Predictive Factors Of Response Research Articles

Predictive Value of Immune Activity Changes in Breast Cancer Patients Treated With Dose-dense Neoadjuvant Chemotherapy: A Retrospective Study.

Dose-dense chemotherapy is recommended for patients with breast cancer who have a high recurrence risk. However, whether dose-dense neoadjuvant chemotherapy (ddNAC) improves patient prognoses compared to the normal-dose regimen remains controversial. In this study, we evaluated the predictive value of immune activities on short-term outcomes for patients treated with ddNAC. We classified 82 patients with human epidermal growth factor receptor 2-negative breast cancer treated with NAC into a normal dose group (62 patients) and ddNAC group (20 patients) and examined the differences in clinicopathological features. The ddNAC group was further divided according to patient responses to NAC and the predictive factors for pathological complete response (pCR) were evaluated. There were no differences in the clinicopathological features before NAC between the normal dose and ddNAC groups. Although the pCR rates tended to be higher in the ddNAC group compared than those in the normal dose group (35.0% vs. 25.8%), there was not significant difference (p=0.264). Among all patients treated with ddNAC, the absolute lymphocyte count decreased and the neutrophil-to-lymphocyte ratio increased during dose-dense doxorubicin plus cyclophosphamide treatment. There was no significant correlation between the pCR and any of the clinicopathological parameters tested including systemic peripheral markers and tumor-infiltrating lymphocyte levels. ddNAC affected the levels of systemic peripheral immune markers. However, monitoring these markers may not be useful for predicting responses to ddNAC.

Predictive factors for pathological complete response to neoadjuvant therapy in locally advanced rectal cancer: a review of current research

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Urine chloride trajectory and relationship with diuretic response in acute heart failure.

Sodium excretion is a well-defined marker used to assess diuretic response in acute heart failure (AHF). Despite a strong pathophysiological background, the role of urine chloride excretion has not been described and established yet. We aimed to evaluate chloride trajectory during intensive diuretic treatment in AHF patients and examine its potential role in predicting poor diuretic response. The study was conducted on 50 AHF patients. Participants were included within the first 36h of hospitalization. They received furosemide dose adjusted for body weight (half in bolus, half in 2h infusion). Post-diuretic hourly urine collection with biochemical analysis was performed. In general, the concentrations of urine chloride (uCl-) and sodium (uNa+) at the baseline samples exhibited a comparable level (71±39 vs. 70±44mmol/L, respectively; P=0.99), but across all post-furosemide study timepoints, uCl- remained significantly higher than uNa+ since 1 to 6h of the study. In this course, both ions (uCl- and uNa+) reached peak values in 2h (114±28 vs. 97±34mmol/L, respectively; P<0.01). The pattern of uCl- dominance over uNa+ concentration was also observed in separate analyses of patients naïve to furosemide and those chronically exposed to furosemide. Regardless of these patterns, naïve to furosemide individuals excreted more ions (both uCl- and uNa+) than chronically exposed patients at all timepoints. Additionally, a strong, linear correlation between uCl- and uNa+ was observed in each post-furosemide timepoint (the strongest in 1h r=0.87; P<0.001). Both interdependent ions concentration was almost parallel when analysed in chronic furosemide users and those naïve to furosemide separately [uCl-=0.85*uNa++28.82, P<0.001, R2=0.83 for chronic furosemide users, and uCl-=0.72*uNa++41.55, P<0.001, R2=0.65 for naïves to furosemide (linear regression model)]. Moreover, uCl- (with cutoff point: 72mmol/L) was a satisfactory predictive factor for poor diuretic response (<100mL/h in 6h since the beginning of furosemide infusion) [odds ratio (OR) 95% confidence interval (CI): 39.0 (3.8-405.00)]. It presented those properties also after adjusting for urine creatinine [cutoff point: 0.296mmol/mg-OR (95% CI): 81.0 (8.0-816.0)]. Urine chloride and sodium are highly interrelated during decongestion of AHF patients. The uCl- (cutoff 72mmol/L) exhibits better prognostic abilities to identify poor diuretic response than uNa+.

Two-year outcomes of intravitreal conbercept therapy for polypoidal choroidal vasculopathy.

This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55μm to 278.31 ± 157.34μm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept.

Are BDNF and Stress Levels Related to Antidepressant Response?

A total of 40 depressed adults were included. We evaluated initial serum BDNF, anxiety through the State-Trait Anxiety Inventory (STAI), and the severity of depressive symptoms by the Hamilton Depression Rating Scale (HDRS). Participants received antidepressant treatment for 8 weeks, and response to treatment was evaluated according to the final HDRS scores. Basal BDNF was higher in responders compared to non-responder depressed patients, in addition to being inversely associated with the severity of anxiety and depression. Baseline BDNF serum is an adequate predictive factor for response to antidepressant treatment with SSRI, with lower pre-treatment levels of BDNF associated with higher anxiety symptoms after treatment. Stress levels could influence the response to treatment, but its association was not conclusive.

Predictive factors for treatment response in active thyroid eye disease

Introduction/objectiveActive moderate-to-severe thyroid eye disease (TED) is a major therapeutic challenge. Pulse therapy with intravenous glucocorticoids is the standard treatment, with variable response. Radioactive iodine therapy (RAI) was reported as a risk factor for onset or worsening of TED. We evaluated putative predictive factors for response to intravenous methylprednisolone in patients with active TED. MethodsData were collected for 64 consecutive patients (45 women) with active moderate-to-severe TED treated with a minimum cumulative dose of 4.5g methylprednisolone. Patients were classified as responders (R) or non-responders (NR) on Clinical Activity Score (CAS), and clinical features were compared between groups. ResultsSixty-two patients had Graves’ disease (GD), and 2 had Hashimoto's thyroiditis (HT). Median age at thyroid dysfunction diagnosis, TED manifestation and pulse therapy was 46, 48 and 51 years, respectively; 56.2% were euthyroid when TED manifested. Among them, 73.4% were responders. R and NR were comparable for gender, age, thyroid function, serum antibodies, disease duration, pre-treatment CAS, smoking, lipid profile, and adverse events. Forty-nine patients were treated with RAI for GD: 15 before the active phase of TED (before pulse therapy), 16 during, 17 after, and 1 both before and after pulse therapy. Response rate was higher in patients who received RAI during than after pulse therapy (P=0.032) and similar to those not treated with RAI at all (P=0,599). ConclusionPulse therapy was effective in the majority of patients. The only factor associated with response to pulse therapy was the timing of RAI, suggesting that it seems to be safe when used concomitantly with pulse therapy.

Predictors of response to accelerated rTMS in the treatment of treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for treatment-resistant depression (TRD). We aimed to investigate the existence of clinical predictive factors in response to accelerated rTMS in the treatment of TRD. In total, 119 TRD patients who received accelerated rTMS were included in this study. The stimulation protocol was 15Hz stimulation over the the left dorsolateral prefrontal cortex. The protocol consisted of 25 sessions, each session lasting 30min for a total of 3000 pulses. Five sessions were applied per day for 5 consecutive days. At baseline (T0), day 5 (immediately after treatment) (T1), 4 weeks after treatment (T2), depression severity was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), cognitive function was evaluated using Wisconsin Card Sorting Test (WCST), the intensity of suicidal ideation was evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS). Systemic immune-inflammation index (SII) was calculated at T0 and T2. The HAMD-17 scores, WCST performance, the C-SSRS scores at T1 and T2 were improved from T0 (P < 0.01). The SII at T2 was lower than at T0 (P < 0.01). The response rates at T1 and T2 were 57.98% (69/119) and 48.74% (58/119), respectively. The results of binary logistic analysis showed that shorter course of depression, two failed antidepressant trials, no history of ECT treatment, and lower levels of SII were predictive factors for accelerated rTMS treatment response at T1 and T2 (P < 0.05), while not having a history of hospitalization was a predictive factor for response at T2 (P < 0.05) but not at T1 (P > 0.05). Based on ROC curve analysis, the optimal cut-off values of SII for discriminating responders from non-responders at T1 and T2 were < 478.56 and < 485.03, respectively. The AUC of SII at T0 predicting response for T1 and T2 were 0.729 and 0.797. We found several clinical predictors of better responses to the accelerated rTMS. Identifying clinical predictors of response is relevant to personalize and adapt rTMS protocols in TRD patients.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy

Introduction: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. Methods: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). Results: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. Conclusion: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

Update on Tolvaptan for the Treatment of Refractory Ascites in Liver Cirrhosis

Ascites is the most prevalent complication of decompensated cirrhosis, and approximately 5%-10% of cirrhotic ascites will develop into refractory ascites (RA). With complicated pathogenesis, obscure treatment strategies and poor prognosis, it is still a challenge for physicians to manage RA properly. Tolvaptan (TLV) is a new type of non-peptide selective arginine vasopressin V2 receptor antagonist targeting at suppressing renal water reabsorption, promoting free water excretion and raising blood sodium levels, which provides a new option for the treatment of RA in liver cirrhosis. In this review, we summarized the mechanisms of TLV's effect and described its efficacy, safety and predictive factors of response in treating RA, intending to provide a supplement for clinical application of tolvaptan in the management of RA.

Predictors and Management of Inadequate Response to JAK Inhibitors in Alopecia Areata.

Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.

Prognostic value of neutrophil to lymphocyte ratio in patients with advanced pancreatic ductal adenocarcinoma treated with systemic chemotherapy

Objectives Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC. Materials and methods A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS). Results A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy. Conclusions This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Real-world experience with long-term albumin in patients with cirrhosis and ascites

Background and AimsLong-term albumin (LTA) is currently standard of care for patients with decompensated cirrhosis in many Italian hepatological centres. This real-life study aimed to describe patient, logistical and treatment-related characteristics in daily clinical practice and to identify predictors of response. MethodsMulticentre, retrospective, observational study in patients with cirrhosis and ascites receiving LTA between 01/2016 and 02/2022 and followed until death, TIPS, transplantation or 02/2023. Results312 patients, the majority with alcohol-related cirrhosis, were included. At baseline, median Child-Pugh was 8, MELD 15, and MELD-Na 18. Ascites was grade 2 in 55% of patients, grade 3 in 35% and refractory in 27%, while 47% had paracentesis in the previous 6 months. Median LTA was 10 months with a median dose of 40 g/week.Ascites resolved to grade 0-1 in 34% of patients within the first 3 months and 56% at the end of treatment. Predictors of ascites resolution were age (p=0.007), baseline grade of ascites (p=0.007), no paracentesis in the previous 6 months (p=0.001), etiological treatment in the past 12 months or during LTA (p=0.005), weekly albumin dose (p=0.014) and serum albumin concentration of 40 g/L after one month of treatment (p=0.017). Of the 83 patients with refractory ascites at inclusion, 26% had grade 0/1 ascites at the last observation. No severe albumin-related side-effects were reported and only 1% discontinued due to logistic reasons. ConclusionsLTA is feasible as an outpatient treatment for the management of ascites. In the current study, more than half of patients receiving LTA on top of diuretics resolved their ascites, including some with refractory ascites. Predictors of response to LTA provide useful information for tailoring treatment. IMPACT AND IMPLICATIONSThe ANSWER randomized clinical trial has shown that long-term albumin treatment (LTA) is an effective approach for the management of patients with cirrhosis and ascites. This observational study provides novel information on target patients, modalities and length of treatment, predictors of ascites resolution, stopping criteria, and clinical trajectories of patients on treatment.LTA is a feasible option in the daily clinical practice for the management of ascites when given on top of diuretics. Rather than an alternative therapy, LTA should be integrated with the other treatments options already available for patients with difficult-to-treat ascites. The predictive factors of response identified in the present study can help physicians to individualize LTA and optimize the decision-making process.

Baseline systemic inflammatory indices and clinicopathological features to predict the outcome of acute tubulointerstitial nephritis : Asingle-center retrospective study.

Acute tubulointerstitial nephritis (AIN) is an immune-mediated disorder that can cause acute kidney injury (AKI). We aimed to investigate the characteristics of patients with AIN and predictive factors for treatment response. In this study, thirty-one patients diagnosed with AIN on kidney biopsy between 2006 and 2021 were included. Baseline clinical, histopathological, and laboratory findings, including complete blood count (CBC), creatinine, erythrocyte sedimentation rate, C‑reactive protein, C3, C4, systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and urinalysis were evaluated. Treatment response, mortality, and creatinine levels at the time of last follow-up were also noted. The median age was 46 years and 80.6% were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 gram/day. The median follow-up period was 14months and 93.5% received immunosuppressives. End-stage kidney disease (ESKD) developed in five patients (16.1%). Renal recovery (creatinine < 1.4 mg/dL) was observed in 17 patients (54.8%). Higher degrees of interstitial fibrosis, tubular atrophy, granuloma formation, global glomerulosclerosis, and higher baseline hemoglobin levels, in addition to alonger interval between first symptom to initiation of immunosuppressives were associated with renal nonrecovery, statistically. Also, patients who progressed to ESKD had higher baseline hemoglobin (p = 0.033) and lymphocyte (p = 0.044) and lower PLR levels (p = 0.016), as well as higher degrees of global glomerulosclerosis (p = 0.014), interstitial fibrosis (p = 0.042), and tubular atrophy (p = 0.030). Treatment response rates are low for AIN, which may lead to ESKD. Besides chronicity in histopathology specimens, higher baseline hemoglobin levels and lower platelet-to-lymphocyte ratio might be prognostic. Further studies should be conducted on new markers for AIN.

Predictive factors of stress response of nursing student repeaters under the background of abolishing the final supplementary examination in China

BackgroundAcademic pressure and frustration stimulation are significant stressors in college students, and response to the prolonged stimuli would cause adverse mental and physical outcomes. However, more is needed to know about the stress response and its predictors among undergraduate nursing students retaking failed course under the background of the abolition of the Final Supplementary Examination in China. This study aimed to investigate the stress response and its predictive factors of nursing student repeaters who are retaking at least one failed course.MethodsA cross-sectional study was conducted, utilizing convenience sampling to recruit 120 nursing student repeaters from four 4-year undergraduate medical universities in China between September 2020 and May 2021. Data collection instruments included a general information questionnaire, a stress response questionnaire, the Connor-Davidson resilience scale, a self-control scale, and a academic self-efficacy questionnaire. The data were analyzed using descriptive statistics, Pearson correlation coefficients, t-tests, analysis of variance (ANOVA), and multiple linear regression.ResultsThe average scores of the total stress response, emotional response, physical response, and behavioral response were 58.07 ± 26.72, 86.97 ± 17.12, 57.69 ± 9.75, 67.16 ± 9.22, respectively. Stress response was predicted by psychological resilience, self-control ability, academic self-efficacy and the number of retaking courses.ConclusionsThe stress response among nursing student repeaters is relatively active. Higher psychological resilience, self-control ability, and academic self-efficacy predict lower levels of stress response. In order to help nursing students with failing and repeating course release their psychological stress and maintain well-being, nursing educators could adopt self-control promotion strategies and emphasize the cultivation of psychological resilience and academic self-efficacy as parts of health promotion programs for this particular student group.

Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort

ObjectiveRheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX).Methods140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels.ResultsA strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [r = 0.44 (0.27 − 0.56); p < 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68NecrosisHIGH (CD68 + Necrosis ≥ 3) and CD68NecrosisLOW (CD68 + Necrosis < 3). CD68NecrosisHIGH exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7); p = 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27), p = 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5); p = 0.003] and CDAI [16 [14.9] versus 10.5 (20.1), p = 0.04]. CD68NecrosisHIGH patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724).ConclusionFN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.

TP53 mutation as predictive factor of platinum response in BRCA-mutated ovarian cancer: A prospective case-series analysis.

128 Background: Platinum sensitivity (PS) is a prerequisite for first-line PARP inhibitors (PARPi) in locally advanced and relapsed high grade serous ovarian cancer (HGS-OC). BRCA mutations are predictive of PS and of response to PARPi. Notably, platinum and PARPi cytotoxic action is mainly related to p53-mediated inducted apoptosis. Therefore, the integrity of p53 machinery is crucial for platinum-related activity whereas the presence of p53 mutation is a fairly frequent event in ovarian cancer, especially in HGS-OC and in BRCA mutated. Methods: We prospectively analyzed 208 women with primary ovarian cancer undergoing surgery at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, Italy, between 2019 and 2023. Somatic NGS analysis was performed to detect BRCA and HRD mutations. TP53 mutations were classified according to according to hotspot, structural (missense/nonsense) and functional classification as “gain of function” (GOF) or “loss of function” (LOF), based on IARC TP53 database. Comparative testing with Fisher's exact test was used to examine TP53 mutation distribution and associations with clinicopathologic factors and PS. BRCA mutation status was further used to stratify the analysis. Results: Globally, we included 127 adult HGS-OC patients (pts). 84.2% had stage III-IV disease. TP53 mutation was found in 83.4% of pts. Somatic BRCA mutations were found in 28.3%. HGS-OC with somatic BRCA mutations had higher TP53 mutation frequency (88.8%) than BRCA WT (81.3%, p=0.1510). Employing the structural classification scheme, most harbored a missense TP53 mutation (76.5%). LOF TP53 mutations were found in 59.4% while GOF in 31.2%. No significant disparity was observed in the distribution of specific TP53 mutations within each classification scheme between cases with BRCA mutations and those without. As for BRCA mutated pts, TP53 WT were all PS. Among those p53 mutated, GOF mutations were associated with PS in 7 pts and platinum resistance in 3 pts; LOF mutations were associated with PS in 7 pts and platinum resistance in 12 pts. The difference in distribution of PS between functional categories of p53 mutations was significant (p=0.0291). As for BRCA WT pts, TP53 WT were all PS. Among TP53 mutated, GOF mutations were associated with PS in 14 pts and platinum resistance in 10 pts, whereas LOF mutations were associated with PS in 19 pts and platinum resistance in 25 pts, even if these findings were not statistically significant (p=0.2357). Of relevance, in 5 cases where LOF mutations of p53 was associated with null HIC p53 expression, pts were refractory to platinum-based chemotherapy. Conclusions: Even if preliminary, our data show that HGS-OC harboring TP53 null mutations are the poorest prognostic subgroup, especially in terms of PS. Further studies are needed to confirm our findings and the role of TP53 mutation as a biomarker of inherent or acquired platinum resistance.

Prediction model for treatment response of primary membranous nephropathy with nephrotic syndrome.

To investigate the predictors and establish a nomogram model for the prediction of the response to treatment in primary membranous nephropathy (PMN) with nephrotic syndrome (NS). The clinical, laboratory, pathological and follow-up data ofpatients withbiopsy-proven membranous nephropathy at the Affiliated Hospital of QingdaoUniversity were collected. A total of 373 patients were randomly assigned into development group (n = 262) and validation group (n = 111). Logistic regression analysis was performed in the development group to determine the predictors of treatment response. A nomogram model was established based on the multivariate logistic regression analysis and validated in the validation group. The C-index and calibration plots were used for the evaluation of the discrimination and calibration performance, respectively. Serum albumin levels (OR = 1.151, 95% CI 1.078-1.229, P < 0.001) and glomerular C3 deposition (OR = 0.407, 95% CI 0.213-0.775, P = 0.004) were identified as independent predictive factors for treatment response in PMN with NS, then a nomogram was established combining the above indicators and treatment regimen. The C-indices of this model were 0.718 (95% CI 0.654-0.782) and 0.789 (95% CI 0.705-0.873) in the development and validation groups, respectively. The calibration plots showed that the predicted probabilities of the model were consistent with the actual probabilities (P > 0.05), which indicated favorable performance of this model in predicting the treatment response probability. Serum albumin levels and glomerular C3 deposition were predictors for treatment response of PMN with NS. A novel nomogram model with good discrimination and calibration was constructed to predict treatment response probability at an early stage.

Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.

KCNT1-related epilepsies encompass three main phenotypes: (i) epilepsy of infancy with migrating focal seizures (EIMFS), (ii) autosomal dominant or sporadic sleep-related hypermotor epilepsy [(AD)SHE], and (iii) different types of developmental and epileptic encephalopathies (DEE). Many patients present with drug-resistant seizures and global developmental delays. In addition to conventional anti-seizure medications (ASM), multiple alternative therapies have been tested including the ketogenic diet (KD), cannabidiol (CBD-including Epidyolex © and other CBD derivatives) and quinidine (QUIN). We aimed to clarify the current state of the art concerning the benefits of those therapies administered to the three groups of patients. We performed a literature review on PubMed and EMBase with the keyword "KCNT1" and selected articles reporting qualitative and/or quantitative information on responses to these treatments. A treatment was considered beneficial if it improved seizure frequency and/or intensity and/or quality of life. Patients were grouped by phenotype. A total of 43 studies including 197 patients were reviewed. For EIMFS patients (32 studies, 135 patients), KD resulted in benefit in 62.5% (25/40), all types of CBD resulted in benefit in 50% (6/12), and QUIN resulted in benefit in 44.6% (25/56). For (AD)SHE patients (10 studies, 32 patients), we found only one report of treatment with KD, with no benefit noted. QUIN was trialed in 8 patients with no reported benefit. For DEE patients (10 studies, 30 patients), KD resulted in benefit for 4/7, CBD for 1/2, and QUIN for 6/9. In all groups, conventional ASM are rarely reported as beneficial (in 5%-25% of patients). Ketogenic diet, CBD, and QUIN treatments appear to be beneficial in a subset of patient with drug-resistant epilepsy. The KD and CBD are reasonable to trial in patients with KCNT1-related epilepsy. Further studies are needed to identify optimal treatment strategies and to establish predictive response factors. We performed an extensive review of scientific articles providing information about the therapeutic management of epilepsy in patients with epilepsy linked to a mutation in the KCNT1 gene. Conventional anti-seizure treatments were rarely reported to be beneficial. The ketogenic diet (a medical diet with very high fat, adequate protein and very low carbohydrate intake) and cannabidiol appeared to be useful, but larger studies are needed to reach a conclusion.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma

BackgroundRadioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored.MethodsIn a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the “Responder group”. Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans.Results333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660–0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12–0.55), P < 0.001.ConclusionStimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.