An improvement of body surface area formulas using the 3D scanning technique.

OBJECTIVES: Body surface area (BSA) is one of the major parameters used in several medical fields. However, there are concerns raised about its usefulness, mostly due to the ambiguity of its estimation. MATERIAL AND METHODS: Authors have conducted a voluntary study to investigate BSA distribution and estimation in a group of 179 adult people of various sex, age, and physique. Here, there is provided an extended analysis of the majority of known BSA formulas. Furthermore, it was supplement with a comparison with the authors' propositions of enhanced formulas coefficients for known formulas models as well as with new power models based on an increased number of anthropometric data. RESULTS: Introduction of the enhanced formulas coefficients cause a reduction of at least 30.5% in mean absolute error and 21.1% in maximum error in comparison with their known counterparts. CONCLUSIONS: In the context of the analysis presented it can be stated that the development of a single universal body surface area formula, based on a small number of state variables, is not possible. Therefore, it is necessary and justified to search for new estimation models that allow for quick and accurate calculation of body surface area for the entire population, regardless of individual body variations. The new formulas presented are such an alternative, which achieves better results than the previously known methods. Int J Occup Med Environ Health. 2024;37(2):205-19.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.

Intradialytic Tolerance and Recovery Time in Different High-Efficiency Hemodialysis Modalities.

There are several forms of maintenance high-efficiency hemodialysis (HD), including hemodiafiltrations (HDF) in different technical modes and expanded HD, using dialyzers with medium cut-off membranes. The aim of the study was to assess the intradialytic tolerance and length of dialysis recovery time (DRT) in these modalities. This is an exploratory, crossover study in maintenance HD patients with low comorbidity and no clinical indications for the use of high-efficiency HD, who were exposed to five intermittent dialyses in random order: high-flux hemodialysis (S-HD), expanded HD (HDx), pre-dilution HDF (PRE-HDF), mix-dilution HDF (MIX-HDF) and post-dilution HDF (POST-HDF). Twenty-four dialysis sessions of each method were included in the analysis. Dialysis parameters, including blood flow rate, dialysis fluid flow rate and temperature, and pharmacological treatment were constant. Average total convection volume for post-HDF, pre-HDF and mix-HDF were 25.6 (3.8), 61.5 (7.2) and 47.1 (11.4) L, respectively. During all therapies, patients were monitored for the similarity of their hydration statuses using bioimpedance spectroscopy, and for similar variability over time in systemic blood pressure and cardiac output, while peripheral resistance was monitored using impedance cardiography. The lowest frequency of all intradialytic adverse events were observed during HDx. Delayed DRT was the shortest during PRE-HDF. Patients were also more likely to report immediate recovery while receiving PRE-HDF. These differences did not reach statistical significance; however, the study results suggest that intradialytic tolerance and DRT may depend on the dialysis method used. This supports the need of taking into account patient preferences and quality of life while individualizing high-efficiency therapy in HD patients.

Cardiovascular risk factors among Polish employees of uniformed services.

OBJECTIVES: Employees of uniformed services (EoUS) were screened for cardiovascular risk factors. MATERIAL AND METHODS: A total of 1138 EoUS (age M±SD 49.9±6.0 years) and 263 controls (age M±SD 54.4±9.7 years) under the care of the cardiology clinic in Gdansk, Poland, were included in the study. Medical history and blood samples were collected, and a physical examination was performed. Ten-year cardiovascular risk of death was calculated using the systematic coronary risk evaluation (SCORE) risk algorithm for high-risk countries. RESULTS: Significantly higher values of mean systolic and mean diastolic blood pressure, mean total cholesterol level and mean BMI were recorded among the EoUS compared to controls (M±SD 141.7±11.6 mm Hg vs. 135.5±11.0 mm Hg, p < 0.001; 90.1±5.9 mm Hg vs. 84.5±6.8 mm Hg, p < 0.001; 6.01±0.76 mmol vs. 5.44±0.87 mmol, p < 0.001; 29.3±4.7 vs. 29.0±4.1, p < 0.001, respectively). Smoking cigarettes was most frequently reported by the youngest group (20-39 years old) - 47.7% and it was significantly higher in the entire EoUS group compared to control group (35.5% vs. 16.7%, p = 0.001). The occurrence of observed risk factors (blood pressure ≥140/90 mm Hg, total cholesterol concentration >5 mmol, smoking,) was significantly higher among EoUS compared to controls (92.1% vs. 57.8%, p < 0.001; 89.0% vs. 66.9%, p < 0.001; 35.5% vs. 16.7%, p < 0.001, respectively). In the male group, the mean calculated ten-year risk of fatal cardiovascular events, the percentage of high calculated risk, and very high risk were higher in the EoUS group compared to controls (M±SD 4.44±3.49 vs. 4.23±3.86, p = 0.001; 23.7% vs. 20.2%, p = 0.007; 7.4% vs. 6.5%, p = 0.03, respectively). CONCLUSIONS: The prevalence of all identified risk factors was found to be higher among employees of uniformed services when compared to the control group. The presence of these risk factors within the population of uniformed service employees results in a greater risk of mortality from cardiovascular diseases. Int J Occup Med Environ Health. 2023;36(5):656-71.

Molecular signature of renal cell carcinoma by means of a multiplatform metabolomics analysis.

Renal cell carcinoma (RCC) is a disease with no specific diagnostic method or treatment. Thus, the evaluation of novel diagnostic tools or treatment possibilities is essential. In this study, a multiplatform untargeted metabolomics analysis of urine was applied to search for a metabolic pattern specific for RCC, which could enable comprehensive assessment of its biochemical background. Thirty patients with diagnosed RCC and 29 healthy volunteers were involved in the first stage of the study. Initially, the utility of the application of the selected approach was checked for RCC with no differentiation for cancer subtypes. In the second stage, this approach was used to study clear cell renal cell carcinoma (ccRCC) in 38 ccRCC patients and 38 healthy volunteers. Three complementary analytical platforms were used: reversed-phase liquid chromatography coupled with time-of-flight mass spectrometry (RP-HPLC-TOF/MS), capillary electrophoresis coupled with time-of-flight mass spectrometry (CE-TOF/MS), and gas chromatography triple quadrupole mass spectrometry (GC-QqQ/MS). As a result of urine sample analyses, two panels of metabolites specific for RCC and ccRCC were selected. Disruptions in amino acid, lipid, purine, and pyrimidine metabolism, the TCA cycle and energetic processes were observed. The most interesting differences were observed for modified nucleosides. This is the first time that the levels of these compounds were found to be changed in RCC and ccRCC patients, providing a framework for further studies. Moreover, the application of the CE-MS technique enabled the determination of statistically significant changes in symmetric dimethylarginine (SDMA) in RCC.

Non-invasive haemodynamic assessments among hypertensive patients in a routine family doctor's office.

INTRODUCTION AND OBJECTIVE: Difficult-to-control blood pressure can be attributed to a mismatch between the haemodynamic type of hypertension and the drug class used in treatment. Impedance cardiography may be a useful tool for enabling the individualization of antihypertensive therapy. The aim was to investigate the distribution of haemodynamic types of HT among hypertensive patients in an outpatient clinic. MATERIAL AND METHODS: This was a prospective, observational study of patients with primary hypertension at an outpatient clinic. A 10-minute ICG examination was performed in 189 consecutive, patients (118 men and 71 women). Patients were divided into groups based on whether their hypertension was well-controlled (140/90 mmHg, n=95). They were also stratified according to haemodynamic states. RESULTS: Patients with poorly controlled blood pressure compared to patients with well controlled blood pressure had a high haemodynamic output in 6.3% vs. 2.1% (p=0.153), and high vascular resistance in 41.1% vs. 27.7% (p=0.037), and balanced haemodynamic states in 52.6% vs. 70.2% (0 80 beats/min) and fluid retention (p<0.01). CONCLUSIONS: Half of the examined patients did not achieve the therapeutic goals for hypertension treatment. Differences in haemodynamic state of well and poor controlled hypertension groups suggests the usefulness of impedance cardiography-targeted hypertension treatment.

Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial.

AIMS: Monotherapy with autologous expanded CD4+ CD25high CD127- T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent-onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown. MATERIALS AND METHODS: We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months. RESULTS: At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%. CONCLUSIONS: Over 2 years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C-peptide levels and the maintenance of remission.

Mesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity.

Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs' potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.

Effects of an outpatient intervention comprising nurse-led non-invasive assessments, telemedicine support and remote cardiologists' decisions in patients with heart failure (AMULET study): a randomised controlled trial.

AIM: Prevention of heart failure (HF) hospitalisations and deaths constitutes a major therapeutic aim in patients with HF. The role of telemedicine in this context remains equivocal. We investigated whether an outpatient telecare based on nurse-led non-invasive assessments supporting remote therapeutic decisions (AMULET telecare) could improve clinical outcomes in patients after an episode of acute HF during 12-month follow-up. METHODS AND RESULTS: In this prospective randomised controlled trial, patients with HF and left ventricular ejection fraction (LVEF) ≤49%, after an episode of acute HF within the last 6 months, were randomly assigned to receive either an outpatient telecare based on nurse-led non-invasive assessments (n = 300) (AMULET model) or standard care (n = 305). The primary composite outcome of unplanned HF hospitalisation or cardiovascular death occurred in 51 (17.1%) patients in the telecare group and 73 (23.9%) patients in the standard care group up to 12 months after randomization [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.99; P = 0.044]. The implementation of AMULET telecare, as compared to standard care, reduced the risk of first unplanned HF hospitalisation (HR 0.62, 95% CI 0.42-0.91; P = 0.015) as well as the risk of total unplanned HF hospitalisations (HR 0.64, 95% CI 0.41-0.99; P = 0.044).There was no difference in cardiovascular mortality between the study groups (HR 1.03, 95% CI 0.54-1.67; P = 0.930). CONCLUSIONS: AMULET telecare as compared to standard care significantly reduced the risk of HF hospitalisation or cardiovascular death during 12-month follow-up among patients with HF and LVEF ≤49% after an episode of acute HF.

Noninvasive Bioimpedance Methods From the Viewpoint of Remote Monitoring in Heart Failure.

Heart failure (HF) is a major clinical, social, and economic problem. In view of the important role of fluid overload in the pathogenesis of HF exacerbation, early detection of fluid retention is of key importance in preventing emergency admissions for this reason. However, tools for monitoring volume status that could be widely used in the home setting are still missing. The physical properties of human tissues allow for the use of impedance-based noninvasive methods, whose different modifications are studied in patients with HF for the assessment of body hydration. The aim of this paper is to present the current state of knowledge on the possible applications of these methods for remote (home-based) monitoring of patients with HF.

Rationale and design of the AMULET study: A new Model of telemedical care in patients with heart failure.

AIMS: Heart failure (HF) is characterized by high mortality and hospital readmission rates. Limited access to cardiologists restricts the application of guideline-directed, patient-tailored medical therapy. Some telemedicine solutions and novel non-invasive diagnostic tools may facilitate real-time detection of early HF decompensation symptoms, prompt initiation of appropriate treatment, and optimal management of medical resources. We describe the rationale and design of the AMULET trial, which investigates the effect of comprehensive outpatient intervention, based on individualized haemodynamic assessment and teleconsultations, on cardiovascular mortality and unplanned hospitalizations in HF patients. METHODS AND RESULTS: The AMULET trial is a multicentre, prospective, randomized, open-label, and controlled parallel group trial (ClinicalTrials.gov Identifier: NCT03476590). Six hundred and five eligible patients with HF (left ventricular ejection fraction ≤49%, at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment) were randomly assigned in a 1:1 ratio to either an intervention group or a standard care group. The planned follow-up is 12 months. The AMULET interventions are performed in ambulatory care points operated by nurses, with the remote support of cardiologists. The comprehensive clinical evaluation comprises measurements of heart rate, blood pressure, body mass, thoracic fluid content, and total body water. A recommendation support module based on these objective parameters is implemented in remote therapeutic decision-making. The primary complex endpoints are cardiovascular mortality and unplanned HF hospitalization. CONCLUSIONS: The AMULET trial will provide a prospective assessment of the effect of comprehensive ambulatory intervention, based on telemedicine and haemodynamically guided therapy, on mortality and readmissions in HF patients.

Nurse-led ambulatory care supported by non-invasive haemodynamic assessment after acute heart failure decompensation.

Heart failure (HF) is characterized by frequent decompensation and an unpredictable trajectory. To prevent early hospital readmission, coordinated discharge planning and individual therapeutic approach are recommended. AIMS: We aimed to assess the effect of 1 month of ambulatory care, led by nurses and supported by non-invasive haemodynamic assessment, on the functional status, well-being, and haemodynamic status of patients post-acute HF decompensation. METHODS AND RESULTS: This study had a multicentre, prospective, and observational design and included patients with at least one hospitalization due to acute HF decompensation within 6 months prior to enrolment. The 1 month ambulatory care included three visits led by a nurse when the haemodynamic state of each patient was assessed non-invasively by impedance cardiography, including thoracic fluid content assessment. The pharmacotherapy was modified basing on haemodynamic assessment. Sixty eight of 73 recruited patients (median age = 67 years; median left ventricular ejection fraction = 30%) finished 1 month follow-up. A significant improvement was observed in both the patients' functional status as defined by New York Heart Association class (P = 0.013) and sense of well-being as evaluated by a visual analogue score (P = 0.002). The detailed patients' assessment on subsequent visits resulted in changes of pharmacotherapy in a significant percentage of patients (Visit 2 = 39% and Visit 3 = 44%). CONCLUSIONS: The proposed model of nurse-led ambulatory care for patients after acute HF decompensation, with consequent assessment of the haemodynamic profile, resulted in: (i) improvement in the functional status, (ii) improvement in the well-being, and (iii) high rate of pharmacotherapy modifications.

The non-invasive evaluation of heart function in patients with an acute myocardial infarction: The role of impedance cardiography.

BACKGROUND: The purpose of this study was to analyze hemodynamic changes in patients treated with percutaneous coronary intervention (PCI) at an early stage of acute myocardial infarction (AMI) and at 1-month follow-up. METHODS: Patients with AMI (n = 27) who underwent PCI were analyzed using impedance cardiography (ICG). ICG data were collected continuously (beat by beat) during the whole PCI procedure and thereafter at every 60 s for the next 24 h. Blood pressure was taken every 10 min and stored for analysis. Additionally the following parameters were measured: cardiac index (CI), stroke volume index (SVi), left cardiac work index (LCWi), contractility index (CTi), ventricular ejection time (VET), systemic vascular resistance index (SVRi), thoracic fluid content index (TFCi) and heart rate (HR). RESULTS: In the first 24 h after PCI all the contractility parameters including CI, SVi, LCWi, CTi and VET significantly decreased, whereas HR, SVRi and TFCi increased compared to baseline. All of the parameters examined got normalized at 1 month. The CI, SVi, LCWi, CTi, SVRi did not significantly differ from baseline, however the HR and VET were significantly lower compared to first day after PCI CONCLUSIONS: Cardiac performance deteriorates early after PCI and normalizes after 1 month in patients with an AMI. ICG is useful for hemodynamic monitoring of AMI patients during and after invasive therapy.

GC-MS-based untargeted metabolomics of plasma and urine to evaluate metabolic changes in prostate cancer.

Prostate cancer (CaP) is a common cancer in men. Its late detection and inefficient diagnosis are a challenge for researchers who are currently searching for new cancer-related indicators that would facilitate better detectability of CaP and explain its pathogenesis. In the present preliminary study, endogenous volatile metabolites were detected in plasma and urine samples by using the metabolic fingerprinting approach. The analyses were performed using the GC-QqQ/MS technique in the scan mode. The detected and putatively identified metabolites were statistically analyzed using advanced univariate and multivariate statistical methods. Eleven urinary and three plasma metabolites were selected as statistically significant in patients with CaP as compared to those in healthy controls. Supervised methods such as logistic regression and quadratic support vector machine were applied to obtain the classification models. The accuracy, sensitivity, and specificity of the models were above 83%, 85%, and 81%, respectively. The putatively identified metabolites were associated with biochemical pathways such as tricarboxylic acid cycle, glycolysis, carbohydrate conversion, and steroidal lipid metabolism that are mainly involved in energy production for cell growth and proliferation.

Non-invasive assessment of haemodynamic parameters in patients after Fontan procedure.

INTRODUCTION AND OBJECTIVE: Single ventricle anomaly is one of the complex congenital heart defects. A dependable non-invasive method of evaluation of Fontan circulation haemodynamics for early diagnosing unstable patients is hardly available in routine clinical practice. The aim of the study is non-invasive evaluation of the haemodynamic parameters in patients after Fontan operation. MATERIAL AND METHODS: The study involved 11 participants (age 24.4±4.3 years) with functionally univentricular hearts after Fontan operation. Evaluation of haemodynamic parameters was performed in supine and sitting positions using the impedance cardiography method. RESULTS: In comparative analysis, heart rate (70.1 vs.78.3 1/min; p=0.001), diastolic blood pressure (73.9 vs. 76.7 mm Hg; p=0.026), mean arterial blood pressure (84.5 vs. 88.0 mm Hg; p=0.013), systemic vascular resistance (1284.8 vs. 1334.9 dyn*s*cm-5; p=0.024), systemic vascular resistance index (2178.7 vs. 2272.8 dyn*s*cm-5*m2 ; p=0.018), pre-ejection period (124.2 vs. 136.2 ms; p=0.009), systolic time ratio (0.43 vs. 0.53; p=0.0001), and Zo (26.2 vs. 28.7 Ω; p<0.00001), were significantly higher in the sitting position. Stroke volume (75.4 vs. 68.5 ml; p=0.013), stroke index (42.7 vs. 39.0 ml*m-2; p=0.014), thoracic fluid content (38.5 vs. 35.4 1*kΩ-1; p=<0.00001), thoracic fluid content index (22.8 vs. 21.0 1*kΩ-1*m-2; p=<0.00001), and leftventricular ejection time 291.1 vs. 260.1 ms; p <0.00001, were significantly higher in the supine position. CONCLUSIONS: In patients after Fontan procedure, impedance cardiography can be a useful tool the assessment of shortterm haemodynamic changes provoked by postural changes. Its clinical value in patients with congenital heart defects should be further investigated.

Cardiovascular testing of seasickness in healthy volunteers on life rafts.

OBJECTIVES: The role of the cardiovascular system in the development of seasickness remains uncertain. MATERIAL AND METHODS: Overall, 18 healthy students (10 males and 8 females) aged 18-24 years volunteered in the project, spending 2-7 h on life rafts. The cardiovascular system was examined with impedance cardiography. Susceptibility and symptoms of seasickness were evaluated by the Motion Sickness Susceptibility Questionnaire Shortform (MSSQ-Short) and the Motion Sickness Assessment Questionnaire (MSAQ). The Visual Analogue Scale (VAS), ranging 0-10, was used to assess nausea, dizziness and mood. The parameters were assessed at 2 time points. RESULTS: Differences in the heart rate (HR), the thoracic fluid content index (TFCI), the stroke index (SI) and the Heather index (HI) before launching the life rafts and after leaving them were observed (78.6, 20.8, 55.6 and 15.9 vs. 70.1, 19.7, 60.5 and 17.9, with p-values of 0.002, <0.001, 0.003 and 0.004, respectively). Females reacted with changes in SI and HR more vividly, whereas males regulated more HI and TFCI. In addition, HR correlated significantly with the central and peripheral symptoms in MSAQ, stroke volume (SV) with peripheral and sopite-related ones, SI with overall ones, and pulse pressure with overall, gastrointestinal and central ones (Spearman's rank correlation coefficient [ρ] was -0.478, -0.711, 0.476, 0.472, 0.525, -0.476, -0.579 and -0.584, respectively). As regards MSSQ-Short, it correlated negatively with sopite-related symptoms in MSAQ (ρ= -0.486). Mood in VAS correlated significantly with gastrointestinal symptoms, SI and the cardiac index (CI) (ρ = -0.752, -0.492 and -0.489, respectively). CONCLUSIONS: It was found that HR correlated negatively, and SV/SI correlated positively, with the severity of seasickness symptoms measured with MSAQ. Gender is probably an independent factor influencing reactions to motion. Women react with SI increase whereas men react with increased heart contractility (HI rise). Negative mood in seasickness evaluated with VAS seems to be mostly determined by gastrointestinal symptoms assessed with MSAQ and diminished cardiovascular indices (both CI and SI). Int J Occup Med Environ Health. 2020;33(4):467-77.

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy.

OBJECTIVE: Here we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets. RESEARCH DESIGN AND METHODS: We compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs. RESULTS: Patients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vß/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures. CONCLUSIONS: T1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs. TRIAL REGISTRATION NUMBER: EudraCT 2014-004319-35.