Search Results (1,251)

Background/Objectives: Trigeminal neuralgia (TN) is a severe chronic neuropathic facial pain condition. Although TN can be amenable to surgical treatments, ~25% of patients may have recurrence of pain. Understanding the role of the central nervous system (CNS) gray matter and its impact on surgical treatment effect remains unclear but is of increasing interest. Previous machine learning models identified 13 neuroanatomical regional predictors of TN surgical response. The implications of these regions and how they might relate to clinical status and surgical outcome are not clear. Here, we attempt to further understand CNS alterations in TN by investigating how these potential regional predictors of surgical response may change following surgical treatment, and whether this is related to the degree of pain relief achieved. Methods: Retrospective imaging was acquired from 115 surgically naïve TN patients who underwent Gamma Knife Radiosurgery at Toronto Western Hospital. Patients obtained magnetic resonance imaging scans and reported pain intensity scores before and 3–12 months after surgery. Patients were categorized as responders (≥75% pain relief), partial responders (50–74% pain relief), and non-responders (<50% pain relief). Results: Eight regions spanning default mode, visual, limbic, and dorsal attention networks had significant changes in cortical thickness. Responders demonstrated post-operative neuroplasticity in a greater number of regions with higher within-group statistical significance than both partial and non-responders. Thickening of the contralateral fusiform gyrus was correlated with the degree of pain reduction. Conclusions: Our findings identify key regions impacted by chronic neuropathic pain, which may be associated with pain relief in TN. Full article

Background: Obesity is a complex, chronic disease with metabolic complications. Many patients respond suboptimally to conventional interventions like the hypocaloric Mediterranean diet (MD), highlighting the need to investigate alternative supervised nutritional strategies in patients with an insufficient response to conventional dietary treatment. Objectives: This study aimed to evaluate the KETOCOMP (Food-Based KETOgenic Nutritional Protocol for Patients with COMPlicated Obesity), a medically and dietitian-supervised, food-based sequential ketogenic nutritional protocol consisting of a ketogenic phase followed by controlled carbohydrate reintroduction, for improving anthropometric and body composition in patients with complicated obesity who were non-responsive to conventional dietary treatment. Methods: In this longitudinal, observational study, adult patients with obesity/overweight and metabolic comorbidities, previously non-responsive to a hypocaloric MD, were identified. Patients followed a 4-week food-based ketogenic diet (approx. 1200 kcal/day, <20 g carbohydrate, CHO) followed by a 4-week low-carbohydrate reintroduction phase (approx. 1300 kcal/day, up to 100 g CHO). Anthropometric and body composition parameters were assessed at baseline (T0), after the MD (T1), after the ketogenic phase (T2), and after the low-carbohydrate phase (T3). Intra-subject comparisons were performed. Results: Across the entire observed nutritional pathway (T0–T3), body weight (BW), body mass index (BMI), and fat mass (FM) decreased by 7.7%, 9.45%, and 23.1%, respectively. Using T1 as the relevant baseline for the second-line KETOCOMP sequence, mean BW and FM decreased by 7.79 kg and 6.29 kg, respectively, from T1 to T3; during the ketogenic phase alone (T1–T2), BW decreased by 6.10 kg and FM by 4.80 kg. Body Cell Mass (BCM) and Phase Angle (PhA) showed no statistically significant changes during the ketogenic and carbohydrate-reintroduction phases, whereas Fat-Free Mass (FFM) decreased significantly. Significant reductions in waist and hip circumferences (WC, HC) were also observed. No serious adverse events were documented among included participants; however, discontinuation rates could not be assessed because completion through T2 formed part of cohort selection. Conclusions: The KETOCOMP protocol may represent a clinically applicable second-line nutritional strategy for patients with obesity and metabolic complications who respond suboptimally to conventional dietary treatment. The observed reductions in body weight and fat mass, together with the absence of significant changes in BCM and PhA, suggest a favorable short-term change in body composition. However, larger prospective controlled studies incorporating standardized clinical and biochemical safety monitoring and direct assessment of skeletal muscle are required to confirm these findings and evaluate longer-term outcomes. Full article

Background: The discovery of non-invasive biomarkers that can predict the therapeutic response in Inflammatory Bowel Disease (IBD) is of utmost importance in the field of personalized medicine. The present prospective cohort study was designed to investigate the use of circulating levels of plasma microRNA-145 (miR-145) and microRNA-191 (miR-191) in the diagnosis and association with therapeutic response in Crohn’s disease (CD) and ulcerative colitis (UC). Methods: The present study was conducted as a retrospective observational cohort study on 183 adult IBD patients, consisting of 96 CD patients and 87 UC patients. Patient data and study parameters were obtained retrospectively from existing clinical records and available laboratory/molecular data collected during routine clinical care. A healthy control group consisting of 92 individuals was included for comparison with the patients with IBD. The circulating levels of miR-145 and miR-191 were assessed in the peripheral blood plasma at baseline using qRT PCR. The clinical response was evaluated at 12 weeks using the CDAI score for CD and the Mayo score for UC. Results: In active IBD, there was significant down-regulation of miR-145 and significant up-regulation of miR-191. Responders at 12 weeks had significantly higher levels of baseline miR-145 (2.0-fold, p < 0.001) and lower levels of miR-191 (1.8-fold, p < 0.001) compared with non-responders. Also, miR-145 negatively correlated with disease activity, and miR-191 positively correlated with acute inflammation markers. ROC curve analysis showed good discriminative values for both miR-145 and miR-191. Conclusions: The level of circulating miR-145 and miR-191 correlates with the activity of IBD. Importantly, the baseline level of miR-145 expression is a non-invasive potential biomarker associated with therapeutic response at 12 weeks. Full article

Emergency department providers may be challenged by the presentation of patients who exhibit movement abnormalities that could indicate conditions requiring interventions to reduce the risk of potential morbidity and mortality. Crucially, interventions for potential neurological diseases that require immediate intervention (e.g., stroke) are contraindicated in patients exhibiting movements that may be voluntary (e.g., emotional expressions and fabricated symptoms) or functional (e.g., functional movement disorders such as functional tremors or psychogenic nonepileptic seizures (PNES)). Current motor assessment relies on subjective visual observation by human examiners, which limits the speed and accuracy of this differentiation. We hypothesize that technology measuring the temporal and spatial characteristics of movement can provide quantifiable signatures to differentiate movement subtypes and reflect the distinct neural pathways underlying voluntary and involuntary movement. To assess clinical and commercial interest in such technology, we conducted exploratory interviews with 17 of 56 invited potential customers (neurologists, biomedical engineers, and other clinicians) through a National Science Foundation I-Corps program where interviewees confirmed motor assessments are often performed without instrumentation and expressed willingness to adopt inexpensive, validated technology. The findings support interest in our proposed approach; however, this evidence is still preliminary as the interview sample was a non-random convenience sample and no comparison of respondents and non-respondents was performed. The sensor-based technology also remains conceptual with no current prototype, indicating the need for further studies utilizing more rigorous sampling and prototype development before clinical application. Full article

Background: Therapeutic drug monitoring (TDM) has emerged as an important strategy for optimizing anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). However, data regarding anti-TNF pharmacokinetics and immunogenicity from Middle Eastern populations remain limited. This study evaluated the associations between serum anti-TNF trough concentrations, anti-drug antibody (ADAb) levels, and therapeutic response among Iraqi patients with IBD receiving infliximab or adalimumab therapy. Methods: This cross-sectional observational study included 80 patients with Crohn’s disease or ulcerative colitis receiving maintenance infliximab or adalimumab therapy at a tertiary Gastroenterology Center in Iraq. Patients were categorized as responders or non-responders according to clinical disease activity indices and biochemical assessment. Serum trough levels of infliximab and adalimumab, as well as ADAb concentrations, were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Responders had significantly higher serum trough concentrations than non-responders for both infliximab [3.75 µg/mL (IQR: 3.40–4.15) vs. 1.05 µg/mL (IQR: 0.92–1.12), p < 0.001] and adalimumab [6.32 µg/mL (IQR: 5.67–7.15) vs. 3.30 µg/mL (IQR: 2.70–4.26), p < 0.001]. Adalimumab-treated non-responders had significantly higher ADAb levels compared with responders (p = 0.047). Conclusions: Favorable therapeutic outcomes in Iraqi IBD patients treated with anti-TNF agents were associated with adequate serum trough levels and low ADAb levels. Reactive therapeutic drug monitoring may provide clinically valuable pharmacokinetic information capable of guiding individualized treatment optimization and identifying mechanisms of treatment failure in patients receiving infliximab or adalimumab therapy. Full article

Background/Objectives: Healthcare students face an occupational risk of hepatitis B virus (HBV) exposure during clinical training, often many years after receiving their primary vaccination series in infancy or childhood. Progressive waning of anti-hepatitis B surface (anti-HBs) antibody titres, heterogeneous vaccination histories in international student cohorts, high rates of underreported needlestick injuries, and variable occupational health protocols across institutions raise important questions about the adequacy of pre-clinical immunization surveillance in this population. This review aimed to synthesize current evidence on hepatitis B immunization among healthcare students, focusing on occupational exposure risk, seroprotection and immunological memory, clinical management of low or absent anti-HB titres including post-exposure prophylaxis, and the specific challenges posed by multicultural academic settings. Methods: A narrative review was conducted through a systematic literature search of PubMed/MEDLINE and Scopus, covering publications from January 2000 to December 2025, supplemented by key seminal references. After the removal of duplicates and stepwise screening, 49 references were selected for final inclusion. Results: Needlestick and sharps injuries occur at measurable rates during clinical training, with medical students accounting for approximately 30% of occupational exposure events in some series, and with underreporting rates estimated at 19–80% across studies. Pooled seroprotection prevalence at clinical training entry is approximately 73.8% (95% CI 69.1–78.0%), with substantially lower rates among students vaccinated in infancy—as low as 28% at 16–20 years post-vaccination in longitudinal data—compared with adolescence immunization. The majority of students with non-protective titres retain immunological memory, with 90.9% (95% CI 87.7–93.3%) demonstrating an anamnestic response after a single booster dose. Post-exposure prophylaxis pathways depend critically on pre-existing immunological status, reinforcing the operational value of pre-clinical serological screening. International student cohorts present additional complexity due to heterogeneous vaccination schedules, documentation gaps, and variable natural immunity profiles. Conclusions: Systematic pre-clinical serological screening (anti-HBs, HBsAg, and anti-HBc), combined with evidence-based stepwise immunization management and structured educational interventions, is essential to protect healthcare students from occupational HBV exposure. The primary operational goal of screening is the identification of the approximately 5% of true non-responders who require tailored occupational health management. These findings support a proactive, integrated approach to hepatitis B immunization surveillance in healthcare education, aligned with the WHO 2030 viral hepatitis-elimination targets. Full article

Carboplatin/paclitaxel (CP) chemotherapy is the cornerstone of therapy for advanced stage ovarian cancer (OC). However, despite initial sensitivity, this regimen cannot avoid the emergence of resistance. Ixabepilone ± bevacizumab (IB) is a combination recently added to NCCN guidelines for the treatment of platinum-resistant OC. It would be desirable to identify biomarkers able to differentiate patients who are resistant to CP and IB, and biomarkers that identify which patients may benefit from IB treatment. We analyzed whole-exome-sequencing (WES) data from 49 OC patients exposed to CP, including 28 platinum-sensitive vs. 21 platinum-resistant, and 31 additional platinum-resistant patients, including 16 responders (i.e., CR/PR) vs. 15 non-responders (SD/PD) to ixabepilone ± bevacizumab. Comprehensive genetic analyses were performed to identify alterations correlated with resistance to CP and IB. WES analysis of CP responders vs. non-responders revealed differences in HRD-signatures (p < 0.05), OS (p < 0.005) and gain/loss-of-function in multiple genes associated with tumor growth/progression including but not limited to ACVR2A, INHBA, MAP3K7, ATG5, SGK1, FYN, RSPO3, NOD1 and LRRK2. WES analysis of platinum-resistant IB-treated patients revealed additional nominally significant genes and deranged pathways including gains in the DROSHA and SDHA genes in responders vs. non-responders (p < 0.05). Patients harboring HRD-signatures showed significantly higher sensitivity to CP and prolonged survival compared to HRD-negative patients. Alterations in genes associated with tumor growth/progression correlated with resistance to CP regimen and may represent novel “druggable” candidate biomarkers for the targeted treatment of CP/IB-resistant patients. Further validation in independent cohorts and preclinical experiments in CP/IB-resistant models are warranted to establish the clinical utility of these findings. Full article

Responsive neurostimulation (RNS) is a neuromodulation option for treatment of drug-resistant epilepsy (DRE). There is limited data reviewing bilateral thalamic and corticothalamic RNS therapy response. We performed a retrospective analysis of 21 patients undergoing RNS implantation with either bilateral thalamic (n = 17) or corticothalamic (n = 4) leads and ≥6 months of follow-up. Patients were classified as responders (≥50% seizure frequency reduction) vs. non-responders (<50% seizure frequency reduction). Among the bilateral thalamic cohort, 12/17 (70.6%) patients were responders, and 15/17 (88.2%) patients reported reduction in seizure severity. Pre-RNS seizure frequency was higher in bilateral thalamic nonresponders, although not found to be significant (median 13 vs. 30 seizures per month, p = 0.20). Among the corticothalamic cohort, 3/4 (75.0%) patients were responders, and all patients demonstrated improvement in seizure severity. These findings suggest that although bilateral thalamic targets were selected at our center more often, both bilateral thalamic and corticothalamic RNS approaches provided seizure frequency reduction. The majority of patients, including non-responders, reported seizure severity alleviation. Full article

B cell aplasia (BCA), the sustained depletion of circulating CD19-positive B cells, is the defining on-target, off-tumor consequence of anti-CD19 chimeric antigen receptor (CAR) T cell therapy. Despite its occurrence across all approved CAR T cell products and all responding patients, BCA has not been systematically reviewed as a standalone clinical and biological phenomenon. This review synthesizes data from landmark trials and real-world cohorts across B cell-acute lymphoblastic leukemia (B-ALL), large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia to characterize BCA incidence, recovery kinetics, prognostic significance, and management implications. Anti-BCMA products, which mechanism of action differs fundamentally, depleting plasma cells rather than B cell precursors, are intentionally excluded from this review. BCA is observed in all responders and is consistently absent in non-responders across reported cohorts , making it a reliable pharmacodynamic marker of CAR T cell activity. Its prognostic significance is disease-specific: in lymphoma, BCA recovery does not predict relapse and durable remission is achievable independent of sustained aplasia; in B-ALL, early BCA recovery within six months is a robust independent predictor of CD19-positive relapse, while persistent BCA correlates with sustained remission. CD19-negative antigen-escape relapse occurs preferentially in the presence of intact BCA and high pre-infusion tumor burden. Combining BCA kinetics with bone marrow next-generation sequencing minimal residual disease assessment at day 28 and month 3 constitutes the most powerful post-infusion risk-stratification framework currently available. BCA is mechanistically dissociated from hypogammaglobulinemia: IgM declines rapidly and profoundly, IgA more slowly, while IgG—maintained by CD19-negative long-lived plasma cells—is the most preserved isotype. No B cell count threshold below which hypogammaglobulinemia becomes clinically significant has been established. Evidence-informed IVIG replacement thresholds are proposed, though no randomized trial data exist to support them, representing a critical gap requiring prospective investigation. Full article

Background and Objectives: To evaluate the efficacy of superior laryngeal nerve block (SLB) in the management of chronic cough associated with refractory laryngeal hypersensitivity. Materials and Methods: Studies assessing Cough Severity Index (CSI) changes before and after SLB or comparing SLB with sham interventions were included. Pooled analyses evaluated CSI reduction, subjective improvement, and adverse events. Results: Twelve studies involving 759 patients were analyzed. SLB significantly reduced CSI, and the improvement was maintained within the available follow-up period, with no difference between short-term (<100 days) and long-term (>100 days) follow-up (p = 0.5145). Most protocols used initial unilateral SLB with contralateral injection for non-responders, resulting in more than two blocks per patient on average. Subjective improvement occurred in 74%, with ≥50% CSI reduction in 55% and satisfactory response after a single block in 17%. No serious treatment-related adverse events were reported, although the available evidence was insufficient to exclude rare or delayed complications. Conclusions: SLB was associated with improvement in refractory chronic cough in predominantly uncontrolled observational studies. Although one small placebo-controlled trial suggested benefit over saline injection, the current evidence remains insufficient to establish definitive efficacy, and adequately powered placebo-controlled randomized controlled trials are needed to confirm its efficacy and durability. Full article

Background/Objectives: Diabetic macular edema is caused by disruptions in the blood–retinal barrier, resulting in leakage and inflammation, appearing in optical coherence tomography as retinal fluid, hard exudates, and hyper-reflective foci. This study aimed to assess volumetric changes in hyper-reflective foci and hard exudates in faricimab-treated diabetic macular edema in real-world practice. Methods: This retrospective longitudinal study included forty-four eyes with faricimab-treated diabetic macular edema and follow-up of ≥40 weeks. Optical coherence tomography scans were analyzed at baseline, post-loading, 6 months and 1 year. Hyper-reflective foci and hard exudates were quantified across macular subfields using a machine-learning algorithm with manual correction. Outcomes included volumetric changes, best-corrected visual acuity, and central subfield thickness. Early morphologic responders were defined post-loading by ≥20% central subfield thickness reduction and/or central subfield thickness below 280 µm. Results: At 1 year, hyper-reflective foci and hard exudate volumes significantly decreased in the central subfield (median differences: −0.025 nL, p = 0.00028; −0.119 nL, p = 0.00025) and outer ring (−0.178 nL, p = 0.00041; −0.612 nL, p = 0.014). Hard exudate volume significantly decreased in the inner ring (−0.740 nL, p < 0.0001). Best-corrected visual acuity and central subfield thickness improved significantly (−0.10 logarithm of the minimum angle of resolution (logMAR), p = 0.0018; −48 µm, p < 0.0001). Total hyper-reflective foci volumes were similar between responders and non-responders. In contrast, hard exudate burden remained numerically higher in non-responders. Conclusions: During the year following the switch to faricimab, HRF and HE burden decreased alongside visual and anatomical improvement. HRF volumes were descriptively similar between early CST responders and non-responders, whereas HE burden remained numerically higher in non-responders. Full article

Background/Objectives: Immune checkpoint blockade targeting the PD-1/PD-L1 axis is a standard treatment for urothelial carcinoma (UC), but 20–30% of patients develop resistance. The underlying mechanisms, particularly regarding tumor microenvironment metabolic reprogramming, remain unclear. Methods: We performed single-cell RNA sequencing on pre-treatment tumors from eight pembrolizumab-treated UC patients (three responders, five non-responders). Bioinformatic analyses included cell clustering, pathway enrichment, and cell–cell communication, validated using public datasets. Functional experiments involved SGPL1 knockdown in MB49 cells and a syngeneic PD-1-resistant murine model (MB49-R5). Results: Responders exhibited a higher proportion of infiltrating T-cells. Unexpectedly, CD4⁺ subsets, rather than CD8⁺ cells, were numerically enriched in responders. However, all T-cell subsets in responders demonstrated enhanced oxidative phosphorylation-dominant metabolic activity. Enhanced macrophage–T-cell crosstalk was observed, with macrophages exhibiting M1-like polarization driven by CD4⁺ T-cell-derived IFN-γ and CD40L signaling. In contrast, non-responders displayed dominant tumor-derived MIF–CD74 signaling and M2 polarization. Integration of public datasets identified SGPL1 as a key metabolic regulator associated with poor prognosis and reduced immune activation. Functional experiments demonstrated that SGPL1 knockdown inhibited tumor proliferation and restored anti-PD-1 sensitivity, accompanied by increased T-cell infiltration. Conclusions: T-cell metabolic activation drives anti-PD-1 responses in UC, and CD4⁺ T-cell-mediated M1 polarization and tumor-intrinsic SGPL1 crucially shape therapeutic outcomes, highlighting SGPL1 as a candidate metabolic target to overcome PD-1 resistance. Full article

Background/Objectives: Early identification of breast cancer patients unlikely to benefit from neoadjuvant chemotherapy (NAC) remains a pressing clinical problem because ineffective therapy delays definitive surgery and exposes patients to unnecessary toxicity. Quantitative ultrasound (QUS) and shear wave elastography (SWE) probe complementary tissue properties—scatterer microstructure and mechanical stiffness—that may change before macroscopic tumor shrinkage. This study aimed to evaluate whether multi-parametric ultrasound (mpUS) radiomic kinetics, analyzed with a machine learning ensemble and interpreted with SHAP, could predict pathologic response to NAC. Methods: A prospective observational cohort enrolled 135 women with biopsy-proven stage II–III breast cancer treated with NAC within the multidisciplinary breast pathway shared between Vasile Goldis Western University of Arad and Victor Babes University of Medicine and Pharmacy Timisoara (Pius Brinzeu County Emergency Hospital). All patients underwent standardized QUS and SWE acquisitions at baseline, week 1, and week 3. Response was defined pathologically at surgery as residual cancer burden (RCB) class 0/I versus II/III. Group comparisons used Welch’s t-test, Mann–Whitney U, chi-square, and Fisher’s exact tests; correlations used Spearman’s rho. A stacked machine learning ensemble (four base learners—XGBoost, random forest, support vector machine, and L2-penalized logistic regression—combined by a separate second-stage logistic meta-learner) was trained with nested 10-fold cross-validation, bootstrap stability assessment, SHAP-based interpretability, and decision curve analysis. Results: Sixty patients (44.4%) were responders and 75 (55.6%) were non-responders. Responders showed greater week 3 increases in mid-band fit (3.4 ± 0.9 vs. 1.2 ± 0.8 dB, p < 0.001), entropy (0.7 ± 0.2 vs. 0.2 ± 0.2, p < 0.001), and more pronounced SWE mean stiffness reduction (−44.1 ± 9.7 vs. −12.1 ± 8.6 kPa, p < 0.001). The stacked ensemble integrating clinical, QUS, and SWE kinetic features reached an AUC of 0.93 (95% CI 0.88–0.97) versus 0.71 for the clinical-only model (all reported performance figures represent internal cross-validation only). SHAP analysis identified Δ MBF and Δ entropy at week 3 as the dominant features, with high bootstrap stability. Conclusions: Multi-parametric ultrasound radiomic kinetics integrated through a machine learning ensemble may provide an interpretable early-response biomarker for NAC in breast cancer, pending external validation. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory disease primarily driven by the interleukin (IL)-23/T helper 17 (Th17) pathway. Despite multiple systemic therapies, treatment response varies considerably, and many patients require sequential switching. We aimed to evaluate circulating blood-derived biomarkers associated with response to systemic psoriasis therapies. Methods: MEDLINE and Web of Science were searched on 8 August 2025, following PRISMA guidance. The protocol was registered in PROSPERO (CRD420251129182). Eligible studies were original English- or Spanish-language studies published within the previous 10 years that evaluated circulating blood-derived biomarkers associated with cutaneous response to approved systemic psoriasis therapies in patients with psoriasis, with or without psoriatic arthritis. Genetic predictors, therapeutic drug monitoring studies, reviews, editorials, letters, conference abstracts, case reports, and non-original publications were excluded. Risk of bias was assessed using QUIPS and PROBAST. Quantitative synthesis included standardized mean difference meta-analysis and exploratory pooled p-value analysis. Results: Twenty-six studies were included. Most evaluated biologic therapies targeting TNF, IL-17, or IL-23; fewer assessed apremilast or methotrexate. Response definitions and follow-up varied across studies. Most studies showed moderate to high risk of bias, mainly due to small sample sizes, exploratory or post hoc analyses, heterogeneous treatment groups, limited confounding adjustment, multiple testing, and lack of external validation. Random-effects meta-analysis of baseline cytokines from two studies, including 71 patients per biomarker, showed no statistically significant differences between responders and non-responders for IL-17A, TNF-α, IL-6, IL-12, or IL-23. Exploratory pooled p-value analyses showed recurrent signals for downstream IL-23/Th17 biomarkers, particularly β-defensin-2 (BD-2; z = 4.63, p < 0.001), IL-17A (z = 3.27, p = 0.001), and IL-17F (z = 2.92, p = 0.003). Conclusions: Downstream IL-23/Th17 biomarkers, particularly BD-2 and IL-17 isoforms, showed recurrent exploratory associations with systemic treatment response. However, these findings should not be interpreted as evidence of superior predictive performance over upstream biomarkers, and no soluble circulating biomarker is currently ready for routine treatment selection. Full article

Background/Objectives: The Bergen 4-Day Treatment (B4DT) is a concentrated form of exposure and response prevention for patients with obsessive–compulsive disorder (OCD). Although response rates for the B4DT are generally high, a proportion of patients does not achieve clinically significant improvements. Quantitative measures can identify non-response, but offer limited insight into processes that may hinder change in highly structured, time-limited interventions. To identify factors potentially related to the lack of improvement, this study explored experiences of patients who had not benefitted from B4DT. Methods: B4DT participants were recruited from an uncontrolled German study. Of 32 patients assessed at three-month follow-up, 12 met the non-response criteria (<35% reduction on the Yale–Brown Obsessive Compulsive Scale), and eight completed semi-structured qualitative interviews 9–14 months after treatment. Interviews were analyzed using grounded theory methods. A brief quantitative comparison examined baseline differences between responders and non-responders. Results: Participants described benefits from B4DT, including improved understanding of OCD, supportive peer contact, and increased courage for exposure tasks. However, they consistently reported difficulties sustaining self-guided exposure after treatment. Within the B4DT framework, one possible interpretation is that the intended shift toward independently approaching anxiety had not yet been fully consolidated. Conclusions: Although quantitatively classified as non-responders, participants described meaningful psychological benefits from B4DT. The findings suggest that non-response may reflect incomplete consolidation of the intended shift from symptom control toward approaching anxiety in service of personally meaningful action, rather than an absence of change. Full article