Search Results (105)

The emergence of anti-TNF agents has revolutionized the management of inflammatory bowel disease, yet a significant proportion of patients experience primary non-response or secondary loss of response due to immunogenicity. As the field of precision medicine advances, genetic predictors such as human leukocyte antigen (HLA) variants are gaining increasing attention. This review provides a comprehensive synthesis of current evidence on the role of HLA genotypes in inflammatory bowel disease susceptibility and disease behavior, with a focus on their mechanistic and clinical relevance in anti-TNF therapy. Special emphasis is placed on HLA-DQA1*05, a validated predictor of anti-drug antibody formation and reduced therapeutic durability. We explore the immunological basis of HLA-mediated immunogenicity, summarize pharmacogenetic and biomarker findings, and discuss how HLA typing may be integrated into treatment algorithms to improve patient stratification and long-term outcomes. As immunogenetics continues to inform clinical decision-making, understanding the interplay between HLA polymorphisms and therapeutic response offers new opportunities for biomarker-guided, personalized care in inflammatory bowel disease. Full article

Background and Objectives: Medication overuse headache (MOH) presents unique clinical challenges in older adults due to age-related changes and comorbidities. However, data on MOH characteristics and treatment responses in this population remain limited. This study investigated the clinical features, treatment patterns, and short-term outcomes of MOH in older patients. Methods: We analyzed data from the RELEASE registry, a nationwide, multicenter prospective cohort of MOH patients in South Korea. Participants were stratified into older (≥65 years) and younger (<65 years) groups. We compared clinical features, treatment patterns, and 3-month outcomes, and identified factors associated with treatment response in the older group. Results: Among 791 patients, 72 (9.1%) were older. Compared to younger patients, older patients reported more monthly headache days (30.0 vs. 27.0, p = 0.012), more days using acute medication (30.0 vs. 20.0, p < 0.001), and fewer headache-free days (0.0 vs. 3.0, p = 0.012). They also experienced more severe headache days (12.5 vs. 10.0, p = 0.056). Despite this, older patients showed lower disability, with significantly lower Migraine Disability Assessment scores (30.0 vs. 46.0, p < 0.001) and a trend toward lower Headache Impact Test-6 scores (64.5 vs. 66.0, p = 0.065). In multivariable analysis, poor adherence to preventive treatment (≤24%) was significantly associated with non-response (OR 0.13, 95% CI: 0.02–0.96, p = 0.045) at 3 months. Conclusions: Older patients with MOH showed distinct clinical features, including higher headache frequency and severity but relatively lower disability. Improving adherence to preventive treatment may enhance treatment response. Age-specific management strategies are needed. Full article

Enterovirus (EV) infections in neonates can be transmitted vertically or horizontally, with symptoms ranging from mild to severe, including myocarditis, meningoencephalitis, and hepatitis. Neonates with EV-induced myocarditis may present severe cardiovascular disease with sudden onset of arrhythmia. Neonatal arrhythmias, particularly in low birth weight or critically ill infants, can impair cardiac function and worsen outcomes. EV targets cardiomyocyte receptors, inducing apoptosis pathways and triggering cardiac conduction disturbances. We present an extremely low-birth-weight preterm infant (GW 27 + 6) who developed EV-induced myocarditis, complicated with a sudden onset of supraventricular tachycardia (SVT), pericardial effusion and bi-atrial enlargement. Despite multi-agent regimen, including propranolol, flecainide, and amiodarone, the infant showed persistent junctional rhythm until seven months of age, later transitioning to atrial rhythm with stable cardiac function. A review of previously published rhythm disturbances due to EV-induced myocarditis is presented. Newborns with EV-induced arrhythmia may require a multi-modal treatment such as a multi-agent medical regimen or, in severe non-responsive cases, an electrophysiological approach. EV infections may cause long-term cardiovascular comorbidities (such as left ventricular dysfunction or mitral valve regurgitation), necessitating continuous monitoring through echocardiography and ECG. Collaboration between neonatologists and pediatric cardiologists is crucial for effective treatment and follow-up. Full article

Background: Remote symptom monitoring via electronic platforms may identify patients at risk for unplanned acute care visits after surgery. Since 2016, the Memorial Sloan Kettering Cancer Center (MSKCC) has employed the Recovery Tracker (RT), a patient-reported outcome (PRO) system, for symptom monitoring after ambulatory procedures. In 2021, RT was extended to patients undergoing inpatient colorectal surgery. Objective: To evaluate the impact of RT implementation on urgent care utilization and readmission rates in patients undergoing elective inpatient colorectal surgery and to determine whether patient engagement with RT influences these outcomes. Methods: In this retrospective observational study at MSKCC, we compared patients undergoing elective colorectal surgery during the RT implementation period (March 2021–December 2022) to a historical control cohort (February 2019–February 2020). The primary outcome was a potentially unnecessary urgent care center (UCC) visits—defined as a visit not requiring inpatient admission. Secondary outcomes included 30-day readmission and survey engagement. Multivariable logistic regression was used for adjusted comparisons. Results: A total of 1941 patients in the RT cohort and 1206 in the control group met the inclusion criteria. The RT cohort had higher rates of UCC visits without admission (4.43% vs. 1.6%) and 30-day readmissions (9.74% vs. 6.88%). RT period surgery was independently associated with increased odds of UCC visits (OR 2.80, 95% CI 1.71–4.58, p < 0.0001) and readmissions (OR 1.43, 95% CI 1.09–1.88, p = 0.0098). Notably, RT users who completed at least one survey (70.2%) had significantly lower odds of readmission (OR 0.56, 95% CI 0.41–0.77, p = 0.0003) compared to non-responders. Discussion: Engagement with the RT system was associated with a 44% reduction in readmission risk, identifying non-responders as a vulnerable subgroup. While the overall rates of post-discharge care utilization increased after RT implementation, active participation in PRO reporting emerged as a protective factor. Conclusions: These findings highlight the need for strategies to promote engagement and support patients less likely to interact with remote monitoring tools. Non-response may signal barriers such as technological challenges or increased vulnerability, warranting proactive engagement strategies. Full article

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA. Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and clinical outcomes. Subgroup analyses were performed to assess the prognostic value of dual-source galactomannan positivity (positive serum and BAL fluid galactomannan levels). Results: Elevated baseline serum galactomannan levels independently predicted treatment non-response (p = 0.039) and 12-week all-cause mortality (p < 0.001). Peak serum and BAL fluid galactomannan levels were strongly associated with poor clinical outcomes (p < 0.01). Compared to single-source galactomannan positivity, dual-source galactomannan positivity was linked to reduced treatment response (22% vs. 43%, p = 0.01) and higher IA-attributable mortality (52% vs. 27%, p = 0.002). Patients with neutropenia had poorer outcomes compared to patients without neutropenia, but neutrophil recovery dramatically improved survival (25% vs. 69% mortality, p < 0.0001). Early galactomannan kinetics and malignancy type had limited prognostic value. Conclusions: Our findings highlight the potential role of galactomannan as a key biomarker for early prognostication for IA. The strong association between galactomannan levels and clinical outcomes suggests its utility in identifying high-risk patients who may benefit from more aggressive management. Further studies are needed to introduce a nuanced and context-specific use of galactomannan into clinical practice and assess its role as a prognostic biomarker. Full article

(1) Background: Neoadjuvant chemotherapy (NAC) is an integral part of breast cancer management, and response to NAC is an important prognostic factor associated with improved survival outcomes. However, the current standard for response assessment relies on post-surgical histopathological analysis, which limits early therapeutic decision-making and treatment personalization. This study aimed to develop and evaluate a machine learning model that integrates pre-treatment MRI radiomics and clinical features to predict response to NAC in breast cancer patients. (2) Methods: In this study, a machine learning model was developed to predict breast cancer response to NAC using pre-treatment magnetic resonance imaging (MRI) radiomics and clinical data. Radiomic features were extracted from contrast-enhanced T1-weighted (CE-T1) and T2-weighted (T2) MRI sequences using both intratumoral and peritumoral segmentations. Furthermore, this study uniquely examined two response assessment criteria: (1) pathologic complete response (pCR) versus non-pCR, and (2) clinical response versus non-response. A total of 254 patients with biopsy-confirmed breast cancer who completed NAC were included. Radiomic features (n = 400) and clinical features (n = 7) were analyzed to build a predictive model employing the XGBoost classifier. Performance was measured in terms of accuracy, precision, sensitivity, specificity, F1-score, and AUC. (3) Results: The integration of radiomic features with clinical data significantly enhanced the predictive performance. For pCR and non-pCR prediction, the combined features model achieved an accuracy of 80% and AUC of 0.85, outperforming both the clinical features model (Accuracy = 68%, AUC = 0.81) and radiomic features model (Accuracy = 66%, AUC = 0.60). Similarly, for the clinical response and non-response prediction, the combined features model achieved an Accuracy of 74% and AUC of 0.75, outperforming both the clinical features model (Accuracy = 63%, AUC = 0.68) and radiomic features model (Accuracy = 66%, AUC = 0.57). (4) Conclusions: These findings highlight the synergistic effect of integrating clinical data and MRI-based radiomics to improve pre-treatment NAC response prediction, which has the potential to enable more precise and personalized treatment strategies. Full article

Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn’s disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms (SNPs) across the TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 genes was performed on a cohort of 127 Japanese patients with CD. The therapeutic responses were evaluated at 10 weeks, 1 year, and 2 years using three different inheritance models. Results: The CD patients with a G/G genotype of rs5743565 in TLR1 were significantly less likely in the responders at 10 weeks compared with the non-responders (p = 0.023, OR = 0.206). The frequencies of the C/T or T/T genotypes of rs5743604 in the TLR1, G/A, or A/A genotypes of rs13105517 in TLR2, both in the minor allele dominant model, were significantly higher in the responders at 10 weeks as compared with those in the non-responders (p = 0.035, OR = 4.401; p = 0.017, OR = 5.473). The patients with an A/A genotype of rs13105517 in TLR2 in the minor allele recessive model were significantly less likely in the responders at one year of IFX treatment compared with those in the non-responders (p = 0.004, OR = 0.195). Conclusions: The polymorphisms of TLR1 and TLR2 can be useful as biomarkers for predicting initial and secondary LOR to IFX in Japanese CD patients. The IFX response in genetic testing may target molecules for new drugs to overcome the non-response and LOR to IFX. Full article

MSI is a crucial biomarker for selecting CRC patients for immunotherapy. Here, we analyze the first results from the observational prospective trial BLOOMSI (NCT06414304), which investigated the impact of MSI/dMMR testing methods and baseline tumor heterogeneity on treatment outcomes. Thirty MSI/dMMR+ CRC patients, who were candidates for immunotherapy, were enrolled. Depending on the local test used for MSI/dMMR, central PCR/IHC was performed. Baseline FFPE and liquid biopsy (LB) were analyzed with NGS. ORR (objective response rate) in the ITT population was 50% (95% CI, 31.3–68.7%). Concordance between local/central dMMR/MSI testing was 81%, and the concordance of IHC, PCR, NGS/FFPE, and NGS/LB was 68.4%. The ORR was similar for IHC+, PCR+, NGS/FFPE+, and NGS/LB+ patients (55.6%, 55.6%, 55%, and 57.9%, respectively). The ORR among patients with discordant IHC/PCR results was 0%, and the ORR among patients with NGS/LB-ORR was 25% (2/8 CR). Next, we performed quantitative MSI analysis, reflecting the clonality of MSI+ tumor cells. Multivariate analysis identified MSI clonality in FFPE (HR 0.63, 95% CI, 0.39–0.99, p = 0.0487) and LB (HR 3.05, 95% CI, 2.01–4.65, p < 0.00001) as independent predictors of progression. The ORR in patients with high clonality (≥7%, n = 4, NGS/LB) was 25%. We describe baseline methodological predictors of non-response to immunotherapy and propose a strategy for selecting potential non-responders. These findings warrant further investigation. Full article

IgG4–related disease (IgG4–RD) is an autoimmune condition marked by IgG4–positive plasma cell infiltration, causing inflammation, fibrosis, and tumor–like lesions, especially in the lacrimal gland (LG). Current diagnostic criteria, based primarily on serum IgG4 levels, face limitations in predicting clinical outcomes and treatment responses. To address this, we conducted a multiplex immaunohistochemical analysis of LG tissues to assess immune checkpoint interactions and immune cell distribution in relation to mass size, fibrosis, and treatment response. Our findings revealed that PD–L1 (Programmed Death–Ligand 1), an immune checkpoint molecule, plays a key role in shaping an immunosuppressive environment that varies by clinical group. In non–responsive patients, increased co–expression of PD–L1 and CD11c+ dendritic cells (DCs) suggested a link to treatment resistance. Spatial analysis highlighted more active immune responses in non–fibrotic areas, while fibrotic regions exhibited stabilized immune interactions driven by PD–L1 expression. These results indicate that PD–L1 contributes to immune regulation and disease progression in IgG4–RD and emphasize its potential as a therapeutic target. This study provides new insights into the immunological landscape of IgG4–RD and paves the way for the development of personalized treatment strategies. Full article

Background/Objectives: Odontogenic cysts are pathological cavities lined by cells arising from odontogenic epithelial cells, occurring mostly on the tooth-bearing areas of the jaws. It is common to find that the apices of the teeth around the cyst are within the cyst’s cavities due to its expansion. This study aims to assess the outcome of cyst enucleation on the associated teeth, specifically the latter’s responsiveness after cyst enucleation. Methods: This retrospective study examined a sample of patients who had been previously treated for odontogenic cysts from 1 January 2000 to 31 December 2021. A list of patients was obtained and included whether they met the imposed inclusion criteria. The data collected included the patients’ preoperative and postoperative electric pulp testing readings and their timings. Results: In total, 77 individual teeth from 19 patients were included after meeting the inclusion/exclusion criteria. Overall, 57 out of the 77 (74%) teeth were responsive following long-term follow-up. Among the 57 teeth with a positive response, 8 teeth were initially non-responsive and regained their responsiveness after a period of time. Pulp responsiveness recovery was seen even 300 days after surgery. Conclusions: It is not certain that a tooth with apices involved in a cyst cavity will be non-vital following enucleation. It is recommended that these teeth be reassessed for a minimum of 10 months postoperatively before proceeding with root canal treatment. Full article

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders influenced by microbial, environmental, genetic, and immune factors. The introduction of biological agents has transformed IBD therapy, improving symptoms, reducing complications, and enhancing patients’ quality of life. However, approximately 30% of patients exhibit primary non-response, and 50% experience a loss of response over time. Genetic and non-genetic factors contribute to variability in treatment outcomes. This systematic review aims to thoroughly analyze and assess existing studies exploring the relationships between genetic variations and individual responses to biologic drugs, in order to identify genetic markers that are predictive of treatment efficacy, risk of adverse effects, or drug toxicity, thereby informing clinical practice and guiding future research. PubMed and EMBASE papers were reviewed by three independent reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. Of the 883 records screened, 99 met the inclusion criteria. The findings of this review represent an initial step toward personalized medicine in IBD, with the potential to improve clinical outcomes in biological therapy. Full article

Background: The aim of this study was to evaluate the serological response after the complete hepatitis B vaccination of patients according to the immunosuppressive treatment they underwent, and to identify potential factors associated with non-responders. Methods: A prospective cohort study was conducted, and patients under immunosuppressive therapies were considered exposed. The main outcome was non-response to hepatitis B vaccination. Bivariate analysis was conducted to detect differences between exposed and non-exposed patients. A multivariable log-binomial regression model was designed to analyze potential factors independently associated with non-responders. Results: A total of 289 patients were included. Immunosuppressive treatment was associated with non-response to hepatitis B vaccination (RR = 2.49, 95% CI: 1.26–4.96). Concretely, the use of cytotoxic therapies showed increased risk, although anti-CD20 and anti-JAK also showed a tendency to be associated with non-responders. Other variables associated with non-responders were older age (6–7% higher risk per year), smoking (RR = 3.08, 95% CI: 1.41–6.74) and certain vaccine regimens. These findings were similar for persistent non-responders despite an additional booster dose. Conclusions: Patients receiving immunosuppressive treatments, who are older in age or who are smokers have a higher risk of non-response to conventional hepatitis B vaccination. These data might serve to optimize hepatitis B vaccination in high-risk patients. Full article

Background: Breast cancer remains the leading cause of cancer-related deaths among women despite advances in early detection. Neoadjuvant chemotherapy (NACT) is now standard for early-stage BC, with vitamin D (VD) emerging as a potential prognostic biomarker considering its positive pleiotropic effects. This review and meta-analysis assess the impact of baseline VD levels on outcomes in BC patients undergoing NACT. Methods: Inclusion criteria required patients to be over 18 years of age, have a pathologically confirmed BC diagnosis, and have their VD levels assessed prior to chemotherapy. Studies were included if they reported odds ratios (ORs) for response and/or hazard ratios (HRs) for PFS with 95% confidence intervals (CIs). A comprehensive literature search of PubMed/MEDLINE and Scopus/ELSEVIER (2014–2024) was conducted, and data were analyzed using fixed- and random-effects models, with Forest plots illustrating the results. Study quality and potential biases were assessed using the MINORS, NOS, and RoB2 scales, and statistical heterogeneity was evaluated with I² statistics and funnel plots. Results: Six studies were included in the analysis. All studies addressed stages II and III, with three also including stage I. The meta-analysis covered data from 722 patients regarding NACT response and 1033 patients for PFS. The results revealed a 22% reduction in the likelihood of non-response to NACT associated with adequate VD levels (low/deficient VD vs. high/sufficient VD; OR: 0.78; 95% CI: 0.30–1.25; p = 0.001) and a 35% reduction in progression risk with sufficient baseline VD levels (low/deficient VD vs. high/sufficient VD; HR: 0.65; 95% CI: 0.33–0.97; p < 0.001). Conclusions: These findings highlight the significance of maintaining adequate vitamin D levels in BC treatment and encourage further studies to unravel the role of VD on cancer biology. Full article

Background/Objectives: Multilevel interventions have demonstrated efficacy in improving obesity and other related health outcomes. However, heterogeneity in individual responses indicates the need to identify the factors associated with responses and non-responses to multilevel interventions. The objective of this report is to identify the potential sources of heterogeneity through the exploration of the moderation effects of participant characteristics (sociodemographic and baseline physical/mental health) in the Strong Hearts, Healthy Communities-2.0 (SHHC-2.0) intervention. Methods: SHHC-2.0 is a 24-week multilevel intervention to improve people’s diet and physical activity evaluated using a cluster-randomized, controlled trial design conducted with women aged 40 and older living in rural communities with an elevated risk of cardiovascular disease, defined as having a BMI > 30, or a BMI 25–30 plus < 1 weekly occurrence of 30 min of physical activity during leisure time. Linear mixed models were used to compare the between-group changes in the outcomes (weight, systolic blood pressure, hemoglobin A1c [HbA1c], and triglycerides), with an interaction term included for each potential moderator. Results: Within the sociodemographic characteristics, there were no differences in effectiveness by age, income, or baseline BMI status, but the participants with a high school education or less experienced less weight loss. Among their health history, only a history of hypertension was associated with differential outcomes; those with a history of hypertension demonstrated a greater reduction in systolic blood pressure. The participants with elevated depressive symptoms demonstrated greater weight loss and a greater reduction in the HbA1c level. Conclusions: SHHC-2.0 was effective across a wide range of participants. The identified moderators (i.e., education level) may inform the future tailoring of the SHHC intervention to optimize the outcomes among participant subgroups, while more broadly, our findings can serve to inform the development and dissemination of multilevel interventions. Full article

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers. Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing clinical and transcriptomic data from 1892 patients diagnosed with melanoma, bladder, ovarian, or pancreatic carcinomas. Real-world data were collected under the Total Cancer Care Protocol and the Avatar^® project (NCT03977402) across 18 cancer centers. Furthermore, we compared the survival outcomes following immune checkpoint inhibitors (ICIs) based on immune cell gene expression. Results: In melanoma and bladder cancer, the estimated infiltration of APA T-cells differed significantly (p = 4.67 × 10⁻¹² and p = 5.80 × 10⁻¹², respectively) compared to ovarian and pancreatic cancers. Ovarian cancer had lower TRM T-cell infiltration than melanoma, bladder, and pancreatic (p = 2.23 × 10⁻⁸, 3.86 × 10⁻²⁸, and 7.85 × 10⁻⁹, respectively). Similar trends were noted with stem-like, early, and late dysfunctional T-cells. Melanoma and ovarian expressed BTN3A isoforms more than other malignancies. Higher densities of stem-like TILs; TRM, early and late dysfunctional T-cells; APA T-cells; and BTN3A isoforms were associated with increased survival in melanoma (p = 0.0075, 0.00059, 0.013, 0.005, 0.0016, and 0.041, respectively). The TRM gene signature was a moderate predictor of survival in the melanoma cohort (AUROC = 0.65), with similar findings in testing independent public datasets of ICI-treated patients with melanoma (AUROC 0.61–0.64). Conclusions: Key cellular elements related to immune activation are more heavily infiltrated within ICI-responsive versus non-responsive malignancies, supporting a central role in anti-tumor immunity. In melanoma patients treated with ICIs, higher densities of stem-like TILs, TRM T-cells, early dysfunctional T-cells, late dysfunctional T-cells, APA T-cells, and BTN3A isoforms were associated with improved survival. Full article