The Role of the Gut Microbiota in the Pathogenesis of Diabetes

Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.

IMMU-51. SINGLE-CELL ANALYSIS OF TUMOR-ASSOCIATED MICROGLIA AND MACROPHAGES FROM HUMAN GLIOBLASTOMA

Patients with glioblastoma, the most frequent and malignant primary brain tumor type, have a poor prognosis with a median survival of 14 months. A major therapeutic problem is chemoresistance. In surgically removed glioblastoma tissue, tumor-associated microglia and macrophages (TAMs) constitute up to 30 % of the total cells. TAMs are capable of secreting cytokines, chemokines and growth factors, thereby influencing the tumor microenvironment. However, the existence of different TAM subtypes and their role in glioblastoma is not fully comprehended and rarely considered therapeutically. This could explain why many glioblastoma clinical trials fail despite of promising preclinical results. This project aims to interrogate the existence and characteristics of different TAM subtypes in human glioblastoma biopsies in order to identify novel subpopulations and therapeutic targets. To study the heterogeneity in TAMs, CD11b+ cells were isolated from glioblastoma patient′s tissue, and single-cell RNA sequencing was performed using the 10X Genomics Chromium platform for single-cell generation and an Illumina NovaSeq6000 system for sequencing. We have sequenced TAMs from three glioblastomas and CD11b+ cells from brain tissue adjacent to two brain metastases samples. In the filtered data set of almost 71,000 CD11b+ cells, we were able to identify recently described TAM populations, such as an interferon-induced, a phagocytic, a hypoxic and a proliferating subset. Interestingly, we also discovered potential novel TAM subsets, such as a pro-angiogenic subset. We have detected a TAM population which is more complex than the established M1 and M2 phenotypes, constituting novel TAM subsets. We are currently investigating these findings to validate specific markers associated with these subpopulations, and for the identification of novel clinically relevant targets.

The use of Jelonet dressings in the treatment of drug toxicity in autologous stem cell transplantation in children. Clinical case presentation

One of the complications arising at the stage of hematopoietic stem cell transplantation (HSCT) is skin lesions. This complication is quite common and represents an important diagnostic and therapeutic problem. The main cause of skin lesions in HSCT is drug toxicity, but also infectious lesions. Each of the complications can manifest itself in varying degrees, as well as be combined with others, having a significant negative effect on the patient’s condition, in severe cases posing a threat to the patient’s life. This paper presents a clinical case of a patient with treosulfan toxicoderma who was treated with JELONET dressings.

Comparative efficacy of intralesional verapamil hydrochloride, triamcinolone acetonide and combination of both drug in hypertrophic scars and keloids at tertiary care center

Background: Keloids and hypertrophic scars are still a therapeutic problem. Despite numerous proposed therapies reported in the literature, the management of keloid and hypertrophic scars is still challenging as there is no universally accepted treatment regimen. Compare the efficacy intralesional verapamil hydrochloride and triamcinolone acetonide separately as well as combination of both drug in treatment of hypertrophic scars and keloids.Methods: A retrospective study was carried out at the general surgery department (plastic surgery unit) at the JNUIMSRC Jaipur, Rajasthan. Total of 150 patients (60 males and 90 females) between 18 to 60 years of age were enrolled fulfilling the inclusion criteria. They were randomly categorized in to three groups (group A, B and C), based on treatment they received viz. verapamil alone, triamcinolone alone and combination of both drugs respectively. Assessment of the scars were done prior to or on the day of the first injection and at 24 weeks after the end of injection scheme by Vancouver scar scale (VSS). The decreasing values reflected clinical improvement of the scar.Results: Better improvement observed in all four parameters: height, vascularity, pliability and pigmentation among patients receiving combination of both triamcinolone-verapamil drugs as compare to those patients receiving drugs separately either verapamil or triamcinolone alone. For parameters height, pliability and pigmentation, the improvement was found to be statistically significant (p<0.05)Conclusions: Study highlights that the combined verapamil and triamcinolone therapy scheme causes remarkable scar improvement in keloid and hypertrophic scars in comparison to single drug scheme.

Nonwoven Releasing Propolis as a Potential New Wound Healing Method—A Review

Wound healing poses a serious therapeutic problem. Methods which accelerate tissue regeneration and minimize or eliminate complications are constantly being sought. This paper is aimed at evaluation of the potential use of biodegradable polymer nonwovens releasing propolis as wound healing dressings, based on the literature data. Propolis is honeybee product with antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, analgesic, and regenerative properties. Controlled release of this substance throughout the healing should promote healing process, reduce the risk of wound infection, and improve aesthetic effect. The use of biodegradable aliphatic polyesters and polyester carbonates as a propolis carrier eliminates the problem of local drug administration and dressing changes. Well-known degradation processes and kinetics of the active substance release allows the selection of the material composition appropriate to the therapy. The electrospinning method allows the production of nonwovens that protect the wound against mechanical damage. Moreover, this processing technique enables adjusting product properties by modifying the production parameters. It can be concluded that biodegradable polymer dressings, releasing a propolis, may find potential application in the treatment of complicated wounds, as they may increase the effectiveness of treatment, as well as improve the patient’s life quality.

Insula activity in resting-state differentiates bipolar from unipolar depression: a systematic review and meta-analysis

Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.

Therapy of Type 2 Diabetes in Patients with SARS-CoV-2 Infection

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.

CONSEQUENCES OF LATE DIAGNOSIS OF LYMPHOMAS IN CHILDREN

Lymphoma is the third leading cause of malignant neoplasms (MNs) in children. Childhood lymphoma is characterized by the prevalence of highly aggressive variants with high proliferation activity and rapid tumor dissimilation. Prolonged diagnosis becomes a reason of advanced-stage therapy. Despite the good results of long-term survival rate in patients, exceeding 90% even with late (III-IV) stages of lymphomas, the persistence of pathogenic (including multi-drug resistant) microorganisms in the patient's body becomes a major therapeutic problem, contamination of which occurs during the patient's stay in various medical organizations at the stage of diagnostics. The case reports of fatal infectious complications with the development of sepsis caused by polyresistant microorganisms in 2 children with anaplastic large cell lymphoma stage IV are presented in this article. Both case reports are unfavourable, despite the use of all medications and effective treatments. The analysis of diagnostic errors and necessity of cancer alarm generation in medical staff and patients' parents will make it possible to reduce the duration of diagnosis and probability of contamination of patient’s body with multi-resistant flora.

Evaluation of the Potential Diagnostic Utility of the Determination of Selected Caspases—Markers Involved in the Regulation of Apoptosis—In Patients with Ovarian Cancer

Ovarian cancer remains a major diagnostic and therapeutic problem in modern gynecological oncology. For this reason, research which focuses on the search for new diagnostic markers and the assessment of their possible usefulness in clinical practice is still being conducted. The aim of this study was to evaluate serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer. Patients with ovarian serous cystadenoma (Cystadenoma serosum) and papillary serous cystadenocarcinoma (Cystadenocarcinoma papillare serosum IIIC) were included in the study, as well as healthy women who constituted the control group. The results of the study revealed a statistically significantly decreased mean serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer as compared to the control group (p ˂ 0.001), which indicates the involvement of the studied parameters in immune system disturbances occurring in the process of apoptosis by the extrinsic and intrinsic pathway and may be one of the mechanisms of immunosuppression accompanying these tumors. Determination of serum levels of examined caspases and CA 125 antigen in women with ovarian cancer in combination with other markers may prove useful in the future in the diagnosis of ovarian cancer, but this requires further studies.