comorbid conditions. Nesterovich I.I., Kotov M.E.

The human body is a single whole, where every organ, every cell is closely interconnected. Only well-coordinated and coordinated work of all organs and systems makes it possible to maintain homeostasis (constancy) of the internal environment of the human body, which is necessary for its normal functioning.

But, as you know, stability in the body is violated by various pathological agents (bacteria, viruses, etc.), leading to pathological changes and causing disease. Moreover, if at least one system fails, many protective mechanisms are launched, which, through a number of chemical and physiological processes, try to eliminate the disease or prevent its further development. However, despite this, the "trace" of the disease still remains. Violation in the work of a separate link in a single chain of the body's vital activity rebounds on the functioning of other systems and organs. This is how new diseases appear. They may not develop immediately, but years after the illness, which served as an impetus for their development. During the study of this mechanism, the concept of "comorbidity" appeared.

Definition and history of occurrence

Comorbidity is understood as the simultaneous occurrence of two or more diseases or syndromes that are pathogenetically (according to the mechanism of occurrence) interconnected. AT literal translation from the Latin language in the word comorbidity there are 2 semantic parts: co - together, and morbus - disease. The concept of comorbidity was first proposed in 1970 by the eminent American epidemiologist Alvan Fenstein. In the open concept of comorbidity, the researcher Fenstein put the idea of ​​the existence of an additional clinical picture against the background of the current disease. The first example of comorbidity studied by Professor Fenstein was a somatic (therapeutic) disease - acute rheumatic fever, which worsened the prognosis in patients suffering from a number of other diseases.

Soon after the discovery of the phenomenon of comorbidity, it attracted the attention of researchers from all over the world. The concept of "comorbidity" changed over time into "polymorbidity", "multimorbidity", "polypathy", "dual diagnosis", "condolence", "pluripathology", but the essence remained the same.

The great Hippocrates wrote: "examination of the human body is a single and whole process that requires hearing, sight, touch, smell, language and reasoning." That is, before starting to treat the patient, it is necessary to comprehensively study general state of his body: the clinical picture of the underlying disease, complications, comorbidities. Only then does it become possible to choose the most rational therapy strategy.

Types of comorbidity

Comorbidity can be divided into the following groups:
1. Causal comorbidity due to parallel damage to organs and systems caused by a single pathological factor. An example of such comorbidity is internal organs with alcoholism.
2. Complicated comorbidity. This type comorbidity appears as a result of the underlying disease, which to some extent destroys the so-called target organs. For example, we are talking about chronic kidney failure, which appeared as a result of diabetic nephropathy (with type 2 diabetes mellitus). Another example of this type of comorbidity is a heart attack (or stroke) that developed against the background of hypertensive crisis with arterial hypertension.
3. Iatrogenic comorbidity. The reason for its appearance is the forced negative impact of diagnosis or therapy on the patient, provided that the danger of any medical procedure is established and known in advance. A striking example of this type of comorbidity is osteoporosis (bone fragility), which develops as a result of the use hormonal drugs(glucocorticosteroids). Such comorbidity can also develop with chemotherapy, which can cause the development of drug-induced hepatitis in a patient.
4. Unspecified comorbidity. This type of comorbidity is spoken of when it is assumed that there are common mechanisms for the development of diseases that make up the overall clinical picture, but certain studies are required to confirm this thesis. For example, a patient suffering from arterial hypertension may develop erectile dysfunction (impotence). Another example of unspecified comorbidity may be the presence of erosions and ulcers on the mucous membrane of the upper digestive tract in patients with vascular diseases.

5. "Random" comorbidity. The combination of a patient with chronic coronary heart disease and the presence of stones in gallbladder(cholelithiasis) shows an example of "accidental" comorbidity.

Some statistics

It has been established that the number of comorbid diseases directly depends on the age of the patient: in young people, this combination of diseases is less common, but the older the person, the greater the likelihood of developing comorbid pathologies. At the age of 19 years, comorbid diseases occur only in 10% of cases, by the age of 80 this figure reaches 80%.

If we consider the data of pathoanatomical studies (autopsies) of those who died from therapeutic pathology in the age category of 67–77 years, then the comorbidity is about 95%. Comorbidity is more common in the form of a combination of two or three diseases, but there are cases when one patient has a combination of up to 6–8 diseases (in 2–3% of cases).

More often than others, doctors experience comorbidity general practice and therapists. However, narrow specialists are also not immune from encounters with this phenomenon. But in this case, doctors often "turn a blind eye" to the phenomenon of comorbidity, preferring to treat only "their own" - a profile disease. And other diseases are left to their colleagues - therapists.

Diagnosis with comorbidity

In the presence of comorbidity, in order to make a correct diagnosis, the patient must follow certain rules: the diagnosis identifies the underlying disease, background diseases, complications, and comorbidities. That is, among the "bouquet" of diseases, it is necessary first of all to determine the disease that requires priority treatment, since it threatens the patient's life, reduces his ability to work, or can provoke dangerous complications. It happens that the underlying disease is not one, but several. In this case, one speaks of competing diseases, that is, diseases that occur simultaneously in the patient, mutually independent in terms of the mechanism of occurrence.

Background pathologies complicate the course of the underlying disease, aggravate the situation, make it more dangerous for the health and life of the patient, and contribute to the development of various complications. The underlying disease, like the main one, requires immediate treatment.

Complications of the underlying disease are associated with it by pathogenesis (the mechanism of occurrence) and can lead to an unfavorable outcome, in some cases even to the death of the patient.

Concomitant diseases are all other pathologies that are not associated with the underlying disease and, as a rule, do not affect its course.

Thus, comorbidity is a negative factor for the prognosis of the disease, which increases the likelihood of a lethal outcome. Comorbid pathologies lead to an increase in the duration of the patient's treatment in the hospital, increase the number of complications after surgery, the percentage of disability, and slow down the patient's rehabilitation.

Therefore, the task of every doctor is to see the clinical picture as a whole, as they say, "to treat not the disease, but the patient himself." With this approach, in particular, the likelihood of severe side effects when choosing pharmaceuticals: the doctor can and should take into account their compatibility with the simultaneous treatment of several pathologies at once, and simply must always remember the saying of E.M. Tareeva: "Each non-indicated medicine is contraindicated."

Many interesting and unusual terms are known to different areas of human life. Many of them are well-known, but most people have not even heard of some. For example,comorbidity. it medical term denoting a very interesting area of ​​​​professional diagnostics and therapy.

History of the term

If you follow the path of a clear professional dictionary, then in medicine there is a term denoting a set of diseases according to certain characteristics - comorbidity. This definition, traditional for medicine, has its roots in Latin. It is from it that two components are taken - coniunctim and morbus - "together" and "disease", which became the basis of an unusual term for a simple man in the street, denoting a complex chronic diseases in one patient, in some way related to each other.

Such a definition of the patient's condition has been considered since the earliest times, at the dawn of the emergence of healing diseases. Both the ancient Greeks and the healers of the Ancient East did not treat the disease itself, as something isolated, but the whole organism suffering from the manifestation of a specific ailment. Doctors of different generations spoke about the relationship of several problems in the state of human health, manifested by certain symptoms, and, therefore, about the treatment of a whole range of diseases. And to date, comorbidity is a clinically proven method for making an adequate diagnosis and competent treatment, which contributes to the preservation of health.

The term "comorbidity" itself was proposed in 1970 by the American epidemiologist and researcher Alvan R. Feinstein (AR Feinstein). At first, this concept was used mainly in clinical epidemiology, but over time it has become the main research technique in various branches of medicine.

Combination of diseases

Turning to the doctor about a specific health problem, a person most often does not suspect that his condition is caused not by one, but by a whole range of problems. And for many specialists, when making an adequate diagnosis, it becomes clear that in a particular case, we can talk about comorbidity. But at the same time, for other doctors, the right direction for diagnosing a disease and prescribing treatment will be multimorbidity, that is, not a combination of diseases at the pathogenetic level, but their presence separately, which gives a general picture of the patient's condition at a given time.

But meanwhile, for the absolute majority of practicing physicians around the world, it is the combined diseases that become the most qualitative definition of diagnosis and treatment. For example,comorbidity in cardiology takes into account, in addition to two main problems of cardio-vascular system- arterial hypertension and coronary heart disease - also problems of the respiratory and urinary systems.

What are the reasons?

For medical practice, comorbidity is a combination of several interrelated diseases that a particular person suffers from. PPractical medicine is faced with the peculiarity that when a patient first visits a specialized medical institution In the vast majority of registered cases, we are talking about one specific disease, for which treatment is prescribed. But in multidisciplinary hospitals, the picture changes dramatically, the same patients receive a diagnosis of comorbidity, which allows them to better prescribe treatment in accordance with a comprehensive vision of the identified pathologies. This is due to the fact that a more thorough observation and examination of the patient in different profiles takes into account all the parties on the basis of which we are talking about concomitant diseases:

• anatomical feature - diseased organs located close to each other;
• a single pathogenetic mechanism for the development of diseases;
• diseases have one causal relationship and are united by a single time threshold;
• one disease "follows" from another, as a complication.

Assuming that the patient has comorbidity, the specialist bases his opinion on the identified or potentially possible factors:

• inflammatory process;
• genetic predisposition;
• infection;
• metabolic changes of an involutive or systemic nature;
• social status;
• ecology of the region of permanent residence;
• iatrogenic - deterioration of the patient's condition (physical and / or emotional due to the fault of a medical worker).

How is the problem being studied?

At the current stage of development of medicine, as a science in various spheres of life human body, the concept of "comorbidity" is a set of diseases interconnected by a pathogenetic mechanism of occurrence, development, manifestation. Observation of the patient's condition from ancient times allowed doctors to conclude that it is impossible to treat only the manifestation of the disease without eliminating the cause of its occurrence, moreover, the disease often does not occur as a separate lesion of an organ or system. In fact, there are several diseases, and they are interconnected. most accurate and ancient method study of such combination - autopsy. It was the post-mortem study of the diseases that a person suffered from that made it possible to conclude that many of them occur together, and thus reveal the presence of comorbidity.

How are comorbidities classified?

Combined diseases are present in different areas of medicine. And conditionally they can be divided into comorbidity in psychiatry and a combination of clinical internal diseases. Medical scientists study related diseases in two directions:

• transsyndromal - syndromes are interconnected by pathogenetic causes;
• transnosological - the diseases present in the patient do not have common pathogenetic causes.

It is this division that makes it possible to differentiate the combination of diseases according to common reasons occurrence or similar clinical manifestations.

Also, comorbidity is divided into the following types:

• causal;
• complicated;
• iatrogenic;
• unspecified;
• "accidental" comorbidity.

Diagnosis and treatment of a complex of diseases

The problems of comorbidity have been studied by medicine from different points of view for many decades. Recently, this issue has been raised sharply again at the highest levels, and potential work is underway to improve diagnostics, treatment methods, and prognosis. World medicine has already developed several methods for measuring comorbidity, each of which works in a specific direction. And the main problem is that each such technique can have different results for the same patient. In determining the presence of comorbidity, and therefore predicting the mortality or quality of life of a patient, practitioners do not have a single tool that operates with specific arguments that allow them to obtain the most accurate result. That is why all these techniques are little used in practical therapy in various areas.

At the present stage of development of medicine, comorbidity is the field of study of existing diseases in one patient, interconnected by causes or symptoms, potentially significant, but little used in practice due to the lack of specific work algorithms.

The review characterizes the features of modern human pathology and is dedicated to the phenomenon of comorbidity, or syntropy - multiplicity, or the coexistence of two or more diseases in one patient. The review summarizes and systematizes modern ideas about comorbidity, introduces the most important aspects of this problem that are currently being studied - epidemiological, clinical, medical and economic, genetic, and also introduces the concept of dystrophy, or reverse comorbidity. Among the numerous aspects of comorbidity, the greatest attention is paid to its clinical and general pathological significance, in particular, the marker of this phenomenon, as well as the most important pathogenetic mechanisms that can cause the development of both syntropia and dystrophy. Among the pathogenetic mechanisms of comorbidity, systemic inflammation, oxidative stress, mesenchymal dysplasia, molecular genetic mechanisms involving common cell signaling pathways, as well as the significance of comorbidity in certain types of pathology, in particular, cardiovascular and oncopathology, are considered.

comorbidity

mechanisms of pathogenesis

clinical and general pathological significance

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To the most important features Modern human pathology includes the predominance of chronic diseases, the genesis of which is predominantly multifactorial in nature, the predominance of diseases that differ in the systemic lesion (atherosclerosis, diabetes, diseases of the connective tissue system, etc.), as well as comorbidity, or the coexistence in one person of several - two or more diseases. All this causes the complexity of diagnosis, treatment, rehabilitation, prevention (there is no one causative factor or risk factor) and the prognosis of the main types of pathology.

However, individual approach to the patient (personalization of treatment) dictates the need for a deep understanding of the genesis of the underlying and concomitant diseases, their causal and pathogenetic relationship, their complex diagnostics and rational treatment.

The term "comorbidity" (from lat. co− together, morbus- disease) was proposed in 1970 by an American researcher of epidemiology noncommunicable diseases A. Feinstein, who understood this as additional clinical conditions, already existing or arising against the background of the current disease and always different from it. As synonyms for "comorbidity", "polypathology" and "multi" or "polymorbidity" are also used, although the discussion on various interpretations these terms continues.

Epidemiological data on the prevalence of comorbidity vary significantly and significantly depend on the sample parameters (patients of a general practitioner or a specialized clinic, gender of patients, age, adherence of researchers to different classifiers of diseases), but in general there is an increase in the frequency of comorbidity with age, especially in women. Thus, the number of coexisting diseases in young people averages 2.8, in older people - 6.8. The incidence of the phenomenon of comorbidity is 69% in patients aged 18-44 years, reaches 93% in patients 45-64 years old and 98% in people over 65 years old. The most significant (92%) proportion of patients with comorbidity is detected among patients with chronic heart failure (CHF), and the most common combinations of diseases include a combination of diabetes mellitus (DM), osteoarthritis (-arthritis) and coronary heart disease (CHD), and also arterial hypertension (AH), obesity and hyperlipidemia (HL). At the same time, comorbidity cannot be described using several simple combinations of diseases, which also do not reflect differences in the severity of the condition, the impact on the level of physiological and mental functions, and disability. We cannot answer, for example, the question - how, with the coexistence of three diseases in each of the patients, a patient with coronary artery disease, hypertension and type 2 diabetes differs from a patient with chronic lung disease, arthritis and depression.

The phenomenon of comorbidity - as a multiplicity, or the coexistence of two or more diseases in one patient, is currently being widely studied from various positions - epidemiological, clinical, medico-economic, genetic, various indices have been proposed to evaluate it. The Charlson Index is used to predict mortality, the Cumulative Illness Rating Scale evaluates all body systems without specific diagnoses, the Index of Coexisting Disease takes into account the severity of the disease and disability. At the same time, the main purpose of these indices is to assess the ratio of the number of coexisting diseases to the economic costs of health care.

The presence of several chronic diseases in one patient is associated with a decrease in quality of life, psychological distress, prolonged hospitalization, an increase in the frequency postoperative complications and high mortality, as well as the high cost of medical care. Comorbidity should be taken into account when organizing the health care system itself, and above all, in order to avoid fragmentation of this care, both in clinical practice and in health care policy.

In our opinion, the most important direction, including one that allows us to understand the above aspects of comorbidity, is the study of its biological essence and general pathological significance. Comorbidity cannot be understood as the sum, or the result of the addition of one or another number of diseases and the automatic aggravation of the patient's condition; behind it, probably, there are those patterns of the formation of human pathology and the essence of the disease that have yet to be studied and understood.

Since it is the general pathological aspect of comorbidity that is of interest to us, then against the background of a largely arbitrary interpretation of this phenomenon, when certain nosological forms with systemic manifestations of (one) disease or its complications fall under “comorbidity” in a number of publications, we are talking, in particular, about DM (systemic manifestations and complications of which are interpreted as comorbidity), atherosclerosis, connective tissue diseases, more precisely, in our opinion, the essence of the coexistence of diseases reflects the term "syntropy", although in many works an equal sign is put between "syntropy" and "comorbidity" . This is also important because, in addition to the general pathological significance of comorbidity, its clinical significance in general, there is another important aspect of this phenomenon - its marker character, or the sign of individual combinations of diseases, which we will discuss further, but it is in this context that the concept of syntropy turns out to be more accurate.

So, there are three forms of coexistence of diseases: comorbidity, or syntropy; "reverse comorbidity", or dystrophy; comorbidity of Mendelian and multifactorial diseases.

The concept of syntropy (“mutual inclination, “attraction” of two or more diseases in one person) was proposed by German pathologists M. Pfaunder and L. Zecht even before the appearance of the term “comorbidity”. The authors immediately pointed out not only the connection of syntropy with the commonality of influencing factors, but also the peculiarities of the body's response, which were associated with the then popular concept of diathesis (special conditions of the body characterized by a tendency to develop certain groups of diseases), which later integrated into the doctrine of human constitutions and the doctrine about mesenchymal dysplasia, or systemic connective tissue dysplasia (CTD).

Syntropy is a type of polypathology in which diseases seem to “stretch” to each other, tend to combine or prepare conditions for one another. At the heart of syntropy, or naturally frequent combinations of certain diseases, it is possible to identify the commonality of etiological factors or pathogenetic mechanisms. By contrast, dystrophy is understood as a rare or even impossible combination of certain diseases. Thus, such syntropies as hypertension and atherosclerosis, diabetes and atherosclerosis are widely known, in which the relationship between diseases is well understood. Known dystrophy includes, for example, a rare combination of pulmonary tuberculosis with mitral stenosis, which is explained by the adverse effect of chronic hypoxia on Mycobacterium tuberculosis, which are aerobes. Rarely, lung cancer and bronchial asthma are combined.

The mechanisms of formation of nosological syntropy are diverse and among them a special place is occupied by hereditary anomalies or diseases with a hereditary predisposition, often these, as already noted, are numerous variants of mesenchymal dysplasia, or DST. The most important role in the formation of comorbidity is played by universal pathophysiological mechanisms and developing general pathological processes (chronic inflammation, dystrophy, disorders of blood and lymph circulation, etc.). On the one hand, the study of most syntropies is limited to the phenotypic level and is characterized by a lack of knowledge of their structural and genetic foundations, on the other hand, the phenotypic level of research is of great practical importance, since it is fundamentally important when detecting certain diseases to diagnose syntropies characteristic of them (marker value of syntropy).

One of the well-known syntropy is the metabolic syndrome - interrelated hypertension, hypercholesterolemia, insulin resistance and obesity, which are often accompanied by cholelithiasis, gout and uric acid diathesis. In the origin of the metabolic syndrome, deviations from normal level metabolic and enzymological (enzymatic) status of the organism, the constitutional-elementary factor (the constitution is just related to the peculiarities of the enzymatic-metabolic status), lifestyle factors. Numerous studies have shown the connection abdominal obesity with insulin resistance and a number of hormonal and metabolic disorders, which, in turn, turn out to be risk factors for the development of atherosclerosis, cardiovascular disease (CVD) and type 2 diabetes. The phenotype of manifestations of the metabolic syndrome depends on the ratio of genetic factors and environmental factors, but insulin resistance is its mandatory component.

One of the urgent health problems is the combination of chronic obstructive pulmonary disease (COPD) and CVD due to the high level of disability, mortality and budget burden. Several studies have shown that chronic inflammation in respiratory tract is a predictor of CHD risk independently of other cardiovascular risk factors. Thus, a 10% decrease in forced expiratory volume in 1 second increases the risk of cardiovascular mortality by 28%, and non-fatal coronary events by 20%, while there is also a problem of adequate use of β-blockers in patients with coronary artery disease, since their long-term use may impair performance external respiration and thus increase cardiovascular risk.

At present, the relationship between exposure to aeropollutants, chronic inflammation in the respiratory tract, HL and the progression of atherosclerosis through the development of a systemic inflammatory response has been confirmed - an increase in the level of pro-inflammatory cytokines (CK) in the systemic bloodstream - tumor necrosis factor alpha (TNF α), interleukin (IL)6 , IL 8, IL 1β. Understanding the pathogenetic foundations of atherogenesis in COPD (entry into the systemic circulation of pro-inflammatory CKs, increased systemic oxidative stress, development of endothelial dysfunction, activation of matrix metalloproteinases) has led to a decrease in cardiovascular mortality in this category of patients due to the use of statins and anti-inflammatory drugs in their treatment.

An inverse relationship is also noted - the effect of CVD on the development of exacerbations of COPD, especially in the presence of cardiac arrhythmias (the risk of iatrogen-induced arrhythmias is also high when using high doses of bronchodilators, β2-agonists). All of the above creates a picture of a kind of vicious circle of the mutual influence of these diseases in their coexistence, or comorbidity.

A certain association was noted between CHF and oncological diseases, it was found that the risk of developing oncological diseases in patients with CHF is 68% higher than in persons without circulatory failure. The reasons for this association may be associated, on the one hand, with a more thorough examination of this category of patients, on the other hand, with the carcinogenic effect of cardiotropic drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers), common risk factors ( chronic hypoxia tissues, systemic inflammatory response as the most important link in the pathogenesis of CHF). Such coexistence is also relevant due to the similarity of many clinical manifestations CHF and oncological diseases (appearance of edema, shortness of breath, pleural effusion, cyanosis, anemia). Comorbidity in this case causes not only differential diagnostic difficulties, but also raises the question of the possibility of a causal relationship between these diseases. CHF is known to be characterized by hyperactivation immune system manifested in increased expression of pro-inflammatory CK not only in the myocardium of the left ventricle, but also in the systemic circulation, as well as a high level of formation of oxygen and nitrogen free radicals that can have a genotoxic effect.

The end stages of chronic kidney disease are also associated with an increased incidence of cancer of various sites, which may be due to a weakened immune system during chronic infection and impaired DNA repair.

Comorbidity in oncology is of great clinical importance. The study of the causes of death based on the results of pathoanatomical reports shows that only in one case out of five it is limited to one cause, the number of causes can reach 16 and averages 2.68. Even if there is malignant neoplasms the coexistence of another chronic non-infectious pathology does not exclude its influence on the deterioration of the patient's condition. Comorbidity leaves a peculiar imprint on the entire “trajectory” of the tumor process: from the formation of a predisposition to it to the establishment of a diagnosis, treatment and rehabilitation.

Thus, concomitant diseases in cancer of various localizations can influence the choice of treatment, determining low tolerance to adjuvant chemotherapy, and affect the delay in the diagnosis of the underlying disease. However, in particular, in the example lung cancer(RL), it has been shown that, despite the predominance (30-50%) among patients with LC of people over the age of 70 years and the high incidence of concomitant diseases (mainly of the cardiovascular system and COPD), the prognostic effect of both age and themselves comorbidities remains controversial. The determining prognostic value may be the nature of concomitant pathology and the biological, rather than the passport age of the patient.

Own studies of comorbidity in gastric cancer (GC) in patients with and without visceral signs of systemic undifferentiated CTD in general showed a high frequency of association of gastric cancer with gastric and ulcerative history in patients (68.2%), chronic pathology of the hepato-pancreato-duodenal zone ( 67.3%), in particular, cholelithiasis (20.0%), chronic diseases of the cardiovascular system (52.7%), polyneoplasia (15.4%), in women with diseases (65.0%), related to clinical markers of hyperestrogenemia (proliferative processes in the endo- and myometrium, ovarian dysfunction, mastopathy). Among the features of comorbidity in patients with gastric cancer and systemic undifferentiated CTD, the following were identified: a high frequency of stigmatization of the gastrointestinal tract (47.6%) and the genitourinary system (42.9%), a high frequency of the phenomenon of cyst formation in various organs (65.1%), but more often in the kidneys (38.1%). The identified features, on the one hand, may have a marker value for the formation of risk groups for the development of gastric cancer (in particular, in patients with CTD), on the other hand, they raise the question of the mechanisms of formation various kinds comorbidity in RJ. In our opinion, the relationship between cyst formation, gastric carcinogenesis and systemic undifferentiated CTD (the latter of which is determined by various defects in the enzymes of the synthesis and breakdown of the extracellular matrix, morphogenetic proteins of the connective tissue, numerous growth factors, their receptors and antagonists, represented mainly by molecules of the adhesive complex) can be explained through the general nature of disturbances in various cell signaling pathways, in particular the Wnt signaling pathway, TGF pathway, disturbances in the expression of a number of common genes, for example, the bone morphogenetic protein gene, changes in the expression of which are associated with various anomalies of the kidneys and other mesenchymal dysmorphias, as well as gastric carcinogenesis .

In general, the pathogenetic relationship of many coexisting diseases still needs to be studied in depth. So, among the syntropies, the combination of peptic ulcer and hypertension deserves attention (the frequency of the combination reaches 12.9%), peptic ulcer and chronic lung diseases (10.6%). The risk of mortality in peptic ulcer disease complicated by bleeding is higher in the presence of 3 or more comorbidities than in the presence of one and two, it is also higher in concomitant diseases of the liver, kidneys, malignant neoplasms than in concomitant diseases of the cardiovascular and respiratory systems.

Feedback is also relevant - a high frequency of gastroduodenal pathology of an inflammatory-degenerative or erosive-ulcerative nature in patients with chronic lung diseases. The frequency of detection of such syntropy, according to different authors, ranges from 2.7 to 98%. More often (from 30 to 100%), gastritis is detected, while the frequency of atrophic gastritis reaches 30% or more. Certain morphological changes in the gastric mucosa are detected even in every second child with chronic diseases of the bronchopulmonary system. With an increase in the severity of chronic respiratory failure, gastric changes are detected, in essence, in every patient. In the pathogenesis of such a combined lesion, the formation of chronic tissue hypoxia, due to impaired microcirculation and rheological properties of blood, a decrease in the regenerative potential of the gastric mucosa (GM), in particular due to a violation of the non-respiratory metabolic function of the lungs and the accumulation of arachidonic acid metabolism products (leukotrienes, prostaglandins, thromboxanes) and other CK, causing the development of a systemic inflammatory response. With a combination of asthma and pathology of the gastrointestinal tract great importance is attached to a single mechanism of immune disorders, in particular at the level of mucosal-associated lymphoid tissue.

According to our data, the frequency of combined atrophic lesions of the mucous membrane of the bronchi and stomach is much higher, and the fact that it depends on the nature of the process in the respiratory system deserves attention. In the pathological series from primary atrophic bronchopathy (ABD), ABP against the background of chronic obstructive pathology and occupational dust pathology of the lungs to RL, the frequency of combined lesions of the coolant and epithelial lining of the bronchi is in the first three variants of the pathological process, respectively, 51.9, 25.6 and 43% cases and reaches a maximum in peripheral LC - 77% of cases, which can probably be considered as a clinical marker of systemic disorders of epithelio-stromal relations, a decrease in the morphogenetic and protective function of the connective tissue system.

AT last years there is not only an increase in the incidence of bronchial asthma (BA), but also the frequency of its combination with obesity varying degrees severity, reaching 28-44%. The formation of a "vicious circle" in the combination of asthma and obesity is determined by numerous common pathogenetic mechanisms. This is an increase in the blood level of pro-inflammatory CKs (TNFα, IL-4, IL-5, IL-6, IL-13, vascular endothelial growth factor), produced by adipocytes and determining both the development of systemic inflammation and the formation of non-eosinophilic in the bronchial mucosa. , and a neutrophilic inflammatory response. Obese patients show an increase immune reactions mediated by T-lymphocyte helper (Th) type 2 under the influence of constant excessive synthesis of IL-6 and, probably, leptin, the expression level of which increases with increasing body weight. The pathogenesis of AD is also based on an imbalance of Th with activation of the Th-2 type, which results in the development of chronic inflammation in the airways. An important link in the pathogenesis of both AD and obesity is oxidative stress, activation of lipid peroxidation (LPO) and a number of proteolytic enzymes (matrix metalloproteinases, cathepsin G, etc.), which damage the endothelium of the pulmonary vessels and pulmonary interstitium, as well as stimulate the formation of angiotensin II and increased vascular sensitivity to it. For the formation of endothelial dysfunction, which has a significant pathogenetic significance in the defeat of the vessels of the small circle and the formation of the cor pulmonale, is also responsible for obesity low level adiponectin, which, in turn, stimulates the synthesis of nitric oxide in the vascular endothelium and inhibits the production of TNFα.

Similar pathogenic mechanisms(chronic systemic inflammation, oxidative stress, free radical DNA damage, etc.) underlie the coexistence of obesity and a number of malignant diseases. Overweight in Europeans is due to 3.2% of cancer cases in men and 8.6% in women. In our study of comorbidity in patients with gastric cancer, overweight (preobesity and obesity of I-III degrees) was noted in 61.5% of patients.

Syntropy, as a natural-species combination of two or more pathological conditions in an individual and his closest relatives, are not random and have an evolutionary-genetic basis. The genes that determine the development of syntropy and are called syntropic are a set of functionally interacting coregulated genes, localized throughout the human genome and involved in the biochemical and physiological pathways common to this syntropy.

Phenotypic information about the combination of human diseases, as genotyping technologies improve, is supplemented by the construction of gene networks with subsequent analysis of "gene-phen" associations. If earlier network tools were used to analyze the interaction of genes in a particular disease, now a conceptual framework has been developed to study the relationship of all human diseases (the "phenomen" of diseases) with a complete list of genes that control the disease (the "genome" of diseases), which creates a global picture "dysoma", which includes all known associations "gene - disease". Disisome is a set of all known gene-disease associations organized into a human disease network (HDN), consisting of nodes (hubs) in which diseases are located, and connecting edges, which are represented by common cause-dependent genes. Thus, the study of the genetic profile (1400 genetic markers were used) in three different samples of the cardiovascular continuum: patients with only CHD, patients with a combination of CHD, type 2 diabetes, hypertension and hypercholesterolemia (HC) and patients with a combination of two diseases - CHD and AH showed that between the combination of several and two diseases (IHD and AH) there were two common genetic markers ( SEZ6L rs663048 and rs6501455); between the combination of coronary artery disease with hypertension and only ischemic heart disease - one common marker ( SCARB1 rs4765623). There were no common genes among those studied between the combination of four diseases and CHD. An analysis of the belonging of associated genes to one or another metabolic pathway showed that lipid metabolism genes are involved in the formation of all three variants of the combination of diseases of the cardiovascular continuum, and immune response genes are specific for IHD and are not involved in the formation of syntropy.

It has now been established that disease associations at the level of clinical phenotypes have a molecular genetic basis - common genes and overlapping metabolic pathways.

Findings in the genetic analysis of reverse comorbidity, or dystropia, turned out to be paradoxical - dystrophic genes turned out to be the same for diseases with contra-associative relationships. So, with the help of transcriptome meta-analysis, molecular evidence of reverse comorbidity for three diseases of the central nervous system: Alzheimer's disease, Parkinson's disease and schizophrenia, and three types of cancer: lung, prostate and rectal cancer. It was found that 74 genes are simultaneously suppressed in the three indicated diseases of the CNS and increase activity in these three types of cancer. In contrast, expression of 19 genes is simultaneously upregulated in the three CNS diseases studied and downregulated in three types of cancer. Theoretically, it cannot be ruled out that some of the drugs used to treat CNS disorders could cause a reversal in the expression of a number of genes that control the development of cancer. The mechanisms of reverse comorbidity may be of great importance in clarifying the pathogenesis and treatment of many widespread and socially significant diseases, in particular - oncopathology.

One of the topical aspects of the problem of comorbidity is the issues of treatment. Being a common phenomenon in the practice of a modern doctor, comorbidity is often accompanied by polypharmacy - the appointment of a large number of medicines in an effort to treat all diseases that make up a specific syntropy, which not only does not lead to the achievement of the goal, but often becomes dangerous, causing iatrogenia.

One of the approaches to the treatment of multiple comorbidities is the "nodal therapy of syntropic diseases", aimed at the modulation or even "disintegration" of nodal networks involved simultaneously in the regulation of several signaling pathways common to the corresponding syntropy. Thus, it has been shown that in patients with early forms of coronary atherosclerosis in combination with autoimmune diseases ( rheumatoid arthritis, psoriasis) statins are common, effective and safe medicine.

The coexistence and mutual influence of diseases complicates the formation of a diagnosis, in the logical structure of which a specific syntropy in a given patient should be reflected. For this purpose, diagnostic headings are used: basic, background, concomitant diseases.

It is legitimate to consider the nosological form that, by itself or as a result of its complications, currently causes the greatest threat to the patient's ability to work and life and requires urgent treatment as the main of several diseases that a patient has.

Formalization of the diagnosis in accordance with the accepted headings is often accompanied by a violation of the logic of the development of the pathological process. Here there is an element of convention, characteristic of any classification, or an element of agreement, agreement reached, in particular, this applies to such a pathological process as atherosclerosis. But, even deviating from the logic of the development of the pathological process in favor of the accepted classification, the doctor must understand the true essence of things.

Bibliographic link

We bring to your attention the journals published by the publishing house "Academy of Natural History"

Comorbid (polymorbid) conditions are a situation when several diseases occur simultaneously in a patient, one reinforces the other, and their negative effect on the body does not add up arithmetically, but multiplies geometrically. Simply put, this is severe patient with a multitude of diseases whose treatment can be hampered by the mutually exclusive control requirements of different diseases.

In the academic environment, sometimes the terms comorbid and polymorbid are not considered synonymous, tying the first of them to a combination of diseases related in origin. We, based on practical benefits, do not make such a division.

What is the complexity of managing a comorbid patient?

Imagine a patient who simultaneously has bronchial asthma and heart failure. Based on the first illness, he needs an adrenostimulator, and adrenoblockers can be dangerous. Based on the second disease - adrenergic blockers are necessary, this is very effective means for the treatment of heart failure. Let's say we went between Scylla and Charybdis and picked up a treatment with a superselective inhaled adrenostimulant and an angiotensin receptor blocker. But widespread atherosclerosis, which caused damage to the heart with heart failure, managed to damage the kidneys, and, after the appointment of an angiotensin receptor blocker, their function began to decline, which we determined by the increase in creatinine and blood potassium. We examine the renal blood flow, find the place of narrowing of the renal artery, artificially expand it with a stent, but…

In this example, the patient had 3 serious diseases interacting with each other. But there may be 10 or more.

Evidence-based medicine, which is the cornerstone of the Dawn philosophy, able to give us answers in most cases, begins to falter in comorbid patients. Because in our beloved randomized clinical trials, drugs are usually studied in one or two diseases. And many chronic diseases(liver cirrhosis, severe diabetes mellitus) are criteria for excluding patients from such trials. How to be? Yes, we do not have a proven algorithm-template for treating such a patient, here the way out is professionalism, doctor's erudition, common sense, readiness to call a colleague in an unclear situation.

We are not afraid of severe comorbid patients. Most doctors of Rassvet have dozens of years of experience in the country's largest hospitals, the processes of interaction between doctors are well-established, material support includes a hospital with an intensive care unit and a centralized supply of medical gases.

Comorbidity is the simultaneous occurrence of different diseases or pathological conditions in a patient.
This is the only common place for the whole variety of interpretations of K., if you try to generalize them.

Synonym (more precisely, in Russian): comorbidity.

1. "TO. - the coexistence of two and / or more syndromes (transsyndromal K.) or diseases (transnosological) in one patient, pathogenetically interconnected or coinciding in time (chronological).
   • (if they did not coincide in time, the word “coexistence” would be inappropriate. It is remarkable that the author specifies: “in one patient” (!). It is also strange that he did not decorate his definition with the term “pathogenetic K.” in brackets ... The prefix "trance" suggests something more than co-occurrence.)
2. . "TO. - a combination of two or more independent diseases or syndromes, neither of which is a complication of the other, if the frequency of this combination exceeds the probability of a random coincidence.
   • (A. Feinstein has both complications and pregnancy).
3. "TO. may be associated with a single cause or common mechanisms of pathogenesis these states, but sometimes due to the similarity their clinical manifestations, which does not allow clear differentiation between them.. An example is atherosclerosis and hypertension.
   • (simply read like this: "may be connected, or maybe not connected - this is unknown to science"!).

A phrase to end this confusion: “So, comorbidity is not an artifact, an atypical phenomenon, or a certain myth and fashion.<…>K. is a clinical reality…”, you need to read exactly the opposite, because there is no greater artifact than the so-called. "clinical reality". And there is no doubt that K. has become fashionable - 500,000 finds on the Internet in Russian; over 3.5 million in English.

When you read that "K. heterogeneous (accidental, causal, complicated, unspecified)”; “transindromal, transnosological, chronological; has “three distinct subtypes: pathogenetic, diagnostic, and prognostic…”, etc. etc., you understand that medical institute- not the best forge of scientific personnel ... The same “clinical mess” is visible in the minds (see Medical classifications), which is also supported by Wikipedia, supplementing the collection with supposedly “Synonyms of K.” ™:

• polymorbidity;
• multimorbidity;
• multifactorial diseases;
• polypathy;
• condolences;
• double diagnosis (why not triple? Not quadruple?);
• pluripathology.

Came to complete clinical nonsense. The complications caused by the doctor in the patient, the underlying disease, began to be called "iatrogenic comorbidity" (exactly like theft - "misappropriation of funds"...). And finally, K. herself is declared "new pathology". "New" - that is, until 2013, patients had "comorbidities", and now (thanks to A. Feinstein or A.L. Vertkin?) - a new pathology!

One thing, gentlemen, comrades! Either “comorbidity” is a term for a combination of pathologies, or the pathology itself. Reading this, you begin to think that it is a “new pathology” exclusively of the thinking of the authors.

It is interesting that many Russian articles on the topic begin with a proclamation of a certain unity of the organism (here are Plato, and Hippocrates, and S. P. Botkin, and G. A. Zakharyin, and whom they just don’t remember yet!), And end with a definition of this unity separating. The coexistence of something implies the presence of two or more units (pieces) of this “something” ... That is, in fact K. is not much different from banal nosological views:
1st nosology + 2nd nosology = comorbidity!
This is her methodological primitivism., so attracting "scientists"-clinicians who practice in the appropriation of new Greek, Latin and English prefixes and roots of the "new clinical essence"!

What is it

Definition of comorbidity coexistence of several diseases refers us to the notion of them as Kant's "Things-in-themselves" (existing outside our consciousness), that is, "really", which "settle" in our body separately... And the term K., as it were, a flirtatious smile to the times when the body was considered as a kind of integrity, instead of which there will now be a “piece of the body”, inhabited, for example, by two or three diseases.

Since every year (we live in difficult times!), As well as with the age of the patient, K. grows, it remains to wait until the whole organism “comorbidizes”. Obviously, this is guaranteed to happen before death, and finally (!), the whole organism will already be sick, and you can begin to treat the patient, and not the disease (as the great classics bequeathed) ...

It is also unclear why the authors of the article on K. on Wikipedia believe that “... a fundamental clarification of the term was given by H.C. Kraemer and M. van den Akker, defining comorbidity as a combination of two and/or more in one patient chronic diseases pathogenetically interconnected or coinciding in time in one patient, regardless of the activity of each of them.

Term, which theoretically should stand for something one, denotes two concepts separated by union "or"… ("Are you married or a girl?" – “Not this, and not another! Hee hee hee…”).

So what is a common pathogenesis or a simple coincidence in time? If both, why is it called “clarification” and even “principled”, because, besides the word “chronic”, does this differ from the definition of A. Feinstein himself? Finally, all chronic diseases were once acute/subacute. So at this stage it is impossible to talk about K.? And generally speaking, why it is important?

And if they have a common pathogenesis (that is, it would seem involving a single pathogenetic treatment), it is not clear how the ideologists of the topic everywhere talk about need at K. combined, polydrug therapy. That is, the head and ass of the worm from the epigraph to this article get different treatment! Or vice versa: if one worm, why do the head and ass have different names? And, finally, if diseases (the worm) are considered as a continuum of conditions, then how can you apply many drugs at the same time, and not sequentially - as you move along the continuum? The above is evidence of a look at K. as a simple collection of diseases.

Since doctors who think of the body as a kind of integrity, with rare exceptions, cannot be found today with fire, everyone likes comorbid diseases in a post-Feinsteinian reading. We still have 2-3-4 and so on. co existing diseases. This allows you to think less and treat according to the cookbooks of the pharmaceutical industry, according to the principle "every disease has its own medicine." This “understanding” of the integrity of the body is cultivated by pharmaceutical companies to expand their sales (we say K., we mean polypharmacy). So you hear: “When buying this drug, they usually also take these drugs” ...

All because this fucking “index disease” has not been translated into Russian anywhere normally and, more importantly, nowhere not explained and hypnotize the audience with it. Perhaps it is necessary to translate it as “indicating illness”? Showing us the way of therapy or knowledge? Travel sickness! Or is it still a primary disease? In all definitions of K. “from A. Feinstein” and their interpretations, either this is implied or directly referred to this main (main, core, leading, etc.) disease. At the same time, the presence, pardon the expression, of an “index disease” is stated as something taken for granted, and how it was formed, it would be inconvenient to ask in a decent society ...

Who and how determines which disease will be the main one? Is it a convention or not? The disease that started earlier or was first discovered? But then what is the role of chance in making a “basic” diagnosis? Did the patient get to a specialist in the "main disease"? Or complained about something in the first place? Is this the disease the researcher is studying? Or maybe the ICD or DSM “orders” us to single out the main disease, and then the accompanying one? And the rest, what, is it a matter of taste?

The "primary" diagnosis may also depend on the time it was carried out: they caught the disease at a late stage - one main disease, more early stage- "other".

What is the subordination of the main and secondary diseases? In what exactly meaning this major disease? Can K. flow into multimorbidity (see below)? All these questions are practically not discussed and, certainly, are not solved, neither by Feinstein himself, nor by his followers.

The “main disease”, which for some reason became the inviolable sacred cow theory of K., apparently burned out not only me. They tried to get rid of her.

The emergence of multimorbidity. What kind of animal?

Comorbidity was invented to be distinguished from multimorbidity (MM), which we were also offered at the same time as a synonym for K!

Don't try to understand why comorbidity decided to separate from multimorbidity. Here, as in a joke, but about the Russian language lesson in a Georgian school: “Children, in Russian a fork and a plate are written without a soft sign, and sol and beans are the other way around. Remember this kids because it is impossible to understand it!».

There is even an international scientific society of multimorbidity ("IRCM" - International Research Community on Multimorbidity). Do not expect (like me) that on the first page of their site you will find the definition of MM.! No. There is not even a clear explanation of when this community arose! But there is a list of theoretical papers, in which chronologically the first is an article that says: “In view of the ambiguity of the term, we propose to distinguish between K., based on the “classical” definition (the assumption of a certain main, “index”, disease) and multimorbidity, meaning any joint occurrence of medical conditions in the subject”.
There is a note on the site by Martin Fortin, from which it follows that colleagues in the IRCM community have created something, but have not yet decided what they will consider MM., as they are confused in the definitions and offer everyone who wants to help them figure it out by answering the question: "How should MM be determined?". Answers are offered, as in the exam:

1. a plurality of coexisting chronic or long-term diseases or conditions, none of which is considered as a leading disease (index Disease);
2. several concomitant diseases or conditions, none of which is considered as a leading disease (index Disease);
3. any of the above definitions;
4. another definition (please provide a definition or link)

In this surprisingly rich variety of responses, the second "definition" just lacks the word "chronic or long-term." Does all the cheese come out - boron due to chronification or duration?

Confusion with K. and MM. exacerbate even banal errors. In the 2014 article, when the authors, as usual, stated “in their own words” what was written by van den Acker and A. Feinstein, the latter, having mixed up the references, attributed the term “MM” and “clarified” (p. 363) that it is based, in contrast to from K., “…it is not a disease, but a specific patient…” (that is, not sour, but round…). Full paragraph. In a word, another exegesis of A. Feinstein and other muddy texts.

And here is another storehouse of wisdom, a certain medical reference book by Belialov F.I. :

Comorbidity is the presence of another disease or medical condition at the same time as the present disease. Multimorbidity A combination of multiple chronic or acute illnesses and medical conditions in one person (National Library of Medicine).

100 1000 rubles to the one who finds the difference. Is it that the first definition refers to two or three people, and not one?

Total

Summarizing what has been written, it is clear that the authors of various definitions of K. and KK, in the process of pounding water in a mortar of clarifications of these concepts, focus either on the presence of a “main” disease, or on the chronification of the process, or on general pathogenesis (risk factors, etc.). ) then in the absence / presence of all of the above, then they include “non-diseases”, then not, etc. etc. Only one Oblomov question remains open - why?

Certainly not K. Feinstein is to blame for this. It's impossible to get rid of the feeling that he just moved their "followers" rewrite in places traditional medicine"in the language of K." The very fact untranslated term, its use in the Cyrillic version is already a claim to the presence of some other meaning in it. Say: "complications" and the pseudo-scientific bubble will immediately burst! There's been a change language, to refer to the formerly known under other names.

Some examples of language transformation

In the form of Russian terms of the followers of Feinstein.

It must be admitted that:

1. The definitions available today and "K" and "MM" mean completely different things. Common to them is only the fact of the joint occurrence of diseases.
2. The term "K". in the author's version, it is unsuccessful from a linguistic point of view, since it pathologizes the norm.
3. In any case, the term K itself, both in its original, Feinstein sense, and in its interpretations does not signify any qualitatively new integrity.
4. The term "K". has gone beyond the “Feinsteinian”, epidemiological meaning, and it will now be very difficult to stop its confusing use in other contexts.

On the example of the history of the term K., one can see how the human consciousness frantically tries to escape from the archetypal opposition Health/Illness, expressed in terms of “the struggle between Good and Evil”. They came up with MM, where (like social development) all diseases acquire "democratic equality", overthrowing the monarchy in the person of the Main disease. But understanding them interactions within the framework of these views impossible, since diseases still exist separately.

It seems that many doctors and researchers were so drawn to the theory of K. because, with varying degrees of awareness, they were interested in interaction(if this word is appropriate at all) of "different" diseases, and not the very fact of their joint occurrence. However, this immediately destroys the concept of nosological form and returns us "to the origins" - to the patient.

Sometimes one wonders how the ideas of the existence of individual diseases are so tenacious when all-penetrating systems have long been discovered: blood circulation, lymph circulation, hormonal, immune, connective tissue, finally, etc.?

46 years have passed since the introduction of the term K. The Internet, the desktop computer; an ebony rotary phone and a TV with a kinescope replaced i-pads and i-phones, but doctors like "Ai-hurts" remained with A. Feinstein's comorbidity ... Let's take a look at what they write about K. today.

Well made epidemiological works of the 21st century, e.g., 2012, this, as Feinstein intended- another study of the joint occurrence of diseases in a particular population, of which tens of thousands have already been done. Clinical epidemiologists are studying them. Their recommendations, which are more suitable for healthcare organization, simply geographically localize more and more data on co-morbidity, and their conclusions are not God knows how complicated.

Numerous attempts to directly adapt such data to the treatment process of individual patients usually end in complete failure. In the articles of the 2000s. recommendations (more precisely, slogans) are as general and banal as they are non-specific.

What do professors tell practical doctors, whose life (like the life of V.S. Chernomyrdin) "... passed in an atmosphere of comorbidity"? Here are some thoughtful recommendations-slogans, apparently selected over the years " scientific work» (A.L. Vertkin, N.O. Khovasova). After stating the fact of an increase in age-related K. and the percentages of their joint occurrence that have already set the teeth on edge, we read the conclusions-recommendations:

Also highlighted in the article as NB! following: “Risk factors in Russia should be considered as diseases that need to be treated!”.<…>"Risk factors, polymorphism of the clinical picture, multiple organ damage, drug polypharmacy - these are the key links that must be taken into account when providing care to a patient with comorbid pathology."

Reading this, you immediately understand that now things will work out for us!

Afterword

Concluding the consideration of the “epoch “K” of A. Feinstein”, we note that the author of the term K. did not claim to study the mutual influence of diseases (pathogenesis mechanisms, etc.) and did not do this, he only stated such a possibility. Let us thank him for pointing out the importance of the joint occurrence of diseases (which was known even before him) and turn now to the consideration interactions that today we still referred to as individual diseases.

From the point of view medical business, as well as for scientific design of general human pathology, talking about the joint occurrence of diseases, etc., makes sense only if they are united by something else, besides the very fact of meeting in the human body (for where else can they meet?). Strictly speaking, it is their meeting in one body that marks their commonality (etiological, pathogenetic, or any other).

Looking ahead, I will say that if there is no community, then such diseases do not meet in the same body! This phenomenon, due to the dominance and fetishization of the term by A. Feinstein, was extremely unsuccessfully called "reverse K." or more adequately dystrophy . Why fail? Well, it's like in the love/hate opposition, calling the latter "reverse love"...

That is, at first they littered everyone’s brains, confused everyone with the concept of K., and then, they were forced to start from this name in order to express something from it, K. is different ...
It turns out that there were times “before the birth of A. Feinstein” (before the Russian Federation), when the problem of the joint occurrence of diseases was considered much more progressively than after the invention of the term K.

Comorbidity was studied in parallel by completely different people who opened the era of Integral Medicine.

Yet

Home reading

• A censored version of this article published in the journal Plastic surgery and cosmetology”, August 2016.