Clinical and epidemiological features of Lyme neuroborreliosis in adults and factors associated with polyradiculitis, facial palsy and encephalitis or myelitis.

The clinical course of Lyme neuroborreliosis (LNB) is highly variable. Delayed diagnosis and treatment still remain actual challenges. Moreover, there is a lack of studies analyzing the factors associated with different LNB syndromes. We aimed to analyze clinical and epidemiological features of LNB in hospitalized adults in eastern Lithuania. A retrospective study was performed for patients presenting in the years 2010-2021. A total of 103 patients were included in the study, 100 with early, and three with late LNB. Patients with early LNB most often presented polyradiculitis [75/100, (75%)], which was also the most common initial neurological syndrome. Peripheral facial palsy was diagnosed in 53/100 (53%) patients, in 16/53 (30.2%) cases both facial nerves were affected. Encephalitis or myelitis was diagnosed in 14% of patients with LNB. A total of 76/103 (73.8%) patients were discharged with residual symptoms or signs. One patient presenting encephalomyelitis died because of bacterial complications. The absence of observed erythema migrans (EM) was the predictor of peripheral facial palsy, while female sex and EM untreated with antibiotics were predictors of isolated polyradiculitis. A fever of ≥ 38 ° °C and pleocytosis of ≥ 300 × 106/l were associated with the development of encephalitis or myelitis in patients with early LNB.

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis.

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes)-blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

Impact of Immunonutrition on T Cell Activation: A Randomized Control Study in Cardiac Surgery Patients.

Background: Cardiac surgery provokes an intense inflammatory response that can cause an immunosuppressive state and adverse postoperative outcomes. We recently showed that postoperative immunonutrition with glutamine in "fragile" low-risk cardiac surgery patients was associated with a significantly increased level of CD3+ and CD4+ T cells. In order to clarify the biological relevance and clinical importance of these findings, we investigated whether an increase in the CD4+ T cell level was caused by changes in the systemic inflammatory response (caused by surgery or infection) and if it was associated with their activation status. Methods: A randomized control study of low operative risk but "fragile" cardiac surgery patients was performed. Patients were randomized into immunonutrition (IN) and control groups (C). The IN group received normal daily meals plus special immune nutrients for 5 days postoperatively, while the C group received only normal daily meals. Laboratory parameters were investigated before surgery and on the sixth postoperative day and the groups were compared accordingly. The expression of the CD69+ marker was investigated to determine T cell activation status. Serum concentrations of cytokines (interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and C-reactive protein (CRP) were determined to assess the systemic inflammatory response, while procalcitonin (PCT) levels were evaluated to confirm or deny possible bacterial infection. Results: Fifty-five patients were enrolled in the study. Twenty-seven (49.1%) were randomized in the IN group. Results show that on the sixth postoperative day, the CD4+CD69+ and CD8+CD69+ counts did not differ between the IN and C groups, accordingly 0.25 [0.16-0.50] vs 0.22 [0.13-0.41], p=0.578 and 0.13 [0.06-0.3] vs 0.09 [0.05-0.14], p=0.178. Also, statistically significant differences were not observed in the cytokine levels (IN and C groups: TNF-α 8.13 [7.32-10.31] vs 8.78 [7.65-11.2], p=0.300; IL-6 14.65 [9.28-18.95] vs 12.25 [8.55-22.50], p=0.786; IL-10 5.0 [5.0-5.0] vs 5.0 [5.0-5.0], p=0.343 respectively), which imply that an elevated T cell count is not associated with the systemic inflammatory response. Also, PCT (IN and C groups: 0.03 [0.01-0.09] vs 0.05 [0.03-0.08], p=0.352) and CRP (IN and C groups 62.7 [34.2-106.0] vs 63.7 [32.9-91.0], p=0.840) levels did not differ between the two groups. Moreover, low levels of PCT indicated that the increase in T cell count was not determined by bacterial infection. Conclusions: Our findings showed that CD4+ T cell levels were associated with neither the systemic inflammatory response nor bacterial infection. Secondly, increases in T cells are not accompanied by their activation status. These results suggest a hypothesis that a higher postoperative T cell concentration may be associated with postoperative immunonutrition in low-risk cardiac surgery patients with intact cellular vitality, i.e. "fragile". However, immunonutrition alone did not affect T cell activation status.

The efficacy of early postoperative enteral immunonutrition on T-lymphocyte count: A randomised control study in low-risk cardiac surgery patients.

BACKGROUND: Patients undergoing cardiac surgery have a pronounced immune response that leads to a reduction in cellular immunity. Immune-modulating nutritional supplements are considered to be beneficial for patients undergoing major surgery. However, due to the lack of studies in the cardiac surgery population, the effect of immunonutrition remains unclear in this patient group. OBJECTIVE: Our purpose was to research the efficacy of early postoperative enteral immunonutrition on T-lymphocyte count in the cardiac surgery population. METHODS: This was a randomised control study of low operative risk adult patients, who underwent elective cardiac surgery. These patients were randomised into immunonutrition and control groups. The immunonutrition group was supplemented with immune nutrients for five postoperative days. The counts of T-lymphocytes, as well as the counts for the CD4+ and CD8+ cell subpopulations were determined on the day of surgery and on the sixth postoperative day. RESULTS: Fifty-five patients were enrolled in the study, the mean age was 69.7 ± 6.3 years, 28 (50.9%) of them were males, the median operative risk was 1.75%. Twenty-seven (49.1%) were randomised into the immunonutrition group. The control and the immunonutrition groups were similar before the intervention. The counts of the CD3+ T cells and CD4+ T cells on the sixth postoperative day were significantly higher in the immunonutrition group compared to the control group with 1.42 ± 0.49 vs. 1.12 ± 0.56 (∗109/l), p = 0.035 and 1.02 ± 0.36 vs. 0.80 ± 0.43 (∗109/l), p = 0.048, respectively. Regression analysis was performed to determine the efficacy of the immunonutrition on the counts of the CD3+ and CD4+ T cells; CD3+ T and CD4+ T cell counts were increased to 0.264 (∗109/l), p = 0.039 and 0.232 (∗109/l), p = 0.021, respectively. CONCLUSIONS: Early postoperative immunonutrition increases the count of the CD3+ and CD4+ T cells in cardiac surgical patients. Clinical trials identifier number: NCT04047095.

CD31+, CD38+, CD44+, and CD103+ lymphocytes in peripheral blood, bronchoalveolar lavage fluid and lung biopsy tissue in sarcoid patients and controls.

BACKGROUND: The mechanisms driving the transition from inflammation to fibrosis in sarcoidosis patients are poorly understood; prognostic features are lacking. Immune cell profiling may provide insights into pathogenesis and prognostic factors of the disease. This study aimed to establish associations in simultaneous of lymphocyte subset profiles in the blood, bronchoalveolar lavage fluid (BALF), and lung biopsy tissue in the patients with newly diagnosed sarcoidosis. METHODS: A total of 71 sarcoid patients (SPs) and 20 healthy controls (HCs) were enrolled into the study. CD31, CD38, CD44, CD103 positive T lymphocytes in blood and BALF were analysed. Additionally, the densities of CD4, CD8, CD38, CD44, CD103 positive cells in lung tissue biopsies were estimated by digital image analysis. RESULTS: Main findings: (I) increase of percentage of CD3+CD4+CD38+ in BALF and blood, and increase of percentage of CD3+CD4+CD44+ in BALF in Löfgren syndrome patients comparing with patients without Löfgren syndrome, (II) increase of percentage of CD3+CD4+103+ in BALF and in blood in patients without Löfgren syndrome (comparing with Löfgren syndrome patients) and increase of percentage of CD3+CD4+103+ in BALF and in blood in more advanced sarcoidosis stage. (III) Increasing percentage of BALF CD3+CD4+CD31+ in sarcoidosis patients when comparing with controls independently of presence of Löfgren syndrome, smoking status or stage of sarcoidosis. Several significant correlations were found. CONCLUSIONS: Lymphocyte subpopulations in blood, BALF, and lung tissue were substantially different in SPs at the time of diagnosis compared to HCs. CD3+CD4+CD31+ in BALF might be a potential supporting marker for the diagnosis of sarcoidosis. CD3+CD4+CD38+ in BALF and blood and CD3+CD4+CD44+ in BALF may be markers of the acute immune response in sarcoidosis patients. CD4+CD103+ T-cells in BALF and in blood are markers of the persistent immune response in sarcoidosis patients and are potential prognostic features of the chronic course of this disease.

Levels of CD4+ CD25+ T regulatory cells in bronchial mucosa and peripheral blood of chronic obstructive pulmonary disease indicate involvement of autoimmunity mechanisms.

INTRODUCTION: Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80%) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of crucial importance. MATERIAL AND METHODS: Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls - 15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I-II) and severe/very severe (GOLD stage III-IV) groups. Digital image analysis was performed to estimate densities of CD4+ CD25+ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3+ CD4+ CD25+ bright lymphocytes by flow cytometry. RESULTS: The number of intraepithelial CD4+ CD25+ lymphocytes mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p < 0,0001). Likewise, the absolute number of Treg (CD3+ CD4+ CD25+ bright) cells in the peripheral blood samples was significantly different between the four groups (p = 0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups. CONCLUSION: Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.

Relationship between radiologic patterns, pulmonary function values and bronchoalveolar lavage fluid cells in newly diagnosed sarcoidosis.

BACKGROUND: The aim of the present study was to identify specious radiologic and/or physiologic prognostic marker(s), which lead to optimize of the patient follow-up frequency. METHODS: Eighty consecutive patients with newly diagnosed pulmonary sarcoidosis. Patients underwent chest radiography, high-resolution computed tomography (HRCT) examination, pulmonary function tests (PFT), bronchoscopy with bronchoalveolar lavage (BAL) and lung biopsy, and bronchoalveolar lavage fluid (BALF) cell examination. RESULTS: The reduction in PFT values seen in radiological sarcoidosis stage III was greater than that seen in stages I and II. The percentage of neutrophils in the lungs was found to increase in stages II and III. PFT indices were correlated negatively with the consolidation and ground glass opacities CT scores, but not with the micronodule or macronodule scores. The rise in the percentage of BALF lymphocytes was associated with the restriction pattern of PFT. The diagnostic value of BALF for sarcoidosis was higher when the typical radiologic patterns of stage I disease were found and that smoking decreased the diagnostic value of CD4/CD8 ratio. CONCLUSIONS: This study supports the opinion that the staging of the pulmonary sarcoidosis with chest X-rays is still valuable from the prognostic point of view, because significant correlations between the radiologic stages of sarcoidosis and PFT parameters were found. Chest HRCT was significantly superior to chest X-ray in detecting mediastinal and pulmonary parenchymal changes. However, the prognostic role of HRCT needs to be better investigated evaluating serial examinations. Only consolidation and ground glass scores (neither of which are frequently found in sarcoidosis) hold prognostic value, since these were negatively correlated with PFT parameters.

[Immunological changes after the Ross operation]. / Imunologiniai pokyciai po Ross'o operacijos.

The aim of present paper is to analyze immunological changes due to Ross operation. Cellular immune response as well as incidence of antibodies directed against human leukocyte antigens were studied in patients who received cardiac valve allografts. Standard microlymphocytotoxicity test was used to determine the percentage of panel reactive antibodies. Activated lymphocyte response to Pokeweed mitogen was revealed in patients after Ross operation. The panel reactive antibodies became positive in 3 out of 6 recipients tested. This production of donor specific anti-HLA antibodies can contribute to graft failure in case of subsequent cardiac transplantation.

BAL fluid cells in newly diagnosed pulmonary sarcoidosis with different clinical activity.

BACKGROUND: Sarcoidosis is associated with an increase in the number of alveolar T cells (CD3(+) cells) and an increase of the CD3(+)CD4(+) lymphocyte subset. However, the number of lymphocytes and the CD4/CD8 ratio in bronchoalveolar lavage (BAL) fluid are highly variable in sarcoidosis. Comparative studies have demonstrated that geographic and ethnic factors are linked to the specific characteristics of patients with sarcoidosis. AIM OF THE STUDY: To investigate peculiarities of BAL fluid (BALF) cell patterns in different clinical activity of pulmonary sarcoidosis at the time of diagnosis. MATERIAL AND METHODS: A total of 308 non-treated patients (138 asymptomatic and 170 with sarcoidosis-related symptoms) and 40 previously empirically steroid-treated patients with newly diagnosed sarcoidosis have been prospectively examined. RESULTS: Significant BAL fluid lymphocytosis and increased CD4/CD8 ratio were characteristic for all three sarcoidosis patient groups. A total of 12% of asymptomatic patients, 3% of patients with sarcoidosis-related symptoms, and 5% of previously treated symptomatic patients had normal BALF cell counts. Non-treated patients with sarcoidosis-related symptoms had significantly higher lymphocytosis (45+/-19% versus 39+/-17%, P<0.01), CD4/CD8 ratio (9.3+/-5.0 versus 5.7+/-4.5, P<0.001), and total BALF cell count (411+/-322 10(6)/mL versus 334+/-273 10(6)/mL, P<0.05), compared with asymptomatic patients. However, previously treated symptomatic patients had lower lymphocytosis (39+/-15% versus 45+/-19%, P=0.058), and total BALF cell count (292+/-166 10(6)/mL versus 411+/-322 10(6)/mL, P<0.05) compared with non-treated symptomatic patients. The same trend was noticed for CD4/CD8 ratio (8.3+/-4.8), although a statistically significant difference was not achieved. CONCLUSIONS: Independently of clinical symptoms at the time of diagnosis sarcoid patients have significantly different BAL fluid cell patterns compared to healthy persons. BAL fluid cell changes are more prominent in corticosteroid non-treated patients with clinically active sarcoidosis. Treatment with systemic corticosteroids may modify typical BALF cellular patterns of sarcoidosis.

Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis.

INTRODUCTION: Bronchoalveolar lavage (BAL) as a method of sampling cells is useful in the diagnosis and differential diagnosis of sarcoidosis. However, CD4/CD8 ratio in BAL fluid (BALF) is highly variable and it generates continuous discussions about its diagnostic role. OBJECTIVE: To prospectively evaluate diagnostic role of BALF CD4/CD8 ratio in pulmonary sarcoidosis manifested in different radiographic and clinical forms in the real clinical practice. MATERIAL AND METHODS: The study population consisted of 318 sarcoid patients with a newly diagnosed disease. Comparator groups consisted of 55 healthy subjects and 130 patients with other disorders who underwent BAL and examination of CD4/CD8 ratio in BALF as a step of diagnostic pathway. Diagnostic accuracy of CD4/CD8 ratio in BALF using receiver-operating characteristic analysis has been calculated. RESULTS: The percentage of BALF lymphocytes in sarcoid patients was significantly different from comparator groups. Normal BALF cell counts were found in 7% of sarcoid patients. However, typical sarcoid BALF cellular pattern was found in 6.2% of all control subjects. We have found that optimal cutoff points for CD4/CD8 ratio are 3.5 and 4.0 for asymptomatic and symptomatic patients, respectively. Sensitivity of the optimal cutoff points of CD4/CD8 ratio was lower in asymptomatic patients compared with symptomatic patients. Sensitivity of the optimal cutoff points decreased with the increased stage of sarcoidosis. CONCLUSIONS: BAL is a valuable method in diagnostic pathway of pulmonary sarcoidosis. However, results of BALF examination must be interpreted considering a specific clinical case. BALF CD4/CD8 ratio depends on clinical and radiographic manifestation.

Sensitisation and post-transplant course after the implantation of ventricular assist device.

The purpose of this study was to evaluate sensitisation, occurring because of bridging with VAD, and development of rejection episodes after transplantation in selected groups of patients using triple drug immunosuppression, without induction or desensitisation therapy. Sensitisation using standard complement dependent cytotoxicity was tested in 16 patients awaiting cardiac transplantation before VAD placement, one month post-implantation and on a six-monthly basis later on. Long-term (955+/-998 days) post-transplant course of six transplanted post-VAD patients was compared with 19 non-bridged recipients (follow-up time 1425+/-1273 days) of the same age. One-third of VAD recipients had developed anti-HLA antibodies one month post-implantation; 4/16 patients were sensitised six months after implantation. No de novo sensitisation development was revealed in VAD group post-transplantation. All sensitised patients independent of VAD placement underwent graft rejection episodes. Only 1 of 6 VAD recipient was treated because of grade 2R rejection, compared to 6/19 in the non-bridged group, P=0.63. None of the patients had failed because of early graft rejection. In conclusion, VAD devices used in our centre cause low level risk for anti-HLA antibodies development. There were no differences in survival due to immunologic reasons between VAD bridged and non-bridged patients.