Different Time Points In Patients Research Articles

Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery

ObjectiveMedullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. MethodsA retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. ResultsA total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69–1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90–975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84–290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27–94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12–36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04–14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06–15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18–7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. ConclusionsNPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

Predictive validity of a pressure injury risk assessment tool at different time-points in patients admitted to the intensive care unit.

Multiple risk assessment scales are available for predicting the development of pressure injuries (PIs) in patients in the intensive care unit (ICU). Most PI risk assessment tools have been validated at the time of admission; however, another time point during treatment could better reflect clinical changes and therefore, the risk of PIs. The study aimed to examine the predictive validity of PI risk assessment scale designed for ICU patients, the conscious level, mobility, haemodynamic, oxygenation and nutrition (COMHON) index, at several time points or intervals during ICU stay. This was an observational prospective study undertaken over a period of 1 year (July 2021-June 2022). Patients admitted to ICU for >3 days were included. The number, location and degree of the PIs were recorded. The level of risk for developing PIs during the stay was determined by calculating the COMHON scores at admission, and 72 h, as well as the highest and mean score. Predictive validity was studied using accuracy parameters and areas under the receiver operating characteristic curve (AUC). The best cutoff point was also determined and used to compare risk between categories. Of the 286 patients included in the study, 160 (59%) were male. The level of severity evaluated using the APACHE II scale was 18.4 ± 5.8 points. Invasive mechanical ventilation was used in 32.1% (n = 92) of the patients and 20.6% (n = 59) received high flow oxygen therapy. The incidence of PI was 15.4% (n = 44), with sacral location in 47.7% (n = 21) and grade II in 75% (n = 33) of the patients. The AUC was 0.907 (0.872-0.942); 0.881 (0.842-0.920); 0.877 (0.835-0.920) and 0.749 (0.667-0.831) at the mean, the highest, 72 h and ICU admission scores, respectively. The best cutoff point was 13 in all patients. The risk of developing a PI was 6.4 times higher in the high-risk group (>13 points). The best predictive capacity for the COMHON index risk assessment was the mean and highest scores. The predictive accuracy was higher on the third day of the patient's stay than on admission, and this was attributed to the clinical changes observed in some patients over the course of their critical illness. Patients in ICU are at high risk of developing PIs, therefore, preventive measures should be maximized. Risk assessment should be carried out sequentially owing to the changes that patients present throughout their ICU stay and preventive measures should be used according to the risk level.

Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation

The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg.

Correlation of serial high-sensitivity cardiac troponin t values to infarct mass determined by cardiac magnetic resonance imaging

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction The extent of myocardial injury is strongly associated with adverse outcome after acute myocardial infarction (AMI). Contrast-enhanced magnetic resonance imaging (CE-MRI) is the preferred technique for myocardial imaging. Its use in daily clinical practise, however, is restricted due to limited availability and high costs. High-sensitivity cardiac troponin T (hs-cTnT) correlates well with the extent of myocardial injury and may therefore be a cost effective and widely available surrogate for the estimation of infarct size. Purpose To validate correlations between CE-MRI infarct mass and hs-cTnT values at different time points in patients with confirmed AMI. Methods Patients presenting with AMI and with available CE-MRI between January 1, 2018 and December 31, 2020 were included. Correlation coefficients between hs-cTnT on admission, after 24h, 48h, 72h, 96h and peak hs-cTnT values and CE-MRI infarct mass were calculated. Correlations between hs-cTnT and CE-MRI infarct mass were compared to those of a 3rd generation cTnT assay from a previously published study of our group. Results 137 patients were included for the present analysis. Median CE-MRI infarct mass was 12,5 g (95%CI: 9.8-16.2 g). Hs-cTnT values and infarct mass correlated well at all time points including admission (r=0.474, [95%CI: 0.331-0.560], p&amp;lt;0.0001), 24h (r=0.508, [95%CI: 0.370-0.625], p&amp;lt;0.0001), 48h (r=0.547, [95%CI: 0.404-0.664], p&amp;lt;0.0001), 72h (r=0.489, [95%CI: 0.320-0.628], p&amp;lt;0.0001), 96h (r=0.509, [95%CI: 0.330-0.653], p&amp;lt;0.001) including peak hs-cTnT values (r=0.547, [95%CI: 0.416-0.656], p&amp;lt;0.0001) and maximum absolute delta changes within 96h (r=0.507, [95%CI: 0.369-0.622], p&amp;lt;0.001). Correlations of the 3rd generation assay could be confirmed for hs-cTnT at all time points. A superior correlation with CE-MRI infarct mass was observed for hs-cTnT values on admission. Conclusions Hs-cTnT values at different time points correlate well with CE-MRI infarct mass. Correlations of admission hs-cTnT values are superior to those of a 3rd generation assay.

Multiplex Polymerase Chain Reaction/Pooled Antibiotic Susceptibility Testing Was Not Associated with Increased Antibiotic Resistance in Management of Complicated Urinary Tract Infections.

To compare antibiotic resistance results at different time points in patients with urinary tract infections (UTIs), who were either treated based upon a combined multiplex polymerase chain reaction (M-PCR) and pooled antibiotic susceptibility test (P-AST) or were not treated. The M-PCR/P-AST test utilized here detects 30 UTI pathogens or group of pathogens, 32 antibiotic resistance (ABR) genes, and phenotypic susceptibility to 19 antibiotics. We compared the presence or absence of ABR genes and the number of resistant antibiotics, at baseline (Day 0) and 5-28 days (Day 5-28) after clinical management in the antibiotic-treated (n = 52) and untreated groups (n = 12). Our results demonstrated that higher percentage of patients had a reduction in ABR gene detection in the treated compared to the untreated group (38.5% reduction vs 0%, p = 0.01). Similarly, significantly more patients had reduced numbers of resistant antibiotics, as measured by the phenotypic P-AST component of the test, in the treated than in the untreated group (42.3% reduction vs 8.3%, p = 0.04). Our results with both resistance gene and phenotypic antibiotic susceptibility results demonstrated that treatment based upon rapid and sensitive M-PCR/P-AST resulted in reduction rather than induction of antibiotic resistance in symptomatic patients with suspected complicated UTI (cUTI) in an urology setting, indicating this type of test is valuable in the management of these types of patients. Further studies of the causes of gene reduction, including elimination of ABR gene-carrying bacteria and loss of ABR gene(s), are warranted.

Correlation of serial high-sensitivity cardiac Troponin T values to infarct mass determined by cardiac magnetic resonance imaging: a validation study.

To validate correlations between contrast-enhanced magnetic resonance imaging (CE-MRI) infarct mass and high-sensitivity cardiac Troponin T (hs-cTnT) values at different time points in patients with confirmed acute myocardial infarction (AMI). Patients presenting with AMI and with available CE-MRI between 1 January 2018 and 31 December 2020 were included. Correlation coefficients between hs-cTnT on admission, after 24, 48, 72, and 96 h, and peak hs-cTnT values and CE-MRI infarct mass were calculated. Correlations between hs-cTnT and CE-MRI infarct mass were compared with those of a third generation cTnT assay from a previously published study of our group. A total of 137 patients were included for the present analysis. Median CE-MRI infarct mass was 12,5 g [95% confidence interval (CI): 9.8-16.2 g]. Hs-cTnT values and infarct mass correlated well at all time points including admission (r = 0.474, 95% CI: 0.331-0.560, P < 0.0001), 24 h (r = 0.508, 95% CI: 0.370-0.625, P < 0.0001), 48 h (r = 0.547, 95% CI: 0.404-0.664, P < 0.0001), 72 h (r = 0.489, 95% CI: 0.320-0.628, P < 0.0001), 96 h (r = 0.509, 95% CI: 0.330-0.653, P < 0.001) including peak hs-cTnT values (r = 0.547, 95% CI: 0.416-0.656, P < 0.0001), and maximum absolute delta changes within 96 h (r = 0.507, 95% CI: 0.369-0.622, P < 0.001). Correlations of the third generation assay could be confirmed for hs-cTnT at all time points. A superior correlation with CE-MRI infarct mass was observed for hs-cTnT values on admission. Hs-cTnT values at different time points correlate well with CE-MRI infarct mass. Correlations of admission hs-cTnT values are superior to those of a third generation assay.

Abstract P5-07-06: Genomic characterization and tumor evolution in matched(primary-relapse)samplesof patients with METAPLASTIC breast cancer

Abstract Introduction and objectives. Metaplastic breast cancer is an heterogenous and infrequent disease (0.5-2%). Histologically, it is defined by differentiation of neoplastic epithelium into squamous or mesenchymal-like elements. Although they are mainly triple negative tumors, they present a more aggressive course with less response to chemotherapy and worse prognosis. The aim of our study was to characterize the molecular profile and tumor evolution in matched (primary-relapse) samples of patients (pts) with metaplastic breast cancer. Material and Methods. Genomic profiling of tumor biopsies from different time points in patients with early-stage metaplastic breast cancer who had disease recurrence/progression, and were treated at our institution between 2010 and 2020. Tumor samples were analyzed by DNA- Next Generation Sequencing (NGS; Illumina 2x75bp) using the ActionOncoKitDX panel (Imegen-Health in Code group). It allowed the study of point mutations in 50 genes, CNVs, fusion genes among 8 genes and pharmacogenetic SNPs associated with treatment efficacy or toxicity. It also determined MSI through 110 markers. The results were classified following the recommendations of the ACMG (American College of Medical Genetics). Only pathogenic and likely pathogenic variants were considered for analysis and afterwards we categorized them following the ComPerMed (The Personalized Medicine Commission) criteria. Results. We have analyzed 21 matched diagnosis-relapse tumor samples (8 primary tumor samples, and 13 loco-regional or metastatic disease) from 8 patients. In 4 patients, genomic characterization was performed at 3 different time points of their tumor evolution. Pathogenic alterations identified were mutations in TP53 (in 100% of the samples), TERT promoter (29%), and MYC amplifications (24% of samples, of which 75% were relapse/progression samples). We didn’t find any mutation in PI3KCA, but PTEN was found to have variations in 38% samples (10% mutations and 38% deletions). Amplification of FGFR1 was identified in 13% of the pts (only in the primary tumor). No ERBB2 or EGFR gene amplifications were detected, neither high grade MSI. We did not find a significant increase in point mutations between primary and relapse/progression samples, although gene amplifications were found more frequently in the former ones. Sixty three percent of the cases were Tier I and II category alterations, which could have future implications in the management of this neoplasia. Conclusion. In our series of metaplastic carcinoma, the most frequent pathogenic alterations occurred in cycle regulation’s genes, including TP53 and TERT promoter mutations, and MYC amplifications. Relapse/progression samples were enriched in MYC amplification and inTP53 allelic frequency. Larger studies are required to better characterize these tumors, and identify new strategies to improve the prognosis of these patients. Citation Format: Mónica Cejuela, Agostina Stradella, Anna Petit, Pablo Gargallo, Jan Bosch, Paula Carbonell, Sabela Recalde, Andrea Vethencourt, Adela Fernández, Catalina Falo, Miguel Gil-Gil, Silvia Vazquez, Rafael Villanueva, Teresa Soler, Inés Calabria, Sonia Pernas. Genomic characterization and tumor evolution in matched(primary-relapse)samplesof patients with METAPLASTIC breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-07-06.

AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation.

Long-term safety of rituximab in rheumatic patients with previously resolved hepatitis B virus infection

Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan-Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan-Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions.

Post-traumatic stress disorder can be predicted in hospitalized blunt trauma patients using a simple screening tool

BackgroundPost-traumatic stress disorder (PTSD) has debilitating psychiatric and medical consequences. The purpose of this study was to identify whether PTSD diagnosis and PTSD symptom scale score (PTSD severity) could be...

Discharge pulmonary artery pulsatility index predicts morbidity and mortality after acute heart failure: From the ESCAPE trial

IntroductionThe pulmonary artery pulsatility index (PAPI) is a newer hemodynamic index used for assessment of right ventricular performance. We hypothesized that PAPI predicts morbidity and mortality in acute systolic heart failure (HF). MethodsThe ESCAPE trial was utilized to identify the prognostic value of PAPI at different time points in patients hospitalized with acute systolic HF who received care assisted with central hemodynamic monitoring. ResultsAmong 167 patients (age 57 years, 71% men), PAPI significantly increased from admission to optimum hemodynamic day (from 2.88 to 4.09, P < 0.001) and final day (from 3.24 to 3.91, P = 0.032), and the magnitude of increase was strongly associated with markers of decongestion. Discharge PAPI was higher among survivors compared to non-survivors (median 3.1 vs. 2.0, P = 0.0008) and among patients who did not require rehospitalization compared to re-hospitalized patients (median 3.33 vs. 2.67, P = 0.017), both at 6-months. Discharge PAPI predicted mortality with AUC of 0.631 (P = 0.0207), rehospitalization (AUC 0.598, P = 0.0303), and composite of death, rehospitalization, cardiac transplant (AUC 0.621, P = 0.0101). An optimal cutoff value of discharge PAPI ≤2 had the highest sensitivity and specificity in predicting 6-month mortality, rehospitalization and the composite endpoint. Discharge PAPI, had a higher (though non-significant) AUC in predicting death and composite endpoint compared to admission PAPI, next day PAPI and optimal day PAPI. Cox proportional hazard analysis showed that discharge PAPI remained an independent predictor of the composite endpoint (hazard ratio 0.890, 95% CI 0.819–0.967, P = 0.006) after covariate adjustment. ConclusionsDischarge PAPI ≤2 is a marker of intermediate-term morbidity and mortality in acute systolic HF.

Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice

Background and aimsImmune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment. MethodsWe reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment. ResultsFrom the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00–10.92]; median overall survival was 12.82 months (95 %CI 10.92–34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions. ConclusionImaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging.

Association of the IL-6 Rs1800796 SNP with Concentration/dose Ratios of Tacrolimus and Donor Liver Function after Transplantation

ABSTRACT Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a range of important roles such as in inflammation, immune response, and cell growth regulation. Here, we aimed to assess the potential influence of the IL-6 single nucleotide polymorphism (SNP) rs1800796 on the concentration/dose (C/D) ratios of tacrolimus and donor liver function in Chinese liver transplant patients. A total of 331 liver transplant patients were included in this study. The C/D ratios and the ALT, AST, T-BIL, ALP, and GGT levels were analyzed at different time points in patients with and without the IL-6 rs1800796 SNP. The IL-6 rs1800796 polymorphism in recipients was found to be correlated with the C/D ratios of tacrolimus at months 2 to month 6 after transplantation. Also, the rs1800796 SNP in donors was found to influence liver function (shown in the data of ALT, AST, T-BIL, ALP and GGT) in recipients at the early post-transplant stage after transplantation. In conclusion, the IL-6 rs1800796 polymorphism was associated with the C/D ratios of tacrolimus and post-transplant donor liver function.

Meta-analysis of Incidence, Predictors and Consequences of Clinical and Subclinical Bioprosthetic Leaflet Thrombosis After Transcatheter Aortic Valve Implantation

Leaflet thrombosis (LT) has been claimed as a potential cause of hemodynamic dysfunction or bioprosthetic valve degeneration of transcatheter heart valves. Sparse and contrasting evidence exists, however, regarding LT occurrence, prevention and treatment. MEDLINE, ISI Web of Science and SCOPUS databases were searched for studies published up to January 2020. Only studies reporting data on incidence and outcomes associated to the presence/absence of clinical or subclinical LT, detected or confirmed with a multidetector computed tomography exam were included. The study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. Two reviewers independently screened articles for fulfillment of inclusion criteria. Data were pooled using a random-effect model. The primary end point was the incidence of LT. Secondary outcomes included: stroke and transient ischemic attacks and mean transvalvular gradients at different time-points in patients with and without LT. Of the initial 200 studies, 22 were finally included with a total of 11,567 patients. LT overall incidence was 8% (95% Confidence Interval [CI]: 5% to 13%, I2 = 96.4%). LT incidence in patients receiving only antiplatelets was 13% (95% CI: 7% to 23%, p <0.0001); patients discharged on oral anticoagulants had a reported incidence of 4% (95% CI: 2% to 8%, p <0.0001). Patients with LT, either clinical or subclinical, were not at increased risk of stroke (OR 1.06, 95% CI: 0.75 to 1.50, p = 0.730, I2 = 0.0%) or transient ischemic attacks (Odds Ratio 1.01, 95% CI: 0.40 to 2.57, p = 0.989, I2 = 0.0%). LT was associated with higher mean transvalvular gradients compared with patients without LT at 30 days post-transcatheter implantation, but not at discharge or at 1 year. LT is a relatively common event that, even when clinically manifest, is not associated with an increased risk of cerebrovascular events. Although patients on anticoagulants appear to be at lower risk of LT, the available evidence does not allow formulation of recommendations for prophylactical anticoagulation nor routine computed tomography after transcatheter aortic valve replacement.

Изменение суточного ритма содержания ингибирующего лейкемию фактора в крови больных эссенциальной гипертензией

Leukemia inhibitory factor (LIF) exerts multidirectional effects in the setting of essential hypertension (EH). There is a mounting body of evidence refuting the postulate about identical STAT3 signaling in cardiomyocytes and endothelial/smooth muscle cells, which is important in the situation of extended exposure to gp 130 ligands (LIF in particular). At the same time, there are no reports on the circadian dynamics of peripheral blood LIF concentrations and possible secondary changes to the pathophysiological effects of this cytokine. This study aimed to analyze the circadian dynamics of LIF concentrations in the peripheral blood serum measured at 5 different time points in patients with stage II EH in the presence/absence of antihypertensive therapy and their relationship with the frequency of complications developing within a 5-year follow-up. Blood serum LIF was measured in 60 patients with stage II EH using ELISA at 8:00, 14:00, 20:00, 2:00, and 8:00 o’clock before putting the patients on antihypertensive therapy and one year after its onset. The identified patterns of diurnal LIF concentrations (a rise by ≥15% at 20:00, p &lt; 0.001; a further rise by ≥22% peaking at 2:00, p &lt; 0.001 relative to the values at 8:00) can be regarded as pathologic; their persistence after one year of antihypertensive therapy is a sign of EH progression and puts the patients at 6-fold risk for cardiovascular complications, including myocardial infarction and acute cerebrovascular events.

Corneal Reinnervation and Sensitivity Recovery after Pterygium Excision.

Purpose To evaluate changes in corneal sensitivity and subbasal nerve density after pterygium excision. Methods This prospective trial included 22 eyes with nasal primary pterygium and 18 controls. Corneal sensitivity was evaluated using a Cochet–Bonnet esthesiometer in the nasal, superior, temporal, inferior, and center quadrants of the cornea before surgery and 10 days, 1 month, and 3months after surgery. The central cornea was analyzed using in vivo confocal microscopy (IVCM) before surgery and 1 and 3 months after surgery. Subbasal nerve density and other nerve parameters were analyzed using NeuronJ. Nerve tortuosity was evaluated and graded in individual IVCM scans. The tear film break-up time (TBUT) test and Schirmer's test were performed before surgery, as well as 1 and 3 months after surgery. All the same tests were performed in the controls. Results All affected eyes showed a significant increase in corneal sensitivity in the nasal corneal quadrant after surgery when compared with preoperative data (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (Conclusion Pterygium patients demonstrated deteriorated corneal subbasal nerve fibers when compared with healthy controls in terms of nerve length, nerve trunks, and nerve branches. Therefore, pterygium excision improves corneal sensitivity and increases corneal subbasal nerve density.

The prognostic significance of neutrophil-to-lymphocyte ratio at different time points in patients with hepatocellular carcinoma receiving liver resection.

BackgroundNeutrophil-to-lymphocyte ratio (NLR) has been demonstrated a significant association with the prognosis of hepatocellular carcinoma (HCC). The current study aimed to evaluate the prognostic value of NLR at different time points in HCC patients receiving liver resection.MethodsData were retrospectively collected from 195 HCC patients receiving liver resection. The preoperative NLR (pre-NLR), postoperative NLR (post-NLR) and corresponding changes of NLR (NLRc) at different time points were calculated. The disease-free survival (DFS) and overall survival (OS) was calculated by the Kaplan-Meier method and compared by the log-rank test. Both univariate and multivariate analyses were performed to evaluate their prognostic values for DFS and OS. And the prognostic significance of pre-NLR, post-NLRs, and NLRcs were further evaluated with subgroup analysis and with early and late recurrence of HCC.ResultsPre-NLR was not significantly correlated with DFS or OS (both P>0.05), whereas higher post-NLR at 4–8 weeks [NLR (4–8 w)] and 3–6 months [(NLR (3–6 m)] predicted worse DFS (P=0.023 and P<0.001, respectively) and OS (P=0.012 and P=0.001, respectively). The value of area under the curve (AUC) of NLR (3–6 m) were higher than NLR (4–8 w) for DFS (0.656 vs. 0.572) and OS (0.650 vs. 0.621). Multivariate analyses showed that NLRc (4–8 w) was not a significant predictor of DFS (P=0.369) or OS (P=0.173), while the NLRc (3–6 m) with 25% increase was found to be an independent factor for adverse DFS in patients with HCC (P=0.041). The AUC of NLRc (3–6 m) for DFS was 0.600. Subgroup analysis showed NLR (3–6 m) was significantly corrected to DFS (P<0.001) and OS (P=0.001) in patients with cirrhosis. And NLR (3–6 m) also showed with significant correlation with early recurrence (P<0.001), while NLR (4–8 w) was found with significant association both with early and late recurrence (P=0.037 and P=0.027, respectively).ConclusionsThe post-NLRs are significant predictors of clinical outcome in HCC patients receiving liver resection, and post-NLR and NLRc with a relatively long-term interval after operation have better prognostic values.

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study

BackgroundAnticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin.MethodsTGF-β, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome.ResultsIn the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD within the fourth course of treatment, compared with patients without progression. TGF-β and IL-8 above the median and IL-21 below the median at T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T1 correlated with survival. At TPD, TGF-β significantly increased in all patients.ConclusionsWe observed a significant correlation between TGF-β decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.

Detection of a Low Level and Heterogeneous B Cell Immune Response in Peripheral Blood of Acute Borreliosis Patients With High Throughput Sequencing.

The molecular diagnosis of acute Borreliosis is complicated and better strategies to improve the diagnostic processes are warranted. High Throughput Sequencing (HTS) of human B cell repertoires after e.g., Dengue virus infection or influenza vaccination revealed antigen-associated “CDR3 signatures” which may have the potential to support diagnosis in infectious diseases. The human B cell immune response to Borrelia burgdorferi sensu lato—the causative agent of Borreliosis—has mainly been studied at the antibody level, while less attention has been given to the cellular part of the humoral immune response. There are indications that Borrelia actively influence the B cell immune response and that it is therefore not directly comparable to responses induced by other infections. The main goal of this study was to identify B cell features that could be used to support diagnosis of Borreliosis. Therefore, we characterized the B cell immune response in these patients by combining multicolor flow cytometry, single Borrelia-reactive B cell receptor (BCR) sequencing, and B cell repertoire deep sequencing. Our phenotyping experiments showed, that there is no significant difference between B cell subpopulations of acute Borreliosis patients and controls. BCR sequences from individual epitope-reactive B cells had little in common between each other. HTS showed, however, a higher complementarity determining region 3 (CDR3) amino acid (aa) sequence overlap between samples from different timepoints in patients as compared to controls. This indicates, that HTS is sensitive enough to detect ongoing B cell immune responses in these patients. Although each individual's repertoire was dominated by rather unique clones, clustering of bulk BCR repertoire sequences revealed a higher overlap of IgG BCR repertoire sequences between acute patients than controls. Even if we have identified a few Borrelia-associated CDR3aa sequences, they seem to be rather unique for each patient and therefore not suitable as biomarkers.

3D Telomere Structure Analysis to DetectGenomic Instability and Cytogenetic Evolutionin Myelodysplastic Syndromes.

The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cytogenetics in 50% of patients with MDS, such distinguishing patterns are lacking in the other 50%. Despite the increase in the prognostic value of some biomarkers, none of them is specific and able to discriminate between stable and unstable patients that subsequently progress to acute myeloid leukemia. This pilot study aimed to investigate the potential use of the 3D telomere profiling to detect genomic instability in MDS patients with or without clonal cytogenetic evolution. The comparison between different time points in patients with cytogenetic changes showed that in the CD34+ MDS cells, there was a significant decrease in the total number of telomeric signals, the average intensity of signals and the total intensity of telomeres. By contrast, the number of aggregates increased during cytogenetic evolution (p < 0.001). This pattern was observed only for MDS patients with cytogenetic evolution but was absent in patients without cytogenetic changes. In conclusion, we demonstrated that the 3D nuclear telomere organization was significantly altered during the MDS disease course, and may have contributed to cytogenetic clonal evolution.