12-month Time Points Research Articles

Assessing the Prognostic Value of 13 Inflammation-Based Scores in Patients with Unresectable or Advanced Biliary Tract Carcinoma After Immunotherapy.

The response of patients with biliary tract carcinoma (BTC) to immunotherapy varies widely, and there is an urgent need for biological indicators. The predictive value of inflammation based score (IBS) for the efficacy of immunotherapy in patients with BTC remains unclear, as the evidence is inconsistent. This study aimed to comprehensively examine the predictive value of IBS in peripheral blood on the survival of BTC patients receiving immunotherapy. We retrospectively assessed 118 patients with advanced BTC who received anti-PD-1 therapy in the first or second line in two medical centers. The Kaplan-Meier, time-dependent ROC, and Harrell's concordance index (C-index) were applied to analyze the predictive value of 13 reported peripheral blood IBS. All 13 IBS were identified as significant prognostic factors for OS in univariate analysis. Pan-immune-inflammation value (PIV) (p=0.005), PILE (composed of PIV, lactate dehydrogenase and Eastern Cooperative Oncology Group performance status) (p=0.033), neutrophil-to-lymphocyte ratio (NLR) (p=0.003), platelet-to-lymphocyte ratio (PLR) (p<0.001), lymphocyte-to-monocyte ratio (LMR) (p=0.006), systemic immune inflammation index (SII) (p=0.039), CRP-to-albumin ratio (CAR) (p=0.025), and Albumin-NLR (p=0.008) were identified as independent prognostic factors for OS in multivariate analysis. PIV and PILE scores were superior to other scores, according to time-dependent ROC curves, and their superiority became more pronounced after the 12-month time point. C-index analysis showed PIV (C-index 0.62, 95% CI: 0.55, 0.68) and PILE (C-index 0.62, 95% CI: 0.55, 0.70), both superior to other IBS. PIV and PILE scores are independent predictors of OS in patients with BTC after immunotherapy and are superior to other IBS. PIV and PILE may be able to help screen out patients with advanced BTC who are less likely to benefit from anti-PD-1 monotherapy. Due to the retrospective nature of this analysis, the predictive value of PIV and PILE require validation in further prospective studies.

Machine-learning-based models for the optimization of post-cervical spinal laminoplasty outpatient follow-up schedules

BackgroundPatients undergo regular clinical follow-up after laminoplasty for cervical myelopathy. However, those whose symptoms significantly improve and remain stable do not need to conform to a regular follow-up schedule. Based on the 1-year postoperative outcomes, we aimed to use a machine-learning (ML) algorithm to predict 2-year postoperative outcomes.MethodsWe enrolled 80 patients who underwent cervical laminoplasty for cervical myelopathy. The patients’ Japanese Orthopedic Association (JOA) scores (range: 0–17) were analyzed at the 1-, 3-, 6-, and 12-month postoperative timepoints to evaluate their ability to predict the 2-year postoperative outcomes. The patient acceptable symptom state (PASS) was defined as a JOA score ≥ 14.25 at 24 months postoperatively and, based on clinical outcomes recorded up to the 1-year postoperative timepoint, eight ML algorithms were developed to predict PASS status at the 24-month postoperative timepoint. The performance of each of these algorithms was evaluated, and its generalizability was assessed using a prospective internal test set.ResultsThe long short-term memory (LSTM)-based algorithm demonstrated the best performance (area under the receiver operating characteristic curve, 0.90 ± 0.13).ConclusionsThe LSTM-based algorithm accurately predicted which group was likely to achieve PASS at the 24-month postoperative timepoint. Although this study included a small number of patients with limited available clinical data, the concept of using past outcomes to predict further outcomes presented herein may provide insights for optimizing clinical schedules and efficient medical resource utilization.Trial registrationThis study was registered as a clinical trial (Clinical Trial No. NCT02487901), and the study protocol was approved by the Seoul National University Hospital Institutional Review Board (IRB No. 1505-037-670).

Abstract C032: Take Charge during Treatment: A randomized exercise trial for breast cancer patients

Abstract Introduction. Breast cancer (BC) is the most frequently diagnosed cancer with over 4 million survivors living in the United States. Recent treatment (Tx) advances such as in targeted (e.g. anti-HER2), systemic (e.g. anthracyclines), or combined therapies have supported the increased survival rates but continue to present adverse effects. Cardiotoxicity, which may be induced during or after Tx, is the second highest cause of mortality in BC survivors and also negatively impacts quality of life (QoL). Black/African American (B/AA) patients have higher rates of this effect along with a higher incidence of aggressive BC types. Limited research has targeted vascular function as an area of focus in the cardio-oncology field. Methods. The Discovery and Elimination of Cardio-Oncology Disparities Toward Equity in the Heartland Center is examining how anti-cancer treatments impact vascular function, the potential mitigating effects of exercise and how socioenvironmental factors moderate these effects. The Take Charge during Treatment randomized trial within this Center is testing the feasibility and acceptability of an exercise during treatment program for B/AA and non-Hispanic White (NHW) women newly diagnosed with BC. The study also examines and compares the effects of exercise on VO2 peak and QoL in participants. The 16-week intervention promotes adherence to the American College of Sports Medicine exercise guidelines for cancer survivors and is guided by a certified exercise trainer. To evaluate the intervention, patient's complete surveys including the FACT-B for QoL, a VO2 peak assessment, physical assessments, and anthropometry measurements at baseline (before BC Tx), after the 16-week program, and at a 12-month timepoint. Socioenvironmental factors are examined using participant addresses. Results. To date, 1330 patients were assessed for eligibility, 60 consented, and 49 enrolled and randomized. Herein, we present data on 45 of the 49 (35 NHW, 10 B/AA). The mean age of participants is 52 years (SD=12), most were diagnosed with Stage I or II BC, and they have varied education and income levels. Baseline (pre-treatment) differences are noted by racial group for QoL (Total score – 88 (SD=9) for NHW vs 74 (SD=29) for B/AA; Physical function – 25 (SD=3) for NHW vs 22 (SD=5) for B/AA; Functional – 21 (SD=4) for NHW vs 18 (SD=8) for B/AA), VO2 peak (22 (SD=5) for NHW vs 17 (SD=6) for B/AA), and obesity (NHW – 30%, B/AA – 70%). Cognitive function, pain interference, social isolation and perceived stress were similar across groups. B/AA women were more likely to report living in a highly redlined area (50%) compared to NHW women (3%), with lower percent tree canopy (13% vs 24%) and lower perceived social cohesion (15 vs 19). Reports of discrimination and resilience were similar across groups. Conclusions. Preliminary baseline results suggest that B/AA women enter BC Tx more vulnerable to developing QoL challenges and cardiotoxicity. Neighborhood environmental factors will be further examined to understand the association with adverse outcomes. Citation Format: Estefania Alonso, Melinda Stolley, Kirsten Beyer, Alison Kriegel, Shane Phillips, Matt Durand, Michael E. Widlansky, Amanda L. Kong, Kent Hoskins, Andreas Beyer. Take Charge during Treatment: A randomized exercise trial for breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C032.

Long-Term Follow Up of Patients Treated for Inflammatory Bowel Disease and Cytomegalovirus Colitis.

Pathological reactivation of latent Cytomegalovirus (CMV) is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, or worse clinical outcomes remains controversial. This study aimed to follow up IBD patients with an index episode of CMV colitis and analyse the clinical outcomes. A retrospective study of patients with IBD treated for CMV colitis was completed. The outcome results were collected at 6-month and 12-month time points after the first episode of CMV colitis. A total of 13 patients with Ulcerative Colitis and 1 with Crohn's Disease were included. CMV colitis recurrence occurred in 29% of patients at 12 months. A total of 43% of patients had changed their biologic dose at 6 months and 29% had escalated their biologic dose at 12 months. At 12 months, 36% of patients had been re-hospitalised, including three colectomies. Disease remission was only achieved by 29% of patients at 12 months. IBD patients with CMV colitis have substantial rates of re-hospitalisation, failed medical therapy, and colectomy. These risks may be greater at <6 months from an index episode of CMV colitis.

Relationship Between Treatment Hours of Selected Disciplines And Change in Pain Impact During the Year Following Referral to an Interdisciplinary Pain Management Center: A Latent Class Analysis.

Introduction: Pain management clinics differ in treatments offered, and little evidence exists regarding which combinations of therapies result in best outcomes. This study analyzed clinical encounters and pain outcomes data for associations between treatment composition and outcomes. Methods: Retrospective observational study of 2,142 predominantly active-duty US service members referred to an interdisciplinary pain management center between 2014 and 2021. Latent class analysis was used to identify treatment groups with distinct outcome patterns during the year following initial assessment. The primary outcome measure was the National Institutes of Health Task Force on Research Standards for Chronic Low-Back Pain impact score. Results: Four distinct treatment groups were identified: 1 group engaged in conventional medical therapies alone (n = 726, median 3.5 treatment hours), and 3 groups used a combination of conventional, psychological, rehabilitative, and complementary therapies, with different levels of treatment hours: low (n = 814, median 15.7 h), medium (n = 177, median 40.1 h), and high (n = 425, median 72.5 h). All groups showed significant improvement in pain impact score from baseline up to 9 months but not at 12 months following initial assessment. At the 6-month time point, the group with high multimodal treatment hours had the most improvement in pain impact (-3.1 [95% CI -3.8, -2.4]) compared with the group using only conventional therapies (-1.0 points [95% CI -1.8, -0.1]) or with low multimodal treatment hours (-1.3 points [95% CI -1.9, -0.7]). There were no between-group differences at the 9- or 12-month time points. Conclusion: These results suggest that a combination of pain therapy approaches results in greater reduction in pain impact than the use of conventional medical treatment alone for up to 6 months after initiating therapy and that there may be a threshold of treatment hours that must be exceeded to achieve this benefit. Clinical trial registration: As this study is not a clinical trial, no registration was required.

Longitudinal outcomes of ischemic versus hemorrhagic stroke: Differences may impact future trial design

ObjectivesPatients with intracerebral hemorrhage (ICH) are more likely to present with severe symptoms than those with ischemic stroke (IS); however, the way in which long-term outcomes differ between groups is less clear. Given that the tissue surrounding ICH is not always irreversibly infarcted, it may have the potential to recover more fully over time. Understanding the differences in expected outcome severity is critical in order to prognosticate and to determine appropriate outcome measures when designing clinical trials. Materials and MethodsWe used our prospectively collected stroke registry to identify and follow a cohort of 300 patients with ICH and 300 patients with IS, matched by age, sex, lesion size, location, and admission date. Paired t-tests were used to compare modified Rankin Scores (mRS) between groups at hospital discharge, 90-day, and >12-month follow-up time points. ResultsNot surprisingly, patients with ICH had worse discharge mRS scores compared to individuals with IS (4.20 (SD 0.09) versus 3.42 (SD 0.08)). However, rather than improving, the long-term outcomes remained significantly worse for ICH patients compared to their IS matches (4.02 (SD 0.15) versus 2.89 (SD 0.14) at 90 days, and 4.32 (SD 0.20) versus 3.16 (SD 0.22) at >12 months (p < 0.001 for all analyses)). ConclusionsThis study longitudinally followed matched cohorts of patients with ICH and IS, confirming that outcomes for those with ICH remain significantly worse over time. Results allow for better long-term prognostication, illustrate the need for further intervention trials to improve outcomes, and inform the development of evidence-based endpoints.

Clinical features and prognostic factors of cryptococcal infections in HIV-infected patients: a 10-year study from an infectious disease specialist hospital.

Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes. We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed. A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately. Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition.

Buprenorphine treatment and clinical outcomes under the opioid use disorder cascade of care

BackgroundChallenges to engagement and retention on buprenorphine undermine treatment of individuals with opioid use disorder (OUD). Under the OUD Cascade of Care framework, we sought to identify patient characteristics and treatment response associated with superior clinical outcomes. MethodsA retrospective cohort study of specialty buprenorphine treatment patients entering treatment (n=19,487) based on EHR records from a large multi-state buprenorphine treatment network (2011–2019). Person-level care episodes were evaluated across treatment intake, engagement (i.e. 2+ visits in the month following intake), and retention at 6, 12, and 24 months. Time to achieving 90 days of continuous opioid abstinence was assessed using Cox proportional hazards regressions models and also assessed as a predictor of long-term retention. ResultsMost patients engaged (82.4 %), but retention steadily declined over 6-month (38.7 %), 12-month (26.2 %), and 24-month (17.1 %) timepoints. Opioid-positive baseline tests were associated with lower hazards of achieving continuous abstinence for both buprenorphine-positive (aHR=0.33, p<.001) and buprenorphine-negative (aHR=0.49,p<.001) intakes. Opioid abstinence was associated with buprenorphine-positive baseline testing (aHR=1.59,p<.001), especially for those testing opioid-negative (aHR=1.82,p<.001). Patients who achieved and sustained abstinence at 6 months in care were 4.1 and 5.5 times as likely to achieve 12-month and 24-month retention, respectively, compared to patients with intermittent opioid use. ConclusionTreatment discontinuation was concentrated early in care and buprenorphine and opioid status at intake were prognostic of achieving and sustaining abstinence. Early abstinence was associated with higher likelihood of subsequent stage progression. Implementing interventions to support early clinical stability for high-risk patients is critical to improve clinical outcomes.

A case management strategy to reduce falls in older people with a history of falls: A randomized controlled trial

The present study aimed to determine whether a remotely delivered intervention, based on an individual case management, can reduce falls and their consequences in community-dwelling older people with a history of multiple falls. In this randomized controlled trial, 32 participants were randomized to the intervention group, which comprised a 16-week case management program involving a multidimensional assessment, targeted interventions according to the identified fall risk factors, and development of individualized care plans. The intervention was performed by trained gerontologists, under weekly supervision of professionals with experience in falls. The control group (n = 30) received usual care. Falls were monitored over 12 months with monthly falls calendars and telephone calls. Remotely delivered case management presented an 82 % uptake of recommendations. There was a trend toward a reduced fall incidence in the intervention vs control group, with lower fall, fall injury and fracture rates in the intervention group compared with the control group at both the 16-week and 12-month time-points, with the difference statistically significant for injurious fall rates at 12 months - IRR=0.18 (95 % CI = 0.04 to 0.74).

Health outcomes of telemonitoring of patients with type-2 diabetes mellitus: One-year results from a randomized controlled trial (Optimizing care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus).

Telehealth increases care accessibility to patients with type-2 diabetes mellitus but the duration of its implementation to sustain optimal glycaemic control remains unclear. This study aimed to assess the health outcomes of these patients using the Optimizing care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus (OPTIMUM) home tele-monitoring (HTM) system 6 months post-intervention, compared to standard care. An open-labelled randomized controlled trial involving 330 participants with type-2 diabetes mellitus, aged 26-65 years, and suboptimal glycaemic control (HbA1c = 7.5%-10%) was conducted. Intervention group received OPTIMUM HTM for 6 months followed by usual care for another 6 months, while control group received usual care for 12 months. OPTIMUM HTM includes in-app video-based tele-education, tele-monitoring of the blood pressure, capillary glucose and weight via Bluetooth devices and mobile applications, followed by algorithm-based tele-management by the OPTIMUM HTM team. Assessments using self-care inventory scale and medication adherence were administered for both groups at baseline, 6-month, and 12-month timepoints. Complete data from 156 (intervention) and 159 (control) participants, with comparable demographic profiles, were analysed. Both groups showed a significant reduction in HbA1c from baseline (p < 0.001). From 6-month to 12-month time-points, the intervention group was twice as likely to maintain their HbA1c ≤ 8% (adjusted odds ratio = 2.02, 95%CI = 1.18-3.49; p < 0.011). The intervention group demonstrated higher scores for self-care behaviours (adjusted odds ratio = 3.83 [95%CI = 1.68-5.97], p = 0.001) and not skipping medications (adjusted odds ratio = 2.32 [95%CI = 1.09-4.97], p = 0.030) at 12 months. The OPTIMUM HTM system enabled patients to maintain their glycaemic control beyond the intervention period. The favourable outcomes could be the effect of telehealth in sustaining self-care behaviour and medication adherence.

Endoscopic dacryocystorhinostomy with and without bicanalicular silicone tube in patients with a small lacrimal sac: a comparative study.

To establish whether bicanalicular silicone tube intubation is required during endoscopic dacryocystorhinostomy (En-DCR) for treating chronic dacryocystitis with a small lacrimal sac. In total, this study enrolled 264 patients diagnosed with unilateral chronic dacryocystitis with small lacrimal sacs via computed tomography-dacryocystography that underwent En-DCR from March 2016-September 2020. Patients were randomized into two treatment groups, with those in group A undergoing tubes intubation and those in group B not undergoing this procedure. The tubes were removed 3 months post-operation in group A. Surgical outcomes and related complication rates were then compared. This study included 242 patients, including124 and 118 in groups A and B, respectively. At the three-month follow-up time point, 12.90% of patients in group A exhibited ostial granulation tissue, with this frequency with no differences observed in group B (11.86%). At 6 months post-surgery, 80.65% of patients in group A and 72.88% of patients in group B exhibited successful surgical outcomes, with no significant differences between groups. At 9 months postoperatively, the overall effective success rate was 60.74%, and the success rate was significantlyhigher in group A relative to group B (group A: 75.81%; group B: 44.92%). There were no failed patient outcomes observed as of the 12-month follow-up time point. While En-DCR-based treatment of chronic dacryocystitis in those with smalllacrimal sacs did not yield satisfactory outcomes with respect to the overall effective success rate, these results suggest that intraoperative intubation may improve success rates in long-term follow-up.

Safety and Efficacy of SGLT2 Inhibitors for Amyloid Light-Chain Cardiomyopathy

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated benefit in patients with heart failure, but minimal data exists around the use of these medications in amyloid light-chain cardiomyopathy (AL-CM). We performed a retrospective study assessing the safety and efficacy of SGLT2i in AL-CM. MethodsWe queried our institutional registry and identified 27 AL-CM patients who received SGLT2i. The safety analysis included all 27 patients and assessed SGLT2i-associated adverse events, hospitalizations, and deaths. To decrease confounding, the efficacy analysis included only a subset of patients with stable disease (on stable anti-plasma cell therapy for ≥2 months prior to baseline and achieved at least a hematologic Very Good Partial Response) and compared disease marker changes in these patients (n=17) with those of a contemporaneous untreated control cohort from our registry (n=21). ResultsThe mean age of the overall population was 68.6 (standard deviation 9.4) years. Seven (14.6%) patients had diabetes, and 19 (39.6%) had chronic kidney disease. In the safety analysis, median follow-up time was 10.9 (interquartile range 7.2) months. Two (7.4%) patients discontinued SGLT2i due to hypovolemia and genital irritation, and 6 (22.2%) additional patients temporarily held SGLT2i due to an adverse event, commonly related to volume depletion. Thirteen hospitalizations, all considered unrelated to SGLT2i use, and no deaths occurred. In the efficacy analysis, SGLT2i-treated patients had more severe disease at baseline than controls, demonstrating significantly higher median troponin-T and loop diuretic dose (P<0.05). Compared with controls, SGLT2i treatment was associated with significantly greater reductions in loop diuretic dose (P<0.001) and NTproBNP (P=0.033) across 3-, 6-, and 12-month follow-up timepoints. SGLT2i treatment was also associated with a significantly greater reduction in mean arterial pressure at 12 months (P=0.031) but not at other timepoints. No significant differences were observed on changes in weight, eGFR, troponin-T, proteinuria, or albumin. ConclusionsIn this small-scale retrospective study, we demonstrate that SGLT2i is well-tolerated by most patients with AL-CM, but volume depletion symptoms may limit continuous use. SGLT2i may aid management of congestion in AL-CM as evidenced by reduced diuretic dose and NTproBNP without adverse renal effects. Larger long-term studies are needed to build on our findings.

Impact of Tafamidis on Delaying Clinical, Functional, and Structural Cardiac Changes in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background: This study aimed to evaluate the effect of treatment with tafamidis on clinical, laboratory, functional, and structural cardiovascular imaging parameters at the 12-month follow-up timepoint in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and to assess the response to treatment in terms of disease progression. Methods: Patients with ATTRwt-CM undergoing treatment with tafamidis for >12 months were included. The patients underwent a comprehensive evaluation (including echocardiography, cardiac magnetic resonance imaging, six-minute walking test, assessment of quality of life, and laboratory tests) at baseline and the 12-month follow-up timepoint. Disease progression was assessed using a set of tools proposed by an international panel of experts, evaluating three main domains (clinical, biochemical, and structural). Results: The study cohort consisted of 25 patients (mean age of 75.9 ± 6.1 years, with 92% males). At the 12-month follow-up timepoint, an improvement in quality of life calculated with the KCCQ overall score (64 ± 20 vs. 75 ± 20, p = 0.002) and a reduction in pulmonary artery pressure (34 ± 10 mmHg vs. 30 ± 5 mmHg, p-value = 0.008) and in native T1 time were observed (1162 ± 66 ms vs. 1116 ± 52 ms, p-value = 0.001). Clinical, biochemical, and structural disease progression was observed in 6 (24%), 13 (52%), and 7 (28%) patients, respectively. Overall disease progression was observed in two patients (8%). Conclusions: This study described the impact of tafamidis treatment on clinical, laboratory, and functional parameters. Disease progression, assessed using a multiparametric tool recommended by a recent position paper of experts, was observed in a minority of patients.

Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure

ObjectiveSodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.Research and design methodsThis randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping.ResultsBetween the baseline and 12-month time point, plasma IL-1B was reduced (− 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (− 158.9 pmole/min/106 cells, P = 0.0497 vs. − 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups.Clinical Trial.gov Registration NCT03782259.

Soft tissue elasticity at teeth and implant sites. A novel outcome measure of the soft tissue phenotype.

To assess ultrasonographic tissue elasticity at teeth and implant sites and its variation after peri-implant soft tissue augmentation with a connective tissue graft (CTG). Twenty-eight patients, each contributing with one clinically healthy dental implant exhibiting a soft tissue dehiscence (PSTD), were included. Implant sites were augmented with CTG and monitored over 12 months. Ultrasonographic strain elastography, expressed as strain ratios (SR1, SR2, and SR3, respectively) was assessed at baseline, 6-, and 12-month, and compared with the corresponding contralateral homologous natural tooth. SR1 assessed the strain/elasticity of the midfacial coronal portion of the soft tissue in comparison to the natural tooth crown/implant-supported crown, SR2 evaluated the strain of the midfacial coronal soft tissue in relation to the one of the alveolar mucosa, while SR3 depicted the strain of the midfacial soft tissue in relation to the interproximal soft tissue on the transverse ultrasound scan. SR1 in natural dentition and at implant sites was 0.20 ± 0.08 and 0.30 ± 0.14, respectively (p = .002), indicating that the coronal portion of the soft tissue around teeth is generally more elastic than its counterpart around dental implants. Soft tissue augmentation with CTG promoted an increased stiffness of the midfacial coronal portion of the soft tissue over 12 months (p < .001 for SR1, SR2, and SR3). Strain ratios at the 12-month time points were significantly higher than the values observed at 6 months (p < .001). Regression analysis demonstrated that strain elastography ratios in natural dentition were significantly associated with keratinized gingiva width, and gingival thickness. At implant sites, SR1 was significantly associated with keratinized mucosa width and mucosal thickness (p < .001 for both correlations), SR2 was significantly associated with keratinized mucosa width (p = .013), and SR3 was significantly associated with the surgical technique performed in combination with CTG (p = .022). Ultrasound strain elastography captures and quantifies tissue elasticity and its changes after soft tissue augmentation. A different baseline tissue elasticity was observed between teeth and dental implants in the most coronal aspect of the soft tissue. The main factors affecting tissue elasticity-related outcomes were the keratinized tissue width, and mucosal thickness.

The effect of cumulative energy in repeated subliminal transscleral cyclophotocoagulation: a retrospective study

BackgroundThe long-term safety and efficacy of repeated applications of subliminal transscleral cyclophotocoagulation (SL-TSCPC) with a focus on cumulative energy was evaluated in glaucoma patients.MethodsIn this retrospective, multicentric study the data of a total of 82 eyes with various causes of glaucoma that were treated with a single or multiple applications of SL-TSCPC were collected. Treatments were performed under general or local anesthesia with an 810 nm diode laser. Power was 2000 mW; duty cycle, 31.3%; total treatment duration, 80–320 s; equaling a total energy of 50–200 J per treatment session. Fifty-five eyes (55 patients) presented for all follow-ups, and these eyes were selected for further statistical analysis. The mean age was 60.0 ± 17.1 years, and 22 (40%) of the patients were female. Intraocular pressure (IOP) and dependence on further glaucoma medication were evaluated at 12 months following the initial treatment.ResultsEyes underwent 1 or 2 consecutive SL-TSCPC treatments. Median (min–max) baseline IOP of 34 (13–69) decreased to 21.5 (7–61), 22 (8–68), 20 (9–68), and 19.5 (3–60) mmHg at the 1, 3, 6, and 12-month postoperative timepoints respectively. The mean (± SD) IOP decrease at 12 months was 26 ± 27%, 39 ± 32%, and 49 ± 33% in the low (below 120 J, n = 18), medium (120–200 J, n = 24), and high (above 200 J, n = 13) cumulative energy groups respectively. At the 12-month timepoint, oral carbonic anhydrase use was discontinued in ¾ of the cases.ConclusionsIt was found that the repeated application of SL-TSCPC safely and efficiently decreases IOP in a Caucasian population with heterogenous causes of glaucoma, eyes with silicone oil responded to a greater extent. Inclusion of cumulative energy scales may contribute to better addressing repeated procedures in a standardized fashion.

Real-world treatment patterns and clinical outcomes among patients with HR+/HER2- advanced/metastatic breast cancer receiving palbociclib in Brazil: IRIS study.

e13088 Background: Palbociclib was approved for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (aBC/mBC) in Brazil in 2018. Worldwide studies explore palbociclib's real-world use and outcomes; however, this data is not available for Brazilian patients. IRIS Brazil study aimed to describe demographic/clinical characteristics, treatment and clinical outcomes of adult female patients who have received palbociclib as first-line treatment for HR+/HER2- aBC/mBC in private healthcare institutions in Brazil. Methods: This retrospective descriptive study included females aged 18 years or older diagnosed with HR+/HER2- aBC/mBC and those who had received palbociclib as their initial line of therapy. The study analyzed variables such as demographics, clinical characteristics, treatment history, palbociclib combinations, and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates at 6- and 12-month time points. Results: A total of 121 patients were included in the study. The mean age was 54.4 years, and 82 (67.7%) were menopausal at diagnosis. A total of 51 patients (42.1%) were treated with palbociclib + fulvestrant, while 67 (55.8%) were treated with palbociclib + aromatase inhibitors. The majority of patients (n = 79; 65.3%) did not require any dose adjustments. Among the 40 patients (33.1%) who required dose adjustments, the main reason was adverse events/toxicity (n = 36; 90%). The PFS rates at 6 and 12 months were 78% and 60%, respectively. The OS rates at 6 and 12 months were 86% and 70%, respectively. Conclusions: Results from this initial real-world assessment of clinical outcomes in Brazil suggest that Palbociclib combinations exhibit favorable effectiveness in treating HR+/HER2- aBC/mBC disease, as measured by PFS and OS rates.

Pilsner Modification of Mesh Sacrohysterocolpopexy(PiMMS): An Initial Report on Safety and Efficacy.

It is reported that up to 60% of women would prefer to spare their uterus during pelvic organ prolapse (POP) repair surgery. A reliable hysteropexy technique is therefore crucial. We aimed to describe the safety profile and initial core patient-reported and clinical outcomes of the Pilsner modification of laparoscopic mesh sacrohysterocolpopexy (PiMMS) in comparison with the laparoscopic sacrohysterocolpopexy technique (standard laparoscopic sacrohysterocolpopexy [sLSH]) previously used in our unit. This was a retrospective cohort study conducted in a single tertiary referral urogynecological center. All patients who underwent laparoscopic mesh sacrohysterocolpopexy between 1 January 2015, and 31 January 2022 were included in the study. Follow-up clinical, patient-reported, and imaging outcomes at the 12-month follow-up time point are presented. A total of 87 patients were included. Of these, 49 (56.3%) and 38 (43.7%) underwent sLSH and PiMMS respectively. Low numbers of perioperative complications were found in both groups with no mesh-related complications reported following PiMMS up to 12months postoperatively. There were no apical compartment failures in either group. There were 8 (17.0%) vs 1 (2.7%) anterior compartment failures (Ba ≤ -1) in the sLSH and PiMMS groups respectively (p = 0.07) at 12months. At the 1-year follow-up, 42 (89.4%) patients reported a Patient Global Impression of Improvement score of ≤ 2 in the sLSH groups compared with 35 (94.6%) patients following PiMMS. The PiMMS technique seems to have comparable safety profile and patient-reported outcomes with the sLSH technique. However, there is a trend toward reduced anterior compartment failures with this modification. The findings of this preliminary report need to be re-evaluated in a well-powered prospective study.

Predicting Postoperative Speech Perception and Audiometric Thresholds Using Intracochlear Electrocochleography in Cochlear Implant Recipients.

Electrocochleography (ECochG) appears to offer the most accurate prediction of post-cochlear implant hearing outcomes. This may be related to its capacity to interrogate the health of underlying cochlear tissue. The four major components of ECochG (cochlear microphonic [CM], summating potential [SP], compound action potential [CAP], and auditory nerve neurophonic [ANN]) are generated by different cochlear tissue components. Analyzing characteristics of these components can reveal the state of hair and neural cell in a cochlea. There is limited evidence on the characteristics of intracochlear (IC) ECochG recordings measured across the array postinsertion but compared with extracochlear recordings has better signal to noise ratio and spatial specificity. The present study aimed to examine the relationship between ECochG components recorded from an IC approach and postoperative speech perception or audiometric thresholds. In 113 human subjects, responses to 500 Hz tone bursts were recorded at 11 IC electrodes across a 22-electrode cochlear implant array immediately following insertion. Responses to condensation and rarefaction stimuli were then subtracted from one another to emphasize the CM and added to one another to emphasize the SP, ANN, and CAP. Maximum amplitudes and extracochlear electrode locations were recorded for each of these ECochG components. These were added stepwise to a multi-factor generalized additive model to develop a best-fit model predictive model for pure-tone audiometric thresholds (PTA) and speech perception scores (speech recognition threshold [SRT] and consonant-vowel-consonant phoneme [CVC-P]) at 3- and 12-month postoperative timepoints. This best-fit model was tested against a generalized additive model using clinical factors alone (preoperative score, age, and gender) as a null model proxy. ECochG-factor models were superior to clinical factor models in predicting postoperative PTA, CVC-P, and SRT outcomes at both timepoints. Clinical factor models explained a moderate amount of PTA variance ( r2 = 45.9% at 3-month, 31.8% at 12-month, both p < 0.001) and smaller variances of CVC-P and SRT ( r2 range = 6 to 13.7%, p = 0.008 to 0.113). Age was not a significant predictive factor. ECochG models explained more variance at the 12-month timepoint ( r2 for PTA = 52.9%, CVC-P = 39.6%, SRT = 36.4%) compared with the 3-month one timepoint ( r2 for PTA = 49.4%, CVC-P = 26.5%, SRT = 22.3%). The ECochG model was based on three factors: maximum SP deflection amplitude, and electrode position of CM and SP peaks. Adding neural (ANN and/or CAP) factors to the model did not improve variance explanation. Large negative SP deflection was associated with poorer outcomes and a large positive SP deflection with better postoperative outcomes. Mid-array peaks of SP and CM were both associated with poorer outcomes. Postinsertion IC-ECochG recordings across the array can explain a moderate amount of postoperative speech perception and audiometric thresholds. Maximum SP deflection and its location across the array appear to have a significant predictive value which may reflect the underlying state of cochlear health.

EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma

AbstractEstimating progression-free survival (PFS) and overall survival superiority during clinical trials of multiple myeloma (MM) has become increasingly challenging as novel therapeutics have improved patient outcomes. Thus, it is imperative to identify earlier end point surrogates that are predictive of long-term clinical benefit. Minimal residual disease (MRD)-negativity is a common intermediate end point that has shown prognostic value for clinical benefit in MM. This meta-analysis was based on the US Food and Drug Administration guidance for considerations for a meta-analysis of MRD as a clinical end point and evaluates MRD-negativity as an early end point reasonably likely to predict long-term clinical benefit. Eligible studies were phase 2 or 3 randomized controlled clinical trials measuring MRD-negativity as an end point in patients with MM, with follow-up of ≥6 months following an a priori–defined time point of 12 ± 3 months after randomization. Eight newly diagnosed MM studies evaluating 4907 patients were included. Trial-level associations between MRD-negativity and PFS were R2WLSiv, 0.67 (95% confidence interval [CI], 0.43-0.91) and R2copula 0.84 (0.64 to >0.99) at the 12-month time point. The individual-level association between 12-month MRD-negativity and PFS resulted in a global odds ratio (OR) of 4.02 (95% CI, 2.57-5.46). For relapse/refractory MM, there were 4 studies included, and the individual-level association between 12-month MRD-negativity and PFS resulted in a global OR of 7.67 (4.24-11.10). A clinical trial demonstrating a treatment effect on MRD is reasonably likely to eventually demonstrate a treatment effect on PFS, suggesting that MRD may be an early clinical end point reasonably likely to predict clinical benefit in MM, that may be used to support accelerated approval and thereby, expedite the availability of new drugs to patients with MM.