No-response Group Research Articles

Exhaustive clinical examination of etiology and initial response to first-line treatment in 577 children with infantile epileptic spasm syndrome children: A 5-year retrospective observational study.

Employing whole-exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short-term responses to first-line treatment. We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. A total of 577 patients were included; 412 completed trio-WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non-spasms at the initial seizure onset. A total of 532 patients completed the first-line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early-onset seizures (≤3 months) than the no-response group (11.3% vs. 23.7%, p < 0.01 and 11.3% vs. 21.5%, p = 0.03, respectively). Logistic regression analysis indicated that earlier initiation of first-line treatment was associated with a higher likelihood of an initial response. However, the etiological classification did not have a significant impact on the initial response. IESS patients with structural abnormalities are more likely to present with non-spasm seizures at initial onset. Early initiation of first-line treatment is crucial; however, initial responses may be less favorable when seizures occur in early infancy.

Nomograms confirm serum IL-6 and CRP as predictors of immune checkpoint inhibitor efficacy in unresectable hepatocellular carcinoma.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has become the first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, only a small portion of patients are responsive to ICIs. It is important to identify the patients who are likely to benefit from ICIs in clinical practice. We aimed to examine the significance of serum IL-6 and CRP levels in predicting the effectiveness of ICIs for uHCC. We retrospectively recruited 222 uHCC patients who received ICIs treatment (training cohort: 124 patients, validation cohort: 98 patients). In the training cohort, patients are categorized into the response group (R) and no-response group (NR). The levels of serum IL-6 and CRP were compared between the two groups. Internal validation was performed in the validation cohort. Survival analysis was carried out using the Kaplan-Meier method and Cox proportional hazard regression model. The nomograms were developed and assessed using the consistency index (C-index) and calibration curve. Serum levels of IL-6 and CRP were significantly lower in the R group than in the NR group (9.94 vs. 36.85 pg/ml, p< 0.001; 9.90 vs. 24.50 mg/L, p< 0.001, respectively). An ROC curve was employed to identify the optimal cut-off values for IL-6 and CRP in both groups, resulting in values of 19.82 pg/ml and 15.50 mg/L, respectively. Multivariate Cox regression analysis revealed that MVI (HR 1.751, 95%CI 1.059-2.894, p=0.029; HR 1.530, 95%CI 0.955-2.451, p=0.077), elevated IL-6 (HR 1.624, 95%CI 1.016-2.596, p=0.043; HR 2.146, 95%CI 1.361-3.383, p =0.001) and high CRP (HR 1.709, 95%CI 1.041-2.807, p=0.034; HR 1.846, 95%CI 1.128-3.022, p = 0.015) were independent risk factors for PFS and OS, even after various confounders adjustments. Nomograms are well-structured and validated prognostic maps constructed from three variables, as MVI, IL6 and CRP. Low levels of IL-6 and CRP have a positive correlation with efficacy for uHCC patients receiving ICIs.

NEOADJUVANT TREATMENT OF LIVER METASTASES OF COLORECTAL CANCER: PREDICTIVE FACTORS OF PATHOLOGICAL RESPONSE.

Surgery after neoadjuvant chemotherapy (CT) improves the prognosis of colorectal liver metastases (CRLM). The aim of this study was to evaluate the predictive factors of the histological response of CRLM after neoadjuvant treatment. A retrospective monocentric study including patients with CRLM operated after neoadjuvant treatment. Assessment of histological response was based on the Rubbia-Brandt tumor regression grading score. The scores were grouped into two types of response: Response Group (R) and No Response Group (NR). The study included 77 patients (mean age=56 years, sex ratio=1.57). Node metastases were noticed in 62% of cases. Synchronous liver metastasis was present in 42 cases (55%) and metachronous liver metastasis in 45%. Neoadjuvant treatment consisted of CT only in 52 patients (68%) and CT with targeted therapy in 25 patients (32%). Chemo-induced lesions were present in 44 patients (57%). Histological response was presented (Group R) in 36 cases (47%) and absent (Group NR) in 41 cases (53%). The overall survival of our patients was 32 months. For Group R, survival was significantly greater (p=0.001). The predictive factors of histological response identified were delay in the onset of liver metastasis greater than 14 months (p=0.027) and neoadjuvant treatment combining CT and targeted therapy (p=0.031). In multivariate analysis, the type of neoadjuvant treatment (p=0.035) was an independent predictive factor of histological response. Predictive factors of histological response would allow us to identify patients who would benefit most from neoadjuvant treatment. These patients with CRLM onset of more than 14 months and treated with CT combined with targeted therapy would be the best candidates for a neoadjuvant CT strategy followed by surgical resection.

Does a Positive Response to Transforaminal Epidural Steroid Injection Identify Patients Who Can Avoid Surgery for Two Years?

Transforaminal epidural steroid injection (TFESI) is widely used to manage lumbar radiculopathy. In clinical settings, patients often undergo repeated transforaminal epidural injections with or without steroid administration. To examine whether a positive response to TFESI at the first month, can in clinical settings, identify patients with radiculopathy who can avoid surgery for two years. Study Design/Setting. This prospective observational study was conducted at an academic medical center. Individuals aged ≥20 years who had been referred to our pain center by spine surgeons were enrolled. All patients were assessed using the Numerical Rating Scale (NRS) at baseline and 1 month after the first TFESI. Patients were divided into two groups according to the NRS decrement: the positive response (PR) group achieved a ≥2.0 decrease on the NRS 1 month after the first TFESI compared to baseline and the no response (NR) group achieved a <2.0 decrease on the NRS. The incidence rates of surgery over two years were compared between the two groups. In addition, we calculated the hazard ratio of the PR group to the NR group regarding the incidence of surgery over two years using the Cox proportional hazard model, adjusting for baseline NRS. Seventy-six patients completed the two-year follow-up. In total, 8 and 68 patients had bilateral and unilateral radiculopathy, respectively. The PR and NR groups included 35 and 41 patients, respectively. The rate of surgery avoidance was 85.7% and 73.2% in the PR and NR groups, respectively. This difference was not statistically significant (p=0.26). After adjusting for baseline NRS, the hazard ratio of the PR group to the NR group regarding the incidence of surgery within two years was 0.35 (95% confidence interval: 0.11-1.11, p=0.08). A positive response to TFESI may not identify patients who can avoid surgery for two years.

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation

BackgroundBronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. MethodsPost-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. ResultsTotal of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. ConclusionsInhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Impact of anti-VEGF therapy on distinctive retina layers in patients with macular edema secondary to branch retinal vein occlusion

BackgroundTo explore the impact of anti-vascular epithelial growth factor (ant-VEGF) on the thickness of each retinal layer in patients with macular edema (ME) secondary to the branch retinal vein occlusion (BRVO).MethodsThis retrospective study included patients with ME secondary to monocular BRVO who received anti-VEGF therapy in Ningxia Eye Hospital between January-December 2020.ResultsForty-three patients (25 males) were included, with 31 showed > 25% reduction in central retinal thickness (CRT) after anti-VEGF therapy (response group), and the others showed a ≤25% reduction in CRT (no-response group). The response group showed significantly smaller mean changes in the ganglion cell layer (GCL) (after 2 months) and inner plexiform layer (IPL) (after 1, 2, and 3 months) and significantly greater mean changes in the inner nuclear layer (INL) (after 2 and 3 months), outer plexiform layer (OPL) (after 3 months), outer nuclear layer (ONL) (after 2 and 3 months), and CRT (after 1 and 2 months) (all P < 0.05) as compared to the no-response group. The mean change in the thickness of each retinal layer IPL (P = 0.006) between the two groups was significantly different after controlling for a time and with a significant time trend (P < 0.001). Additionally, patients in the response group were more likely to have an improvement in IPL (43.68 ± 6.01 at 1 month and 41.52 ± 5.45 at 2 months vs. 39.9 ± 6.86 at baseline) after anti-VEGF therapy, while those in no response group might show improvement in GCL (45.75 ± 8.24 at 1 month, 40.00 ± 8.92 at 2 months, and 38.83 ± 9.93 at 3 months vs. 49.67 ± 6.83 at baseline).ConclusionsAnti-VEGF therapy might help restore the retinal structure and function in patients with ME secondary to BRVO, and those who have a response after anti-VEGF therapy are more likely to improve IPL, while those having no response might show improvement in GCL.

Combining Clinicopathology, IVIM-DWI and Texture Parameters for a Nomogram to Predict Treatment Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

ObjectivesThis study aimed to create a nomogram for the risk prediction of neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC).MethodsClinical data in this retrospective study were collected from a total of 135 LARC patients admitted to our hospital from June 2016 to December 2020. After screening by inclusion and exclusion criteria, 62 patients were included in the study. Texture analysis (TA) was performed on T2WI and DWI images. Patients were divided into response group (CR+PR) and no-response group (SD+PD) according to efficacy assessment. Multivariate analysis was performed on clinicopathology, IVIM-DWI and texture parameters for screening of independent predictors. A nomogram was created and model fit and clinical net benefit were assessed.ResultsMultivariate analysis of clinicopathology parameters showed that the differentiation and T stage were independent predictors (OR values were 14.516 and 11.589, resp.; P<0.05). Multivariate analysis of IVIM-DWI and texture parameters showed that f value and Rads-score were independent predictors (OR values were 0.855, 2.790, resp.; P<0.05). In this study, clinicopathology together with IVIM-DWI and texture parameters showed the best predictive efficacy (AUC=0.979). The nomogram showed good predictive performance and stability in identifying high-risk LARC patients who are resistant to nCRT (C-index=0.979). Decision curve analyses showed that the nomogram had the best clinical net benefit. Ten-fold cross-validation results showed that the average AUC value was 0.967, and the average C-index was 0.966.ConclusionsThe nomogram combining the differentiation, T stage, f value and Rads-score can effectively estimate the risk of nCRT resistance in patients with LARC.

Serial ctDNA profiling in patients with metastatic prostate cancer undergoing treatment with radium-223.

e17018 Background: Assessment of the anti-tumor response to radium-223 (Ra-223) treatment is difficult in individuals. PSA levels seldom fall and imaging of existing bone metastases is imprecise. Circulating tumor DNA (ctDNA) is a non-invasive marker of prostate tumor DNA, with static measurements demonstrating high concordance rates with tumor DNA. Serial monitoring of ctDNA levels may provide insights into therapy response, targetable mutations, and progression of disease. We report changes in ctDNA profiles and clinical associations of 10 patients who had serial ctDNA profiles during Ra-223 treatment. Methods: Serial ctDNA analyses of mutations (73 genes) and amplifications (18 genes) were performed via a commercial provider (Guardant 360; Guardant Health). Assays were performed before treatment, after the third Ra-223 dose, and after the final Ra-223 dose. ctDNA data (minor allele frequencies for mutations, copy number for amplifications) were reviewed to identify clonal mutations with at least 50% change in highest allelic frequency or 30% change in copy number during treatment. Clinical data (performance status (PS), PSA, pain score, prescribed oral morphine equivalents (OME), imaging, progression free survival (PFS), and overall survival) were gathered via chart review. Clinical progression was defined by an increase in at least 2 bone lesions on bone scan, progression of soft tissue disease by RECIST, worsening PS, or at least 20% increase in OME. Results: Three of 10 patients had a reduction in the proportion of mutated or amplified tumor DNA as measured by ctDNA profiling, after receiving Ra-223 (response group). Median PFS defined by time to PSA rise of at least 25% in this group was 120 days (95% CI 83 to 237) compared to 29 days (95% CI 21 to 145) in the group without a reduction (no response group). Median clinical PFS defined as above was 266 days (95% CI 109 to 291) in the response group compared to 83 days (95% CI 33 to 182) in the no response group. There was no difference in baseline pain score between the two groups, though median baseline PSA was higher in the no-response group (97.14 compared to 20.05). Reductions in allelic frequency were noted in several mutated genes, including AR, ARID1A, CDK12, and TP53(G245C), during Ra-223 therapy of subjects in the response group. Decreases in copy number were also seen in several amplified genes, including AR, CCNE1, CDK6, FGFR1. In the no-response group, 4/7 patients had an increase in AR amplification; 3/7 patients had an increase in variant allele fraction of TP53 mutations. In the response group of 3 patients who had a reduction in clonal mutations, none had an increase in the AR amplification. Conclusions: A reduction in proportion of clonal mutations or gene amplification measured in ctDNA may be associated with a longer PFS in patients treated with Ra-223. Mutations in the TP53 gene and amplification of AR gene were associated with shorter PFS.

Can 3D pseudo-continuous arterial spin labeling perfusion imaging be applied to predict early response to chemoradiotherapy in patients with advanced nasopharyngeal carcinoma?

Background and purposeChemoradiotherapy (CRT) has been widely applied in patients with advanced nasopharyngeal carcinoma (ANPC). However, limited imaging modality exists on the evaluation of early response to CRT. The purpose of this study was therefore to investigate whether 3D pseudo-continuous arterial spin labeling (3D pCASL) perfusion imaging could predict early response to CRT in ANPC patients. Materials and methodsSeventy ANPC patients who received CRT underwent pre-treatment MRI including 3D pCASL perfusion measurements, and were categorized into response group (RG) and no-response group (NRG) according to RECIST 1.1. Pre-treatment 3D pCASL derived cerebral blood flow (CBF) values in tumors were compared between RG and NRG patients. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal diagnostic cutoff value for CBF in predicting tumor response to CRT. Clinicopathological variables were also analyzed by using univariate and binary logistic regression. The corresponding obtained variables with statistical significance were further applied to create a nomogram in which the bootstrap resampling method was used for calibration. ResultsForty-eight patients in RG had significantly higher pre-treatment CBF values in tumors compared with 22 patients in NRG (P < 0.001). CBF showed the high area under the ROC curve (AUC = 0.843) in distinguishing RG from NRG patients. The corresponding cutoff value for CBF was 103.68 ml/100 g/min, with respective accuracy, sensitivity and specificity of 82.86%, 87.50% and 72.73%. The nomogram was generated by binary logistic regression results, incorporating three variables: CBF value, clinical stage and pathological type. The AUC, accuracy, sensitivity and specificity of the nomogram was respectively 0.893, 84.28%, 81.25% and 90.91% in predicting tumor response to CRT. Moreover, as shown in the calibration curve, a strong agreement was observed between nomogram prediction probability and actual clinical findings (P = 0.309). Conclusions3D pCASL derived CBF in tumor could act as a noninvasive effective biomarker to predict tumor response to CRT in ANPC patients before clinical treatment. Furthermore, the nomogram combining CBF and clinicopathological variables could serve as a novel clinical analysis tool for treatment response prediction.

Pre-treatment Apparent Diffusion Coefficient Does Not Predict Therapy Response to Radiochemotherapy in Cervical Cancer: A Systematic Review and Meta-analysis.

Magnetic resonance imaging is used for staging purposes in cervical cancer (CC). Diffusion-weighted imaging and the apparent diffusion coefficient (ADC) are associated with tumor microstructure. The present analysis sought to compare pre-treatment ADC values to predict treatment outcome of radiochemotherapy for CC based upon a large patient sample. MEDLINE library and SCOPUS databases were assessed for suitable articles up to May 2020. The primary endpoint was the mean ADC value of CC according to the treatment response to radiochemotherapy. In total, 16 studies were included in the analysis. For the response group, 416 patients were included in the analysis (72.5%) and for the no-response group 158 patients were included (27.5%). The mean ADC value of patients with CC with treatment response was 0.87×10-3 mm2/s (95% confidence interval=0.81-0.94×10-3 mm2/s), and for the patients with no response was 0.92×10-3 mm2/s (95% confidence interval=0.85-0.98×10-3 mm2/s). Pre-treatment ADC values alone cannot be used to reliably predict treatment response to radiochemotherapy in CC.

Can the mesorectal fat tissue volume be used as a predictive factor in foreseeing the response to neoadjuvant chemoradiotherapy in rectum cancer? A CT-based preliminary study.

This study was to investigate the effect of mesorectal fat tissue volume (MRV) on the pathological response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. 88 patients who had been diagnosed with locally advanced rectal cancer between January 2017 and June 2020 were reviewed retrospectively. The total abdominal, subcutaneous, visceral, and mesorectal fatty tissue components were measured semiquantitatively by two radiologists using computed tomography (CT)-based findings. The patients were divided into two groups as those with and without a pathological response to nCRT. The relationship of MRV with the other fat tissue components of the body was also evaluated. We performed a retrospective analysis of 88 patients (mean age 62.7years [range, 33-90years]; 31 males and 57 females). A positive response to nCRT was present in 47 patients. There were 59 patients with stage 3 disease. 46 patients demonstrated lymph node involvement. The mean MRV was 69.6 ± 31.0ml in no-response group and 105.8 ± 47.5ml in response-positive patients (p < 0.05). MRV showed the highest correlation with visceral fat volume (VFV). There was a negative correlation between the MRV and the N stage. A cut-off value of ≥ 69.4 for MRV predicted the repsonse to nCRT, with 82.9% sensitivity and 58.5% specificity [AUC: 0.757 (0.653-0.842), p < 0.001] in receiver operating characteristic (ROC) curve analysis CONCLUSIONS: MRV can be used as a novel parameter in predicting of pathological response to nCRT in locally advanced rectal cancer patients.

Clinical significance of neutrophil-to-lymphocyte ratio in assessing response to cardiac resynchronization therapy in elderly patients

Objective To investigate the clinical significance of neutrophil-to-lymphocyte ratio(NLR)in assessing response to cardiac resynchronization therapy(CRT)in elderly patients. Methods Clinical data of 105 elderly patients with chronic heart failure(CHF)who had received CRT at our hospital from January 2006 to January 2017 were retrospectively analyzed, and patients were divided into a no-response group(n=42)and a response group(n=63)according to CRT outcomes after 6 months.General clinical data were compared between the two groups.Factors influencing response to CRT were analyzed by logistic regression model analysis.The receiver-operating characteristic(ROC)curve was used to assess the predictive value of NLR in response to CRT. Results Compared with the response group, the no-response group had increased baseline levels of initial QRS width, serum creatinine(Scr)and uric acid(UA)(P 0.05). After 6 months of CRT, the LVEDD, NYHA functional class, neutrophil count and NLR were higher, and LVEF and lymphocyte count were lower in the no-response group than in the response group(P<0.05). The difference in NLR between 6 months after CRT and before CRT(ΔNLR)was higher in the no-response group than in the response group(P<0.05). Multi-factor Cox regression analysis showed that NLR(OR=1.895, 95%CI: 1.538~5.284, P=0.031)and ΔNLR(OR=2.579, 95%CI: 2.110~8.329, P=0.005)were independent risk factors for CRT(HR=1.590, 95%CI: 1.215~2.146, P=0.013). ROC curve analysis showed that ROCAUC of ΔNLR in the no-response group was 0.891, 95%CI: 0.832~0.937, which was higher than that at 6 months after CRT(0.813, 95%CI: 0.765~0.864)(Z=2.712, P<0.05). Conclusions The increase in NLR after CRT may be an early sign for no-response to CRT, and dynamic monitoring of NLR should be promoted to assess the prognosis of patients undergoing CRT. Key words: Neutrophil; Lymphocyte; Heart failure

In Vivo Imaging Markers for Prediction of Radiotherapy Response in Patients with Nasopharyngeal Carcinoma: RESOLVE DWI versus DKI

In this prospective study, we compared the performance of readout segmentation of long variable echo trains of diffusion-weighted imaging (RESOLVE DWI) and diffusion kurtosis imaging (DKI) for the prediction of radiotherapy response in patients with nasopharyngeal carcinoma (NPC). Forty-one patients with NPC were evaluated. All patients underwent conventional MRI, RESOLVE DWI and DKI, before and after radiotherapy. All patients underwent conventional MRI every 3 months until 1 year after radiotherapy. The patients were divided into response group (RG; 36/41 patients) and no-response group (NRG; 5/41 patients) based on follow-up results. DKI (the mean of kurtosis coefficient, Kmean and the mean of diffusion coefficient, Dmean) and RESOLVE DWI (the minimum apparent diffusion coefficient, ADCmin) parameters were calculated. Parameter values at the pre-treatment period, post-treatment period, and the percentage change between these 2 periods were obtained. All parameters differed between the RG and NRG groups except for the pretreatment Dmean and ADCmin. Kmean-post was considered as an independent predictor of local control, with 87.5% sensitivity and 91.3% specificity (optimal threshold = 0.30, AUC: 0.924; 95% CI, 0.83–1.00). Kmean-post values of DKI have the potential to be used as imaging biomarkers for the early evaluation of treatment effects of radiotherapy on NPC.

Genomic Analysis to Predict Response to Neoadjuvant Chemoradiation Therapy in Rectal Cancer

The role of preoperative chemoradiation therapy is well established in the treatment of locally advanced rectal cancer. However, there remains significant heterogeneity in response to CRT, with only 50% of patients having some degree of response to neoadjuvant therapy. Currently, there is no established method to identify the subset of patients that do not response to treatment. Therefore, the purpose of this study was to utilize next generation DNA sequencing to assess for variants among a panel of 160 cancer-related genes to identify gene signatures among patients with pathologic complete response (pCR) compared to patients with no response (NR). A cohort of patients treated with neoadjuvant CRT followed by definitive surgery were selected from our clinical database and pathology archive (N=16). The pCR group included patients who had no evidence of residual tumor on pathologic assessment (N=8). In contrast, the NR group included patients who had >50% original tumor on final assessment. Tumor DNA was extracted from formalin-fixed paraffin-embedded tissue and libraries constructed with Comprehensive Cancer Panel (Qiagen). Sequencing was performed with Illumina NextSeq 500 and alignment was achieved using Biomedical Genomics Workbench with subsequent analysis with Ingenuity Variant Analysis. A comparison of the pretreatment biopsies from non-responders (n=8) versus complete responders (n=8) identified 178 individual variants in 71 genes. However, of these only 2 variants were found in more than one non-responder which were absent in all the complete responders. These variants were found in KDM6A and DNMT3A. Pathway analysis of all the variants found in non-responders identified “colorectal cancer metastasis signaling” as being highly altered. Analysis at the gene level identified 27 variants in 11 genes that were altered in the non-responder compared to the responders. There genes were CTNNB1, PIK3CA, APC, ECT2L, MET, ABL1, ATM, KRAS, AKT1, TP53 and EP300. Several of these genes were represented in the “epithelial-mesenchymal transition pathway”. This preliminary study has identified mutated genes which are present in the pretreatment biopsies of rectal cancer patients who do not respond to neoadjuvant chemoradiation. Genes involved in DNA repair, cell survival and epithelial-mesenchymal transition were amongst the genes altered. Several drug targets including PIK3CA, MET and DNA damage response may offer new avenues for combination therapy for these patients.

Serum IFN-\u03b3 levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis

BackgroundTo explore the mechanism of the different clinical efficacies of mesenchymal stem cell transplantation (MSCT) and identify a possible serum biomarker for predicting the therapeutic effect of MSCT in rheumatoid arthritis (RA) patients.MethodsA total of 105 patients with persistently active RA and poor responses to traditional medication were randomly divided into MSCT and control groups. Outcomes were evaluated according to the 28-joint Disease Activity Score and Health Assessment Questionnaire, serological indicators, regulatory T cell (Treg) to T helper 17 (Th17) cell ratio, and inflammatory cytokine levels. Twelve weeks after MSCT, the outcomes of the MSCT group were evaluated according to the European League against Rheumatism response criteria. Patients with a good or moderate response were added to the response group, and those with no response were added to the no-response group.ResultsNo serious adverse events were reported for either MSCT subgroup (28 in the response group and 24 in the no-response group). The therapeutic effects lasted for 48 weeks without continuous administration. Notably, a transient increase in serum IFN-γ (>2 pg/ml) levels was observed in the response group, but not in the no-response group. Furthermore, an increase in IL-10 levels and the Treg/Th17 ratio and a reduction in IL-6 levels appeared 2–3 weeks after the transient IFN-γ increase.ConclusionsAllogeneic MSCT is safe and feasible, and we propose high serum IFN-γ levels as a potent biomarker for predicting MSCT response.Trial registration chictr.org, ChiCTR-ONC-16008770. Registered 3 July 2016, http://www.chictr.org.cn/showproj.aspx?proj=14820

Expression of TP53 and IL-1α in unicystic ameloblastoma predicts the efficacy of marsupialization treatment.

In this study, we evaluated the effects of marsupialization in treating unicystic ameloblastoma (UA) and investigated the relationship between TP53 and interleukin 1 α (IL-1α) expression and the clinical outcome of UA treated with marsupialization.Consecutive patients treated with marsupialization and curettage at Shanghai Ninth People's Hospital were included. According to the unified standard, 48 patients were included in this study. Of these, 20 showed a good response, 10 a partial response, and 18 no response, based on the outcome of the marsupialization procedure. The expression of proteins TP53 and IL-1α was detected with immunohistochemistry (IHC). The clinical and pathological characteristics of the patients were analyzed.Analysis of the clinical and pathological characteristics showed that the effects of marsupialization treatment were significantly associated with lesion location (P < .001) and tumor diameter (P = .01). IHC showed that TP53 expression was significantly higher in the good-response group than in the partial- or no-response group (P = .02), and IL-1α expression was significantly higher in the good-response group than in the partial- and no-response groups (P = .03).Marsupialization is an effective preliminary procedure for treating UA before curettage and peripheral ostectomy. The expression of the TP53 and IL-1α proteins correlates directly with the outcome of UA treated with marsupialization.

The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial.

BackgroundAppropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (NCT01282073).MethodsA total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared.ResultsThe level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks.ConclusionIn combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT01282073

Parameters for Contrast-Enhanced Ultrasound (CEUS) of Enlarged Superficial Lymph Nodes for the Evaluation of Therapeutic Response in Lymphoma: A Preliminary Study.

BackgroundThe aims of this preliminary study were to evaluate contrast-enhanced ultrasound (CEUS) imaging and the therapeutic response of enlarged superficial lymph nodes in patients with lymphoma before and after chemotherapy and to determine the most useful CEUS response parameters.Material/MethodsForty-three patients with lymphoma, with 43 enlarged superficial lymph nodes, underwent CEUS and conventional ultrasound (US), before treatment and after the first three cycles of chemotherapy. Clinical responses included overall response (OR) and no response (NR). Imaging parameters by time-intensity curve (TIC) included basic intensity (B), wash-out slope and/or decent slope (K), wash-in slope or rise slope (C), time to peak (TTP), area under the gamma curve (Area), arrive time(ATM), peak intensity (PI), change of peak intensity (I) were compared. And receiver operating characteristic (ROC) curve analysis was operated.ResultsQuantitative parameters of CEUS before and after the first three cycles of chemotherapy showed a significant difference in the AreaΔ, PIΔ, and IΔ in the OR group compared with NR group (P<0.05). There was a significant difference in the Cpre, Areain, PIin, Iin, AreaΔ, PIΔ, and IΔ in the OR group compared with NR group (P<0.05). The effectiveness of the therapeutic response was predicted by the CEUS parameters of IΔ (P<0.05). And ΔArea has the highest diagnostic performance of ineffectiveness.ConclusionsThe findings of this study have shown that quantitative analysis by CEUS may be a useful, and objective, imaging method for the evaluation of the therapeutic response of enlarged superficial lymph nodes in lymphoma before and after chemotherapy.

Evaluation of the Effectiveness of a Short-term Treatment and Repeat Treatment of Nocturnal Enuresis Using an Enuresis Alarm

To evaluate the effectiveness of a 3-month enuresis alarm (EA) treatment and repeat EA treatment among pediatric patients with nocturnal enuresis, and to compare patient characteristics among "responders" and "nonresponders" to treatment. Clinical outcomes were retrospectively evaluated for 137 children (94 boys and 43 girls, mean age, 10.1 years). Effectiveness was evaluated after an initial 3-month treatment, using the International Children's Continence Society criteria. Among children in the no-response group at 3 months, those who continued the EA treatment for ≥4 months were subclassified into group 1, whereas children who repeated the EA treatment at an interval ≥6 months were subclassified into group 2. Among our 137 cases, 19 achieved complete response and 47 achieved partial response at 3 months, for an overall treatment effectiveness rate of 48%. Among the no-response group, treatment was extended in 17 cases (group 1), with 3 (18%) achieving a successful outcome. Treatment was repeated in 18 cases (group 2). In group 2, 8 (44%) achieved successful outcome at 3-month time point. Daytime urinary incontinence did not modify treatment effectiveness. EA treatment should be given for a short period of time and should not be continued without a definite purpose or clear response. Suspending and then repeating this treatment after an appropriate interval is effective for patients who do not respond to the initial course of treatment.

Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

BackgroundBronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT.MethodsAfter diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score.ResultsAfter 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036).ConclusionCombination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.