Responder Group Research Articles

Preoperative Hip Injection Response Does Not Reliably Predict 2-Year Postoperative Outcomes After Hip Arthroscopy for Femoroacetabular Impingement

PurposeTo determine whether response to preoperative local anesthetic or corticosteroid intra-articular injections can predict 2-year postoperative outcomes in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). MethodsThis was a retrospective analysis of patients undergoing hip arthroscopy for FAIS at a single institution from 2014-2020. Patients who underwent preoperative intra-articular hip injection were classified based on injection type (local anesthetic, corticosteroid) and whether they experienced pain relief following injection (responders, non-responders). Responders were matched 2:1 by age, BMI, and sex with non-responders. Patient reported outcomes (PROs) including Hip Disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form Survey mental (SF-12-MCS) and physical component summary (SF-12-PCS) and visual analogue scale (VAS) pain were collected preoperatively and 2-years postoperatively. Mean score change and Minimal Clinically Important Difference (MCID) achievement were calculated and compared between groups. ResultsThe matched cohort included 126 total patients (42 non-responders, 84 responders; 74.6% female; mean ± SD age: 30.9 ± 9.9 years; BMI: 24.7 ± 3.7 kg/m2) with no differences in demographic or radiographic hip variables. Both groups demonstrated significant 2-year postoperative score improvements across all PROs, except SF-12-MCS, which remained unchanged. There was no difference in mean score change or MCID achievement across all PROs between corticosteroid injection responder and non-responder groups. In the local anesthetic group, MCID achievement was similar across all PROs, except VAS pain which showed greater percentage of MCID achievement among local anesthetic non-responders relative responders (Responders: 55.0%, Non-responders: 89.5%; p = 0.03). Significant ceiling effects were most readily apparent among the injection responders group with greater percentages of patients achieving maximal 2-year postoperative survey scores (36.9% HOOS-ADL, 19.0% HOOS-Pain, 15.5% HOOS-QoL, 32.1% HOOS-Sport). ConclusionsResponse to preoperative injection with either corticosteroid or local anesthetic did not predict 2-year outcomes after hip arthroscopy in patients with FAIS. Level of EvidenceLevel III, retrospective matched cohort study.

Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates

High human leukocyte antigen (HLA) sensitization limits access to compatible transplantation. New CD38-targeting agents have been shown to reduce anti-HLA antibodies, although with important interpatient variability. Thus, pretreatment identification of responder and nonresponder (NR) patients is needed for treatment decision-making. We analyzed 26 highly sensitized (HS) patients from 2 desensitization trials using anti-CD38 monoclonal antibodies. Hierarchical clustering identified 3 serologic responder groups: high responders, low responders, and NR. Spectral flow cytometry and functional HLA-specific memory B cell (mBC) assessment were first conducted on peripheral blood mononuclear cells and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBCs, ultimately reducing frequencies of HLA-specific immunoglobulin G (IgG)-producing mBCs. Multidimensional spectral flow cytometry with partial least squares discriminant analysis revealed that pretreatment abundance of specific circulating mBC phenotypes, especially CD38neg class-switch mBCs, accurately distinguished between high serologic responders and low responders or NR (AUC 0.958, 0.860-1.000, P = .009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBCs (P < .0001). This phenotypical mBC signature predicting response to therapy was validated in an external HS patient cohort (n = 10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBC subset phenotypes that distinguish HS patients with successful serologic responses to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.

Can the efficacy of a medical treatment be predicted based on the type of idiopathic premature ventricular contraction?

BackgroundPremature ventricular contractions (PVCs) are common arrhythmias with diverse clinical implications. This retrospective study aimed to evaluate the efficacy of medical treatments using various clinical, imaging, and electrocardiographic parameters in patients with idiopathic PVCs. MethodsA total of 1051 patients with idiopathic PVCs were retrospectively analyzed. Patients were categorized into three groups based on treatment response: beta-blocker (BB) responders (479 patients), calcium-channel blocker (CCB) responders (335 patients), and class 1c antiarrhythmic (AA) responders (237 patients). Clinical, imaging, and electrocardiographic data were collected and analyzed to assess the factors influencing treatment response. ResultsAge, left ventricular ejection fraction (LVEF), PVC QRS duration, CI variability, and multiple PVC morphologies were identified as significant factors affecting treatment response. Older age and lower LVEF were associated with better response to BB treatment, whereas CCB responders showed narrower QRS complexes. BB responders also exhibited higher CI variability, possibly linked to automaticity mechanisms. Moreover, the BB responder group had a higher frequency of multiple PVC morphologies. ConclusionThese findings emphasize the importance of tailored treatment approaches based on individual patient characteristics.

Factors that Determined a Positive Response to Resynchronization Therapy in Patients With Chronic Heart Failure and Cardiac Dyssynchrony. One Center Experience.

To evaluate the efficacy of cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF) associated with cardiac dyssynchrony and to identify the factors that influence the CRT efficacy. This retrospective study included 155 patients after implantation of CRT devices. The CRT devices with a built-in cardioverter-defibrillator (CRT-D) and without it (CRT-P) were implanted in 139 (89.7%) and 16 (10.3%) patients, respectively. The follow-up period was 52.37±35.94 months. Based on the study results, two groups of patients were formed depending on the presence of a clinical response to CRT, responders and non-responders. The factors that influenced the clinical response to CRT were studied. The effect of the baseline state of patients on the effect of therapy was assessed. The need for CRT optimization and a possibility of using electrocardiographic criteria for that purpose were studied. Modern devices and leads for CRT, their functional capabilities and their influence on the CRT efficacy were characterized. Statistical analysis was performed with an IBM SPSS Statistics 21.0 (Chicago, USA) package. CRT implantation with the left ventricular lead placement according to the traditional technique, through the coronary sinus, was successful in 130 (87.9%) patients. Difficulties with the left ventricular lead placement were noted in 13 (8.3%) patients when other techniques were used. After 6 months, a hemodynamic and clinical response was observed in 112 (72.2%) patients, and no positive response in 43 (27.8%). The increase in left ventricular ejection fraction in the responder group was more than 21.8±3.7%, which was associated with an improvement of the 6-minute walk test results. Th clinical response was significantly influenced by the possibility of stimulation from the basal parts of the heart; the use of more modern devices for CRT and quadripolar left ventricular leads; timely CRT optimization; and persistent dyssynchrony in non-responders. During the follow-up period, 34 (21.9%) patients died. The death rate in the non-responder group was significantly higher than in the responder group, 18 (41.3%) vs. 16 (14.3%), p=0.001. The main cause of death in the group of non-responders was CHF. Heart transplantation was performed in 3 (1.9%) patients. CRT increases the life span and improves the quality of life in patients with CHF and cardiac dyssynchrony. There was a group of patients with no benefit from CRT in this study. Modern devices allow increasing the number of patients who benefit from CRT. Periodic optimization of CRT is necessary. When optimizing CRT, it is possible to use electrocardiographic criteria of effectiveness: duration of the QRS complex and changes in the position of the electrical axis of the heart.

Utility of interim apparent diffusion coefficient value in predicting treatment response among patients with locally advanced cervical cancer treated with radiotherapy

BackgroundFor locally advanced cervical cancer (LACC), treatment response to radiotherapy (RT) can vary significantly even among those with the same stage classification of International Federation of Gynecology and Obstetrics (FIGO). This study investigated the value of ADC metric for forecasting end-of-treatment outcomes in LACC patients referred for RT. MethodsEighty patients with pathologically confirmed cervical squamous cell carcinoma with (SCC) were included in the research. Abdominal or pelvic MRI scans were conducted at least three times for all participants: before RT, three weeks after beginning of RT and approximately two months after RT was finalized. Calculated apparent diffusion coefficient (ADC) values of the LACC include: pre-ADC, interim-ADC, ΔADC and Δ%ADC. Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,subjects were calculated and subsequently categorized into good responders group (complete response) and poor responders group (progressive disease, stable disease or partial response). ResultsCompared to good-responders, subjects of poor-responder group showed significantly lower values of interim-ADC, ΔADC, and Δ%ADC (all P < 0.05). To distinguish between good and poor responders, the optimal cutoff values of interim-ADC, ΔADC, and Δ%ADC were determined to be 1.067 × 10−3 mm2/sec, 0.209 × 10−3 mm2/sec, and 30.74 % using the ROC curve, with corresponding sensitivities of 83.78 %, 86.49 %, 75.68 %, and specificities of 88.37 %, 86.49 %, 75.68 %, respectively. Multivariate logistic regression revealed that the baseline tumor diameter and interim-ADC were significant prognostic factors for treatment response with an odds ratio (OR) of 0.105 (95 % confidence interval [95 % CI] 0.018–0.616) for baseline tumor diameter and 42.896 (95 % CI 8.205–224.262) for interim-ADC. ConclusionThe interim-ADC value and baseline tumor diameter surfaced as possible indicative factors for predicting the response to RT in patients with LACC.

Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: breast tissue composition changes and collagen discriminative potential.

The purpose of this clinical study is to test a broad spectral range (635-1060 nm) time-domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breasts. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on 10 patients' data show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, p = 0.0020), collagen (-36%, p = 0.0039) and water (-15%, p = 0.0195), and increase in lipids (+39%, p = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, a, increases slightly (+15%, p = 0.0039) by the end of the therapy compared to the baseline, while the scattering slope, b, shows no significant change (+4%, p = 0.9219). Some change in the constituents' concentrations was also noticed in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. We observed that collagen seems to be the only component distinguishing between complete and partial responders by the end of 2-3 weeks from the baseline. In the complete responder group, collagen significantly decreased after 2-3 weeks with respect to baseline (p = 0.0423). While the partial responder group also showed a decrease, it did not reach statistical significance (p = 0.1012). This suggests that collagen could serve as a potential biomarker to measure NAC effectiveness early during treatment. Even though obtained on a small group of patients, these initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.

Combinatorial Genomic Biomarkers Associated with High Response in IgE-Dependent Degranulation in Human Mast Cells.

Mast cells are the major effector cells that mediate IgE-dependent allergic reactions. We sought to use integrated network analysis to identify genomic biomarkers associated with high response in IgE-mediated activation of primary human mast cells. Primary human mast cell cultures derived from 262 normal donors were categorized into High, Average and Low responder groups according to their activation response profiles. Transcriptome analysis was used to identify genes that were differentially expressed in different responder cultures in their baseline conditions, and the data were analyzed by constructing a personalized perturbed profile (PEEP). For upregulated genes, the construction of PEEP for each individual sample of all three responder groups revealed that High responders exhibited a higher percentage of "perturbed" samples whose PEEP values lay outside the normal range of expression. Moreover, the integration of PEEP of four selected upregulated genes into distinct sets of combinatorial profiles demonstrated that the specific pattern of upregulated expression of these four genes, in a tandem combination, was observed exclusively among the High responders. In conclusion, this combinatorial approach was useful in identifying a set of genomic biomarkers that are associated with high degranulation response in human mast cell cultures derived from the blood of a cohort of normal donors.

Objective Response Rate is a Surrogate Marker for Long-Term Overall Survival in Metastatic Urothelial Carcinoma Patients Treated With Immune Checkpoint Inhibitors

BackgroundThis study aimed to evaluate the utility of RECIST criteria-based objective response rate (ORR) as a potential surrogate endpoint for long-term overall survival (OS) in patients with metastatic urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs). MethodsThe primary endpoint was overall ORR and OS, duration of treatment (DoR) with ICIs. ORR was analyzed using Fisher's exact test. Median follow-up and OS were estimated by using the Kaplan–Meier method. ResultsThe median follow-up was 58 (1.15-71) months. Progression developed in 94 (47%) patients during the first 3 months of ICIs therapy. The treatment response to ICIs included complete response (CR), partial response (PR) and stable disease in 10% (n = 20), 23% (n = 46), and 20% (n = 41) of patients, respectively. The responder and nonresponder groups differed in terms of certain baseline characteristics, such as Bellmunt risk factors, and neutrophil-to-lymphocyte ratio (NLR). The 5-year OS rates for patients with CR and PR were 73% and 23%, respectively. The median DoR for CR, PR, and SD were 51.8 months (44.5-59.1), 20.7 months (16.7-24.6), and 8.8 months (5.5-12.1), respectively. Overall, 16(80%) patients with CR and 14(30%) patients with PR had an ongoing response at the time of the analysis. In the univariate analysis, NLR > 3, liver metastases, ECOG PS ≥ 1, and hemoglobin levels < 10 mg/dl, as well as the PR and CR, were all significantly associated with OS. In multivariate analysis, presence of liver metastases (HR 2.3; 95% CI, 1.3-4.2; P < .004) was found to be an independent determinant of short OS, while PR (HR 0.3; 95% CI, 0.15-0.5; P < .001) and CR (HR 0.06; 95% CI, 0.014-0.27; P < .001) were associated with improved OS. ConclusionsIn conclusion, this 5-year analysis of real-world data in the setting of metastatic urothelial cancer indicated a significant correlation between ORR, especially CR, and OS in patients who received ICIs. Therefore, identifying a potential surrogate marker for survival in patients treated with ICIs would represent an important advance in the early identification of patients’ response or resistance to ICIs.

Does adding coenzyme Q10 to dehydroepiandrosterone sulphate positively impact fertility outcomes in young, poor responder infertile women undergoing antagonist protocol for IVF/ICSI cycles?

Background. One of the biggest issues in reproductive medicine is treating women with low ovarian reserves or a poor ovarian response (POR) to stimulation. Oxidative stress was suggested as one of the major contributors to POR. However, the pathophysiology remains unknown. Focusing on certain subpopulations within the diverse group of poor responders may help determine the best therapy for these patients. Objective. To investigate the effect of adding coenzyme A Q10 to dehydroepiandrosterone (DHEA) in young, poor responder infertile females undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Methods. One hundred and sixty-eight females with poor ovarian response (Poseidon Group 3) from multiple centres were randomly divided into two groups. The first group received DHEA orally along with coenzyme 10, while the second group received only DHEA. Both groups underwent controlled ovarian stimulation. Results. There was a significant improvement in the quality of oocytes and the number and quality of embryos transferred in the coenzyme A Q10 group. However, no significant differences were observed in other parameters between the groups. Conclusion. In young, poor-responder women with decreased ovarian reserve, pretreatment with CoQ10 enhances oocyte and embryo quality and boosts ovarian response to stimulation. An improvement in clinical pregnancy and live birth rates may be possible.

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.

Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma

AbstractA phase 2, international, open-label, nonrandomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary end point was objective response rate (ORR); secondary end points included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n = 38 angioimmunoblastic T-cell lymphoma (AITL), n = 25 PTCL not otherwise specified, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [CI], 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in patients with AITL (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228.

Dynamic alterations in gene co-expression networks and gene-transcript associations characterize co-morbidities in cocaine use disorder.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. We conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. Genes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. We demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Can Ultrasound Evaluation of Lymph Node Size and Necrosis Rate Predict Chemotherapy Response in Cervical Tuberculous Lymphadenitis?

To explore the relationship between the initial size and the necrotic rate of lymph nodes evaluated by ultrasound in patients with cervical tuberculous lymphadenitis (CTL) and therapeutic response. Overall, 55 patients were included in this study. Conventional ultrasound and contrast-enhanced ultrasound examination were performed before anti-tuberculosis chemotherapy. Based on the different therapeutic outcomes, they were divided into responder groups (n = 39) and non-responder groups (n = 16). The relationship between the initial size (maximum area, length diameter, short diameter), rate of necrosis, and therapeutic response were compared and analyzed between two groups. There was a significant difference in maximum area, short diameter and rate of necrosis of lymph nodes between the responder groups and the non-responder groups (P < 0.05). The receiver-operating-characteristic (ROC) curve analysis was used to differentiate the two groups, it showed that the area under the curve was 0.746 for maximum area and 0.721 for short diameter, respectively. The cut-off value for the lymph node maximum area and short diameter based on ROC curve analysis was determined as 3.94cm2 (sensitivity 76.9%, specificity 68.7%) and 1.15cm (sensitivity 59.0%, specificity 93.7%), respectively. A negative correlation was observed between maximum area, short diameter, and therapeutic response. The initial maximum area and short diameter of lymph nodes were found to have a negative correlation with chemotherapy response in patients with CTL. The treatment outcomes are typically unsatisfactory for lymph nodes exhibiting an initial necrosis rate of 50% or higher. These findings may be helpful for evaluating therapeutic response.

Nutritional Status Is Associated With Physical Improvement of Palliative Cancer Patients During Cancer Rehabilitation.

Physical decline is accompanied with malnutrition in advanced cancer patients, thus nutritional care is often provided with cancer rehabilitation. However, a limited number of studies have focused on which nutritional index serves as an important marker to provide more intensive nutritional support for patients. We retrospectively reviewed advanced cancer patients who received chemotherapy and rehabilitation during hospitalization. In analysis 1, patients were divided into two groups: a Well group with caloric intake ≥ basal metabolism, calculated by the Harris-Benedict equation, and a Poor group with caloric intake less than their basal energy expenditure. The primary endpoint was the ratio of patients whose Eastern Cooperative Oncology Group Performance Status (ECOG PS) or Barthel index (BI) was maintained during rehabilitation. In analysis 2, the cohort was restratified into Responders, whose ECOG PS and BI improved, and Non-responders, comprising the remaining patients. Several nutritional indices were compared between the groups. Eighty-four patients were evaluated in analysis 1, namely 51 Well patients and 33 Poor patients. The ECOG PS-maintained rate was 98% and 91% (p=0.29), and the BI-maintained rate was 100% and 88% (p=0.02) in the Well and Poor groups, respectively. In analysis 2, 72 patients were evaluated after excluding 12 patients who lacked nutritional data after rehabilitation. Compared with the Responders group, caloric intake appeared worse in the Non-responders group, although their nutritional background tended to be better. Insufficient caloric intake might be a predictive marker of poor outcomes after rehabilitation in advanced cancer patients.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II

BackgroundThe REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, “responders” (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. ObjectivesThis study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. MethodsThe study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. ResultsIn 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). ConclusionsAt 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033)

Which factors help to determine the long-term response to first-line tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma: A Turkish multi-centre study.

Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder's group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases.

Predicting Acupuncture Efficacy in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Study on Model Development and Result Visualization.

Acupuncture is one of primary treatment options for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but its efficacy varies among patients. This study aimed to develop and validate a nomogram for predicting the efficacy of acupuncture in CP/CPPS. This study enrolled 220 patients with CP/CPPS who received acupuncture. Patients were divided into a responder group and nonresponder group based on the reduction in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). Potential variables were selected using the least absolute shrinkage and selection operator regression, and a nomogram was established using the multivariable logistic regression model. The performance of the nomogram was assessed by the receiver operating characteristic curves and calibration curves. Two Hundred Twenty men were randomly assigned to the training cohort (n = 154) and the internal test cohort (n = 66). The developed nomogram included age, current drinking status, sedentary lifestyle, habit of staying up late, expectations for acupuncture, comorbidities, NIH-CPSI pain subscale and total scores. The area under the curve of the prediction model was 0.777 (95% CI: 0.702-0.851) in the training cohort, 0.752 (95% CI: 0.616-0.888) in the internal test cohort, demonstrating satisfactory discriminative ability as indicated by the calibration curve. The nomogram accurately identified CP/CPPS patients who would benefit from acupuncture. Factors such as youth, abstention from alcohol, avoiding sedentary habits and staying up late, having high expectations for acupuncture, being free from comorbidities, and baseline high scores on both the NIH-CPSI pain subscale and total scores may positively affect the efficacy of acupuncture. Further validation of our findings requires multicenter and large-sample prospective studies.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56months. The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.

Histogram analysis of multiple diffusion models for predicting advanced non-small cell lung cancer response to chemoimmunotherapy

BackgroundThere is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC.MethodsSeventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model.ResultsADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P < 0.05). The mean value of each parameter was better than or equivalent to other histogram metrics, where the mean value of f obtained from whole tumor and single slice both had the highest AUC (AUC = 0.886 and 0.812, respectively) compared to other single parameters. The combined model improved the diagnostic efficiency with an AUC of 0.968 (whole tumor) and 0.893 (single slice), respectively.ConclusionsWhole tumor volume ROI demonstrated better diagnostic ability than single slice ROI analysis, which indicated whole tumor histogram analysis of IVIM and DKI hold greater potential than single slice ROI analysis to be a promising tool of predicting therapeutic response to chemoimmunotherapy in advanced NSCLC at initial state.