Non-responder Group Research Articles

Myocardial single photon emission computed tomography imaging to identify non-responders to cardiac resynchronization therapy in patients with non-left bundle branch block

Abstract Background Non-response to cardiac resynchronization therapy (CRT) is an important issue in the treatment of heart failure with reduced ejection fraction (HFrEF) and non-left bundle branch block (LBBB). Although the QRS duration and morphology are crucial parameters for selecting CRT candidates, electrocardiogram (ECG) markers may inadequately represent the mechanical activation patterns within the heart. Owing to limitations associated with the ECG criteria, there is increasing interest in advanced multimodality imaging to improve patient selection. Recently, myocardial single-photon emission computed tomography imaging (G-MPI) is used for assessing left ventricular (LV) dyssynchrony. This technique is mostly automatic and has high intra- and inter-observer reproducibility and repeatability. Objectives This study aimed to examine whether preoperative G-MPI evaluation could predict non-responsiveness to CRT in patients with HFrEF with non-LBBB. Methods Between January 2021 and December 2022, 128 patients underwent CRT, of whom 73 with pre-operative evaluation using G-MPI were selected. Forty-three patients with non-LBBB (21 and 22 CRT responders and non-responders, respectively) were assessed. These patients were divided into CRT responder and non-responder groups. We evaluated the cut-off and clinical impact of pre-operative G-MPI parameters in predicting non-responsiveness to CRT. In addition, 30 patients with LBBB were analyzed. Results Among patients with non-LBBB, CRT responders and non-responders showed no significant differences in baseline characteristics, except for the LV dimension. A receiver operating characteristic curve analysis identified 108° and 27.7° as the optimal cut-offs for the bandwidth and phase standard deviation (SD), respectively, to predict non-responsiveness to CRT (area under the curve [AUC]=0.762; 95% confidence interval [CI]: 0.601–0.923 and AUC=0.742; 95% CI: 0.576–0.909, respectively). A multivariate analysis revealed that a cut-off bandwidth of ≥108° and phase SD of ≥27.7° are independent predictors of non-responsiveness to CRT in patients with non-LBBB (hazard ratios 5.65; 95% CI: 1.53–20.9; P=0.009). In contrast, there were no relationships between G-MPI parameters and non-responsiveness to CRT in patients with LBBB. Conclusions Pre-operative G-MPI findings were associated with non-responsiveness to CRT in patients with non-LBBB. The identification of potentially nonresponsive patients could influence patient management and alter outcomes.

Investigation of Blood Count-Based Inflammatory Biomarkers as Predictors of Response to Dupilumab Treatment in Patients with Chronic Rhinosinusitis with Nasal Polyps

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often resistant to standard treatments. Dupilumab, a monoclonal antibody targeting the IL-4α receptor, has shown efficacy in CRSwNP, but a significant subset of patients do not respond to this therapy. This study aims to investigate pretreatment complete blood count (CBC)-based inflammatory biomarkers as predictors of response to dupilumab in patients with CRSwNP. Methods: This mono-centric, retrospective, single-arm longitudinal cohort study included 80 patients with uncontrolled CRSwNP who received dupilumab treatment at the Medical University of Graz. Patients were classified into responder and non-responder groups based on a reduction of >1 in nasal polyp score (NPS) and a sinonasal outcome test-22 (SNOT-22) score <40 points at six months. Pretreatment CBC-derived biomarkers, including eosinophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation indices including the aggregate inflammation systemic index (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), were analyzed for their predictive value. Results: Of the 80 patients, 72.5% were classified as responders, while 27.5% were non-responders. A significant positive correlation was found between baseline eosinophil count and NPS reduction (p = 0.027), suggesting that higher eosinophil levels may predict higher NPS reduction in dupilumab treatment. However, no significant associations were observed between NLR, PLR, and systemic inflammation indices with treatment outcomes. Conclusions: Pretreatment eosinophil count may serve as a potential biomarker for predicting nasal polyp reduction in dupilumab treatment of CRSwNP. Other CBC-based inflammatory markers did not show significant predictive value. Further prospective studies are needed to validate these findings and explore additional, reliable biomarkers to optimize treatment outcomes for CRSwNP patients.

Preventive treatment effects on brain structures and functions in patients with chronic migraine: A multimodel magnetic resonance imaging study.

Patients with chronic migraine (CM) often exhibit structural and functional alterations in pain-matrix regions, but it remains unclear how preventive treatment affects these changes. Therefore, this study aimed to investigate the structural and functional changes in pain-matrix regions in CM patients after 6-month treatment. A total of 24 patients with CM and 15 healthy controls were recruited for this study. Patients were divided into responder group (N = 9) and non-responder group (N = 15). After completing the Migraine Disability Assessment (MIDAS) questionnaire, all patients underwent whole-brain high-resolution T1-weighted images, diffusion-weighted imaging, and resting-state functional magnetic resonance imaging at baseline and 6-month follow-up. Whole brain gray matter volume and white matter diffusion indices were analyzed using voxel-based analysis. Structural and functional connectivity analyses were performed to understand brain changes in patients after 6-month preventive treatment. The responder group exhibited significantly higher MIDAS scores than the non-responder group at baseline, but no significant difference between the two groups at follow-up. No significant interval change was noted in gray matter volume, white matter diffusion indices, and structural connectivity in CM patients after 6-month treatment. Nonetheless, the functional connectivity was significantly increased between occipital, temporal lobes and cerebellum, and was significantly decreased between parietal and temporal lobes after 6-month preventive treatment. We concluded that resting-state functional connectivity was suitable for investigating the preventive treatment effect on CM patients.

Effects of vagal nerve stimulation parameters on heart rate variability in epilepsy patients

IntroductionVagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment.MethodsOur study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG.ResultsThe mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9.ConclusionIn conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS.

Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis

BackgroundLow-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE.MethodsWe pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results.ResultsRash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2.ConclusionsThese findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Efficacy and safety of orelabrutinib in relapsed/refractory idiopathic multicentric Castleman disease: A single-centre, retrospective study.

Idiopathic multicentric Castleman disease (iMCD) is a rare and heterogeneous lymphoproliferative disorder that lacks standardised treatment options for patients with refractory or relapsed (r/r) disease. Blocking Bruton's tyrosine kinase (BTK) has emerged as a promising therapeutic approach for iMCD without depleting B cells. This single-centre, retrospective study enrolled 10 patients with r/r iMCD who were treated with orelabrutinib, a novel, next-generation BTK inhibitor. The median age at orelabrutinib initiation was 48 (range: 31-58) years. The overall response rate was 70% (7/10 patients, 95% CI: 34.8-93.3), with 20% (n = 2) achieving complete response and 50% (n = 5) achieving partial response. The median time to response was 9.8 (range: 5.9-20.5) months. Patients in the non-responder group also demonstrated a continuous improvement in haemoglobin (91-105 g/L) and albumin (32-38 g/L) levels at month 12 of treatment despite not fulfilling response criteria. No grade 3 or higher adverse events occurred during the median time to the next treatment of 29.0 (range: 15.0-36.2) months. No patient mortality was recorded during the median follow-up duration of 32.8 (range: 15.0-36.9) months. In conclusion, orelabrutinib is a safe and effective regimen for r/r iMCD.

Predicting response to immunotherapy in oral squamous cell carcinoma via a CT-based radiomics model

BackgroundTo investigate whether radiomics models derived from pretreatment CT could help to predict response to immunotherapy in oral squamous cell carcinoma (OSCC).MethodsRetrospectively, a total of 40 patients with measurable OSCC were included. The patients were divided into responder group and non-responder group according to the comparison of pre-treatment and post-treatment CT findings. Radiomics features were extracted from pre-treatment CT images, and optimal features were selected by univariate analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis. Neural network, support vector machine, random forest and logistic regression models were used to predict response to immunotherapy in OSCC, and leave-one-out cross validation was employed to assess the performance of the classifiers. The area under the curve (AUC), accuracy, sensitivity and specificity were calculated to quantify the predictive efficacy.ResultsA total of 7 features were selected to build models upon machine learning methods. By comparing different machine learning based models, the neural network model achieved the best predictive ability, with an AUC of 0.864, an accuracy of 82.5%, a sensitivity of 82.5%, and a specificity of 82.5%.ConclusionsThe pretreatment CT-based radiomics model showed good performance in predicting response to immunotherapy in OSCC. Pretreatment CT-based radiomics model might provide an alternative approach for the selection of patients who benefit from immunotherapy.

Gut microbiota as a prognostic biomarker for unresectable hepatocellular carcinoma treated with anti-PD-1 therapy.

To investigate the relationship between the gut microbiome and the response to anti-PD-1-based combination therapy in unresectable hepatocellular carcinoma (HCC). We aimed to identify potential non-invasive biomarkers and new strategies to modulate immunotherapy in HCC. In this study, fresh stool samples and clinical data were collected from unresectable HCC patients treated with anti-PD-1-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2020 and December 2021. The patients were divided into two groups based on their response to treatment: the treatment responder group (R group) and the treatment non-responder group (NR group). The composition and diversity of the gut microbiome were bioinformatically analyzed by using the Whole Genome Shotgun strategy, including taxonomic composition analysis, Alpha diversity analysis, Beta diversity analysis, and differentially enriched bacterial taxa analysis. Differentially enriched bacterial taxa between R and NR groups were identified based on the magnitude of the linear discriminant analysis effect size (LEfSe) and analyzed for their impact on the survival of the patient. A total of 45 eligible patients with unresectable HCC treated with anti-PD-1-based combination therapy participated in this study. The gut microbiological composition and Alpha diversity of patients were not statistically different, but there was a statistically significant difference in Beta diversity between the R and NR groups. (PERMANOVA tests, P = 0.006). We further identified 56 enriched bacterial taxa in the R group and 44 enriched bacterial taxa in the NR group based on the LEfSe analysis (LDA >2.66, P< 0.05). Patients with a high abundance of Collinsella genus, Ruminococcus_AM4211, and Ruminococcus_AF25_28AC had a longer median PFS and median OS compared to those with low abundance (P < 0.05). On the contrary, the median PFS and OS of patients with a high abundance of Bacteroides_AF20_13LB and Veillonella_atypica were significantly shorter than those of patients with low abundance (P < 0.05). The multivariate analysis showed that the abundance of Bacteroides_AF20_13LB and Ruminococcus_ AF25_28AC was independent related factors for PFS, and the abundance of Bacteroides_AF20_13LB was an independent related factor of OS. The enrichment of specific gut microbiota affected clinical efficacy and survival benefits in HCC treated with anti-PD-1 therapy and may be a promising non-invasive gut microbial biomarker and a new strategy for modulating immunotherapy in HCC.

Evaluating the predictive efficacy of real-time 3D echocardiography in cardiac resynchronization therapy

BackgroundThe aim of this study is to assess the predictive efficacy of real-time three-dimensional echocardiography (RT-3DE) and QRS wave duration in determining the response to cardiac resynchronization therapy (CRT) and assessing left ventricular systolic function pre- and post-CRT device implantation.MethodA total of 51 patients with heart failure undergoing CRT at the Second Affiliated Hospital of Nantong University between January 1, 2013, and October 31, 2020, were enrolled in this study. Traditional two-dimensional echocardiography and RT-3DE were performed pre and post-CRT, with QRS wave width data from electrocardiograms and additional clinical information collected. Patients were categorized into CRT responder (n = 36) and CRT non-responder (n = 15) groups based on their response to CRT device implantation. Comparative analyses were conducted on the general characteristics of both groups, as well as the predictive efficacy of RT-3DE and QRS wave width for CRT responsiveness and left ventricular systolic function. Data on the standard deviation (Tmsv16-SD, Tmsv12-SD, Tmsv6-SD) and maximum difference (Tmsv16-Dif, Tmsv12-Dif, Tmsv6-Dif) of left ventricular end-systolic volume (LVESV) at segments 16, 12, and 6, as well as QRS wave width, were collected and analyzed.ResultsThe indicators Tmsv6-Dif, Tmsv12-Dif, Tmsv16-Dif, Tmsv6-SD, Tmsv12-SD, Tmsv16-SD, and QRS wave width exhibited significantly higher values in the CRT responder group when compared to the CRT non-responder group (P < 0.05). Among these, Tmsv16-SD demonstrated superior predictive performance for post-CRT response, with a sensitivity of 88.9%, specificity of 80.0%, and a diagnostic cut-off value of 6.19%. This predictive capability exceeded that of the conventional indicator, QRS wave width.ConclusionRT-3DE enables accurate prediction of post-CRT patient response and significantly facilitates quantitative assessment of CRT therapy efficacy.

Qingchang suppository ameliorates mucosal inflammation in ulcerative colitis by inhibiting the differentiation and effector functions of Th1 and Th17 cells

Ethnopharmacological relevanceQing Chang Suppository (QCS), a traditional Chinese medicine formula, has been shown to effectively alleviate mucosal inflammation in patients with ulcerative colitis (UC). While the mechanism of QCS appears to be related to the regulation of CD4+T cell subset responses, direct evidence demonstrating that QCS inhibits Th1 and Th17 cell activation in UC (particularly based on human data) remains lacking. Additionally, the precise mechanisms through which QCS affects these cells have yet to be fully elucidated. Aim of studyThis study aimed to investigate the effects of QCS on Th1 and Th17 cell responses in UC and to explore the underlying mechanisms. Materials and methodsTwenty-eight patients with mild-to-moderate UC were recruited and treated with QCS for 12 weeks. Symptoms were assessed every two weeks, with sigmoidoscopies performed at baseline and at week 12. Intestinal mucosal biopsies and peripheral blood (PB) were collected at these time points. At the end of the trial, patients were categorized into responder and non-responder groups based on a modified Mayo disease activity index score. Healthy controls (HCs) were defined as subjects without IBD or colorectal carcinoma but with colon polyps. The frequencies of IFN-γ+CD4+T cells and IL-17A+CD4+T cells in PB and colonic mucosa were measured using flow cytometry. The expression levels and localization of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A were determined via immunofluorescence, and JNK signaling activation was assessed through immunoblotting and immunohistochemistry. All parameters were compared across the three groups. ResultsAt week 12, responders showed a significant reduction in colonic mucosal inflammation compared to baseline, accompanied by decreased frequencies of IFN-γ+CD4+T and IL-17A+CD4+ T cells in both PB and the colonic epithelial layer. Notably, Th1 and Th17 cell activity around intestinal epithelial cells (IECs) was nearly undetectable, as evidenced by the diminished expression of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A. Additionally, JNK phosphorylation in these cells was significantly reduced. In contrast, non-responders exhibited no meaningful improvement; colonic pathology remained unchanged, and elevated levels of IFN-γ+CD4+T and IL-17A+CD 4+T cells persisted in both the PB and colonic epithelial layer. The presence of Th1 and Th17 cells and their associated cytokines around IECs remained substantial, and there was no significant change in JNK activation. ConclusionQCS attenuates mucosal inflammation in UC patients by inhibiting the differentiation and effector functions of Th1 and Th17 cells, primarily through the regulation of the JNK signaling pathway.

First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients

BackgroundRimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.MethodsThis was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.ResultsBy November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.ConclusionsIn the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.Trial registrationClinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.Graphical

Increased levels of Escherichia-Shigella and Klebsiella in the gut contribute to the responsivity of placebo analgesia

Placebo analgesia is observed in both humans and animals. Given the complexity of placebo analgesia involving a variety of neurobiological, psychological, and psychosocial processes, further investigation into its underlying mechanisms is essential. Gut microbiota has been implicated in the responsivity of placebo analgesia, but its precise role remains unknown and warrants further investigations. Here, we conducted a conditioning training model with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in mice, associating parecoxib with different cues. Hierarchical clustering analysis of placebo analgesia behaviors was employed to classify mice into responders and non-responders phenotypes. Approximately 40% of CFA mice undergoing conditioning training exhibited placebo analgesia. Notably, placebo analgesia responders displayed reduced anxiety-like behaviors. 16S rRNA results revealed a distinct composition of gut microbiota composition among the control, placebo analgesia non-responders and responders groups. Notably, levels of Escherichia Shigella and Klebsiella in the gut were increased considerably in the placebo analgesia responders as compared to both control and non-responders groups. In conclusion, placebo analgesia responders demonstrated marked analgesia, reduced anxiety-like behaviors, and increased levels of Escherichia-Shigella and Klebsiella, implying a potential linkage between gut microbiota and placebo analgesia.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study

BackgroundDisorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies.MethodsTwenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated.ResultsOne-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031).ConclusionsApplying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy.Trial registrationwww.ClinicalTrials.gov, identifier: NCT05187000.

Systematic analysis of serum peptidase inhibitor 3 in psoriasis diagnosis and treatment.

Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis. Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2). In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment. Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments.

Decoding heterogeneity in data-driven self-monitoring adherence trajectories in digital lifestyle interventions for weight loss: a qualitative study

BackgroundData-driven trajectory modeling approaches have been used to identify participant subgroups with differing responses to digital lifestyle interventions. Identifying contributing factors to different participant subgroups can inform tailored strategies to early “rescue” intervention non-responders. Self-monitoring (SM) is a central mechanism in lifestyle interventions for driving behavior change and can serve as an early indicator for later intervention response. This qualitative study aimed to compare SM experiences between intervention response subgroups and to identify contributing factors to intervention response subgroups in a 6-month digital lifestyle intervention for adults with overweight or obesity.ResultsParticipants were middle-aged (52.9 ± 10.2 years), mostly female (65%), and of Hispanic ethnicity (55%). Four major themes with emerged from the thematic analysis: Acceptance towards SM Technologies, Perceived SM Benefits, Perceived SM Barriers, and Responses When Facing SM Barriers. Participants across both subgroups perceived SM as positive feedback, aiding in diet and physical activity behavior changes. Both groups cited individual and technical barriers to SM, including forgetfulness, the burdensome SM process, and inaccuracy. The Responder Group displayed positive problem-solving skills that helped them overcome the SM barriers. In contrast, some in the Non-responder Group felt discouraged from SM. Both subgroups found diet SM particularly challenging, especially due to technical issues such as the inaccurate food database, the time-consuming food entry process in the Fitbit app.ConclusionsOur study indicates that qualitative analysis is valuable for translating data-driven findings to actionable intervention improvement strategies. Our findings may inform the development of practical SM improvement strategies in future digital lifestyle interventions for weight loss. Notably, building problem solving skills emerge as a key approach to prevent potential non-responders from intervention disengagement.

HLA-DQB1 as a potential prognostic biomarker of hormonal therapy in patients with non-obstructive azoospermia

The gonadotropin treatment of infertile men may improve spermatogenesis and lead to sperm cell production, however, only a small fraction of treated patients positively responds to such therapy. To identify individual treatment prognostic biomarkers associated with responsiveness to gonadotropins, we compared the gene expression profiles of testicular oligobiopsies from 3 patients with non-obstructive azoospermia (NOA) who positively responded to therapy with a combination of human chorionic gonadotropin and recombinant follicle-stimulating hormone (hCG/rFSH) to those of 3 non-responders. We used Affymetrix Human Gene 1.0 ST microarrays. The results of the microarray evaluation were validated by the qPCR technique while gene variants of the HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) were subsequently sequenced. In our microarrays, we have identified most significantly 5 transcripts with different expression levels in responders versus non-responders groups. Our interest has been primarily focused on the transcript associated with the HLA-DQB1 gene. Because the expression of this gene was up-regulated in the non-responding patients and only patients with heterozygotic alleles of HLA-DQB1 turned out to be positive to gonadotropin therapy, we suggest that this gene may be a biomarker of potential significance for the gonadotropin treatment of male infertility. We also compared the testicular gene expression profile in one individual before and after gonadotropin treatment. In the re-biopsied sample, we have identified over 600 genes that showed differences in testicular expression; some of these genes are critical for spermiogenesis. Thus, we documented that the applied gonadotropins successfully stimulated the spermatogenetic wave in patients with NOA.

Correlation between Serum Levels of Factor I, CD59, Interferon-gamma, and Interleukin-6 with the Response to Rituximab in Iraqi Patients with Rheumatoid Arthritis

Background: Rituximab is a chimeric IgG1 kappa immunoglobulin that has been genetically modified to incorporate human constant region sequences together with murine light- and heavy-chain variable region sequences. People use it to treat rheumatoid arthritis and certain malignancies. Objective: The study aimed to assess the potential association between the serum levels of Factor I, CD59, interleukins (IL)-6, and interferon-gamma (IFN)-γ and the response to Rituximab treatment in Iraqi rheumatoid arthritis patients. Methods: A cross-sectional study was conducted at the rheumatology center at Baghdad Teaching Hospital. Ninety adult patients who have been diagnosed with rheumatoid arthritis and are receiving Rituximab intravenous infusions were included. The enrolled patients were divided into a responder group (45 patients) and a non-responder group (45 patients). The response to Rituximab was assessed according to the 28-joint Disease Activity Score (DAS28). Results: The serum levels of Factor I and CD59 were significantly higher in the non-responders group in comparison to the responders group. In addition, the serum IL-6 and IFN-γ levels were significantly elevated in the non-responders group in comparison to the responders group. The estimated marker serum levels showed a strong, significant correlation with the 6-month change in DAS28. Conclusions: In Rituximab nonresponder RA patients, serum levels of Factor I, CD59, Factor H, IL-6, and IFN-γ are higher, and they have good potential to be used in the assessment of the response to Rituximab therapy.

The Association between the Response to Rituximab with Sociodemographic Data and Disease Characteristics Among a Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Rituximab (RTX), a monoclonal antibody with anti-CD20 action, is now used as a treatment. Even with proper RTX use, some patients showed variations in response. Objective: To assess the association of different sociodemographic data and disease characteristics with RTX responsiveness in RA patients. Methods: A cross-sectional study was conducted in the Specialized Center of Rheumatology at Baghdad Teaching Hospital in Baghdad, Iraq. The study included 90 RA patients who received a 1000mg RTX intravenous infusion for at least six months. The collected sociodemographic data included age, gender, smoking status, body mass index (BMI), disease characteristics such as co-morbidities, and the use of previous biological agents. The activity of RA was assessed by the 28-joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI). Results: Upon measuring the DAS28, the enrolled patients were divided into RTX responders (50 patients) and RTX non-responders (40 patients). Patients with a family history of RA were significantly higher in the RTX responders (21% versus 2% in the non-responders group). The responders had a significantly longer RA duration (p=0.030).The mean of CDAI and DAS28 were significantly higher in patients with no family history of RA than in those with a family history of RA. Conclusions: Disease duration, family history, and the use of previous biological agents could be considered as possible predictors of response to RTX, thereby saving time and treatment costs.

Deep brain stimulation targets in drug-resistant epilepsy: Systematic review and meta-analysis of effectiveness and predictors of response

PurposeAnterior nucleus of the thalamus (ANT) is the only deep brain stimulation (DBS) target that is approved by the FDA for treatment of drug-resistant epilepsy (DRE). Hippocampus (HC) and centromedian nucleus (CMN) have been reported as potential DBS targets for DRE. This study aimed to assess the effectiveness and predictors of response among DRE patients treated with DBS in general and among ANT, HC and CMN DBS-targets. MethodsA systematic search was executed on PubMed, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases between Jan 1, 2000 and June 29, 2020. Patients with DRE who underwent DBS treatment with at least three months of follow-up were included. Individual patient data (IPD) meta-analysis was conducted on DBS studies with available IPD. Response was defined as ≥50 % reduction in seizures frequency. Responders group was compared with non-responders group in terms of demographics, epilepsy/seizure characteristics, MRI findings, and DBS targets and duration of use. Subsequently, predictors of response to different DBS targets were investigated. ResultsThirty-nine studies with a total of 296 patients (ANT: 69 %, HC: 11 %, CMN: 21 %) were included. The responders group constituted of 209 patients (70.6 %). The response was significantly higher in patients with generalized seizures compared to those with focal seizures (93.2% vs 63.9 %; p < 0.001). Response was significantly higher with CMN (83.9 %) and HC (77.4 %) compared with ANT (65.5 %) as DBS targets (p = 0.014). Response was also significantly associated with longer duration of DBS use (p = 0.008). The responder rate was higher among the patients with lesional MRIs (76.7 %) than those with non-lesional MRIs (66.7 %), but with no statistically significant difference (p = 0.134). Age, gender, epilepsy etiology, onset zone of focal seizures, and previous use of VNS had no significant differences between the responders and non-responders. A binary logistic regression including the seizure type, MRI findings, DBS targets, and DBS duration showed, after controlling for confounders, that the duration of DBS use was the only significant predictor of response (adjusted OR 1.061; 95 % CI 1.019–1.106; p = 0.005). Regarding DBS targets, the response rate in patients with symptomatic etiology was significantly higher with HC or CMN targets than the ANT (p = 0.003). In patients with non-lesional MRI, response rate was significantly higher with the CMN target compared to the other two targets (p = 0.008). ConclusionDBS proves to be effective in DRE, with progressive success upon longer treatment and possibility of improving quality of life. In addition to focal seizures, DBS has potential for treating generalized seizures as well. While the ANT stands as the most utilized and only approved DBS target for DRE, CMN and HC are alternative targets with high seizure control potential. Patients with symptomatic etiology showed significant seizure reduction when HC or CMN were targeted. Studies revealed noticeable effectiveness of CMN-DBS in treating patients with non-lesional MRI. Despite ANT prominence in research, our findings suggest promising outcomes with CMN and HC, emphasizing the need for future larger-scale comparative clinical trials to better understand the efficacy of different DBS targets.

18F-FDG brain PET: a metabolic predictive factor for gait improvement after cerebrospinal fluid shunting in normal pressure hydrocephalus?

The pathophysiology of normal pressure hydrocephalus (NPH) has not been fully elucidated. Treating NPH with cerebrospinal fluid shunts to improve gait disturbances may have some risks and inconsistent benefits. No clear predictive factor has been identified thus far. This preliminary study aimed to evaluate the predictive value of preoperative brain 18F-FDG positron emission tomography (PET) on overall gait response in patients with NPH. Sixteen patients with NPH who underwent 18F-FDG PET before shunt surgery between 2012 and 2022 were included retrospectively and separated into two groups based on their gait response one year after surgery: responders (R) or nonresponders (NR). Brain glucose metabolism was assessed using visual and semiquantitative analyses using SPM8 software (Welcome Department of Cognitive Neurology, University College, London, UK). Five regions of interest were selected: global cortex, cerebellum, thalamus, striatum, and midbrain. Visual interpretation showed more frequent hypometabolism of the striatum, thalamus and global cortex in NR. None of the patients showing hypometabolism of these regions were R. Based on these results, the visual interpretation allowed us to identify 3/8 NR and 8/8 R. Semiquantitative analysis confirmed significantly lower thalamic metabolism in the NR group (P=0.037) and a trend towards lower metabolism of the striatum (P=0.075) with an area under the curve of 0.77 for thalamic metabolism to discriminate between R and NR. This preliminary study using brain 18F-FDG PET suggests that reduced brain metabolism in the thalamus and striatum along with cortical hypometabolism may be associated with poorer gait response to CSF shunting in normal pressure hydrocephalus (NPH). Although these findings suggest that preoperative brain 18F-FDG PET could potentially aid in selecting appropriate candidates for shunt surgery, further research with larger sample sizes is needed to confirm these results.