds has been achieved. Thus, the right upper limb was prepared for further surgical treatment.

Thus, the proposed method for assessing the patient’s condition has the following advantages: the possibility of repeated examination for a dynamic assessment of the patient’s condition, allows you to diagnose and predict the development of purulent-inflammatory processes, exclude or confirm a neoplasm in the bone tissue and diagnose hematogenous osteomyelitis of the helpless form, thereby giving a more accurate information about the pathological process in comparison with the classic X-ray examination, does not require deficiency expensive expensive drugs and equipment, the duration of the study is a maximum of 4 hours.

Claims (1)

A method for assessing a patient’s condition, including blood sampling, analysis of an immunological indicator in blood serum at any selected time interval during patient observation, characterized in that the staphylococcal antitoxin titer is determined in the blood serum, its level is estimated, and if the titer is in the range of 0 5 to 2.0 AU / ml, then the prognosis of the course of a traumatic disease or postoperative period is considered favorable; if the titer is higher than 2.0 AU / ml, the possibility of an inflammatory process or its aggravation is predicted, and if the titer is lower than 0.5 AE / ml, this indicates an inhibition of the immune system and the likelihood of prognosis of a neoplasm in bone tissue, if the titer in the dynamics of the survey, a tendency to increase from 0.5 to 2.0 AU / ml, the patient’s condition is also linked to the inflammatory process.