Adequate Therapy Research Articles

СОВРЕМЕННЫЕ ТЕНДЕНЦИИ АНТИБИОТИКОУСТОЙЧИВОСТИ ПАТОГЕННЫХ МИКРООРГАНИЗМОВ ПАЦИЕНТОВ ХИРУРГИЧЕСКОГО ПРОФИЛЯ

Background. To carry out adequate antibacterial therapy directed against pathogenic microflora in patients with surgical infection it is necessary to take into account indicators of antibiotic resistance of leading etiological agents. The aim of the work is to study the spectrum and current dynamics of changes in antibiotic resistance of purulent pathogens in soft tissues of surgical patients. Material and methods. An analysis of the results of antibiotic resistance of the seeded leading microflora in patients with purulent processes of soft tissues was made. Results. Isolates of Staphylococcus aureus from surgical patients are characterized by high resistance to all β-lactam antibiotics, the combination drug trimethoprim-sulfamethoxazole, and macrolides. The resistance of Klebsiella pneumoniae and Proteus mirabilis to all studied β-lactam antibiotics, as well as fluoroquinolones, aminoglycosides, tetracyclines, nitrofurans, and chloramphenicol ranges from 37 to 100%. Escherichia coli resistance to β-lactams, fluoroquinolones, carbapenems, and aminoglycosides reaches 50-73%. A high level of antibacterial resistance is also characteristic of other bacteria most often cultured in surgical patients. Conclusions. The most frequently cultured strains of both gram-positive and gram-negative groups of microorganisms from surgical patients are characterized by a high level of antibacterial resistance, reaching 100%. Currently, cases of polyantibiotic resistance and resistance even to reserve antibiotics are not uncommon. All this dictates the need to search for new classes of substances that have an antimicrobial effect, and metal nanoparticles may be one of them.

Community-acquired Klebsiella pneumoniae pneumonia in ICU: a multicenter retrospective study

BackgroundAlongside the recent worldwide expansion of hypervirulent Klebsiella pneumoniae (KP) infections, the available literature regarding cases of community acquired pneumonias (KP-CAP) remains scarce but reports a strikingly high and early mortality. We performed a retrospective multicenter study (7 ICU in France) between 2015 and 2019, comparing prognosis and severity of KP-CAP versus Streptococcus pneumoniae - CAP (SP-CAP).MethodsFor each KP-CAP, three SP-CAP admitted in ICUs within the same center and within the same 6-month window were selected. When available, KP strains were studied, and bacterial virulence was genetically assessed for virulence factors. The primary outcome was in-hospital mortality. Associations between clinical outcomes and type of infection were tested using univariate and multivariate logistic regressions, adjusted for pairing variables.ResultsTwenty-seven KP-CAP and 81 SP-CAP were included. Respective in-hospital mortality rates were 59% (n = 16) and 17% (n = 14, p < 0.001), despite adequate antibiotic therapy. KP-CAP median time from admission to death was 26.9 h [IQR 5.75–44 h] and were significantly associated with higher rates of multiple organ failures (93% vs. 42%, p < 0.001), disseminated intravascular coagulation (12% vs. 1.3%, p = 0.046), septic shock (median lactate on ICU admission 4.60 vs. 2.90 mmol/L, p = 0.030) and kidney failure (KDIGO-3: 87% vs. 44%, p < 0.001). Interestingly, alcoholism was the only identified predisposing factor of KP-CAP. Severity on ICU admission (2-fold higher for KP-CAP) was the only factor associated with mortality in a multivariate analysis.ConclusionWe described a strong association between KP-CAP infection and higher and earlier mortality when compared to SP-CAP. Moreover, alcoholism was the sole predisposing factor associated with KP-CAP infection. These findings should raise awareness of clinicians involved in the management of severe CAP about this microbiological etiology. Future prospective studies are needed to confirm these results and to design strategies to improve the prognosis of such infections.

Adequate antiviral treatment lowers overall complications of cytomegalovirus colitis among inpatients with inflammatory bowel diseases

BackgroundCytomegalovirus (CMV) colitis significantly complicates the course of inflammatory bowel disease (IBD), frequently leading to severe flare-ups and poor outcomes. The role of antiviral therapy in hospitalized IBD patients with CMV colitis is currently under debate. This retrospective analysis seeks to clarify the influence of antiviral treatment on these patients.MethodsWe retrospectively reviewed IBD patients diagnosed with CMV colitis via immunohistochemistry staining from colonic biopsies at a major tertiary center from January 2000 to May 2021. The study focused on patient demographics, clinical features, risk factors, prognostic indicators, and antiviral treatment outcomes.ResultsAmong 118 inpatients, 42 had CMV colitis. Risk factors included hypoalbuminemia and antibiotic use. IBD patients with CMV colitis receiving < 14 days of antiviral therapy had higher complication (72% vs. 43%, p = 0.028) and surgery rates (56% vs. 26%, p = 0.017) compared to those without CMV. Adequate antiviral therapy (≥ 14 days) significantly reduced complications in the CMV group (29% vs. 72%, p = 0.006), especially in Crohn’s disease (20% vs. 100%, p = 0.015). Independent predictors of IBD-related complications were CMV colitis (Odds Ratio [OR] 3.532, 90% Confidence Interval [CI] 1.012–12.331, p = 0.048), biological treatment failure (OR 4.953, 95% CI 1.91-12.842, p = 0.001), and adequate antiviral therapy (OR 0.108, 95% CI 0.023–0.512, p = 0.005).ConclusionCMV colitis and a history of biological treatment failure increase complication risks in IBD patients. Adequate antiviral therapy significantly mitigates these risks, highlighting its importance in managing IBD patients with CMV colitis.

The revision and factor analytic evaluation of the German version of the depression literacy scale (D-Lit-R German)

BackgroundDepression is a common mental health disorder and the second leading cause of disability worldwide. In people with depression, low depression literacy, which could be characterized by a poor recognition of depressive symptoms and less knowledge about the availability of treatment options, can hinder adequate therapy for depression. Nevertheless, questionnaires measuring depression literacy in Germany are rare. Consequently, for the present study, the German Depression Literacy Scale (D-Lit) has been revised and evaluated.MethodsFirst, a team of clinical psychologists revised the D-Lit German scale. Next, cognitive interviews were conducted with patients with depression to improve the comprehensibility of the scale items. Our revision of the D-Lit-R German scale was then subjected to an anonymous online study. Finally, the data went through an exploratory factor analysis, and sociodemographic subgroup analyses were performed.ResultsN = 524 individuals (age 18–80) completed the D-Lit-R German scale and a questionnaire on their sociodemographic data. Cronbach´s alpha was estimated as α = .72, and McDonald's Omega (categorical) was estimated as ω = .77. The mean Item difficulty was M = .75 (SD = .15). An EFA was performed for a unidimensional model, a 5-factor-model and at last a 3-factor-model. The 5-factorial model showed a good model fit (χ2emp,WLSMV(131) = 92.424, p > .05; CFI = 1, RMSEA = 0, SRMR = .07) but was rejected since the content of the potential 5 factors could not be determined. The 3-factor model showed an arguable model fit. The Chi2 test was significant (χ2emp,WLSMV(168) = 199.912, p < .05), but the CFI and the RMSEA met an acceptable model fit (CFI = .990, RMSEA of .019, 90% CI[.003, .029]). Substantively, the three factors were defined as (1) Distractors and other symptoms, (2) Depressive symptoms, and (3) Pharmacological and psychotherapeutic depression treatment. Furthermore, there were significant differences in sum scores regarding the subgroup's gender, treatment for mental health problems, depression treatment, experience with depression, and different career fields.ConclusionsThe D-Lit-R German scale is a time-efficient scale to assess some aspects of the depression literacy construct that can be easily applied. Since there was no perfect model fit, it is recommended to continue to revise the scale. Further evaluation studies could ask for knowledge of the etiological factors of depression. Future studies could then use this instrument to convey depression literacy. This instrument could assess the growth of knowledge after psychoeducational interventions in different settings.Trial registrationThis trial was preregistered at the platform osf.io (https://osf.io/49xdh).Registration number: https://doi.org/10.17605/OSF.IO/49XDHDate of registration: 28 April 2022.

Risk Factors and Scoring Systems to Predict the Mortality Risk of Afebrile Adult Patients with Monomicrobial Gram-Negative Bacteremia: A 10-Year Observational Study in the Emergency Department.

The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).

The Spectrum of Cutaneous Manifestations in Lupus Erythematosus: A Comprehensive Review.

Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited solely to the skin. Cutaneous LE (CLE) manifests with a wide range of skin lesions divided into acute, subacute and chronic subtypes. Despite classic forms of CLE, such as malar rash or discoid LE, little-known variants may occur, for instance hypertrophic LE, chilblain LE and lupus panniculitis. There are also numerous non-specific manifestations including vascular abnormalities, alopecia, pigmentation and nail abnormalities or rheumatoid nodules. Particular cutaneous manifestations correlate with disease activity and thus have great diagnostic value. However, diversity of the clinical picture and resemblance to certain entities delay making an accurate diagnosis The aim of this review is to discuss the variety of cutaneous manifestations and indicate the clinical features of particular CLE types which facilitate differential diagnosis with other dermatoses. Although in diagnostically difficult cases histopathological examination plays a key role in the differential diagnosis of LE, quick and accurate diagnosis ensures adequate therapy implementation and high quality of life for patients. Cooperation between physicians of various specialties is therefore crucial in the management of patients with uncommon and photosensitive skin lesions.

The impact of peritoneal dialysis on oxypurinol and urate elimination in people with gout.

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.

Correlation of Blood Pressure, Heart Rate and Pain with Anxiety, and Importance of its Prevention in Surgery of Impacted Third Molars Under Local Anesthesia

Aim: To examine whether there is a correlation between blood pressure, heart rate, and pain with the level of preoperative and postoperative anxiety in surgery of impacted third molars under local anesthesia. Subjects and Methods: In the study, which included adult patients of both sexes with an indication for surgical extraction of impacted third molars, research parameters were measured as follows: 1st measurement (day of examination) - blood pressure, heart rate, preoperative anxiety with Spielberger’s State-Trait Anxiety Inventory (STAI); 2nd measurement (immediately before the intervention) - blood pressure, heart rate, preoperative anxiety with STAI; 3rd measurement (day after intervention) - blood pressure, heart rate, postoperative anxiety with STAI, postoperative pain with visual analog scale. Results: The values of preoperative and postoperative anxiety and the measured parameters of blood pressure, heart rate, and postoperative pain were statistically significantly positively correlated with each other during all measurements. Conclusion: In order to increase the satisfaction of both the patient and the ordinarius, and to prevent possible complications in this type of oral surgical intervention, it would be useful to consider adequate therapy in order to prevent the development of anxiety, considering the confirmed correlation with the measured parameters.

Successful Treatment of Cerebral Tuberculoma in Acquired Immune Deficiency Syndrome Patient a Case Report

Introduction: Tuberculosis (TB) remains a leading problem in developing and endemic countries. Cerebral tuberculosis is a rare but dangerous complication of tuberculosis infection in the central nervous system. The immunosuppressive condition in human immunodeficiency virus infection is a risk factor for severe tuberculosis. Case Report: An Indonesian man, 32 years old, married, came with complaints of headaches, dizziness, delirium, nausea and vomiting since 1 month before the examination. He had a history of TB treatment 1 year before the examination. The results of the neurological examination were within normal limits, the HIV test was reactive and there was a decrease in CD4. Head MRI examination with contrast showed multiple solid nodules in the thalamus with the largest size 2.3×2.7 cm, indicating cerebral tuberculoma. Chest x-ray was normal, GeneXpert MTB sputum was not detected. Next, primary treatment is given with anti-tuberculosis drugs, Highly Active Antiretroviral Therapy (HAART), co-trimoxazole, and dexamethasone. There was clinical, laboratory and radiological improvement after 12 months of treatment. Viral load is undetectable, CD4 is elevated. A head CT scan did not show tuberculoma. He became healthy and was able to return to work Discussion: Cerebral tuberculoma is a condition characterized by the presence of intracranial tuberculoma. The clinical manifestations are non-specific, such as headaches or seizures. This is caused by space occupying lesions and increase intracranial pressure. In this case, the diagnosis of cerebral tuberculoma was made through head MRI with contrast. TB therapy and co-trimoxazole are given as soon as the diagnosis is made, while antiretrovirals are given 2 weeks after he has tolerated the TB medication. The minimum duration of therapy for cerebral tuberculosis is 12 months. He require lifelong antiretroviral medication. Conclusion: Tuberculoma should be considered as differential diagnosis of space-occupying lesions in patients HIV/AIDS. Early diagnosis, adequate therapy, patient adherence and family support can cure severe tuberculosis.

Development of a multiplex real-time PCR assay for simultaneous detection of common colistin and carbapenemase genes

Carbapenem and colistin are often used as last-resort treatment for Gram-negative multi-drug resistant (MDR) bacteria. Nevertheless, co-resistance of these drugs is threatening the global healthcare system. Rapid and accurate detection of carbapenem and colistin resistant bacteria is critical for adequate antibiotic therapy and infection control, particularly in the context of an outbreak. The presence of blaNDM, blaKPC, blaIMP-1 and blaOXA-48 is responsible for greater than 95% phenotypic resistance in carbapenem-resistant Enterobacteriaceae, while mcr-1 is the most prevalent and well disseminated of all mcr genes in colistin-resistant strains. In this study, we aim to develop a multiplex real time-PCR assay for simultaneous detection of the five genes blaNDM, blaKPC, blaIMP-1, blaOXA-48 and mcr-1. The melting curve-based multiplex real time PCR assay was established with the dissociation temperature range extended from 76°C to 87°C. The whole process is completed within one hour and half, allowing rapid screening of the five genes in cultured bacteria samples with a limit of detection of 10 CFU/ml. The proposed multiplex real-time PCR assay is a robust, reliable and rapid method for the detection of bacterial strains carrying blaOXA-48, blaIMP, blaNDM, blaKPC and mcr-1 gene individually or in cocktail of genes. This assay will be a valuable tool for surveillance and monitoring of MDR bacteria additionally resistant to either carbapenem or colistin or both drugs.

Pharmacoresistant epilepsy with electrical status epilepticus during slow-wave sleep: a clinical case

The article presents a clinical case of epilepsy with electrical status epilepticus during slow-wave sleep, the example of which shows the relevance of the issue of timely diagnosis and prescription of adequate anti-epileptic therapy in this syndrome. The role of regular electroencephalographic sleep monitoring in order to monitor the effectiveness of therapeutic measures is emphasized, and the main difficulties in making this diagnosis and choosing the correct anti-epileptic treatment are shown.

Protoplast-mediated transformation of Madurella mycetomatis using hygromycin resistance as a selection marker.

Madurella mycetomatis is the main cause of mycetoma, a chronic granulomatous infection for which currently no adequate therapy is available. To improve therapy, more knowledge on a molecular level is required to understand how M. mycetomatis is able to cause this disease. However, the genetic toolbox for M. mycetomatis is limited. To date, no method is available to genetically modify M. mycetomatis. In this paper, a protoplast-mediated transformation protocol was successfully developed for this fungal species, using hygromycin as a selection marker. Furthermore, using this method, a cytoplasmic-GFP-expressing M. mycetomatis strain was created. The reported methodology will be invaluable to explore the pathogenicity of M. mycetomatis and to develop reporter strains which can be useful in drug discovery as well as in genetic studies.

Next-generation microbiological testing in intraabdominal infections with PCR technology

PurposeIntraabdominal infections (IAI) are increasing worldwide and are a major contributor to morbidity and mortality. Among IAI, the number of multi-drug resistant organisms (MDRO) is increasing globally. We tested the Unyvero A50® for intraabdominal infections, compared the detected microorganisms and antibiotic resistance, and compared the results with those of routine microbiology.MethodsWe prospectively compared samples obtained from surgical patients using PCR-based Unyvero IAI cartridges against routine microbiology for the detection of microorganisms. Additionally, we identified clinical parameters that correlated with the microbiological findings. Data were analyzed using the t-test and Mann–Whitney U test.ResultsSixty-two samples were analyzed. The PCR system identified more microorganisms, mostly Bacteroides species, Escherichia coli, and Enterococcus spp. For bacterial resistance, the PCR system results were fully concordant with those of routine microbiology, resulting in a sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 100%. The sensitivity, specificity, PPV, and NPV for the detection of microorganisms were 74%, 58%, 60%, and 72%, respectively. CRP levels were significantly higher in patients with detectable microorganisms. We identified more microorganisms and bacterial resistance in hospital-acquired intra-abdominal infections by using the PCR system.DiscussionIAI warrants early identification of the microorganisms involved and their resistance to allow for adequate antibiotic therapy. PCR systems enable physicians to rapidly adjust their antibiotic treatment. Conventional microbiological culture and testing remain essential for determining the minimal growth inhibition concentrations for antibiotic therapy.

Late Tuberculosis Reactivation After Severe Covid-19.

Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic. The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased. Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated. Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.

The effect of hydrocortisone versus hydrocortisone plus fludrocortisone on duration of shock: A propensity score-weighted analysis.

The 2021 Surviving Sepsis Campaign Guidelines recommend the use of hydrocortisone in patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. Fludrocortisone has been used concomitantly with hydrocortisone in some studies without a clearly defined role or known clinical benefit. The purpose of this study was to assess the impact of fludrocortisone added to hydrocortisone on shock-free days for septic shock. A single-center, retrospective propensity score-weighted study was conducted to compare hydrocortisone versus hydrocortisone plus fludrocortisone for septic shock. Adults admitted to the medical intensive care unit (ICU) from 2015 to 2020 were included in the study. All patients received ≥200 mg/day hydrocortisone for at least 24 h ± fludrocortisone initiated within 72 h of vasopressors. The primary outcome was shock-free days by day 14. The secondary outcomes included duration of shock, change in Sequential Organ Failure Assessment (SOFA) score, hospital and ICU length of stay, and all-cause inhospital mortality. A total of 228 patients met inclusion criteria with 212 patients retained after propensity score weighting. There was no difference between groups in 14-day shock-free days (6.3 vs. 6.1 days; P = 0.781). Furthermore, no significant differences were observed for the secondary outcomes of ICU/hospital length of stay, duration of shock, change in SOFA score, and all-cause inhospital mortality. The addition of fludrocortisone to hydrocortisone in septic shock did not increase shock-free days by day 14. These results suggest that the use of hydrocortisone alone may be an adequate adjunctive therapy in septic shock. A prospective randomized controlled trial is needed to confirm results.

НАСЛЕДСТВЕННАЯ ТУБУЛОПАТИЯ: ФОСФАТ-ДИАБЕТ (Два клинических наблюдения)

Introduction. Phosphate diabetes is a representative of a group of diseases known as tubulopathies. It is more often of a hereditary nature. The disease manifests at an early age with symptoms similar to alimentary rickets, which creates problems for diagnosing and prescribing an adequate therapy. In this case, the current situation leads to the development of bone deformities and disability, delayed physical development, and the need for surgical treatment, which reduces the quality of life of the patients for a long time. Aim: To consider two clinical cases of phosphate diabetes with typical symptoms, demonstrate the diagnosing challenges, and analyze the treatment effects. Materials and Methods. Two clinical cases of phosphate diabetes are presented. The first patient: 16 years old, observed from the age of 2, and takes vitamin D and inorganic phosphates from the diagnosis date. The geneticist found the autosomal dominant of the pathology. The girl underwent two surgeries for her leg deformity. The second patient, 10 years old, was diagnosed at the age of 4 years. DNA diagnostics detected a mutation in the COL9A3 gene. They refused the complete DNA exome sequencing. From the diagnosis date, the patient is treated with the active vitamin D metabolite and inorganic phosphates. Results and Discussion. Clinician-observed: Patient 1 had leg deformities, painful legs, and disharmonious physical development caused by her growth retardation. Blood concentrations of calcium and phosphorus are within normal, there is hypocalciuria typical of phosphate diabetes in the urine, while phosphates are within normal. The patient’s kidney function is not impaired. Clinician-observed: Patient 2 is physically retarded, there are varus foot deformities and pes planovalgus feet. Kidney function is not impaired, the level of alkaline phosphatase is increased, the total blood calcium levels are decreased with phosphorus indicating normal values, and the urine phosphaturia and hypocalciuria are within normal ranges. Due to the COL9A3 mutation detected, Stickler syndrome was excluded. Orthopedic surgeon recommended surgical treatment of her leg deformities. Conclusions. The examination showed that the therapy allows keeping phosphate diabetes under control and avoiding the side effects of taking vitamin D.

Post Resuscitation Care

After successful resuscitation, further treatment has a decisive influence regarding patient outcome. Not only overall survival, but also the neurological outcome that is crucial for patients' quality of life can be positively influenced by optimized post-cardiac arrest treatment. The management of various consequences of post-cardiac arrest syndrome is discussed in the current version of the ERC-guidelines in the chapter "post resuscitation care". A step-by-step approach based on an algorithm provides the necessary structure. The immediate treatment and stabilization of patients after ROSC is followed by the diagnosis of the triggering pathology in order to initiate adequate therapy. During the subsequent intensive care treatment, the focus is on optimizing neurological recovery.

Short Registry of Terminal Forms of Chronic Heart Failure in the Samara Region.

To study the clinical characteristics and prognosis of patients with functional class (FC) III-IV chronic heart failure (CHF) who meet the criteria for inclusion in the palliative care program. A short registry of severe CHF forms was conducted at 60 outpatient and inpatient clinics in the Samara region for one month (16.05.2022-15.06.2022). The registry included patients with FC III-IV CHF who sought medical help during that period. Lethal outcomes were assessed at 90 days after the inclusion in the registry using the Mortality Information and Analytics system. 591 patients (median age, 71.0 [64.0; 80.0] years were enrolled, including 339 (57.4%) men, of which 149 (24.1%) were of working age (under 65 years). The main cause of CHF was ischemic heart disease (64.5%). 229 (38.7%) patients had left ventricular ejection fraction &lt;40%. During the past year, 513 (86.8%) patients had at least one hospitalization for decompensated CHF. 45.7% of patients had hydrothorax, and 11.3% of patients had ascites. Low systolic blood pressure was observed in more than 25% of patients; 14.2% required in-hospital inotropic support; and 9.1% received it on the outpatient basis. 4.2% of patients received outpatient oxygen support and 0.8% required the administration of narcotic analgesics. 12 (1.9%) patients were on the waiting list for heart transplantation. In this study, there was an inconsistency in the number of patients with ventricular tachycardia and/or left bundle branch block (LBBB) who were implanted with cardiac resynchronization therapy devices (CRTD) or an implantable cardioverter defibrillator (ICD), a total of 19 patients (11 patients with CRTD and 8 patients with ICD), while 58 (9.8%) patients had indications for CRTD/ICD implantation. Within 90 days from inclusion in the registry, 59 (10.0%) patients died. According to binary logistic regression analysis, the presence of LBBB, hydrothorax, the requirement for outpatient oxygen support, and a history of cardiac surgery were associated with a high risk of death. Patients with severe forms of CHF require not only adequate drug therapy, but also dynamic clinical observation supplemented with palliative care aimed at improving the quality of life, including the ethical principles of shared decision-making and advance care planning to identify the priorities and goals of patients in relation to their care.

Стан вивчення поліморфізму окремих генів у виникненні бронхіальної астми

The study of the polymorphism of individual genes is the basis of both preventive medicine and is used in the selection of adequate therapy. Polymorphism of individual candidate genes in bronchial asthma (BA) is studied taking into account many personal characteristics and the influence of environmental factors. Aim - to analyze the status of the study of the role of polymorphism of β2-adrenoceptors (ADRβ2) in the pathogenesis of bronchial asthma in children and to compare them with our own findings. Materials and methods. The results of research on polymorphism of individual genes in children with BA, which includes the PubMed database, were analyzed. An in-depth study of the anamnesis data (disease, life, hereditary), a complex clinical and laboratory examination of children (n=101) of school age with BA was carried out (the average age was: for boys 11.15±0.48 years; for girls - 10.63±0.7 years). Patients were diagnosed with BA in accordance with the GINA recommendations of the current revision. Determination of the Arg16Gly polymorphism of the ADRβ2 gene (rs 1042713) was performed by the polymerase chain reaction method followed by restriction enzyme analysis. The obtained data were processed in the Statsoft STATISTICA software package. Mean values were given as (M±m), Student's test was used for comparison. Results. The assessment of the frequency of polymorphism of the Arg16Gly gene in BA established that two variants prevailed in boys: Arg16Gly and Gly16Gly; at that time, the Gly16Gly genotype prevailed among girls, which, according to individual studies, is associated with good effectiveness of the applied therapy (nebulization of salbutamol). Mutations in the ADRβ2 gene in patients with BA were twice as frequent in the Arg16Gly genotype and three times as frequent in the Gln27Glu genotype, in contrast to healthy children. Such a polymorphism affects the functional activity of ADRβ2, the occurrence and course of BA. Conclusions. The Arg16Gly polymorphism of the ADRβ2 gene in children with BA largely determines the sensitivity of ADRβ2 to the applied exacerbation therapy and the effectiveness of basic treatment. In patients with the Gly16Gly genotype, most researchers note the good clinical effectiveness of both fast broncholytic drugs (β2 short-acting agonists) and basic anti-inflammatory drugs. The diagnosed homozygous Arg16Arg genotype of the ADRβ2 gene mostly accompanies the uncontrolled (or partially controlled) course of asthma in children. The revealed features of the Arg16Gly polymorphism of the ADRβ2 gene will help the doctor to draw up an adequate treatment plan, which is based on the genetically determined sensitivity of ADRβ2 receptors to medical preparations. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.