Post-treatment Concentration Research Articles

Abstract PO5-16-05: Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory Breast Cancer

Abstract Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, comprising only between 1-5% of all breast cancer cases in the United States. Despite its low incidence, IBC accounts for 10% of breast cancer-related deaths and is often diagnosed with metastasis, resulting in shorter survival compared to non-IBC cases. The 5-year relative survival rate for all stages of IBC is 39%, dropping to 19% for patients with distant metastasis. Liquid biopsy-based biomarkers have emerged as potential analytes for predicting prognosis and monitoring response to therapies in IBC patients. We explored the prognostic role of liquid biopsy encompassing both CTCs and cfDNA in the blood of patients with stage III/IV IBC and their clinical outcomes. Methods: CTC and cfDNA analysis was performed on 90 blood samples from 47 patients with stage III and IV IBC. Samples were collected before (pre-treatment, n=43) initiation and after (post-treatment, n=47) completion of neoadjuvant chemotherapy. CTCs were enriched and enumerated using the CellSearch® platform (Menarini-Silicon Biosystems). CfDNA was extracted from plasma using MagMax™ Cell-Free Total Nucleic Acid Isolation Kit (Applied Biosystems™) and quantified using the Qubit™ dsDNA High Sensitivity kit (Invitrogen™). Differences in cfDNA concentrations were used to plot a receiver operating characteristic (ROC) curve which was then used to determine Area Under the Curve (AUC) and a cfDNA cut-off point. ROC cut-off was calculated based on Youden Index J. Survival analysis was performed by the Kaplan-Meier estimator and Cox regression models. P-values were measured using the Student t-test. Results: Prior to neoadjuvant treatment, CTC was detected in 51% of patient samples, and the median cfDNA concentration was 5.87 ng/mL (range 0.95-24.11 ng/mL). After completion of neoadjuvant treatment, CTC was detected in 25% of patient samples, and the median cfDNA concentration was 11.19 ng/mL (range 3.41-88.13 ng/mL). The cut-off points determined for pre-treatment and post-treatment cfDNA concentration was >4.2 ng/mL and >9.5 ng/mL respectively. At pre-treatment, CTC detection and cfDNA concentration >4.2 ng/mL were independently associated with disease relapse (P=0.007, 0.016, respectively). The combination of CTC detection and cfDNA concentration >4.2 ng/mL was significantly associated with disease relapse (P=0.0004), decreased relapse free survival (RFS, P=0.005) and overall survival (OS, P=0.007). At the post-neoadjuvant treatment time point, the combination of CTC detection and cfDNA concentration >9.5 ng/mL was significantly associated with relapse regardless of pCR status (P=0.02). Conclusion: The combined presence of CTCs and elevated cfDNA concentrations in patients with stage III/IV IBC after completion of neoadjuvant chemotherapy was associated with disease relapse regardless of pCR status. A combination of elevated cfDNA and CTC detection signatures after completion of neoadjuvant chemotherapy may be useful for risk stratification and adjuvant systemic therapy planning. Citation Format: Sridevi Addanki, Salyna Meas, Vanessa Sarli, Abdulkader Almosa, Wendy Woodward, Dhruvajyoti Roy, Anthony Lucci. Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-05.

Dissipation of spring-applied methiozolin in turfgrass systems

AbstractMethiozolin is applied five or more times per year to control annual bluegrass (Poa annua L.) in cool, temperate areas, but high market demand in the southern United States and recent registration in Australia has expanded the product’s use in variable climates. To better design weed control programs for variable turf types, more information is needed to characterize methiozolin dissipation in different turf systems. Methiozolin was applied biweekly three times to a Kentucky bluegrass (Poa pratensis L.) lawn and adjacent bare soil in New Jersey and on 12 hybrid bermudagrass [Cynodon dactylon (L.) Pers. × Cynodon transvaalensis Burtt Davy] putting greens in Virginia. Soil samples were collected immediately following each application and biweekly for 12 additional weeks. Methiozolin was extracted from each soil sample and analyzed using liquid chromatography with tandem mass spectrometry. Methiozolin was detected only within the top 2 cm of the soil (including verdure), but not below 2 cm, demonstrating its limited vertical mobility. Dissipation was significantly faster in turf-covered soil compared with bare soil. The time required for 50% methiozolin dissipation was 13 and 3.5 d in bare soil and turf-covered soil, respectively. In Virginia, methiozolin dissipation in the 1-m span of three sequential applications differed between years. Methiozolin concentration immediately following the third biweekly application to C. dactylon ×transvaalensis greens was approximately 105% and 180% of the concentration immediately following the initial application, in 2021 and 2022, respectively. This difference in methiozolin accumulation following three applications was attributed to differential C. dactylon ×transvaalensis green up during methiozolin treatments each year. Despite differences in posttreatment methiozolin concentration between years, the temporal dissipation rate later into the summer was consistent. Following the final application on C. dactylon ×transvaalensis greens, methiozolin dissipated 50% and 90% in 14 and 46 d, respectively. These data suggest that methiozolin dissipates more rapidly in turfgrass systems than in bare soil.

Post-treatment level of LDL cholesterol and all-cause mortality in patients with atherosclerotic cardiovascular disease: evidence from real-world setting.

This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD). Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C ≥ 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality. Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.

Unraveling the Angiogenic Puzzle: Pre-Treatment sVEGFR1 and sVEGFR2 Levels as Promising Prognostic Indicators in Early-Stage Breast Cancer Patients.

Despite the advancements in breast cancer (BrC) diagnosis and treatment, a considerable proportion of patients with early-stage disease still experience local recurrence or metastasis. This study aimed to assess the levels of specific angiogenic parameters in the EDTA plasma of BrC patients before and after treatment and to explore their clinical and prognostic significance. The levels of vascular endothelial growth factor A (VEGF-A), soluble form of vascular endothelial growth factor receptor type 1 (sVEGFR1), and soluble form of vascular endothelial growth factor receptor type 2 (sVEGFR2) were measured in 84 early BrC patients, both prior to surgery and within a median time of nine months post-treatment. Prognostic significance was evaluated using Kaplan-Meier survival and Cox regression analyses. Linear regression models were employed to examine the independent impact of selected angiogenic factors on DFS in breast cancer patients. The results of uni- and multivariate analyses indicated that a pre-treatment concentration of sVEGFR1 above 30.99 pg/mL was associated with improved disease-free survival (DFS) (p < 0.0001 for both analyses), while a pre-treatment concentration of sVEGFR2 above 9475.67 pg/mL was associated with an increased risk of BrC relapse (p < 0.0001 for both analyses). Additionally, a post-treatment concentration of sVEGFR2 above 7361.71 pg/mL was associated with better overall survival (OS) based on the Kaplan-Meier survival analysis (p = 0.0141). Furthermore, linear regression models revealed a significant inverse association between pre-treatment levels of sVEGFR1 and the risk of relapse (standardized β -0.2578, p = 0.0499) and a significant positive association of VEGF-A levels with the risk of recurrence (standardized β 0.2958, p = 0.0308). In conclusion, the findings suggest that both pre- and post-treatment levels of sVEGFR1 and sVEGFR2 may hold promise as potential prognostic markers for BrC patients.

Complex Analysis of Endothelial Markers as Potential Prognostic Indicators in Luminal Invasive Breast Carcinoma Patients: Outcomes of a Six-Year Observational Study.

(1) Background: Metastasis is a complex process in which the primary cancer cells spread to a distant organ or organs, creating a secondary tumor location, which in many patients leads to treatment failure and death. The aim of the present study was to assess the association of endothelial markers (i.e., sP-selectin, sE-selectin and von Willebrand factor) with the leptin-to-adiponectin ratio (LAR) and to perform an analysis of the predictive value on the survival of patients with luminal A and B invasive breast cancer (IBrC). (2) Methods: The trial included 70 treatment-naïve early-stage IBrC patients with a median age of 54.5 years and a median tumor diameter of 1.5 cm. The median duration of follow-up was 5.7 years, with a relapse rate of 15.71%. Specific immunoenzymatic kits were used to determine pre- and post-treatment concentrations of analyzed factors. (3) Results: Regardless of the treatment pattern, endothelial marker concentrations and the LAR increased after adjuvant treatment. The follow-up showed a significantly higher relapse rate in patients with IBrC who had higher pre-treatment sP-selectin and post-treatment LAR levels. According to receiver operating characteristic (ROC) analysis, a post-treatment LAR with a sensitivity of 88.9% and specificity of 57.9% discriminating cases with or without disease relapse. Additionally, a higher risk of breast cancer relapse was associated with a lower post-treatment sP-selectin concentration. (4) Conclusions: Our results showed mainly that pre-treatment sP-selectin levels and post-treatment LAR may have value as prognostic indicators and may contribute to predicting the future outcomes in patients with early-stage IBrC.

(181) Combination Clomiphene Citrate and Anastrozole Therapy Iimproves Semen Parameters in a Multi-institutional Cohort of Men with Idiopathic Infertility

Abstract Introduction Clomiphene citrate (CC), a selective estrogen receptor modulator, and anastrozole, a selective aromatase inhibitor, are common empiric medical therapies for men with idiopathic infertility. The effects of jointly administering these agents are not well understood. Objective The objective of this study is to compare semen parameters in men treated with clomiphene citrate and anastrozole (CC-A) combination therapy to those in men taking anastrozole alone. Methods We performed a multi-center, retrospective cohort study of men with idiopathic infertility prescribed anastrozole at two tertiary referral institutions. Demographic, laboratory, and prescription data were captured. The subset of patients taking CC at the time of anastrozole initiation were identified. Patients with pre-treatment normozoospermia, recent or current exogenous testosterone or human chorionic gonadotropin use, previous orchiectomy, and scrotal surgery during the treatment period were excluded. Outcome measures included changes in World Health Organization sperm concentration category (WHO-SCC) following initiation of anastrozole therapy. Linear and logistic regression models were constructed to evaluate the association of combination therapy with these outcomes. Results 72 men were included in the analysis cohort, including 54 men taking anastrozole alone and 18 men on CC therapy who subsequently started taking anastrozole (CC-A). Men on CC-A relative to anastrozole monotherapy were older (40 vs. 35 years, p=0.03) and had a lower BMI (30 vs. 34 kg/m^2, p=0.05), respectively. Pre-treatment LH levels (5.6 vs. 7.6 IU/L, p=0.25) and testosterone (336 vs 263 ng/dL, p=0.32) were similar. Baseline semen parameters including sperm concentration (3.7 vs. 2.3 M/mL, p=0.26) and motility (41 vs. 36%, p= 0.17) were also comparable. However, post-treatment median sperm concentration (6.9 vs. 3.4M/mL, p=0.02) and the change in mean sperm concentration (17.5 vs. 6.2 M/mL, p=0.03) were significantly higher in the CC-A combination group. Univariate linear regression also revealed an association between the use of CCA combination therapy and increase in sperm concentration (p=0.05). Despite these differences, WHO-SCC upgrade rates between groups were comparable (56 vs. 39%, p=0.22) in the setting of similar post-treatment levels of LH (7.4 vs. 8.6 IU/L, p=0.5), FSH (8.6 vs. 9.4 IU/mL, p=0.19), and testosterone (537 vs. 415 ng/dL, p=0.09). Conclusions Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment sperm concentration when compared to anastrozole monotherapy. Combination empiric medical therapy using clomiphene citrate and anastrozole offers a small, but significant, clinical benefit over anastrozole alone for infertile men Disclosure No

High Post-Treatment Leptin Concentration as a Prognostic Biomarker of the High Risk of Luminal Breast Cancer Relapse: A Six-Year Comprehensive Study.

(1) Background: Nowadays, obesity is well-recognised as a significant risk factor for many chronic diseases, for example, hypertension, diabetes, atherosclerosis and cancer. This study is designed to investigate the prognostic value of the pre- and post-treatment serum levels of adiponectin and leptin in luminal A and B invasive breast cancer (IBrC) patients based on six-years follow-up. (2) Methods: Among 70 patients who underwent breast surgery, 35 were Stage I and 35 were Stage II. The concentrations of pre- and post-treatment adiponectin and leptin were evaluated with a specific ELISA kit. The median follow-up was 68.5 months (inter-quartile range (IQR) = 59-72 months) with a recurrence rate of 15.71%. (3) Results: Generally, concentrations of leptin and adiponectin increased after adjuvant therapy. Follow-up showed a significantly higher incidence of disease relapse in IBrC patients with a high post-treatment concentration of leptin (25.71% vs. 5.71% of cases with a low post-treatment concentration of leptin). A post-treatment leptin concentration of 26.88 ng/mL with a specificity of 64.9% and a sensitivity of 88.9% was determined as the best cut-off value to distinguish patients with disease recurrence from those without disease relapse. (4) Conclusions: Our results demonstrated that only the post-treatment serum leptin concentration may be of value as a prognostic indicator and could contribute to predicting a future outcome for patients with early-stage IBrC.

Comparison between Aqua-acupuncture and Trazodone on Mitigation of Fear, Anxiety and Stress in Healthy Dogs during Routine Veterinary Examination

Fear, anxiety and stress (FAS) are significant factors in human-animal interactions in veterinary hospital settings. The objective of this study was to determine the effect of aqua-acupuncture (Aqua-AP) compared with trazodone on the mitigation of FAS indicators in healthy, stressed dogs during routine veterinary examination and procedures. Fifty-five dogs exhibiting signs of FAS or history of significant FAS in veterinary hospital settings completed the study. Except for those premedicated with trazodone (Group 4), dogs were randomly assigned to 3 treatment groups. Groups 1 (An-shen) and 2 (GB-21) were treated with Aqua-AP bilaterally, while Group 3 served as untreated controls. Stress data, including heart rate, panting respiratory rate, behavior and saliva cortisol concentration were taken at T0 (baseline) and T30 (30 minutes post-treatment). Comparison of group outcome data found that Aqua-AP groups had significant decreases for heart rate (p = 0.004 and p = 0.0005, respectively) and behavior score (p = 0.0002 and p = 0.008, respectively) from T0 to T30, and posttreatment values were not higher than the pharmaceutical-treated subjects (noninferiority). In addition, Group 1 had significant reduction (p = 0.04) in incidence of panting respiratory rate. No significant stress parameter changes were observed in controls. The cortisol concentration change was not significant in any group, but the post-treatment cortisol concentration in both Aqua-AP groups was not greater than the trazodone group (p = 0.004 and p = 0.018, respectively). These results suggest that Aqua-AP at An-shen or GB-21 is effective in mitigating FAS in healthy dogs during routine veterinary examination and demonstrates noninferiority to premedication with trazadone.

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis.

Background and AimsHepatocellular carcinoma (HCC) developing in the context of preexisting cirrhosis is characterized by impaired autophagy that results in increased exosome release. This study was conducted to determine whether circulating exosomes expressing glypican 3 (GPC3) could be utilized as a biomarker for HCC detection and treatment response in patients with cirrhosis.MethodsImmunohistochemistry was performed to assess p62 and GPC3 expression in the lesion and adjacent tissue from cirrhosis with HCC. GPC3-enriched exosomes were captured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic specificity of serum exosome-derived GPC3 (eGPC3) was determined using samples obtained from malignancy-free controls, malignancy-free cirrhotics, cirrhotics with confirmed HCC, and patients with a non-HCC malignancy. The performance of eGPC3 was validated using serum samples of HCC patients received chemotherapy.ResultsWe found that the expression of p62 and GPC3 was significantly increased in HCC tissues compared to adjacent cirrhotic liver. Impaired autophagy and exosome shedding were confirmed in HCC cell lines. Mass spectroscopic analysis revealed that GPC3 was enriched in exosomes isolated from HCC cell lines. An affinity ELISA assay was developed that specifically captures GPC3 positive exosomes in the serum. Total exosome concentration and eGPC3 were significantly elevated in cirrhotic patients with HCC as compared to the reference control groups. Furthermore, decreases in post-treatment exosome concentration and eGPC3 levels were more closely correlated with response to locoregional chemotherapy compared to change in serum AFP in HCC patients awaiting liver transplantation.ConclusionWe developed an affinity exosome capture assay to detect GPC3 enriched exosomes. Our preliminary assessment shows that GPC3 positive exosomes can be used for HCC detection and prediction of treatment outcomes.

Radioactive iodine dose and survival in cats with hyperthyroidism (2015-2020).

Radioactive iodine (131I) is the preferred treatment for feline hyperthyroidism but neither the optimal 131I dose nor consistent predictors of post-treatment azotaemia have been determined. The aims of the study were to evaluate the relationships between: (1) 131I dose and survival; and (2) pretreatment and post-treatment serum creatinine concentration. Medical records of hyperthyroid cats treated with 131I at a single referral hospital were reviewed. Information regarding signalment, body weight, pretreatment and post-treatment serum total thyroxine concentration (TT4), serum creatinine concentration, 131I dose and survival were determined. Multivariable Cox proportional hazards analysis was used to identify variables associated with survival. Multivariable linear regression analysis was used to identify variables associated with post-treatment serum creatinine concentration. One hundred and ninety-eight (79 male, 119 female) cats were treated for hyperthyroidism with 131I (median dose 138 MBq; interquartile range 92-168). Median survival time was 1153 days (range 16-1871). Post-treatment serum creatinine (P <0.001) and age (P = 0.049) were significantly associated with survival. Every 10 µmol/l increase in post-treatment serum creatinine concentration and every year increase in age was associated with a 1.07-fold (confidence interval [CI] 1.04-1.11) and 1.17-fold (CI 1.00-1.37) increase in the daily hazard of death, respectively. Pretreatment serum creatinine concentration was directly, and post-treatment serum TT4 concentration was inversely, associated with post-treatment serum creatinine concentration. Every 1 μmol/l increase in pretreatment serum creatinine concentration was associated with an increase in post-treatment serum creatinine concentration of 0.7 μmol/l (SE 0.17; P <0.001). Conversely, every 1 nmol/l decrease in post-treatment serum TT4 concentration was associated with a 1.2 μmol/l (SE 0.61; P <0.001) increase in post-treatment serum creatinine concentration. Post-treatment serum TT4 concentration was associated with post-treatment azotaemia, which was associated with survival. Although 131I dose was not directly associated with survival, dosing strategies that minimise post-treatment hypothyroidism and azotaemia could improve patient survival.

Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study.

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

Acute Exposure to the Cold Pressor Stress Impairs Working Memory Functions: An Electrophysiological Study.

The results of previous literature focusing on the effects of acute stress on human working memory (WM) are equivocal. The present study explored the effects of acute stress on human WM processing using event-related potential (ERP) techniques. Twenty-four healthy participants were submitted to stressful treatments and control treatment at different times. Cold pressor stress (CPS) was used as stressful treatment, while warm water was used as the control treatment before the WM task. Exposure to CPS was associated with a significant increase in blood pressure and salivary cortisol. After the 3-min resting period, systolic blood pressure (SBP) and diastolic blood pressure (DBP) for the CPS session significantly increased relative to the control treatment session (all p ≤ 0.01), and data also showed a significant increase of 20-min post-treatment cortisol concentration (p < 0.001) for CPS. Data from the CPS session showed significantly longer reaction times, lower accuracy, and WM capacity scores than that of the control treatment session. Interestingly, a difference between the two sessions was also found in N2pc and the late contralateral delay activity (late CDA) components. Specifically, although non-significant main effects of treatment were found for N2pc amplitudes, there was a significant interaction between treatments and stimuli conditions (processing load) [F(2,46) = 3.872, p = 0.028, η2 p = 0.14], which showed a pronounced trend toward equalization of N2pc amplitude across stimuli conditions during the CPS session clearly different from that of control treatment. As for amplitudes for late CDA, a nearly significant main effect of Treatment was found (p = 0.069). That is, the mean amplitude of the late CDA (−2.56 ± 0.27) for CPS treatment was slightly larger than that (−2.27 ± 0.22) for warm water treatment. To summarize, this study not only reported performance impairments in the WM task during CPS trials but also provided high temporal resolution evidence for the detrimental effects of acute stress on processes of information encoding and maintenance.

Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation.

BackgroundSerum neurofilament light chain concentration is a proposed biomarker of axonal injury in multiple sclerosis. Mesenchymal stem cells have anti-inflammatory and repair-promoting activities, making them of interest for potential multiple sclerosis treatment.ObjectivesThe purpose of this study was to assess correlation of serum neurofilament light chain concentration and measures of multiple sclerosis disease activity/severity, longitudinal stability of serum neurofilament light chain concentration, and treatment effect of mesenchymal stem cell transplantation on serum neurofilament light chain concentration.MethodsTwenty-four multiple sclerosis patients underwent intravenous infusion of autologous mesenchymal stem cells. Clinical assessments, serum collection, and brain magnetic resonance imaging were performed at months –1, 0 (transplant), 1, 3, and 6. Matched control serum was collected once (n = 10). Serum neurofilament light chain concentration was measured by single-molecule array. Serum neurofilament light chain concentration correlations with disease measures were analyzed by Spearman correlations and linear mixed effect models. Pre-post transplant serum neurofilament light chain concentration was compared by Wilcoxon signed rank testing.ResultsThere were significant (p<0.01) correlations between serum neurofilament light chain concentration and gadolinium-enhancing lesion number (rho = 0.55) and volume (rho = 0.65), and new/enlarging T2 lesions (rho = 0.65). Patients without disease activity had lower fluctuation in serum neurofilament light chain concentration (p = 0.01). Mean pre- versus post-treatment serum neurofilament light chain concentration values were not significantly different.ConclusionsSerum neurofilament light chain concentration correlated with magnetic resonance imaging measures of disease activity cross sectionally and longitudinally, and was stable in patients without disease activity. There was no clear treatment effect of mesenchymal stem cell transplantation on serum neurofilament light chain concentration.

Does Carcinoembryonic Antigen Serum Concentration Decrease Predicts Overall Survival in Patients with Unresectable Rectal Cancer after Radical Radiotherapy or Radiochemotherapy?

To evaluate whether post-treatment carcinoembryonic antigen (CEA) serum concentration decrease corresponds with the outcome of definitive radiotherapy (RT) or radiochemotherapy (RT-CHT) in primary unresectable rectal cancer patients (pts). Inclusion criteria of this retrospective study were: primary unresectable, locally advanced rectal cancer with histopathological confirmation, RT/RT-CHT as a radical treatment and measured CEA post-treatment level. Between 2000 and 2016 145 pts were treated due to unresectable rectal cancer. Primary aim of the treatment was tumor downsizing allowing further radical surgery. Among them, 71 had pre- and post-treatment CEA and 10 post-treatment CEA measurements, therefore the group of 81 pts (60 men, 21 women) was evaluated in this study. Out of 81 pts: 33 (41%) received RT (accelerated hyperfractionation: 66 Gy in 1.5 Gy fx twice a day or conventional fractionation: 60-66 Gy in 2 Gy fx) and 48 (59%) RT-CHT (54 Gy/1.8 Gy fx +2 cycles of 5-Fu LV). Six to eight weeks after RT or RT-CHT tumor resectability was evaluated again using physical examination and imaging studies. Pts were divided in two groups: group A: pts with CEA post-treatment concentration decrease or below 5 ng/ml and group B: pts without post-treatment decrease of CEA or concentration above 5 ng/ml. Statistical test used were Kaplan-Meyer survival analysis, log rank test and Cox regression model. Median follow-up after the end of RT/ RT-CHT was 5.5 years. Fifty four pts (67%) had radical resection after neoadjuvant RT/RT-CHT and 27 (33%) were still unresectable. CEA serum concentration decrease or level below 5ng/ml (group A) was observed in 63 pts (77%), CEA serum concentration increase or level above 5ng/ml (group B) in 18 (23%). In univariate analysis pts in group A had better overall survival (OS) compared to group B (p=0.039, median OS of 40 months vs 87 months, respectively). Five-year OS was 62% in group A compared to 30% in group B. Moreover, pts who received RT-CHT had better 5-year OS compared to RT (63 vs 44%) respectively (p=0.04). Pts after radical resection had better 5-year OS than those still unresectable (71% vs 21%, p=0,000). Significant factors were then checked in multivariate analysis. Only radical surgery had reached statistical significance (p=0,000) for OS. Pts with post-treatment serum CEA concentration decrease or level below 5 ng/ml tend to have better overall survival compared to those in whom CEA concentration did not decrease after the neoadjuvant treatment. Post-treatment decrease in serum CEA concentration in primary unresectable rectal cancer patients who received definitive RT/RT-CHT can be a useful predictor of outcome.

Therapeutic efficacy of artesunate\u2013amodiaquine and artemether\u2013lumefantrine combinations for uncomplicated malaria in 10 sentinel sites across Ghana: 2015\u20132017

BackgroundRoutine surveillance on the therapeutic efficacy of artemisinin-based combination therapy (ACT) has been ongoing in Ghana since 2005. The sixth round of surveillance was conducted between 2015 and 2017 to determine the therapeutic efficacy of artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) in 10 sentinel sites across the country.MethodsThe study was a one-arm, prospective, evaluation of the clinical, parasitological, and haematological responses to directly observed treatment with AS–AQ and AL among children 6 months to 9 years old with uncomplicated falciparum malaria. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used for the study with primary outcomes as prevalence of day 3 parasitaemia and clinical and parasitological cure rates on day 28. Secondary outcomes assessed included patterns of fever and parasite clearance as well as changes in haemoglobin concentration.ResultsDay 3 parasitaemia was absent in all sites following treatment with AS–AQ whilst only one person (0.2%) was parasitaemic on day 3 following treatment with AL. Day 28 PCR-corrected cure rates following treatment with AS–AQ ranged between 96.7% (95% CI 88.5–99.6) and 100%, yielding a national rate of 99.2% (95% CI 97.7–99.7). Day 28 PCR-corrected cure rates following treatment with AL ranged between 91.3% (95% CI 79.2–97.6) and 100%, yielding a national rate of 96% (95% CI 93.5–97.6). Prevalence of fever declined by 88.4 and 80.4% after first day of treatment with AS–AQ and AL, respectively, whilst prevalence of parasitaemia on day 2 was 2.1% for AS–AQ and 1.5% for AL. Gametocytaemia was maintained at low levels (< 5%) during the 3 days of treatment. Post-treatment mean haemoglobin concentration was significantly higher than pre-treatment concentration following treatment with either AS–AQ or AL.ConclusionsThe therapeutic efficacy of AS–AQ and AL is over 90% in sentinel sites across Ghana. The two anti-malarial drugs therefore remain efficacious in the treatment of uncomplicated malaria in the country and continue to achieve rapid fever and parasite clearance as well as low gametocyte carriage rates and improved post-treatment mean haemoglobin concentration.

Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level

ObjectiveTo determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. Study designA retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015.Men treated with CC for at least 3 months were included if they presented with:•infertility•plasma T level less than 11 nmol/l and low or normal FSH and LH levels•sperm concentration >0.1 millions/ml. Results18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration.The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. ConclusionCC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.

Clinical effect and mechanism of acupuncture and moxibustion on occupational hand-arm vibration disease: A retrospective study

IntroductionThis is a retrospective study exploring clinical effect of acupuncture and moxibustion on upper limb disorder induced by occupational hand-arm vibration disease (OHAVD), and preliminarily exploring mechanism of the effect. Methods43 patients diagnosed with occupational HAVD were divided into experimental group (n = 21) and control group (n = 22). Before and after 4 weeks treatment, the occurrence of vibration-induced white finger(VWF) was observed, upper limb function was assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, based on which the DASH scores were determined, and the serum concentration of TNFα was detected using ELISA. ResultsPre-treatment DASH score was not significantly different between two groups, but post-treatment score was significantly lower in experimental group than in control group (21.94 ± 5.79vs.35.87 ± 3.80, p < 0.05).Post-treatment the occurrence of VWF in experimental group was significantly lower than that of pre-treatment (χ2 = 5.081, p = 0.024).88.37% of the pretreatment serum TNFα concentration was above reference range 8.1 pg/ml, and it was not significantly different between two groups. However, post-treatment TNFα concentration in experimental group was significantly lower than that in control group (10.51 ± 3.68 pg/ml vs.14.72 ± 8.66 pg/ml, p = 0.045). Further, the difference in DASH score and TNFα concentration before and after treatment was statistically significant between groups (p < 0.05). ConclusionsCombination of acupuncture and moxibustion may be an effective treatment for occupational HAVD, the mechanism is possibly related to reduction of the serum TNFα levels.

Haemogram and hormonal profile of WAD bucks treated with leaf ethanolic extract of &lt;i&gt;Spondias mombin&lt;/i&gt;

Twelve post pubertal West African Dwarf (WAD) bucks of average age of 1.8 ± 0.19 years and average weight of 8.76 ± 0.72 kg were experimentally treated orally with 800mg/kgBW of ethanol extract of Spondias mombin. Experiment was carried out in the month of August at Abeokuta, South West Nigeria with temperature range of 24oC and 33oC on Latitude 07o 10’N and Longitude 03o 2’E. The goats had well-formed pendulous scrotum with well descended free bilateral testicles. The goats were kept in a standard goat pen and fed with fresh green centrosema leaves in the morning and commercially prepared ration in the evening. Water was served ad libitum. Pre-treatment haematological and hormonal profiling after aseptical collection of blood from the bucks was followed with 14 days of oral treatment with ethanol extract of Spondias mombin at the dosage rate of 800mg/kg BW. Post-treatment haematological and hormonal studies followed after. The hormones assayed were follicle stimulating hormone (FSH), luteinising hormone (LH), testosterone, progesterone, estrogen and prolactin. The haemogram revealed significantly (p &lt; 0.05) higher PCV (24.33±0.6 %) in pre-treatment compared to 19.92± 1.1 % recorded for post-treatment. However, both were lower in values than normal range. WBC and RBC did not change significantly but while RBC values for pre-treatment and post-treatment fell within normal range, only the WBC value of post-treatment did. Assay of FSH, progesterone, estrogen and prolactin revealed no significant (p . 0.05) difference between pre-treatment and post-treatment; however, noticeable higher pre-treatment LH concentration and elevated post-treatment testosterone concentration were observed. The work showed that Spondias mombin at 800mg/kgBW has profertility tendencies in the buck and can be considered as an aphrodisiac in goat breeding in developing countries probably at a higher dosage.Keywords: Buck, Ethanol, Extract, Leaf, Spondias mombin

Guided longer pulses from a diagnostic ultrasound and intraclot microbubble enhanced catheter-directed thrombolysis in vivo.

The mechanism of ultrasound thrombolysis (UT) is generally attributed to cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei in the vessel-obstructing thrombi significantly reduces the effectiveness of UT. Taking advantage of the widely performed catheter-directed therapy (CDT), in a thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA thrombolysis procedure, guided moderate mechanical index longer pulses from a modified diagnostic ultrasound transducer, combined with an intraclot infusion of MB, significantly accelerated the thrombolysis process. The higher thrombolysis efficacy score and consistent elevated post-treatment plasma concentration level of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT over CDT/UT alone. Pathologic examination of the treated occluded IVC segments revealed an almost complete dissolution of the thrombi treated with CDT + UT. There was no evidences of thrombo-embolism or local thrombus formation in the cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer pulse ultrasound from a diagnostic transducer is able to safely and significantly improve a catheter-directed thrombolysis procedure. It thus has the potential to achieve earlier clot removal, administration of a lower dosage of thrombolytic agent and, consequently, a lower incidence of thrombolysis-related side effects.

Spermiogram and testicular morphological studies of the buck after treatment with ethanol leaf extract of &lt;i&gt;Spondias mombin&lt;/i&gt;

Twelve sexually matured West African Dwarf bucks from were used for the experiment. Plant extraction was by cold extraction method using hexane and ethanol as solvents. All the goats had bilaterally well descended free testicles. They were kept in standard goat pen, were served water ad libitum, centrosema plant and ration. They were stabilised for two weeks after which pre-treatment spermiogram was done followed by 14 days of oral administration of 800mg/kg ethanol leaf extract of Spondias mombin. Spermiogram was repeated after treatment. Two randomly selected goats were then castrated through a midline pre-scrotal incision for morphological study and histology of the testes and epididymides. Total spermatozoa morphological abnormalities in pre-treatment of 17.1% was significantly (p≤0.05) higher than the 10% recorded for post-treatment. Curved mid-piece (1.8%) and bent tail (1.8%) constituted the highest abnormalities post-treatment while curved tail (3.5%) was highest pre-treatment. Mean values of progressive motility and percentage liveability were significantly higher (p≤0.05) in post- treatment (96.17±3.10% and 98.25±1.36% respectively) compared to pre-treatment (80.83±11.84% and 78.75±9.56% respectively). Post-treatment sperm concentration (2.50±0.32 x109 cells/ml) compared with pre-treatment (2.32±0.36 x109 cells/ml) was not significantly different. Post-treatment gross and histological features of the bucks’ testes and epididymis were normal. The work revealed that Spondias mombin at 800mg/kgBW improved semen quality in bucks indicating its usefulness as a potential profertility agent.Keywords: Buck, Morphological, Spondias mombin, Spermiogram, Testicular