Sepsis: The New Approach to The Successful Solving of The Problem

Research Article | DOI: https://doi.org/10.31579/2767-7370/047

Sepsis: The New Approach to The Successful Solving of The Problem

  • Lesia Ostapiuk *

Lviv Regional Public Health Centre, Lviv, Ukraine.

*Corresponding Author: Lesia Ostapiuk, Lviv Regional Public Health Centre, Lviv, Ukraine, National Pirogov Memorial Vinnitsya Medical University, Vinnitsya, Ukraine.

Citation: Lesia Ostapiuk (2023), Sepsis: The New Approach to The Successful Solving of The Problem, J New Medical Innovations and Research, 4(1); DOI:10.31579/2767-7370/047

Copyright: © 2023, Lesia Ostapiuk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 06 February 2023 | Accepted: 15 February 2023 | Published: 23 February 2023

Keywords: pathogenetic model; sepsis; method of fluorescence spectroscopy

Abstract

Background: The significant improvement of immediate and long-term functional results of treating of patients is the fundamental problem of modern medical science. A deep understanding of the pathogenesis is the key point in creating the management strategy for patients with various diseases. Information about the mechanisms of origin and development of purulent-inflammatory diseases and sepsis is essential for finding effective ways to prevent and treat them.

The aim of the research is to use the method of fluorescence spectroscopy in creating pathogenetic diagnostic and treatment model for the prevention and treatment of purulent-inflammatory diseases and sepsis.

Methods:

 Stage 1 consisted of an in vitro study, Stage 2 covered - 100 patients with surgical purulent-inflammatory diseases (including 15 patients with sepsis), Stage 3 engaged 180 women with postpartum purulent-inflammatory diseases (main group), 40 women with uncomplicated course of the postpartum period (control group), Stage 4 involved 20 patients with burn injury (main group), 35 people with burn injury (comparison group). In addition to standard treatments, patients also underwent serum studies using the method of fluorescence spectroscopy.

Result(s): We have proposed the pathogenetic concept of diagnostic and treatment approach for purulent-inflammatory diseases and sepsis. As part of the method of fluorescence spectroscopy, thorough studies of the serum of patients with postpartum purulent-inflammatory diseases, of patients with a surgical profile, including sepsis, as well as burns trauma were conducted. A thorough analysis of the obtained results was provided.

Conclusion(s): Based on our proposed pathogenetic concept, the possible mechanisms of sepsis and effective methods of diagnosis, monitoring and prognosis for its spread are discussed in details. It is proposed to use the pathogenetic component of the treatment of purulent-inflammatory diseases and sepsis on the basis of the pathogenetic model, which has been developed by us.

Introduction

Sepsis occurs when the body's response to the infection causes damage to its own tissues and organs and can cause the significant deterioration of the patient's condition and even his death. It is estimated to affect more than 30 million people each year and can kill 6 million people [1]. This problem is quite typical for low- and middle-income countries. According to the WHO, sepsis occurs annually in 3 million newborns and 1.2 million of children [2]. One of ten maternity deaths is due to obstetric sepsis. 95% of maternal sepsis deaths occur in low- and middle-income countries [3].  1 million newborns die each year from maternal infections, including maternal sepsis [4]. Over the past 25 years, the definition of sepsis and septic shock has changed three times; every four years the international intensive care protocol was updated with the participation of dozens of leading organizations and experts [5]. Thus, the urgency of the problem is obvious and requires modern knowledge from scientists and doctors for early diagnosis and timely, targeted treatment of sepsis and septic shock, including in obstetrics [6]. According to the 1991 definition at the conciliatory conference of the American College of Thoracic Surgeons and the Society for Critical Medicine (ACCP / SCCM) in Chicago (USA), sepsis is a systemic inflammatory response syndrome (SIRS), caused by a source of infection. In 2001, the working group understood the shortcomings of such a definition, but did not offer any alternative [7]. In 2016, criteria for the diagnosis of sepsis by rapid dynamic assessment of organ failure (qSOFA) were proposed. According to experts of this consensus [8], organ dysfunction caused by sepsis can be hidden. Thus, its presence should be considered in any patient with an infection. According to the WHO, sepsis is the dangerous dysfunction of the internal organs caused by dysregulation of the body's response to infection. At the same time, insufficient attention was paid to the pathogenetic assessment of the development of purulent-septic complications, including sepsis. The issues of early diagnosis of purulent-inflammatory conditions, especially their monitoring and treatment, are not completely resolved. These issues need quick solution by using contemporary scientific approaches to the choice of diagnostic methods and optimization of treatment tactics. In this regard, in May 2017, the 70th session of the World Health Assembly adopted a resolution on sepsis on the basis of the report of the WHO Secretariat. According to it, the primary attention should be focused on improving early diagnosis, finding new markers and improving treatment tactics and monitoring of patients. Therefore, the aim of our research is to use the method of fluorescence spectroscopy in pathogenetic diagnostic and treatment model for the prevention and treatment of purulent-inflammatory diseases and sepsis. There is sufficient information about the pathogenetic factors of sepsis, but changes occuring at the molecular level are studied insufficiently. Their understanding is very important for understanding and development the pathogenetic component of treatment of sepsis. Without the in-depth understanding of these aspects, the diagnosis and treatment of sepsis may not be effective enough. Especially important is the detoxification function of albumin, which is especially evident in patients with moderate endogenous intoxication. Due to the changes in the conformation of its molecules, albumin interacts with hydrophobic molecules of endotoxins and promotes their excretion from the body. In patients with purulent-inflammatory diseases and sepsis with increasing endogenous intoxication, most of the binding centers of albumin molecules are blocked by the products of bacterial metabolism. Although the total concentration of albumin in the blood of patients may be within normal limits, its actual "effective concentration" is much lower [9]. This leads to the violation of the basic functions of the body and requires timely implementation of effective treatment measures.For this aim, the pathogenetic concept of diagnostic and treatment model of purulent-inflammatory diseases and sepsis was created. It is based on the fact that albumin molecules have the ability to complex. In the diseases which are accompanied by endogenous intoxication, part of the albumin molecules in the blood of patients are blocked by toxins. As a result, there are two types of albumin molecules in their blood: normal (concentration: X) and blocked by toxins: pathological (concentration: 1-X).  So, pathological albumin molecules lose the ability to perform their basic functions, namely transport and detoxification. The new definition of sepsis is to define Х* - the maximum minimum value of the concentration of normal albumin molecules in the case of presence of a septic condition. If Х is more than Х*, this ensures the viability of the organism to some extent. Then at Х less Х*, exitus letalis develops.

Materials and Methods

Among the research methods, we used clinical, laboratory (general and biochemical blood tests, general urine test, examination for viral hepatitis B and C, syphilis and HIV), instrumental methods (bacteriological examination of the content of the uterine cavity, histologic analysis of metroaspirate, method of fluorescence spectroscopy (MFS), mathematical and statistical methods (logit regression and ROC analysis)). The study of biological objects by using the method of fluorescence spectroscopy makes it possible to detect pathological processes in living organisms, even at an early stage of their origin. The method of mathematical modeling has been used as well, including the simulation of changes of the characteristics of blood serum (BS) in patients with sepsis in vitro by diluting the BS with the bacterial culture of Staphylococcus aureus. The method of mathematical modeling was also used, including the simulation of changes of the characteristics of blood serum (BS) in patients with purulent-inflammatory diseases and sepsis in vitro. As part of the research were the stages of in vitro and in vivo studies. In vitro studies (stage 1) were conducted in 2001-2003 in the Ambulance Municipal City Clinical Hospital (Lviv).   In vivo studies were conducted from 2001 to 2019 at three clinical bases: the Ambulance Municipal City Clinical Hospital (Lviv), Department of Gynaecology № 2 of Vinnytsia Council Clinical Hospital № 2 and the burn department of Lviv Communal City Clinical Hospital №8. The samples of BS of patients with purulent-inflammatory diseases and sepsis, covering the postpartum period, were the object of study. The study was designed by the following groups of patients. Stage 2 was performed from 2001 to 2008 and included studies of fluorescence spectra (FS) of BS of 100 patients, including 42 patients with aseptic pathology, 43 ones with preseptic pathology, 15 patients with sepsis and 40 healthy subjects of the control group.  Stage was conducted from 2013 to 2019 on the basis of the Department of Gynaecology № 2 of Vinnytsia Council Clinical Hospital № 2 and included the study of 180 mothers with postpartum purulent-inflammatory diseases and 40 healthy mothers with uncomplicated postpartum period. Stage 4 was conducted from 2013 to 2019 on the basis of burn department of Lviv Communal City Clinical Hospital № 8. It included studies of 20 patients with burn trauma (main group), for which the study of the BS by the MFS was done, as well as 25 healthy individuals of the control group. Also within this stage, the study design included the presence of the comparison group (35 patients), for which we also used improved treatment tactics, developed on the basis of analysis and interpretation of the results of the study of BS of patients of the main group within the MFS. Luminescence is the result of the absorption of light by the system under study and is caused by the transition of its molecules from the energized state to the basic state. Fluorescence is the partial case of luminescence with  t < 10>

Results of the research

The aim of the in vitro study stage was to study the changes of the spectral-fluorescent characteristics of BS [10-12], that occur in patients with purulent-inflammatory diseases and sepsis (dilution of BS by bacterial cultures of Staphylococcus aureus), diabetes mellitus (dilution of BS with sugar broth) and to study the effect of massive infusion therapy (dilution of BS with distilled water). Also, studies of FS of dilutions of BS with 20% albumin solution, the spectral-fluorescent characteristics of which were used in our studies as a reference. The main studied indicators were the fluorescence intensity (IF) and the position of the fluorescence maximum (λmax).The dilution  of BS with distilled water decrease the concentration quenching of albumin molecules  and increase  the fluorescence intensity, which is also typical  because of the physiological increase of circulating blood volume (this situation occurs during pregnancy)[13].The FS dilutions of BS by bacterial culture (6-day culture of Staphylococcus aureus on sugar broth), starting with 20% of the content of centrifuged or non-centrifuged crops in BS allow to reproduce the proportions that are characteristic of FS of BS in sepsis in vivo. In this case, the fluorescence (І) intensity gradually decreases by more than 30% with an increase of the content of bacterial culture in the solution due to the blocking of normal albumin molecules by toxins. There is also a long-wavelength shift of the fluorescence bands (λ) of the dilutions (more than 10 nm). A similar nature of the behavior of the spectral-fluorescent characteristics occurs for dilutions of BS with sugar broth. According to the pathogenetic concept in this case there is a blockade by sugar residues of full-fledged albumin molecules. In the case of dilutions of BS with 20% albumin solution, the fluorescent characteristics of these dilutions do not change. In vivo studies included the study of the spectral-fluorescent characteristics of BS in patients with purulent-inflammatory diseases and sepsis. Three main scenarios for the development of sepsis have been identified and described [12, 14]. We will dwell on two of them in more detail (Fig.1, 2). In patient with sepsis (Fig.1, table 1) BS of the fluorescence intensity decreased by 70%, and the long-wave shift of FS of BS reached 40 nm, which is consistent with the results of in vitro studies [10, 12] (dilution of BS by centrifuged and non-centrifuged cultures of bacteria). This long-wave (septic) peak (curve 1) is mainly due to the glow of "pathological" albumin molecules. The patient underwent the complete clinical and laboratory examination and was prescribed antibiotic and infusion therapy (8-10 liters daily). This case allows us to illustrate within the MFS the successful outcome of treatment of the patient with sepsis who was admitted to the hospital in serious condition. The patient underwent a complete clinical and laboratory examination, antibiotic and infusion therapy was prescribed in a volume of 8-10 liters daily. At the same time, the results of standard clinical and laboratory data were not informative enough. The patient underwent a thorough examination and surgery to remove the source of infection in the body (massive retroperitoneal pelvic phlegmon, which caused sepsis-epiduritis), He was also prescribed a complex infusion, antibacterial and anti-inflammatory therapy, which contributed to the progression of this patient. Undoubtedly, this was facilitated by her young age (33 years) and the absence of comorbidities. The survival of this patient in such a serious condition was possible due to X> X*. In this case, although the patient was admitted to the hospital not at the stage of formation of the septic condition, but on the background of its manifestation, MFS helped us to identify the septic peak (Figure.1, curve 1) and determine the rational choice of treatment tactics. 

Figure 1: Fluorescence spectra of blood serum of septic patient: 1 – 28.12.; 1′– 02.01.; 2 – 04.01.; 3 – 12.02.; 4 – 19.03. 5 – 04.06. and donor of BS (340 nm – «normal peak», 380nm – « septic peak»).

Figure 2. FS of BS of patient 3 with    sepsis and diabetes: 1 - 03.06; 2 –   05.06; 3 – 06.06 and donor BS. λex =280 nm

Nd    1     1′     1′     2      3      4    5
Date28.12.28.12.02.01.02.01.04.01.12.02.19.03.04.06.
λmax, nm340  380 380   345345337349340
IF, r.u.1.0  0.3  0.09    0.151.070.460.390.79

Table 1: Changes in the spectral -fluorescent characteristics of the serum of a patient with sepsis

Nd123
Date03.0603.0605.0606.06
λmax , nm338342347351
IF, r.u.1.00.410.400.15

Table 2: Changes in the spectral - fluorescent characteristics of the serum of person 2 with sepsis

Suppression of bacteremia helped to reduce the number of pathological albumin molecules in the patient's blood. This also contributed to the process of restoring the synthesis of endogenous albumin by the liver. This was mainly due to the young age of the patient. The next measurement of the FS of BS on the 4 January (Figure. 1, curve 2)    showed the increase   of  fluorescence up to  1.07 IF. It was unexpectedly at first glance. In fact, this process was expected. As a result of an in-depth analysis of the described above situation (growth of  X), we modeled the fluorescence curve  on  2 January (curve 1′). The right maximum indicates a decrease in the concentration of pathological albumin, and the left - a certain increase in the concentration of the complete albumin in the patient's blood. Subsequent studies of the fluorescence spectra of this patient showed, that the bacteremia was not completely overcome (Fig. 1, curves 3,4), although the long-wave septic peak disappeared. At that time, the patient's body continued the competition between bacteremia and the compensatory properties of her body in combination with complex therapeutic measures. Only a further long process of treatment under the influence of complex therapy led to the significant suppression of bacteremia and notable improvement of the patient's condition (Fig.1, curve 5). At the time of treatment of this patient the pathogenetic model had not yet developed, and therefore, unfortunately, no infusion therapy with a solution of donor albumin was prescribed. We are convinced, that this procedure could significantly accelerate the healing process of this patient. The second scenario clearly demonstrates the behavior of the spectral-fluorescent characteristics of another person with sepsis (Fig. 2). This person was admitted to the hospital at the beginning of the formation of the septic condition in her body. Therefore, the study of the FS of BS did not reveal a two-peak structure, because a pathological "septic" peak in the region of 380 nm has not been formed yet. But there was the decrease in the fluorescence intensity of the BS, which persisted for some time against the background of ongoing bacteremia. After surgery on the background of intensive antibacterial and anti-inflammatory therapy, the patient's condition remained unchanged for three days. Unfortunately, this scenario was not so optimistic. This patient had another comorbidity - diabetes. In this case, there were two types of pathological albumin molecules: blocked by toxins and blocked by increasedamount of glycosylated albumin. The condition of this patient suddenly deteriorated within one day after surgery on the background of intensive antibiotic therapy, which can be explained by the presence of the number of severe comorbidities and her advanced age. The patient died as a result of an advanced process of generalization of infection and multiple organ failure. However, such a severe disease scenario, presented in Fig. 2, does not deprive us the opportunity to discuss another, in our opinion, the scenario of treatment of this patient, starting from 3 June, which, unfortunately, was not implemented. It could be implemented (Table 3) starting from 3 June if the pathogenetic concept of the development of purulent-inflammatory diseases and sepsis at that time had been proposed. According to this scenario, the patient had to obtain 3 June 200 ml of albumin solution and continue daily infusion of 150 ml of albumin until complete recovery. Although this did not give a complete guarantee of the patient's recovery, the procedure had to be performed, giving the patient the last chance to survive. The scenario of such a variant of the treatment process for patient 2 in the possible case of her recovery is presented in table 3.

Nd12345
Date03.0603.0605.0607.0609.0611.06
λmax, nm338342347345340338
IF, r.u.1.00.410.400.380.430.51

Table 3: Changes in the spectral -fluorescent characteristics of the serum of person 2 with sepsis

Particular attention should be also paid to the urgency of this problem, especially in high-income countries due to the growing number of pregnant women with obesity and diabetes, which contributes to an increased risk of postpartum purulent-septic complications. Obesity can affect negatively a woman's health, cause insulin resistance, dyslipidemia, hormonal and psychological problems and also sexual problems during menopause [15]. About 6% of albumin molecules in the BS of healthy donors are glycosylated. At the same time, in patients with diabetes mellitus due to the presence of hyperglycemia 9-12% of albumin molecules are glycosylated [13]. Therefore, it is possible that patients with diabetes have a tendency to develop purulent-septic processes in the body and their long course. It is logical to hypothesize that "sugar-laden albumin" is not able to bind and eliminate completely toxic products from the body, which leads to a deepening of endogenous intoxication. Therefore, pregnant women with diabetes are at risk for the formation of postpartum purulent-inflammatory diseases. If the medical institution is not able to control the treatment process within the MFS, it is necessary to conduct a detailed monitoring of the patient's health and in case of deterioration to carry out additional examinations and use appropriate treatment tactics and use infusions of 20% albumin solution. Also it is necessary to conduct detailed monitoring of the course of diabetes in the patient. Figure. 3 and tables 4,5 present the results of research in the dynamics of FS of the BS of the patient with severe postpartum endometritis. In the same figure and in tables 4-5 for comparison the corresponding results for the third of the above-mentioned persons with sepsis, who was treated in 2002 also are depicted. She had a complicated somatic and gynecological anamnesis. In childbirth, the anhydrous period duration was 6 hours 30 minutes. In the postpartum period, anemia, proteinuria, 3rd-degree purity of the vagina and the expansion of the uterine cavity according to ultrasound examination were revealed.  She had risk factors for emerging postpartum endometritis. This patient showed a significant decrease in fluorescence intensity up to 0.35 r.u. and a noticeable long-wavelength shift of the fluorescence band. As the condition of this patient was satisfactory, she underwent manual vacuum aspiration of the walls of the uterine cavity. After this procedure and antibacterial and uterotonic therapy, the patient's condition improved. It is very important to choose the optimal time for manual vacuum aspiration. On the one hand, it should be carried out in a timely manner, without delay, and on the other hand, it is necessary to stabilize the patient's condition by this time and start effective anti-inflammatory and antibacterial therapy at the normal body temperature.

Figure 3: Fluorescencespectra of serum of the woman after childbirth with endometritisin dynamics (3.1 - 14.02.2015; 3.2 - 17.02.2015, 3.2′- 17.02.2015), a woman with uncomplicated course of postpartum period (2), patient with sepsis (1′ ,2′, 3 ′, 4′, 5′) and 20% donor albumin (a).                    

Albumin23.13.23.2′1′2′3′4′5′
Date14.0214.0214.0217.0217.023.065.066.067.0610.06
λmax, nm330.1330.1343.1337.1343.1335.2335.2334,1331,6331
IF, r.u.1.00.910.350.610.270.630.430.160.400.76

Table 4

Albumin3.13.23.33.43.51′3′4′5′
Date14.0214.0217.0220.0222.0225.023.066.067.0610.06
λmax, nm330.1343.1348.2339.0336334335.2334,1331,6331
IF, r.u.1.00.350.270.380.550.680.630.160.400.76

                                                                                                    Table 5

After the correction of the treatment in the next experiment, the marked increase in IF of BS of this patient to 0.61 r.u. and the long-wavelength shift of the fluorescence band was leveled. Nevertheless, without correcting treatment tactics on February 14 the patient's condition could in principle deteriorate (curve 3.2′) with the subsequent transition to the septic condition (curve 3′), as in the above-mentioned patient with sepsis. It is very important to monitor the treatment process within the MFS as well as to monitor closely patients’ health. Curve 3.2′ could be obtained by us within the MFS. In this case, the correction of treatment tactics with infusions of 100-150 ml of 20% albumin solution several times until recovery was done. This scenario of the disease of the above-mentioned patient is presented in Table 5. We analyzed two possible scenarios of the treatment process for the above-mentioned patient with postpartum endometritis. The first scenario is optimal, because in the second case, the disease could progress. In this case, the chances of full recovery would be much lower. Without the use of MFS, it would be difficult to expect a successful completion of the treatment process.In low-income countries, it is necessary to conduct available research methods, including the ultrasonographic examination of the pelvic organs to assess the condition of the uterine cavity objectively. If necessary, invasive procedures (the manual vacuum aspiration of the walls of the uterine cavity or hysteroscopy) and infusions of 100-150 ml of 20% albumin solution of at a time, which can dramatically change patients’ health in many cases, are scheduled.Nevertheless, as based on the analysis of the results of treatment at our clinical base at the Gynaecological Department No. 2 over 300 patients with postpartum purulent-inflammatory diseases for 6 years, no case of septic complication was detected. This can be explained by the high qualification of medical staff and the use of modern treatment tactics and diagnostic methods, including MFS. Otherwise, due to doctors’ low qualifications, it is difficult to hope for a positive result in the treatment of women with postpartum purulent-inflammatory diseases.Fig. 4 presents the results of research in the dynamics of fluorescence spectra, and Table 6 shows data for the spectral-fluorescent characteristics of the BS of the patient with the burn injury (area of ​​the burn surface 38%), who was admitted to the hospital on 27 June 2015 [16]. He was immediately prescribed appropriate treatment, including antibiotic therapy and infusion therapy with 2-3 liters daily.

Figure 4: FS of BS of patient 6 with a burn injury, who was hospitalized in Communal City Clinical Hospital №8, Lviv in 2015 in dynamics during treatment (6.1 - 3.07., 6.2 - 8.07., 6.3 - 13.07., 6.4 -17.07., 6.4′ -17.07., 6.5 - 20.07., 6.6 - 24.07.) and a patient with sepsis, who was treated in 2002 in Ambulance hospital (1 ′ - 03.06., 2 ′ - 05.06., 3 ′ - 06.06., 4 ′ - 07.06., 5 ′ – 10.06) and 20% albumin solution (a), ex = 280 nm.

a6.16.26.36.46.4’6.56.61’2’3’4’5’
Date3.073.078.0713.0717.0717.0720.0724.073.065.066.067.0610.06
λmax, nm327336.1332.2341.1335.1341.1333.1335.1335.2335.2334.1331.6331
IF, r.u.10.880.880.350.640.270.760.800.630.430.140.40.76

Table 6

Staphyloccus aureus 105 and Pseudomonas aeruginosa 106 were verified on the basis of microbiological examination. Due to infusion therapy, the fluorescence intensity of BS was not significantly reduced during the first 6 days (IF = 0.88 r.u.), which correlated with the results of in vitro studies. No shift of BS of fluorescence spectra to the long-wavelength region was detected, despite the verification of two pathogens in the patient. The studies of the fluorescence spectra of this patient’s BS on 13 July 2015 (Figure. 4, Curve 6.3) showed a significant decrease of its IF up to 0.35 r.u. and a shift of the fluorescence spectra in the long-wavelength region by 9 mm. The d eterioration of this patient’s clinical condition was also revealed. This indicated the deepening of endogenous intoxication. The treatment process was corrected, including the use of 100 ml of 20% donor albumin solution infusion for 8 times on different days. The subsequent sampling of the BS revealed a gradual normalization of the spectral-fluorescent characteristics of the patient’s BS (see Table 6). Therefore, he was discharged from the hospital in satisfactory condition on 24 July 2015. Figure 4 shows that the spectral-fluorescence characteristics of this patient are qualitatively correlated with the corresponding results of the patient with sepsis, presented in the same figure by dashed curves (Curves 1′-5′). This patient was treated in the hospital in 2002. Without the correction of the treatment process, the condition of the patient with the burn injury could continue to deteriorate (Fig. 4, Curve 6.4′) with subsequent transition to the severe septic condition, as it was in the case with the patient with sepsis. In order to correct the treatment process of the patient with the burn injury, the information about the behavior of the spectral-fluorescent characteristics of the patient with sepsis  was significant (Curve 3′). It is important that the behavior of the spectral-fluorescent characteristics of the patients with sepsis, including burn injury, is determined by the contributions of two types of albumin molecules: complete and "blocked by toxins". Figure 1 shows that most of the albumin molecules of the patient with severe sepsis (Curve 1) are blocked by toxins (long-wave peak). Only a small number of complete molecules of albumin provide support the vital functions of the patient's body (fluorescence in the region of 330 nm). In such a serious condition of the patient, the synthesis of albumin is very slow. However, if this patient (Fig. 1) had been given the infusion of 20% albumin solution, the additional peak in the region of 330-345 nm could have appeared in her fluorescence spectrum, which could have led to the improvement in her condition. But this is only our assumption. For this patient, the possible changes in the fluorescence spectrum during infusion of 20% albumin solution were not proved. This may be the subject of our further studies of the spectral-fluorescence characteristics in patients with severe sepsis and with severe burn injury. Regardless of the etiological factors of sepsis, the pathogenetic mechanisms of septic complications are unified. Patients with severe burns are model objects for studying the patterns of behavior of the spectral-fluorescent characteristics of patients with sepsis. Serum albumin molecules have the ability to complex. In the case of presence of endogenous intoxication in the body, they are blocked by the products of bacterial metabolism. Understanding of the microscopic mechanisms of the theory of pathological albumin formation is the basis for the development of pathogenetical treatment tactics. The most optimal approach for the detection of septic conditions in patients is the study of spectral-fluorescent characteristics of BS with the method of fluorescence spectroscopy. There is the high risk of septic condition in patients with burn injury in two cases: with the large area and depth of burns and inadequate treatment at the initial stage of the disease. Consequently, the key thesis of the successful treatment is the comprehensive approach to the prevention of the development of bacteremia through early surgical treatment and comprehensive therapy. The fundamental idea of the ​​successful completion of the treatment is its constant monitoring within the method of fluorescence spectroscopy of the treatment process with the possibility of its correction. The intensity and position of the fluorescence maximum are the important parameters in the treatment process. The lower the fluorescence intensity and a more noticeable long-wave shift, the higher is the probability of exitus letalis.

Conclusiоns

The significant improvement of the functional results of treating patients is the fundamental problem of medical science. The study of the biological objects with the method of fluorescence spectroscopy makes it possible to detect pathological processes in living organisms at different stages of their development. The main and very significant advantage of this method is the combination of high sensitivity and expressiveness with the possibility of non-destructive control of biological objects. The deep understanding of pathogenesis is the key point in creating the strategy of the treatment tactics of patients with various diseases. Obtaining the information about the mechanisms of origin and evolution of purulent-inflammatory diseases and sepsis is extremely important for the rapid search for the effective ways to treat them.  This is why we have proposed the pathogenetic concept of diagnostic and therapeutic approach for purulent-inflammatory diseases and sepsis. It is based on the fact that in patients with these diseases part of the albumin molecules in the BS are blocked by the products of bacterial metabolism, i.e. toxins. These pathological molecules of albumin are unable to perform their main functions: transportation and detoxification. Even in healthy people, about 6% of albumin molecules in the blood are glycosylated. At the same time in patients with diabetes mellitus, 9-12% of them are glycosylated. So, the sum of the concentrations of pathological and glycosylated albumin molecules together forms concentration X. As a result, the sum of the concentrations of pathological and glycosylated albumin molecules is concentration X. The new definition of sepsis is to define X*, i.e. the maximum minimum concentration of albumin in patients with sepsis. If X>X*, it ensures the viability of the organism in patients with this disease (X –is the concentration of normal albumin molecules in patients with this disease). If X< X> X*). It was proposed to use infusions of 20% albumin solution in order to overcome endogenous intoxication. In this case, the control and monitoring of the treatment process of patients, especially in serious condition, can be properly provided within the MFS. It is connected with the fact that we can clearly assess the effects of bacteremia and treatment by applying patients' fluorescent characteristics, and we can control and adjust the treatment process. It is very important to analyze our proposed different scenarios of the treatment process in detail. Maybe this can help to implement some of the scenarios. We have analyzed in detail the various scenarios for the development of purulent-inflammatory diseases and sepsis and offer alternative scenarios, which can be implemented without the use of MFS. During the pandemic of COVID-19, there were difficulties in using MFS in the treatment process, in particular for patients with burn injury. The analysis of the obtained results of the treatment of patients with burn disease [16] with the use of MFS helped to treat successfully over 35 patients with burn injuries.

References

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Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

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Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

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Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

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Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

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Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

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Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann

I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.

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Zhao Jia