Nonspecific Inflammatory Reaction Research Articles

Tocilizumab in Severe and Critical COVID-19 Pneumonia: Streamlining the Mixed Signals

Four years since the start of the pandemic, the first lockdown in Manila happened on March 15, 2020 causing a pandemonium in the metro as the Filipinos gear up for the unexpected. As the suspected and confirmed cases grew, case numbers of unidentified patients soon became friends, relatives, and loved ones. As of May 2023 1 , there have been more than 1.3 million confirmed COVID-19 cases in Metro Manila alone with almost 14,000 deaths from severe and critical cases.
 The current knowledge about the disease as well as the explanation of its widely varied symptomatology continues to evolve. 2-4 At the center of the discussion for severe and critical COVID-19 requiring hospitalization is the hyperactivation ofthe inflammatory response resulting to simultaneous increase in multiple cytokines. 4,5 Such an inflammatory cascade results in nonspecific inflammatory reaction from damaged or dysfunctional virus-infected host cells making it difficult to identify a specific mediator of inflammatory response. 5,6 It is therefore not surprising that multiple therapeutic trials done targeting specific cytokines such as IL-6 and TNF-a have also led to mixed results. 7-10
 Since 2020, aggressive research has allowed both the development of new medications as well as repurposing of other molecules in the treatment of COVID-19. Antiviral drugs, monoclonal antibodies, IL-6R inhibitor/immune modulators, andsystemic corticosteroids have become household names. 6 IL-6, an identified key propagator of the cytokine storm in severe and critical COVID, has been the focus of the noise as mechanistically, IL-6 blockers including tocilizumab and sarilumabtheoretically disrupt the inflammatory cascade. 5-7
 If mechanistically, IL-6 blockers, particularly tocilizumab can block the inflammatory cascade, why are there mixed signals on its benefit based on real-world evidence? 7-10
 One of the largest and most recently published systematic review and meta-analysis of 15 randomized and two non- randomized clinical trials evaluating the effect of tocilizumab on the clinical outcomes of COVID-19 patients11 showed acombined cumulative risk of death in COVID-19 patients of 0.93 (RR 0.93, 95% CI 0.86 – 1.00, i 2 72.39%). The need for invasive ventilation, ICU admission was at 1.04 (RR 1.04, 95% CI 0.90 – 1.20, i 2 0.00). These figures indicate a 7% decreasedrisk of death with a 4% increased risk of ICU admission and need for invasive ventilation, again indicating mixed signals on the perceived benefit of tocilizumab. 11 Limitations in the study results compared to controlled clinical trials are probablydue to (1) heterogeneity of the patients with severe and critically ill COVID-19 patients potentially having different degrees of inflammatory activities; (2) timing of administration of tocilizumab; (3) different administrative and hospital policies inthe management of more ill patients suffering from COVID-19; and (4) presence of multiple inflammatory cytokines aside from IL-6, making it difficult to pinpoint the specific key mediator of inflammatory response on a per-patient basis.
 The local randomized controlled trial published by Amante et al.12 agree with these mixed signals from the published literature in COVID-19. In both intention-to-treat and per-protocol-analysis, there was no statistical significance and clinicalbenefit of using tocilizumab for severe and critically ill patients. Four years later, the picture is clearer now as real-world evidence coupled with carefully conducted clinical trials provide us a better understanding of the use of tocilizumab for current cases. However, back in 2020, when this mysterious respiratory illness is wreaking havoc, medications both newly developed and repurposed were offered as the medical research community was challenged by a pandemic in an unprecedented manner.
 As COVID-19 becomes endemic, the search for the cure for severe COVID-19 remains to be discovered. Given its mixed signals, shared decision making (pending confirmation in further studies) between the patient, caregiver, and the physician remains the cornerstone of management.

Gut microbiota – a new link in the pathogenesis of osteoarthritis (literature review)

The intestinal microbiota (IMB) can indirectly affect the course of ostearthritis (OA) at the systemic level by stimulating a chronic nonspecific inflammatory reaction in the synovial membrane and subchondral bone, the cause of which is an increase in the amount of circulating lipopolysaccharides (LPS) of the bacterial wall, as well as provoke the development of metabolic syndrome, which links the two necessary components of the pathogenesis of OA. The result of direct exposure is the formation of leaky gut syndrome with the activation of LPS of the bacterial wall of mild inflammation, provoking the production of proinflammatory cytokines, the effect of which on synoviocytes and chondrocytes leads to their activation with subsequent production of IL-6 and IL-8, which contributes to the persistence of inflammation. By correlation analysis, the relationship of three taxa with OA joint damage was proved, namely, the order Desulfovibrionales and the genus Ruminiclostridium 5 – with knee joint OA, Methanobacteriaceae – with knee joint OA, and OA of any localization, and the appearance and degree of contamination with the genus Streptococcus correlated with the severity of pain syndrome. The metabolic syndrome itself can provoke the development of dysbiosis, so it can also be its consequence. A change in the composition of the microbiota in the form of the predominance of the genus Clostridium and the species Staphylococcus aureus with a decrease in the diversity of microorganisms is associated with an increase in the amount of adipose tissue in the body, dyslipidemia, insulin resistance with impaired carbohydrate metabolism. Low levels of LPS in the blood are found in obese patients even in the absence of an obvious focus of infection due to violations in the CMB, they signal TLR-4, triggering systemic inflammation. Studies have shown a positive effect of prescribing proand prebiotics on the course of OA, which makes IMB a promising target for the treatment and prevention of OA.

Protective role of forsythoside B in Kawasaki disease-induced cardiac injury: Inhibition of pyroptosis via the SIRT1–NF-κB–p65 signaling pathway

Kawasaki disease (KD), an acute exanthematous febrile pediatric illness involving systemic non-specific inflammatory reactions in small- and medium-sized arteries, poses a significant risk of coronary artery and myocardial inflammatory injury. Developing new KD treatments with improved safety and fewer side-effects is highly desirable. Forsythoside B (FTS-B), extracted from the Forsythia suspensa plant, exerts anti-inflammatory activity by inhibiting NF-κB, which is regulated by SIRT1, the reduced expression of which is strongly associated with cardiovascular disease. However, it has yet to be established whether FTS-B influences KD-related inflammatory damage. In this study, we investigated the effects of FTS-B on inflammation in cellular and murine models of KD. Our findings revealed that KD is associated with cardiac dysfunction and inflammatory injury to myocardial and human coronary artery endothelial cells (HCAECs), resulting in a pyroptosis-feedback loop. Both cellular and KD models were characterized by reduced SIRT1 expression and increased NF-κB p65 expression. Contrastingly, the rates of pyroptosis in both murine model myocardial tissues and HCAECs were significantly alleviated in response to FTS-B treatment. Also in both models, we detected an increase of SIRT1 expression and a decrease in the expression of p65. Further examination of the protective mechanism of FTS-B using the SIRT1-specific inhibitor, EX 527, revealed that this inhibitor blocked the palliative effects of FTS-B on inflammatory injury-induced pyroptosis. These results highlight the potential utility of the SIRT1–NF-κB–p65 pathway as a therapeutic target for KD treatment and demonstrate that FTS-B can alleviate KD-induced cardiac and HCAEC inflammatory injury via inhibition of pyroptosis.

Gastric foreign body granuloma resembling gastric cancer: a case report

Fishbones are frequently swallowed by foreign objects that can penetrate the gastrointestinal tract. Nonetheless, it is quite uncommon for these fishbones to become lodged within the tract, resulting in the formation of foreign body granulomas that resemble submucosal tumors. When encountering this situation, it's important to consider differential diagnoses such as gastric intestinal stromal tumor, gastric leiomyoma, and gastric neurofibroma. We present a case of gastric foreign body granuloma that presents with dull aching epigastric pain. The patient gave a vague history of displaced intrauterine contraceptive devices (IUCD). Contrast CT and PET scan showed a gastric antral mass possibly a gastric cancer or a migrating IUCD. Endoscopic ultrasound (EUS) suggested a perigastric foreign body reaction due to the presence of a linear echogenic structure in between the markedly thickened gastric antral wall and the right lobe of the liver. EUS-guided fine needle biopsy (EUS-FNB) revealed non-specific inflammatory reaction. Afterward, surgical exploration unveiled the cause of the mass as a foreign body granuloma caused by a perforating fishbone.

Клинические аспекты ведения пациентов с острой и хронической болью

Pain syndrome is one of the most common reasons to seek medical help. The paper considers an issue of pain syndrome in patients with various diseases. Various pathogenetic variants of dorsalgia development in the setting of inflammatory and degenerative-dystrophic changes are presented. The main biomechanical and biochemical processes associated with the pain syndrome are summarized. Several features of the course and therapeutic methods of the back pain syndrome associated with ankylosing spondylitis, osteoarthritis, as well as gouty and rheumatoid arthritis are considered. The paper outlines general principles of therapy for acute and chronic nociceptive pain syndromes. Medicinal and non-medicinal therapeutic methods are discussed. Since specific and non-specific inflammatory reactions represent a key pathogenetic mechanism in most of the reviewed cases of acute and chronic pain syndrome, anti-inflammatory drugs play a leading role in the condition therapy. We considered the possibility to use nonsteroidal anti-inflammatory drugs (NSAIDs) and B vitamins. KEYWORDS: back pain, osteoarthritis, ankylosing spondylitis, rheumatoid arthritis, chronic pain syndrome, acute pain syndrome. FOR CITATION: Barulin А.Е., Kurushina O.V., Puchkov A.E. Clinical aspects of management of patients with acute and chronic pain. Russian Medical Inquiry. 2024;8(10):576–581 (in Russ.). DOI: 10.32364/2587-6821-2024-8-10-5

Aptabinding of tumor necrosis factor-α (TNFα) inhibits its proinflammatory effects and alleviates islet inflammation.

Pancreatic islet cell transplantation (ICT) has emerged as an effective therapy for diabetic patients lacking endogenous insulin production. However, the islet graft function is compromised by a nonspecific inflammatory and thrombotic reaction known as the instant blood-meditated inflammatory reaction (IBMIR). Here, we report the characterization of four single-stranded DNA aptamers that bind specifically to TNFα - a pivotal cytokine that causes proinflammatory signaling during the IBMIR process - using single molecule binding analysis and functional assays as a means to assess the aptamers' ability to block TNFα activity and inhibiting the downstream proinflammatory gene expression in the islets. Our single-molecule fluorescence analyses of mono- and multivalent aptamers showed that they were able to bind effectively to TNFα with monoApt2 exhibiting the strongest binding (Kd ∼0.02±0.01nM), which is ∼3 orders of magnitude smaller than the Kd of the other aptamers. Furthermore, the in vitro cell viability analysis demonstrated an optimal and safe dosage of 100μM for monoApt2 compared to 50μM for monoApt1 and significant protection from proinflammatory cytokine-mediated cell death. More interestingly, monoApt2 reversed the upregulation of IBMIR mediating genes induced by TNFα in the human islets, and this was comparable to established TNFα antagonists. Both monoaptamers showed high specificity and selectivity for TNFα. Collectively, these findings suggest the potential use of aptamers as anti-inflammatory and localized immune-modulating agents for cellular transplant therapy.

Phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen worldwide

ABSTRACT Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

MORPHOLOGICAL CHANGES OF THE BLADDER WALL AS A RESULT OF THE ACTION OF EPIRUBICIN

Summary. Intravesical administration of chemopreparations is widely used in clinical practice and in experiments. However, there are practically no data on morphological changes during the action of chemotherapy drugs on the mucous membrane of the urinary bladder. Aim: to establish the patterns of morphological changes in the layers of the bladder wall during intravesical administration of epirubicin. Object and methods: the studies use white outbred rats (females, weight 200-250 g). Epirubicin was administered intravesically. Morphological changes of the bladder wall were assessed by light microscopy of fixed preparations of cells stained with hematoxylin and eosin after 2 hours; 3, 7 and 21 days after administration of the epirubicin. The obtained results were analyzed by the method of variational statistics. Results: the obtained data indicate significant disorders on the side of the bladder wall, namely atrophic changes and fibrosis of the submucosal base. Morphological changes indicated circulatory disorders in the vessels of the bladdemucous membrane and the submucosal base, which was accompanied by a significant nonspecific inflammatory reaction. Conclusions: obtained morphological and morphometric data indicate significant changes in the bladder wall of rats under the action of the chemotherapy drug epirubicin.

Delayed cerebrospinal fluid ascites following ventriculoperitoneal shunt

Background: Cerebrospinal fluid (CSF) ascites is an abnormal accumulation of CSF within the peritoneal cavity caused by the peritoneum's inability to absorb the CSF, following a ventriculoperitoneal (VP) shunt surgery. Excessive CSF production (e.g, choroid plexus papilloma and choroid plexus villous hypertrophy), high CSF protein secondary to chronic infection (e.g. tuberculosis), and brain tumours (e.g, optic gliomas and craniopharyngiomas) have all been suggested as contributing factors to the formation of CSF ascites. Peritoneal inflammation as a result of several shunt revisions or some non-specific inflammatory reaction to shunt material has also been explored.
 Case Presentation: A 3-year-old girl with lumbar myelomeningocele and delayed CSF ascites following VP shunt is reported. Therapeutic paracentesis was employed to relieve abdominal distension, although recurring accumulation was common. The VP shunt was removed and instead of a Ventriculo-atrial shunt, she underwent Endoscopic Third Ventriculostomy (ETV). CSF ascites gradually disappeared after ETV over a two-week period.
 Conclusions: Abdominal paracentesis to relieve ascites and conversion of a Ventriculoperitoneal shunt to a Ventriculo-atrial shunt are commonly used to treat CSF ascites, however Endoscopic Third Ventriculostomy, where feasible, is another alternative treatment that can be performed to treat this condition.

Reduction of Cancer-Induced Thrombocytosis as a Biomarker of Improved Outcomes in Advanced Gastric Cancer.

Background: Interplay between non-specific inflammatory reaction and tumor microenvironment in gastric cancer (GC) can be measured indirectly by assessing fluctuations in concentration of platelets. Cytotoxic chemotherapy affects these morphotic elements directly by inducing myelosuppression. It was hypothesized that chemotherapy not only directly affects malignant cells, but also through immunomodulation related to myelosuppression. Methods: Metastatic GC patients (N: 155) treated with chemotherapy +/− trastuzumab were enrolled in this retrospective study. Platelet pretreatment concentration (PLT-count) and the deepest level of platelet reduction, as well as other inflammatory and general confounders were collected in the first 12 weeks of treatment (PLT-red). Martingale residuals were used to visualize the relationship between PLT-count, PLT-red, and overall survival (OS). Multiple multivariate Cox regression models were built to assess the impact of platelet reduction on OS and progression-free survival (PFS). Results: Reduction of PLT (PLT-red) to 60% of baseline concentration was associated with improved survival rates (HR = 0.60, p = 0.026 for OS and HR 0.56, p = 0.015 for PFS). Cross-classification into four groups based on PLT-count (high vs low) and PLT-red (high vs low) showed significantly worse survival rates in both high PLT-count (HR = 3.60, p = 0.007 for OS and HR = 2.97, p = 0.024 for PFS) and low PLT-count (HR = 1.75, p = 0.035 for OS and HR = 1.80, p = 0.028 for PFS) patients with insufficient platelets reduction. Conclusion: Thrombocytosis reduction represents a novel, clinically important, prognostic factor for OS and PFS in patients with stage IV GC.

Nonspecific inflammatory reaction after implantation of palpebral implants

To identify the possible cause of an inflammatory reaction to a Russian-manufactured palpebral implant made of gold in the long term after surgery, and to determine the clinical and morphological changes in the tissues of the upper eyelid when the presence of the implant caused the inflammatory reaction. The results of 150 operations with placement of a palpebral implant were analyzed. In 12 cases, a nonspecific inflammatory reaction was revealed within 2 to 4 weeks after the operation, in 7 cases it necessitated explantation, in 5 cases the local long-term use of an ointment with a corticosteroid made it possible to avoid extrusion and explantation. Chemical microanalysis of the palpebral implant and fragments of the removed capsule was performed using scanning electron microscopy (SEM), as well as immunohistochemical (IHC), macro- and microscopic examination of the fragments of connective tissue capsule was carried out after removal of the palpebral implant. The obtained data confirm the chemical purity of the implant, the absence of abnormal accumulation of metals in the tissues of the eyelid. IHC, macro- and microscopic examination of the presented fragments of the connective tissue capsule revealed signs characteristic of an inflammatory reaction to a foreign body. Further research is needed to establish the factors and predictors for the development of inflammatory reactions to a foreign body and, in particular, to gold.

990. Fungal Malignant Otitis Externa: Clinical and Therapeutic Features

Abstract Background Fungal malignant otitis externa is a rare, but a serious infection that might lead to death if not promptly diagnosed and treated. We aimed to study the clinical, therapeutic and evolutionary features of fungal malignant otitis externa. Methods We conducted a retrospective study including all cases of fungal malignant otitis externa hospitalized in the infectious diseases department between 2003 and 2020. Results We included 35 patients with a mean age of 68±11 years. There were 18 males (51.4%). All patients were diabetics, and 7 patients had a previous medical history of otitis externa (20%). The use of topical corticosteroids was noted in 10 cases (28.5%). The revealing symptoms were otalgia (97.1%), otorrhea (82.9%) and cephalalgia (54.3%). Physical examination revealed tenderness to palpation of the mastoid bone in 21 cases (60%) and the temporomandibular joint in 16 cases (45.7%). Facial paralysis was noted in 14.3% of the cases. Otoscopic examination revealed stenosis of the external auditory canal (94.3%), granulation tissue (34.3%) and a polyp (31.4%). Candida species were isolated in 22 cases (62.8%) represented by Candida parapsilosis in 15 cases (42.8%) and Candida albicans in 5 cases (14.2%). Serological tests detecting Candida were positive in 12 cases (34.2%). Aspergillus species were isolated in 13 cases (37.1%) represented mainly by Aspergillus flavus in 7 cases (20%). Positive serology results for Aspergillus were noted in 8 cases (22.8%). A polyp or granulation tissue biopsy, performed in 12 cases (34.2%), revealed non-specific inflammatory reaction (28.5%) and the presence of fungal hyphae and spores (5.7%). After empirical antibiotics treatment, patients received fluconazole in 18 cases (51.4%) and voriconazole in 17 cases (48.6%). The median duration of treatment was 3 [1.5-12] months. Both surgery and hyperbaric oxygen therapy were indicated in one case (2.8%). Complications including the onset of contralateral otitis (14.3%) and endocranial extension (8.6%) were noted. The disease evolution was favorable in 65.7% of the cases. Four patients were dead (11.4%). Conclusion Involvement of fungal species in malignant otitis externa should be considered in front of the absence of improvement with antibiotic. Prompt treatment might prevent complications. Disclosures All Authors: No reported disclosures

Tre-P-23 - Papuloerythroderma of Ofuji successfully treated with oral retinoids

Papuloerythroderma of Ofuji (PEO) is a rare skin disorder, which affects predominantly older males with male to female ratio 4:1. It is characterized by pruritic erythematous papules, which might progress to erythroderma. Exanthema typically spares the skin folds (deck-chair sign). Common laboratory findings include lymphopenia, peripheral eosinophilia and elevated serum IgE. Histological image generally shows non-specific inflammatory reaction and needs to be correlated with clinical and laboratory findings. PEO has been associated with cutaneous T-cell lymphomas (CTCL). However, this relationship remains poorly understood. Diagnosis of PEO should be established by exclusion and PEO individuals should be closely monitored for possible onset of CTCL. Case 1: A 85-year-old man with a 2-year history of pruritic non-confluent erythematous papules sparing the skin folds. Lymphopenia, eosinophilia and elevated serum IgE. Histology shows edematous changes of papillary dermis with mixed inflammatory infiltrate comprising multiple mast cells, eosinophils as well as isolated plasma cells. The diagnosis of PEO was made based on the typical clinical, laboratory and histopathological features. Case 2: A 95-year-old man with a 3-month history of pruritic maculopapular exanthema. Indolent multiple myeloma has been diagnosed 4 years prior to rash onset. Histology shows a non-specific spongiotic dermatitis with multiple eosinophils. In this context, eosinophilia found in the laboratory work-up allows to establish probable diagnosis of PEO. Pathogenesis of PEO is poorly elucidated and development of effective treatment guidelines thus remains challenging. As skin-homing Th2/Th22 cells seem to play a role in the pathogenesis of PEO, use of dupilumab, monoclonal antibody against IL-4Rα, has recently been investigated. We report a successful resolution in two patients with PEO using combination therapy of oral retinoids (acitretin, 10 mg/d) and local treatment (topical corticosteroids, tacrolimus, polidocanol). Our findings correlate well with recent reports suggesting higher success rates of oral retinoids compared to PUVA therapy or oral corticosteroids, yet with a more favourable safety profile and patient tolerance. Papuloerythroderma of Ofuji (PEO) is a rare skin disorder, which affects predominantly older males with male to female ratio 4:1. It is characterized by pruritic erythematous papules, which might progress to erythroderma. Exanthema typically spares the skin folds (deck-chair sign). Common laboratory findings include lymphopenia, peripheral eosinophilia and elevated serum IgE. Histological image generally shows non-specific inflammatory reaction and needs to be correlated with clinical and laboratory findings. PEO has been associated with cutaneous T-cell lymphomas (CTCL). However, this relationship remains poorly understood. Diagnosis of PEO should be established by exclusion and PEO individuals should be closely monitored for possible onset of CTCL. A 85-year-old man with a 2-year history of pruritic non-confluent erythematous papules sparing the skin folds. Lymphopenia, eosinophilia and elevated serum IgE. Histology shows edematous changes of papillary dermis with mixed inflammatory infiltrate comprising multiple mast cells, eosinophils as well as isolated plasma cells. The diagnosis of PEO was made based on the typical clinical, laboratory and histopathological features. A 95-year-old man with a 3-month history of pruritic maculopapular exanthema. Indolent multiple myeloma has been diagnosed 4 years prior to rash onset. Histology shows a non-specific spongiotic dermatitis with multiple eosinophils. In this context, eosinophilia found in the laboratory work-up allows to establish probable diagnosis of PEO. Pathogenesis of PEO is poorly elucidated and development of effective treatment guidelines thus remains challenging. As skin-homing Th2/Th22 cells seem to play a role in the pathogenesis of PEO, use of dupilumab, monoclonal antibody against IL-4Rα, has recently been investigated. We report a successful resolution in two patients with PEO using combination therapy of oral retinoids (acitretin, 10 mg/d) and local treatment (topical corticosteroids, tacrolimus, polidocanol). Our findings correlate well with recent reports suggesting higher success rates of oral retinoids compared to PUVA therapy or oral corticosteroids, yet with a more favourable safety profile and patient tolerance.

IMMUNE STATUS OF PATIENTS WITH LUNG TUBERCULOSIS AND ALCOHOL CONSUMPTION

Tuberculosis is a great medical and social problem. An important risk factor for tuberculosis progress is the systematic use of alcohol. The relationship between alcohol intake and TB has been clear after numerous studies and meta-analyzes. However, there are still open questions about whether alcohol is the direct cause of TB development, which doses of alcohol have the greatest trigger value in progress of TB process, what kind of immunological reactions are significantly associated with alcohol intake and what immune background can determining role of alcohol in progression of TB infection. The features of the immune response in TB patients with different value of alcohol use remain poorly understood. The aim of the research - to investigate the immune status in patients with firstly diagnosed pulmonary tuberculosis with various levels of alcohol consumption. Materials and methods. We selected for participating in the study 102 males with tuberculosis and alcohol consumption. Examination of the patients included: clinical methods, chest X-ray, sputum tests, Alcohol Use Disorders Identification Test and immunological blood analysis. Results. Patients with tuberculosis and alcohol consumption, have increase inflammatory response: higher level of stab neutrophils, CRP, ESR, as well as phagocyte activity, circulating immune complexes levels and medium molecular weight peptides levels. On the other hand we found decreasing of phagocytic number, index of phagocytosis completeness and differentiation clusters CD2+, CD3+, CD4+, CD8+ of T-lymphocytes` sub-populations. The highest changes were observed in the group of alcohol abusers. Conclusions. Patients with tuberculosis and alcohol intake, even at low levels of its consumption, have a dysregulation of their immune response. On the one hand, there is an increase of non-specific inflammatory reactions, and on the other - a situation, when antigen-presenting cells cannot adequately to process and present the antigen to phagocytes. This prevents the immune system from responding quickly, correctly evaluating and suppressing foreign agents.

Therapeutic Effects of Baoxin Capsules in Combination with Trimetazidine Tablets on Type 2 Diabetes Complicated with Chronic Heart Failure

To evaluate the therapeutic effects of Baoxin’an capsules combined with trimetazidine tablets on type 2 diabetes with chronic heart failure. A total of 168 patients with type 2 diabetes complicated with chronic heart failure treated in our hospital from January 2016 to December 2017 were selected. They were randomly divided into two groups (n=84), both receiving diet control. On the basis of routine medication, the control group was given trimetazidine tablets. The observation group was administered with Baoxin’an capsules plus trimetazidine tablets. 30 d were employed as a course of treatment and the entire duration was 6 mo. The clinical symptoms, cardiac function classifications and the changes of plasma N-terminal pro–Btype natriuretic peptide and high-sensitivity C-reactive protein levels before and after treatment were compared. The overall effective rate of the observation group was 90.48 % which was significantly higher than that of the control group (73.81 %) (χ2=7.954, p=0.005). The increases in blood flow peak velocity ratio of left ventricular diastolic late phase to early phase, left ventricular ejection fraction, cardiac output and stroke volume of the observation group were significantly higher than those of the control group (p<0.05). After treatment, fasting plasma glucose, plasma pro–B-type natriuretic peptide and serum high-sensitivity C-reactive protein levels were significantly decreased (p<0.01). The above indices of the observation group were all significantly lower than those of the control group (p<0.05). After treatment, there were no obvious abnormal changes in routine blood, routine urine or liver and kidney function tests. Baoxin’an capsules in combination with trimetazidine tablets can inhibit non-specific inflammatory reaction of type 2 diabetes with chronic heart failure, alleviate myocardial damage and ventricular remodeling, improve cardiac function and enhance clinical therapeutic effects.

Патоморфологические изменения жизненно важных органов волжских рыб

The paper presents monitoring of pathological changes in the microstructure of cells and tissues of fish organs living in the lower reaches of the Volga River due to the need to identify the consequences of the environmental impact of oil and gas production enterprises located in the Astrakhan region. There have been revealed the research results of studying the state of some Volga fish species in modern conditions of their habitat. A histological analysis of the organs and tissues of pike, asp and perch was carried out. In the course of studies it was found out that all fish species studied, especially pike, had encapsulated helminthic cysts in the muscles, gills and intestines. In the fish kidneys there have been found signs of nonspecific inflammatory reactions (microcirculatory disorders, alteration and proliferation of tissues) with a predominance of dystrophic and necrotic phenomena. Fatty degeneration of varying degrees of development was detected in the liver of fish; in addition, there were observed growing connective tissues and microcirculation disorders. In all organs of the fish studied, especially in the liver, hemosiderosis was found. Epithelial proliferation and goblet cell hypertrophy were detected in the gills and intestines.

Diffusion-Weighted Image in Correlation with T2 Sequence as an Imaging Biomarker for Urinary Bladder Cancer

AbstractBackground: Recent functional diagnostic imaging tech-niques have emphasized the role and importance of MRI in pelvic organs imaging. Functional imaging by means of Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) and ADC value are now considered an essential part of the standard imaging protocols for evaluation of the pelvic organs.DWI depends on the fact that water molecules can diffuse freely in low cellular tissues, while increased cellularity restricts its diffusion, a phenomenon called 'Brownian motion'. Therefore, in cases of malignant lesions which have high cellularity, water diffusion is restricted and appear as bight lesions, in contrary to most benign tumors which have low cellularity.Aim of Study: To assess the diagnostic value of DWI in correlation with T2WI for preoperative urinary bladder tumor T-staging.Patients and Methods: This is a prospective study that included twenty-six patients with hematuria and suspicious urinary bladder mass lesion on ultrasonography, age ranged from 54 to 70 years old, 22 patients were male while 4 were female. The patients were referred from the Urology Clinics, Ain Shams University, before cystoscopy and initial biopsy confirmation. MRI examination with DWI and T2WI was performed at the Radiology Department of Ain Shams Uni-versity Hospital in a period of 6 months from January to June 2018.Results: In this study, 24 patients were confirmed to have urinary bladder cancer while one patient had nonspecific inflammatory reaction and another patient had infiltrating prostatic cancer. Regarding the detection of urinary bladder carcinoma the overall sensitivity, specificity, and accuracy using T2 images alone were 71.8, 73.2 and 72.4%, respectively, using DWI alone were 87.8, 87.8 and 88%, respectively and by using T2 plus DWI images were 87.8, 95.5 and 91.6%, respectively. The ADC value of 0.8 X 10–3mm2/sec was found to be a cut off value for differentiating low grade tumors (grade I-II) from high grade tumors (grade III) with sensitivity, specificity and accuracy of 71, 55.5 and 65% respectively. Conclusion: DWI has several advantages that can provide information regarding the lesion's size, number, location, local staging. The estimation of ADC value helps to predict the tumor nature and grade. The sensitivity and accuracy of DWI is higher when correlated with T2WI, which greatly help in guiding the surgeons performing conventional cystoscopy.

USE OF PLATELETS RICH PLASMA AS A FACTOR OF THE REDUCTION OF THE RISK OF EARLY POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH POSTOPERATIVE VENTRAL HERNIAS

Non-tensioned allohernioplasty with a polypropylene mesh implant has several disadvantages associated with the local occurrence of non-specific long-lasting inflammatory reactions in response to a foreign body. Excessive exudation in the implantation zone leads to the formation of seromas, requiring puncture aspiration, which significantly increases the treatment time. In the long-term, chronic prolonged inflammatory process leads to the formation of coarse connective tissue, which explains the development of biomechanical complications. Growth factors, introduced by platelet rich plasma (PRP), stimulate the release of regenerative cytokines, reduce local inflammatory manifestations in the integration of homoplastic grafts and reduce the incidence of postoperative complications. Aim: through the use of plasma enriched with platelets reduce the severity of early postoperative complications in patients with postoperative ventral hernias. Materials and methods. A clinical study was performed in the surgical department of the center for reconstructive and restorative medicine (university clinic) of the Odessa National Medical University (ONMedU) in the period from 2013 to 2019: 84 patients were operated because of postoperative ventral hernia. The average age of patients was 60.1±7.6 years. The size of hernial defects was on average 8.2 cm. The average BMI was 31.8 kg/m2. According to indications, patients underwent a standard surgical extent of intervention: hernia repair, allohernioplasty of the anterior abdominal wall with a lightweight (80 g/m2) polypropylene implant. After the plastics of the main group, a prosthesis implantation zone was infiltrated with activated autologous PRP, which was prepared by double centrifugation, in a volume of 14–38 ml. There was a control group in which PRP infiltration was not performed. The cavity above the mesh implant was actively drained by Redon for 2–4 days. An ultrasound examination was performed and, if necessary, fine needle aspiration of serous fluid over the mesh was done. Results. The evaluation of the postoperative period (up to 28 days) in patients of both groups. In none of the cases were manifestations of allergic, pyrogenic, local inflammatory or infectious complications. According to the quantitative assessment of early postoperative complications as well as the assessment of the degree of pain syndrome subjectively, according to VAS, the postoperative period in the main and control study groups was almost identical. The need for puncture aspirations and the total volume of discharge was significantly less in the main study group. The dependence of the severity of the effect of the proposed technology on such factors as the size of the hernial defect, the nature of plastics, and body mass index was noted. The greatest efficacy was demonstrated in the group of patients undergoing plastic surgery with the placement of a mesh implant in direct contact with subcutaneous fatty tissue for large-sized hernias (W2+) in the presence of concomitant obesity. Conclusions: the risk of development and the severity of fluid accumulations in the area of allohernioplasty can be predicted taking into account such risk factors as the size of the hernial defect, the nature of plastics, the presence of concomitant pathology, overweight. The technique of soft tissue infiltration in contact with a polypropylene prosthesis is safe, without significantly increasing the risk of local or systemic complications. The proposed method significantly reduces the risk of development and the severity of fluid accumulations in the area of implantation of the prosthesis. The effectiveness of technology is significantly higher compared to groups of patients with a high risk of seromas formation.

Layer-by-Layer Cerium Oxide Nanoparticle Coating for Antioxidant Protection of Encapsulated Beta Cells.

In type 1 diabetes, the replacement of the destroyed beta cells could restore physiological glucose regulation and eliminate the need for exogenous insulin. Immunoisolation of these foreign cellular transplants via biomaterial encapsulation is widely used to prevent graft rejection. While highly effective in blocking direct cell-to-cell contact, nonspecific inflammatory reactions to the implant lead to the overproduction of reactive oxygen species, which contribute to foreign body reaction and encapsulated cell loss. For antioxidant protection, cerium oxide nanoparticles (CONPs) are a self-renewable, ubiquitous, free radical scavenger currently explored in several biomedical applications. Herein, 2-12 alternating layers of CONP/alginate are assembled onto alginate microbeads containing beta cells using a layer-by-layer (LbL) technique. The resulting nanocomposite coatings demonstrate robust antioxidant activity. The degree of cytoprotection correlates with layer number, indicating tunable antioxidant protection. Coating of alginate beads with 12 layers of CONP/alginate provides complete protection to the entrapped beta cells from exposure to 100 × 10-6 m H2 O2 , with no significant changes in cellular metabolic activity, oxidant capacity, or insulin secretion dynamics, when compared to untreated controls. The flexibility of this LbL method, as well as its nanoscale profile, provides a versatile approach for imparting antioxidant protection to numerous biomedical implants, including beta cell transplantation.

Idiopathic inflammatory diseases of orbit and ocular adnexa: Histopathological and immunochemical analysis.

PurposeTo present histopathological and immunohistochemical analysis of idiopathic inflammatory diseases of orbit and ocular adnexa.Methods:Design- A retrospective laboratory-based study. The study was carried out in an ocular pathology laboratory in a tertiary institute of northeast India where analysis of 93 cases was done in 5 years, during the period from 2011 to 2016. Hematoxylin--eosin and special stains were done for the diagnoses. Immunohistochemistry (IHC) panel was also carried out. For infectious pathology, Grocott's methenamine silver (GMS) stain for fungus, tissue Gram's stain for bacteria's, and acid-fast stains for tubercular bacilli were done. IHC panels were done for CD 20 (B-cells), CD-3 (T-cells), CD-45 (Leukocyte common antigen, LCA), BCL-2, CD-138 (Plasma cells), Kappa, Lambda, IgG-4 in tissue, IgG-4 in serum, etc. IHCs were done using kit methods (standardized) and adequate controls were taken for each sample.Results:93 cases of nonspecific orbital inflammation were reported out of 1,467 specimens. Orbital pseudotumors (idiopathic orbital inflammatory disease, IOID) were seen in 27 cases (sclerosing variety-6); benign lymphoid hyperplasia in two cases; reactive lymphoid hyperplasia in 10 cases; atypical plasma lymphoproliferative reactive (polyclonal immunophenotypically, IgG4 negative) lesions in four cases; IgG-4 related disease in one case; nonspecific inflammatory reactions (conjunctiva, sclera, and lid) in 49 cases. In all the diagnoses, infections and lymphomas were excluded.Conclusion:Biopsy supported study on nonspecific orbital inflammation was important to know the pattern.