scholarly journals Early isolated V-lesion may not truly represent rejection of the kidney allograft

2018 ◽  
Vol 132 (20) ◽  
pp. 2269-2284 ◽  
Author(s):  
Mariana Wohlfahrtova ◽  
Petra Hruba ◽  
Jiri Klema ◽  
Marek Novotny ◽  
Zdenek Krejcik ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Hierarchical Cluster ◽  
Study Groups ◽  
Molecular Study ◽  
Control Group ◽  
Unsupervised Hierarchical Cluster ◽  
Kidney Allograft ◽  
Vascular Rejection

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

VEGFR2 expressions in Th1 and CD8+ cytotoxic T lymphocytes (CTL) in colon cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Mehmet Artac ◽  
Ayca Ceylan ◽  
Melek Karakurt Eryılmaz ◽  
Murat Araz ◽  
Mustafa Karaagac ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Study Groups ◽  
T Cell Subsets ◽  
Control Group ◽  
Study Group ◽  
Metastatic Colon Cancer ◽  
Vegf Receptors ◽  
Cancer History

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p < 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p < 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.

scholarly journals Analysis of KIF2C, 4A, 10, 11, 14, 18B, 20A, and 23 in HCC and their clinical significance as new-born prognostic markers of HCC

2020 ◽  
Author(s):  
Meng-jun Qiu ◽  
Qiu-shuang Wang ◽  
Xiao-xiao He ◽  
Qiu-ting Li ◽  
Xin Jiang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Prognostic Markers ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Normal Control Group ◽  
Gene Set Enrichment Analysis ◽  
Control Group ◽  
Gene Set Enrichment ◽  
Different Levels

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. However, the molecular mechanism of its pathogenesis remains to be studied. This study aimed to identify potential KIF genes associated with HCC progression. Methods: We used bioinformatics to initially analyze the expression level and prognostic significance of KIF factors in HCC. Results: We found that compared with the normal control group, KIF2C, 4A, 10, 11, 14, 18B, 20A, and 23 mRNA expression levels increased significantly in HCC. 8 KIF factors had different levels of gene amplification, depth to delete, and missense mutation, and were closely related to the clinical-pathologic stage. Gene set enrichment analysis showed that high mRNA expression of 8 KIF factors in HCC patients were associated with cell cycle, mismatch repair, homologous recombination, and DNA replication. Conclusions: This study expands our understanding of KIF factors in HCC and can provide a theoretical basis for further basic and clinical research in HCC.

scholarly journals Genomic and Transcriptomic Profiling of Brain Metastases

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5598
Author(s):  
Christopher P. Wardell ◽  
Emilie Darrigues ◽  
Annick De Loose ◽  
Madison P. Lee ◽  
Murat Gokden ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Mechanisms ◽  
Prognostic Significance ◽  
Hierarchical Cluster ◽  
Molecular Characteristics ◽  
Unsupervised Hierarchical Cluster ◽  
Metastatic Progression ◽  
Poor Survival ◽  
Mutational Signatures ◽  
Black Race

Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes (p < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.

scholarly journals Prognostic significance of application the non-invasive method of evaluating the functional state of residual parencheme of the liver in patients with focal liver education

2018 ◽  
Vol 11 (1) ◽  
pp. 10-15
Author(s):  
Sergey V Tarasenko ◽  
Uliana V Juchkova ◽  
Alexander A Kopeykin ◽  
Timur S Rachmaev ◽  
Irina V Baconina
Keyword(s):  
Functional State ◽  
Hepatic Failure ◽  
Prognostic Significance ◽  
Preoperative Assessment ◽  
Acute Hepatic Failure ◽  
Liver Parenchyma ◽  
Study Groups ◽  
Control Group ◽  
Non Invasive ◽  
Definition Of

The aim of the study was a determination of the prognostic significance of a non-invasive preoperative assessment to evaluate the functional state of residual liver parenchyma in order to prevent the development of acute hepatic failure. 76 patients with focal liver formation were examined. The first group included 46 patients, who were examined using the method of a non-invasive preoperative assessment of the functional state of residual liver parenchyma, which developed by the authors. The definition of the "resectional index" (IR) was made using the following formula: IR = Vint / TP (U), where Vint - the volume of intact liver parenchyma (cm3); TP - total protein of blood serum (g /l). The second group consisted of 30 patients, whose results of surgical treatment were analyzed retrospectively. Major hepatic resections were performed in 26 (56.52%) patients in the primary and 20 (66.67%) in the control group. The study conducted a comparative intergroup analysis of the frequency and severity of developing complications in the study groups. The complications were distributed according to the Dindo-Clavien classification scale, according to which the life-threatening complication rate was 8.7% and 26.67%, severe postoperative hepatic-cell insufficiency was detected in 2.17% and 16.67% of patients in the main and control group. The differences were statistically significant. It was defined value of the "resectional index" (more than 20 U), the excessing of which statistically significantly increased the risk of severe postoperative complications, in particular acute hepatic failure.

А Study of the Amount of CD57+ Cytotoxic T-lymphocytes in Bone Marrow associated with the Development of Small Round Cell Sarcomas in Children: A Retrospective Cohort Study

2018 ◽  
Vol 5 (1) ◽  
pp. 32-40
Author(s):  
Olga P. Kolbatskaya ◽  
Tatiana V. Gorbunova ◽  
Nikolai N. Tupitsyn
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Retrospective Cohort ◽  
Prognostic Significance ◽  
Control Group ◽  
Healthy Children ◽  
Round Cell ◽  
Small Round Cell

Background.There is little data on the number of CD57+ cytotoxic T-lymphocytes (CTL) in the bone marrow of healthy children and children with developing small round cell sarcomas (rhabdomyosarcoma and Ewing`s sarcoma).Objective.Our aim was to study the amount of CD57 + CTL in bone marrow of children with developing small round cell sarcomas.Methods.A retrospective cohort analysis was conducted for the period of 2006–2011. It enrolled 47 patients aged 1–17 y.o. (mean age — 8.6 years) who underwent the bone marrow aspiration; the examination results were studied with morphological and immunocytometric method. The obtained mean values of CD57+ T-cell were processed by the statistical program SPSS17.Results.Rhabdomyosarcoma (RMS) was diagnosed in 16 patients, Ewing`s sarcoma (ES) — in 16 patients. The control group included 15 patients with no malignant tumours. In patients with ES, higher percent of CD3+CD57+ (p=0.022) and CD8+CD57+ (p=0.028) subpopulations was registered. The percentage and absolute level of CD3+CD57+ and CD8+CD57+ T-cells in the bone marrow of patients with RMS did not differ from the control (p=0.125 and р=0.181 respectively). Comparison of percentage of CD3+CD57+ and CD8+CD57+ T-lymphocyte subpopulations in subjects of both groups revealed no differences (р=0.091 and р=0.060 respectively). We registered higher amount of CD3+CD57+ and CD8+CD57+ T-cell subpopulations in patients with ES than in patients with RMS (p=0.009 and p=0.014 respectively).Conclusion.Each malignant disease when diagnosing is characterized by specific changes in the patterns of CD57 + CTL subpopulations derived from the bone marrow which allows to reveal its clinical and prognostic significance, understand better the mechanisms of interaction between the tumor and the immune system, and serve for the development of immunotherapy programs.

scholarly journals Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients

2020 ◽  
Author(s):  
Karim El Sakhawi ◽  
Giovanna Melica ◽  
Anne Scemla ◽  
Dominique Bertrand ◽  
Cyril Garrouste ◽  
...  
Keyword(s):  
T Cell ◽  
Opportunistic Infections ◽  
Survival Rates ◽  
Hiv Positive ◽  
Control Group ◽  
Allograft Survival ◽  
Serious Adverse Events ◽  
Kidney Allograft ◽  
Cell Counts

Abstract Background Kidney allograft survival in human immunodeficiency virus (HIV)-positive patients is lower than that in the general population. Belatacept increases long-term patient and allograft survival rates when compared with calcineurin inhibitors (CNIs). Its use in HIV-positive recipients remains poorly documented. Methods We retrospectively report a French cohort of HIV-positive kidney allograft recipients who were switched from CNI to belatacept, between June 2012 and December 2018. Patient and allograft survival rates, HIV immunovirological and clinical outcomes, acute rejection, opportunistic infections (OIs) and HLA donor-specific antibodies (DSAs) were analysed at 3 and 12 months, and at the end of follow-up (last clinical visit attended after transplantation). Results were compared with HIV-positive recipients group treated with CNI. Results Twelve patients were switched to belatacept 10 (2–25) months after transplantation. One year after belatacept therapy, patient and allograft survival rates scored 92% for both, two (17%) HIV virological rebounds occurred due to antiretroviral therapy non-compliance, and CD4+ and CD8+ T-cell counts remained stable over time. Serious adverse events included two (17%) acute steroid-resistant T-cell-mediated rejections and three (25%) OIs. Kidney allograft function significantly increased over the 12 post-switch months (P = 0.009), and DSAs remained stable at 12 months after treatment. The control group showed similar results in terms of patient and kidney allograft survival rates, DSA characteristics and proteinuria Conclusions Switch from CNI to belatacept can be considered safe and may increase long-term kidney allograft survival in HIV-positive kidney allograft recipients. These results need to be confirmed in a larger cohort.

Prognostic role of results of dynamic capnography in integral assessment of parameters of respiratory system in 6-minute walk test in patients with chronic heart failure

2020 ◽  
Vol 28 (3) ◽  
pp. 290-299
Author(s):  
Kira A. Ageeva ◽  
Evgenii V. Filippov
Keyword(s):  
Respiratory System ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Walk Test ◽  
Ventricular Ejection Fraction ◽  
6Mwt Distance ◽  
6 Minute Walk Test ◽  
Minute Walk

Aim. To study the prognostic value of the results of dynamic capnography in the complex assessment of parameters of the respiratory system in 6-minute walk test in patients with chronic heart failure (CHF). Materials and Methods. 73 Patients were examined: the group of study included 48 patients with IIA or IIB stage CHF (mean age 57.94.6 years, 23 men), the control group included 25 practically healthy volunteers (mean age 47.63.5 years, 9 men). The patients were conducted complex determination of parameters of the respiratory system: clinical scaling before and after 6-minute walk test (6MWT), instrumental examinations including spirometry, capnography and pulse oximetry before, during and after physical activity. The analysis of survival was conducted on the basis of the dynamic follow-up of patients within 5 years (60 months). Results. In the analysis of parameters of dyspnea at rest, all the parameters were higher in the group of patients with CHF (р0.05). The distance walked by the patients with CHF in 6 minutes was 488.2390.84 m, which was significantly less than in the control group (815.6053.89 m, р=0.009). Dyspnea as the cause of stoppage/slowing down of walking in 6MWT, was also more often recorded in patients with CHF (93.83.0% and 48.05.1%, р=0.049). Besides, in 6MWT the patients noted: weakness in legs (50.15.0% in the group of CHF and 40.05.0% in the control group, р=0.014), palpitation (29.04.6% and 20.04.1%, respectively, р=0.004). Worsening of dyspnea parameters in 6MWT was more evident in patients with CHF than in the control group (р0.01). In the CHF group, hypocapnic type of ventilation was revealed in 6MWT, analysis of РЕТСО2 trend graphs revealed a wave-like increase in the parameters, the so called periodic breathing (PB). CO2 trend was recorded in CHF group in 58.31.0% of cases (the difference with the control group with р=0.046), the trend of heart rate in 18.80.3% of cases (р=0.027). Cox proportional hazards regression analysis of mortality in patients with CHF showed a prognostic significance of a complex model comprising the following parameters of a patient: body mass index (р=0.005), left ventricular end-diastolic dimension (р=0.034), left ventricular end-systolic dimension (р=0.002), left ventricular ejection fraction (р=0.041), 6MWT distance (р=0.004), desaturation (р=0.009), and the presence of signs of PB during 6MWT (р=0.005). Model coefficients were statistically significant at р0.0001. Conclusions. Dynamic capnography and pulse oximetry allow to identify signs of PB in patients with CHF during 6MWT which may deepen a complex assessment of parameters of the cardio-respiratory system in patients with CHF in order to determine tolerance to physical exercise as well as the effectiveness of the conducted treatment. Complex assessment of survival of patients with CHF showed prognostic significance of the following parameters of a patient: body mass index, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, 6MWT distance, desaturation, PB during 6MWT.

Sucrose and Facilitated Tucking for Pain Among Neonates Receiving Vaccination, in Puducherry

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Sujatha S. ◽  
Rebecca Samson ◽  
Christopher Amalraj ◽  
Sundaresan Sundaresan
Keyword(s):  
Sucrose Solution ◽  
Study Groups ◽  
Primary Outcome Measure ◽  
Intradermal Injection ◽  
Control Group ◽  
Intradermal Vaccination ◽  
Term Neonates ◽  
Bcg Vaccination ◽  
Pharmacologic Agents ◽  
Study Intervention

Neglected pain in neonates leads to various ill effects and it can be prevented by using simple and safe non-pharmacological pain relieving measures. Pharmacologic agents are not recommended in neonates for acute pain due toinvasive procedures however, administration of 24% oralsucrose solutionis found to be effective. The objective of this study was to assess the efficacy of 24%oral sucrose in combination with Facilitated tucking during BCG Vaccination through intradermalroute in term neonates which is not done elsewhere. Fifty five healthy term neonates who fulfilled the inclusion criteria such as gestational age above 37 weeks, within 24 hoursof birth age, and neonates delivered only through spontaneous vaginal delivery were included in the study. The study intervention consists of administration of 2 ml of oral 24% sucrose 2 minutes before BCG Vaccination through intradermal route and Facilitated tuckingat the time of vaccination. The primary outcome measure of cumulative NIPS score at 0, 3,5 minuteswas not significant in both the study groups. Whereas there was significant reduction in the level of pain and mean cry time in the neonates of sucrose group. Heart rateand oxygen saturation after intradermal injection also showed significant (p less than 0.001) differenceamong the neonates, who received 24% of oral sucroseand Facilitated tucking than for neonates of control group. Thus oral (24%)sucrose solution given 2 minutes before injection was effective in reducing level of neonatal pain following Intradermal Vaccination. It is a simple, safe and fast acting analgesic and should be considered for minor invasive procedures in term neonates which last for 5-7minutes.

Employing Gamma Ray Irradiated Giardia lamblia as Trialed Vaccine in Experimental Animal

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Amal Kamil Abdul Sada ◽  
Amany Mohamed Al-Kaysi
Keyword(s):  
Giardia Lamblia ◽  
Gamma Ray ◽  
Age Groups ◽  
Active Phase ◽  
Study Groups ◽  
Negative Control ◽  
Control Group ◽  
High Dose ◽  
Histopathological Changes ◽  
Gamma Irradiated

This is an experimental trial to prepare a vaccine from gamma-irradiated Giardia lamblia which is evaluated in experimental animals. The study was conducted from December 2015 to April 2016. The field survey of the parasite was conducted from those patients attending the laboratories of the Alawi Children's Hospital in Rusafa and the Al-Yarmouk Teaching Hospital in Karkh, through which 1250 stool samples of different age groups were examined. Five groups of mice were used in the study; the first was injected with normal saline and considered as a negative control group, the second was injected with cystic form of non-irradiated Giardia lamblia and considered as a positive control group, whereas the other three groups were injected with gamma irradiated Giardia lamblia at three different doses 10, 15 and 25 rad respectively. Giardia lamblia was primarily cultivated in liver infusion agar for ten days to obtain the active phase. On the sixth day, the cystic phase was purified and standardized to be used in the infection of mice with or without the exposure of gamma rays. Mice showed high sensitivity to parasitic infestation, in the gamma non-irradiated and the irradiated with gamma 10 rad, and 15 rad irradiated groups which was 100%. The results expressed an excystation process of the depleted phases and the release of the feeder phases. The results of the three irradiated groups consisted of histopathological changes of the small, and the rectum by dissection after two weeks of infection, with intestine amputation lesions, as well as ulceration and inflammation of the inflammatory cells represented in small numbers of neutrophil, lymphocytes, and eosinophils. The presence of ulceration and fall of epithelial cells in the intestinal cavity has been shown, and different forms of the parasite have been observed. Mice which was injected with irradiated G lamblia at high dose (25 rad), not show and sensitivity to the challenge infection and no excystation of thy parasite had been done. After 2 wreaks, a comparison was achieved between all study groups in which no histopathological changes were noticed in the mice irradiated with dose of25 rad. After another two weeks, a challenge dose was given (un-attenuated G lamblia) and mice were dissected after another two weeks, no changes on the level of histopathology of intestinal tissue were noticed the results suggested that mice acquire an immunity against the parasite infection.

PREDICTIVE SIGNIFICANCE OF HIGH SERUM FERRITIN LEVELS IN THE DEBUT OF MALIGNANT LYMPHOMA

2020 ◽  
pp. 74-81
Author(s):  
Babaeva T.N. ◽  
Seregina O.B. ◽  
Pospelova T.I.
Keyword(s):  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Prognostic Significance ◽  
Average Concentration ◽  
High Serum ◽  
Control Group ◽  
Malignant Neoplasms ◽  
Significant Prognostic Factor ◽  
Malignant Lymphomas

At present, the serum ferritin level is not included in the list of prognostic factors; however, it is known that its increased serum level in patients with malignant neoplasms relates with the tumor burden, the degree of disease activity and correlates with a worse prognosis in patients with hematologic malignancies.The normalization of serum ferritin level during remission period confirms the involving of hyperferritinemia in mechanisms of tumor progression and may testify for clinical importance of measurement of serum ferritin level in patients, including those with malignant lymphomas. Objective:The aim of this study was to assess of the prognostic significance of high ferritin levels at the onset of the disease in patients with malignant lymphomas. Materials and methods:98 patients with malignant lymphomaswere enrolled in this study, including 72 patients (73.5%) with non-Hodgkins lymphomas (NHL) and 26 patients (26.5%) with Hodgkin’s lymphoma (HL). The increased serum ferritin level (more than 350 ng/ml) was found in 53 (54.2%) patients with malignant lymphomas at the onset of disease and its average concentration was 587,62±131,6 ng/ml (8.3 times higher values of control group, p<0.001).Also the positive statistical correlationsbetween increased ferritin level and increased level of LDH (r=0.47, p<0.001, n=98) and C-reactive protein (r=0.41, p<0.001, n=98) as well as the presence of B-symptomswere found. The median OS was significantly shorter in the group of patients with increased ferritin level (more than 350 ng/ml) at the onset of disease in comparison with group of patients with normal ferritin level, where the median OS was not reach during the observation period. Patients with increased ferritin level before starting chemotherapy also showed worse results of overall survival and increased mortality risk (OR 8.122; 95% CI, 1.764-37.396;р<0.05) compare with a group of patients with ferritin level ˂350 hg/ml at the onset of disease. Conclusion:These results make it possible to include lymphomas’s patients with increased ferritin level at the onset of disease in the group with poor prognosis and lower OS, while the increased ferritin level in patients without previous blood transfusions should be considered as a significant prognostic factor.

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