Citations

Abstract Background This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine-refractory differentiated thyroid cancer. Methods Eligible patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of vascular endothelial growth factor receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2. Results Among 11 patients enrolled, the median age was 69 years. Prior vascular endothelial growth factor receptor-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 13.4 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months (95% CI, 3.0–not reached) and median overall survival was 19.2 months (95% CI, 4.6–not reached). Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold. Conclusion CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs. Clinical Trial Registration NCT03914300

Background: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15–30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. Materials and methods: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. Results: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. Conclusion: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

Abstract Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 patients with CCUS investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count of <100 × 109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the clonal cytopenia risk score (CCRS), which stratified patients into low- (score of <2.5 points), intermediate- (score of 2.5 to <5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray test (P < .0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P = .005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.

Background Despite the introduction of the Centers for Disease Control and Prevention's opioid prescribing guidelines, studies indicate that a significant proportion of opioids prescribed at hospital discharge remains unused. Little is known if improved provider awareness of guidelines and metrics would facilitate rightsizing opioid prescriptions at hospital discharge. Our institution created opioid prescribing guidelines and a key metrics dashboard and subsequently disseminated these tools to our institution's leadership and prescribers. We aim to evaluate the effectiveness of these efforts in reducing hospital discharge opioid prescriptions, especially those for acute pain exceeding 100 morphine milligram equivalents (MME). Methods Following the development of practice-specific opioid prescribing guidelines in 2017, a key metrics dashboard was created in 2021 to display the percentage of hospital discharges with opioids prescribed and the percentage of discharges with opioids prescribed for acute pain exceeding 100 MME. These metrics were broken down into calendar years between 2018 and 2022, and by the 7 major practice regions across our institution spanning 5 U.S. States. Results From 2018 to 2022, all regions showed a decline in the percentage of hospital discharges with opioids prescribed (range 2.7%-9.4%). In the same period, 5 of 7 regions showed a decline in discharge opioid prescriptions exceeding 100 MME for acute pain (range 8.8%-23.2%). Two sites showed an increase of 2.4% and 2.7%. Conclusion Downward trends in hospital discharge opioid prescriptions were observed for most practice regions following the introduction of our institution's opioid prescribing guidelines and key metrics dashboard.

Background: The first pediatric appropriate use criteria (PAUC) were recently published for initial outpatient transthoracic echocardiography (TTE). We sought to determine the effect of release of the PAUC on the appropriateness of TTE ordering patterns of pediatric cardiologists. Methods: Data were prospectively collected from patients having initial outpatient TTE ordered prior to (Phase I, 6 mo) and 3 months after release (Phase II, 4 mo) of PAUC. Site-investigators determined the indication of the study and assigned appropriateness rating based on the PAUC document [Appropriate (A), May Be Appropriate (M), or Rarely Appropriate (R)] or "Unclassifiable" (U). Results: A total of 4562 TTEs (2655 Phase I, 1907 Phase II) were ordered by 103 physicians at 6 sites. Overall comparison of appropriateness rating for Phase I and II showed no change in the rate for A or M, but a decline in the rate of R and increase in U. Similar results were noted when comparisons were made for physicians that ordered at least 20 TTEs during each phase (N = 30/103, 29%), Table 1. There was no change in any appropriateness rating at 3 sites, a decline in R at 2, an increase in A at 1, and an increase in U at 2 sites. Overall and site-specific comparisons of rate of R TTEs are shown in Fig 1. Conclusions: The release of PAUC document had only a small impact on physician ordering behavior for initial TTEs, including a small decrease in R. Overall, these data suggest that more focused interventions are required to fully implement guideline recommendations and improve the appropriate use of pediatric TTE. This information should be helpful in designing educational interventions to reduce the rate of TTEs ordered for R indications.

Purpose To use Google trends to explore differences in public interest among types of anterior cruciate ligament (ACL) autografts, specifically quadriceps tendon, patellar tendon, and hamstring tendon autografts, between 2008 and 2019. Methods Data were obtained by querying Google Trends for key terms and phrases for online search data ranging from January 2008 to December 2019. Relative search volumes were created based on searches related to ACL reconstruction with comparative analysis generated for search terms related to quadriceps ACL, patellar tendon ACL, and hamstring ACL autografts. Statistical analysis included linear regression analysis, comparison of quarterly search volume trends over time, and comparison of cumulative annual search volumes for 2008 versus 2019. Results Linear models for respective search terms were statistically significant for the quadriceps ( P < .001) and patellar ( P = .007) tendon autograft groups but not the hamstring group ( P = .129). The quadriceps autograft group demonstrated a 12‐year search volume trend change of 0.56, which was significantly greater than the hamstring (0.07; P < .001) and patellar tendon (0.168; P < .001) groups. There was no significant difference in the trend change between hamstring and patellar tendon groups ( P = .20). Percent change in cumulative relative annual search volumes between 2008 and 2019 was 112% for the quadriceps tendon group, 12.9% for the hamstring group, and 18.6% for the patellar tendon group. Conclusions This study indicates a consistently increasing public interest in quadriceps tendon autograft for ACL reconstruction. The quadriceps autograft group demonstrated a significantly greater 12‐year online search volume, greater linear correlation, and larger percent change between 2008 and 2019 compared with patellar tendon or hamstring autograft groups. Clinical Relevance Awareness of patient perceptions has value in informing shared decision‐making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Background: Carpal Tunnel Syndrome (CTS) is associated with a significant personal and societal burden. Evaluating access to care can identify barriers, limitations, and disparities in the delivery of healthcare services in this population. The purpose of this study was to evaluate access to overall healthcare and healthcare utilization among patients with CTS. Methods: This is a retrospective cohort study conducted with the All of Us database. Patients diagnosed with CTS that completed the access to care survey were included and matched to a control group. The primary outcomes were access to care across 4 domains: (1) delayed care, (2) could not afford care, (3) skipped medications, and (4) over 1 year since seeing provider. Secondary analysis was then performed to identify patient-specific factors associated with reduced access to care. Results: In total, 7649 patients with CTS were included and control matched to 7649 patients without CTS. In the CTS group, 33.7% (n = 2577) had delayed care, 30.4% (n = 2323) could not afford care, 15.4% (n = 1180) skipped medications, and 1.6% (n = 123) had not seen a provider in more than 1 year. Within the CTS cohort, low-income, worse physical health, and worse mental health were associated with poor access to care. Conclusion: Patients experience notable challenges with delayed care, affordability of care, and medication adherence regardless of having a diagnosis of CTS. Targeted interventions on modifiable risk factors such as low income, poor mental health, and poor physical health are important opportunities to improve access to care in this population.

OBJECTIVE Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.