Citations

Objectives: Modifiable lifestyle factors are associated with morbidity and mortality in hematopoietic stem cell transplant (HSCT) survivors. The aims of the study were to examine: (a) receipt of provider advice to change behaviors, (b) health behavior change, and (c) how modifiable lifestyle factors might cluster together. Methods: Patients within a large HSCT program completed a survey (N =870) of lifestyle factors at pre-HSCT evaluation. The survey assessed self-reported adherence to American Cancer Society and HSCT guidelines for cancer survivorship in the year prior to a pre-HSCT evaluation. Lifestyle factors of interest were physical activity, fruit and vegetable consumption, tobacco use, alcohol use, and height/weight to calculate Body Mass Index (BMI). Results: Among patients not meeting all five guidelines (98%), 31% received provider advice to change. Between 10% and 42% reported healthy behavior change since diagnosis. Physical activity, fruit and vegetable consumption, and BMI were the most commonly clustered lifestyle behaviors. Conclusions: A considerable proportion of patients did not meet national guidelines for lifestyle factors. Results highlight an immediate opportunity to improve health care delivery and transplant outcomes via pre-HSCT lifestyle screening and implementation of effective health behavior change interventions.

ABSTRACT Background and hypothesis Podocytopathy associated with likely pathogenic/pathogenic variants of Transient receptor potential cation channel subfamily C member 6 (TRPC6) (TRPC6-AP) has been recognized for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype–phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterized clinical, histological and genetic correlates of familial and sporadic patients with TRPC6-AP. Methods In this multicentre observational study, an online questionnaire followed by a systematic literature review was performed to create a cohort with comprehensive data on genetic and clinical outcomes [age of onset, clinical presentation, treatment response, kidney biopsy findings and progression to kidney failure (KF)]. Logistic regression, Cox proportional hazards model and Kaplan–Meier analyses investigated the associations between genetic variants and disease progression. Results Among 87 families (96 familial and 45 sporadic cases), 31 distinct missense TRPC6 variants (including 2 novel) were identified, with c.2683C>T p.(Arg895Cys) and c.523C>T p.(Arg175Trp) the commonest variants. Proteinuric kidney disease/nephrotic syndrome was the most common clinical presentation (83.7%), while focal segmental glomerulosclerosis was the most common histological finding (89.4%). By 33 (interquartile range 17–40) years, 48.9% (69/141) of patients had progressed to KF. Sporadic TRPC6-AP demonstrated an earlier progression to KF than familial cases (P = .001) and were more likely to present with nephrotic syndrome [odds ratio 4.34 (1.85–10.15); P = .001]. Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs 44.4%; P = .004). Compared with patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to KF earlier [median kidney survival of 21 years, hazard ratio 2.985 (95% confidence interval 1.40–5.79); and 38 years, hazard ratio 1.65 (95% confidence interval 1.01–2.81), respectively, log-rank P = .005]. Conclusion Our study shows unique clinical and genetic correlations of TRPC6-AP, which may enable personalized care and promising novel therapies.

Summary The eosinophilic esophagitis (EoE) Endoscopic Reference Score (EREFS) measures endoscopic severity. While a score of ≤2 has been proposed for endoscopic response, it is unknown whether achieving this threshold results in clinically important outcomes. We aimed to determine whether an EREFS response to topical steroids (tCS) is associated with a decreased need for future esophageal dilation. In this retrospective cohort study, we included patients with a new diagnosis of EoE who underwent esophageal dilation, were then treated with tCS, and had at least two follow-up endoscopies. Endoscopic response was defined as EREFS ≤2. Histological and global symptom responses were recorded. We compared patients with and without endoscopic response and calculated the number of subsequent dilations in each group. Of 113 EoE patients, 55 (49%) had endoscopic response post-tCS. Compared to endoscopic non-responders, responders were older (43.4 vs 34.4 years; p = 0.001) and had lower EREFS (4.4 ± 1.6 vs. 6.3 ± 1.5; p < 0.001) at baseline. EREFS responders required fewer dilations on their initial post-treatment endoscopy (65% vs 90%; p = 0.002) and had greater symptom (92% vs 64%; p = 0.005) and histologic responses (82% vs 24% <15 eos/hpf; p < 0.001). Over the median follow-up time of 1106 days, EREFS responders required fewer dilations than non-responders (4.5 ± 2.9 vs 6.2 ± 4.5; p = 0.03). Endoscopic responders to tCS required fewer esophageal dilations compared to non-responders. Responders also had better symptom and histologic responses. These results provide evidence that endoscopic response is associated with important clinical outcomes including a reduction in future esophageal dilations.

Objectives: To determine associations between physician sex and use of postoperative healthcare resources among patients undergoing common surgeries in Ontario, Canada. Background: Prior studies have shown that patients of female physicians experience better outcomes and have lower healthcare costs compared with patients of male physicians. Understanding differences in resource utilization may offer insights into the care pathways and practice patterns contributing to these differences. Methods: We conducted a population-based, retrospective cohort study of adults (≥18 years of age) undergoing 1 of 25 common surgeries, between January 1, 2007, and December 31, 2019, in Ontario, Canada. The primary outcome was the utilization of one of the following: intensive care unit admission, other medical interventions (eg, tracheostomy, new dialysis starts, and home oxygen), and discharge care needs (eg inpatient rehab, long-term care, and home care use) within 30 days. The data were summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results: This population-based study included 1,100,193 patients (61.8% female). Patients treated by male surgeons had higher use of postoperative resources versus those with female surgeons within 30 days (adjusted rate 33.1; 95% confidence interval [CI]: 28.0–39.2 versus 31.2; 95% CI: 25.8–37.7), 90 days, and 1 year. Consistent with these findings, following adjustment for patient, surgeon, procedural, and hospital characteristics, patients treated by male surgeons were significantly more likely to utilize postoperative resources within 30 days (adjusted odds ratio: 1.14; 95% CI: 1.03–1.27; P = 0.010) and at other time points. This difference was primarily driven by the higher use of home care among patients with a male versus female surgeon at all time points (30 days: adjusted odds ratio, 1.13; 95% CI: 1.05–1.21; P = 0.002). Conclusions: Patients with male surgeons had higher postoperative resource utilization when compared with those treated by female surgeons, which was almost entirely driven by the higher use of home care. Further mixed-methods investigation is needed to better understand other potentially relevant factors including surgical outcomes, individual patient preferences, and surgical team decision-making.

Abstract The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. ctDNA minimal residual disease after chemoradiotherapy (CRT) for non–small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. In this study, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration is prognostic for disease progression and integrate additional pre-CRT risk factors, including radiomics, into a combined model that improves outcome prediction. Our results suggest that tumor features, radiomics, and mid-CRT ctDNA analysis are complementary and can identify patients at high and low risk of progression to potentially enable response-adapted therapies. Significance: This study demonstrates that combining tumor features, radiomics, and ctDNA analysis improves outcome prediction in NSCLC treated with CRT therapy. Our integrated model could enable personalized and response-adapted therapies to reduce toxicity and improve outcomes in patients. See related commentary by Anagnostou and Aggarwal, p. 1534

» Femoroacetabular impingement (FAI) is the premature contact of the femoral head-neck junction with the superior acetabular rim during hip range of motion, which may further damage intra-articular soft tissue structures and lead to the accelerated development of osteoarthritis. » FAI syndrome is diagnosed by a triad of symptoms, clinical signs, and imaging findings, and is a common cause of hip pain in young patients that have a significant impact on patient hip-related function and quality of life. » The treatment of FAI syndrome begins with noninvasive nonoperative modalities such as patient education and supervised exercise-based physical therapy. For recalcitrant symptoms, various injections have been explored for both diagnostic and therapeutic purposes; however, the efficacy of these interventions have generally not been demonstrated outside of the short term » In this article, we examine the available literature regarding the nonoperative treatment of FAI and provide insight into the effectiveness of current treatment modalities.

Abstract Increased innate immune activity promotes neurodegeneration and contributes to progression in multiple sclerosis. This prospective case-control study aims to investigate thalamic microglia density on 18kDa translocator protein PET in patients with multiple sclerosis using a third-generation radioligand, 11C-ER176, and investigate the associations of 11C-ER176 PET uptake with imaging and clinical measures of progression in multiple sclerosis. Patients with multiple sclerosis (n = 50) and controls (n = 55) were prospectively enrolled and they underwent 11C-ER176 PET and MRI including diffusion MRI with neurite orientation dispersion and density imaging. Disease characteristics, expanded disability status scale and multiple sclerosis functional composite scores were obtained in patients with multiple sclerosis. Age at imaging (mean ± standard deviation: patients = 49.6 ± 12.9 years, controls = 48.2 ± 15.4 years, P = 0.63) and sex (female ratio; patients = 72%, controls = 65%, P = 0.47) were not different between the groups. Thalamus 11C-ER176 PET uptake was highest in patients with progressive multiple sclerosis (1.272 ± 0.072 standardized uptake value ratio), followed by patients with relapsing multiple sclerosis (1.209 ± 0.074 standardized uptake value ratio) and lowest in controls (1.162 ± 0.067 standardized uptake value ratio, P < 0.001). Patients with thalamic lesions had higher thalamus 11C-ER176 PET uptake than those without thalamic lesions in both relapsing multiple sclerosis and progressive multiple sclerosis (P < 0.001). In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake correlated with lower thalamic volume (r = −0.45, P = 0.001), higher mean diffusivity (r = 0.56, P < 0.001), lower neurite density index (r = −0.43, P = 0.002), lower orientation dispersion index (r = −0.40, P = 0.005) and higher free water fraction (r = 0.42, P = 0.003) in the thalamus. In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake also correlated with higher mean diffusivity (r = 0.47, P < 0.001) and lower neurite density index (r = −0.36, P = 0.012) in the corpus callosum. In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake correlated with worse expanded disability status scale scores (r = 0.33, P = 0.02), paced auditory serial addition test scores (r = −0.43, P = 0.003) and multiple sclerosis functional composite z-scores (r = −0.46, P = 0.001). Microglia density in the thalamus is highest in patients with progressive multiple sclerosis and is associated with imaging biomarkers of neurodegeneration and clinical disease severity. As a signature imaging biomarker of progression in multiple sclerosis, effectively reflecting the global disease burden, 11C-ER176 PET may aid development and efficacy evaluation of therapeutics targeting microglia.

PURPOSE Monitoring with electronic patient-reported outcome (ePRO) systems can improve cancer outcomes and is increasingly recommended. Optimal implementations of ePROs in routine clinical care are not yet known. Perspectives from clinicians, clinic staff, and patients who used ePROs can provide real-world insights for optimizing the design, efficiency, and effectiveness of future implementations. METHODS Providers, clinic staff, and patients receiving treatment for metastatic cancer from community oncology practices that implemented ePROs as part of the national PRO-TECT trial (Alliance AFT-39) participated in semi-structured interviews related to ePROs. Perceptions from clinicians on perceived benefits, usefulness, acceptability, impact on quality of care, and required effort; from staff on clinical integration and effort; and from patients on ease of use, usefulness, and effort were collected. Themes, subthemes, and recommendations were identified via a standardized coding-based directed thematic analytic approach. RESULTS Ninety-eight clinic members and 67 patients participated from 25 intervention sites. Four themes were identified: (1) positive impact of ePROs on cancer care quality, communication, and relationship-building; (2) ePRO system usability; (3) challenges to ePRO integration with clinical workflow; and (4) recommendations for improving ePRO systems and implementation. Subthemes related to the impact of ePROs on cancer care included enhanced communication with care team, increased awareness of symptoms, and increased ability to self-manage symptoms. Actionable recommendations for future initiatives were to engage and train clinicians, staff, and organizational support for ePRO-related activities; tailor content of ePRO surveys to be clinically actionable; integrate ePRO alert notifications and reports with existing information systems; and optimize integration of ePROs with existing clinic workflow processes. CONCLUSION Experiences of care team members and patients were positive, with actionable recommendations identified to guide future ePRO implementations.

ABSTRACTThe optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34+ cell dose were collected. Full‐dose melphalan (≥ 180 mg/m2) was administered in 63.7% of the patients, and 80.4% had melphalan split into 2‐day conditioning. A rest day (day −1) between the conditioning regimen and stem cell infusion was provided in 52.5% of patients. The median infused CD34+ cell count was 4.7 × 106/kg. An infused CD34+ cell count ≥ 4.5 × 106/kg was associated with a shorter time to neutrophil and platelet engraftment. In a nominal regression analysis, full‐dose melphalan, 1‐day melphalan conditioning, and omitting a rest day between conditioning and stem cell infusion were independent predictors of post‐ASCT higher deep hematological response. The median follow‐up was 8.6 years, and 38% of patients died. Independent predictors of superior overall survival in multivariate Cox regression analysis included full‐dose melphalan, having no rest day, and infused CD34+ cells ≥ 4.5 × 106/kg. Independent predictors of higher day‐100 transplant‐related mortality (TRM) in nominal logistic regression analysis included poorer performance status, NT‐proBNP/BNP ≥ 1800/400 pg/mL, serum albumin < 2.5 g/dL, CD34+ cells < 4.5 × 106/kg, and not having a rest day. In conclusion, 1 day of melphalan conditioning and administration of CD34+ cells ≥ 4.5 × 106/kg are recommended for ASCT in AL amyloidosis.