Citations

Abstract Over the last 30 years, axillary surgery in patients with breast cancer has undergone a consistent patient-centered, evidence-based de-escalation of surgical intervention, including considerable practice changes over the last decade. As surgical approaches change, the role of breast imaging radiologists and axillary imaging must also evolve. Axillary imaging remains variable across radiology practices, with implementation of new protocols occurring at various speeds. Breast radiologists must be aware of recent trials and remain agile in adopting or responding to changing treatment paradigms. Breakthrough studies, such as the SOUND (Sentinel Node Vs Observation After Axillary Ultra-souND) trial, must be vetted and evaluated by individual practices before adoption. Breast radiologists should play a key role in multidisciplinary collaboration with colleagues involved in breast cancer care to assist with strategic planning and appropriate resource utilization.

Circulating glucagon concentrations differ between individuals with no diabetes (ND) and those with type 1 diabetes (T1D). We combined an isotope dilution technique using stable tracers [6,22-13C9,15N1]glucagon and [6,14,19,22-13C9,15N1]glucagon with splanchnic and leg catheterization in participants with ND (n = 8; age 23.1 ± 2.9 years, BMI 26.6 ± 3.5 kg/m2, HbA1c 5.0 ± 0.2% [31 ± 2 mmol/mol]) and T1D (n = 6; 29.0 ± 8.8 years, BMI 26.3 ± 5.0 kg/m2, HbA1c 7.9 ± 0.8% [63 ± 8 mmol/mol]) in the overnight fasted state. After baseline period, exogenous glucagon was infused at rates designed to achieve plasma glucagon concentrations spanning the physiological ranges, to determine the effects of rising glucagon concentrations on splanchnic and leg glucagon balance. At baseline, splanchnic glucagon extraction (SGE) was similar (30.7 ± 2.7 vs. 29.1 ± 2.9%) but leg glucagon extraction (LGE) was lower (27.0 ± 4.2 vs. 40.6 ± 3.1%) in participants with T1D versus those with ND. However, with increasing plasma glucagon concentrations, while SGE remained unchanged within and between groups, LGE fell in participants with ND (41 vs. 31 vs. 24%) but did not change in those with T1D. Despite a numerically lower net splanchnic glucagon production in participants with T1D than in those with ND, no changes were observed with increasing glucagon concentrations within the physiological range in both groups. This is the first human study applying novel glucagon isotopes that describes regional glucagon metabolism in participants with ND and T1D. Our observations provide translational relevance for dual hormone closed-loop systems and provide tools for probing the effects of GLP-1, dual, and triple receptor agonists on pancreatic α-cell functions. Article Highlights This study was conducted to assess splanchnic and leg glucagon metabolism in humans using stable glucagon isotopes. We wanted to evaluate whether splanchnic and leg glucagon metabolism differed between participants with no diabetes (ND) and those with type 1 diabetes (T1D) at glucagon concentrations spanning the physiological range. Whereas splanchnic glucagon extraction did not differ between participants with ND and those with T1D, leg glucagon extraction fell in those with ND but did not change in those with T1D as glucagon concentrations increased. Net splanchnic glucagon production did not change with exogenous glucagon infusion. Our study has implications for dual hormone closed-loop control in T1D where glucagon is infused for prevention of hypoglycemia and for investigating the effects of emerging GLP-1, glucose-dependent insulinotropic polypeptide, and glucagon receptor agonists on endogenous glucagon secretion and clearance.

Abstract Motivation Single-cell RNA sequencing (scRNA-seq) has become an important method for characterizing cellular heterogeneity, revealing more biological insights than the bulk RNA-seq. The surge in scRNA-seq data across multiple individuals calls for efficient and statistically powerful methods for differential expression (DE) analysis that addresses individual-level biological variability. Results We introduced DiSC, a method for conducting individual-level DE analysis by extracting multiple distributional characteristics, jointly testing their association with a variable of interest, and using a flexible permutation testing framework to control the false discovery rate (FDR). Our simulation studies demonstrated that DiSC effectively controlled the FDR across various settings and exhibited high statistical power in detecting different types of gene expression changes. Moreover, DiSC is computationally efficient and scalable to the rapidly increasing sample sizes in scRNA-seq studies. When applying DiSC to identify DE genes potentially associated with COVID-19 severity and Alzheimer’s disease across various types of peripheral blood mononuclear cells and neural cells, we found that our method was approximately 100 times faster than other state-of-the-art methods and the results were consistent and supported by existing literature. While DiSC was developed for scRNA-seq data, its robust testing framework can also be applied to other types of single-cell data. We applied DiSC to cytometry by time-of-flight data, DiSC identified significantly more DE markers than traditional methods. Availability and implementation The R software package “SingleCellStat” is freely available on CRAN (https://cran.r-project.org/web/packages/SingleCellStat/index.html) and GitHub (https://github.com/Lujun995/DiSC). The replication code for reproducing the analyses in this study is publicly accessible at https://github.com/Lujun995/DiSC_Replication_Code. The scRNA-seq expression matrix and metadata utilized in our simulations and analyses can be retrieved from https://cells.ucsc.edu/autism/rawMatrix.zip, https://cellxgene.cziscience.com/collections/1ca90a2d-2943-483d-b678-b809bf464c30, and https://covid19.cog.sanger.ac.uk/submissions/release1/haniffa21.processed.h5ad.

Objective: To assess the efficacy of trichloroacetic acid (TCA) as treatment for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). Methods: Retrospective study of patients with CIN 2 or greater treated with TCA from 2016 to 2022. Patients who desired future childbearing had a satisfactory colposcopy and had not received prior treatment for CIN. Patients were offered excision as initial treatment and for lesions that did not regress. TCA was discussed as an alternative, off-label treatment. Under colposcopic guidance, 85% TCA was applied to the transformation zone and distal endocervix. Patients were followed with colposcopy and cytology every 3–6 months and subsequently underwent excision or reapplication of TCA. Primary outcomes were regression and remission after a minimum of 6 months of treatment with TCA. Results: A total of 43 patients elected treatment with TCA. The mean age was 28.6 years with a median follow-up time of 12 months. The majority of patients were nonsmokers (95.3%) and White (73.9%). Pretreatment diagnosis was CIN3 and CIN2 in 32.6% and 67.4% of cases, respectively. After a median of three TCA treatments, 23.3% regression and 55.8% remission were noted for an overall cytological response rate of 79.1%. 16.3% required excision within 1 year. There were no cervical cancer diagnoses. The median time to regression and remission was 9 months and 6 months, respectively. Conclusion: In patients with high-grade CIN, treatment with TCA may have favorable short-term outcomes. TCA may represent an alternative to excision in reproductive-aged patients, though additional studies are needed with a larger cohort in a prospective manner.

Abstract Background In two 12‐week, randomized, placebo‐controlled trials (RCTs) in individuals with alcohol use disorder (AUD), topiramate significantly reduced heavy drinking days (HDDs), and alcohol‐related problems. In a secondary analysis of those findings, we examined four broad measures of genetic risk—polygenic scores (PGS)—of problematic alcohol use (PAU), drinks per week (DPW), and time to relapse to any drinking (TR) and heavy drinking (THR) as moderators of topiramate's effect on HDDs and alcohol‐related problems. Methods We analyzed data from 285 individuals with AUD (65.6% male) of European‐like ancestry, who were treated with either topiramate (49.1%) or placebo (50.9%). All patients underwent genome‐wide array genotyping, and PGS were calculated using summary statistics from genome‐wide association studies of PAU, DPW, and TR and THR (two time‐to‐event outcomes among patients treated in AUD pharmacotherapy trials). We hypothesized an interaction effect in which greater genetic risk—particularly for PAU—would be associated with a greater therapeutic response to topiramate than placebo. Results As shown previously, topiramate significantly reduced both HDDs (odds ratio [OR] = 0.50, p < 0.001) and Short Index of Problems (SIP) scores ( b = −3.04, p < 0.001) more than placebo. There were nonsignificant associations of higher PGS with more HDDs (OR = 1.17, 95% CI = 0.98–1.41, p = 0.091) and a greater reduction in HDDs in the topiramate group (OR = 0.80, 95% CI = 0.62–1.03, p = 0.089). There were also significant interaction effects with treatment on SIP score by PGS for PAU ( b = −1.64, SE = 0.78, p = 0.033), TR ( b = −2.16, SE = 0.72, p = 0.003), and TRH ( b = −2.17, SE = 0.72, p = 0.003). Conclusions These findings provide proof of principle for the use of alcohol‐related PGS as moderators of the effects of topiramate for treating AUD. Larger RCTs of topiramate are needed to provide adequate statistical power to validate this pharmacogenetic approach to precision AUD treatment.

AbstractBackgroundWorkforce engagement can provide structure, income, feelings of accomplishment, and personal contacts, growing an individual's recovery capital (RC). Employed individuals are also more likely to complete addiction treatment. We sought to investigate whether changes in employment status from alcohol treatment admission to discharge correlated with changes in alcohol use frequency over those time points.MethodsThe Treatment Episode Dataset—Discharges (2017–2021) provided the data. Employment status (full‐time, part‐time, unemployed, and not in labor force) and alcohol use frequency (daily use, some use, and no use in past month) were assessed at treatment admission and discharge. Changes in alcohol use frequency during treatment were recorded as Reduction or No reduction. Logistic regression using reduced alcohol use frequency as the dependent variable included employment status at admission and discharge separately. A second analysis included employment status at both admission and discharge and their interaction term. An adjusted model included all covariates (race, ethnicity, age, education, and referral source), with its results being used to derive the marginal probabilities of reduced alcohol use frequency.ResultsThere were 856,085 alcohol treatment admissions over the 5 years, with 221,724 (25.9%) first admissions. Transitioning from not in the labor force or unemployed to full‐time saw the largest percentage of encounters decreasing alcohol use frequency: 71.9% (95% CI: 70.0–73.7) and 69.3% (95% CI: 68.1–70.5), respectively. Those remaining unemployed had the lowest reduction at 26.7% (95% CI: 26.3–27.1), with a sample reduction of 42.7% (95% CI: 42.5–42.9) overall. Far more people (60.4%) completed treatment within the Reduction group than in the No reduction group (30.2%).ConclusionsFindings suggest that improving employment status may be relevant for reducing alcohol use frequency. This aligns with past work showing overall improved health outcomes with lower unemployment levels. Incorporating vocational training and workforce engagement activities into outpatient treatment may help augment traditional approaches to improve an individual's RC.

Background: The objective of this research article is to compare endoscopic treatment versus shunting procedures for failed endoscopic third ventriculostomies (ETVs) in pediatric patients with hydrocephalus. Methods: We did a systematic review based on preferred reporting items for systematic reviews and meta-analyses guidelines on Studies involving pediatric patients (aged 0–18 years) diagnosed with hydrocephalus, reporting on the use of repeat ETV (Re-ETV) or Ventriculoperitoneal shunting (VPS) as a treatment option following failed ETV. Comparative studies, including randomized controlled trials, cohort studies, and any prospective studies, are included. Studies published in the English language conducted between 2001 and 2023 are included. Results: Forty articles were selected for full-text review. Out of which nine articles that clearly addressed the topic of Re-ETV and/or VPS placement after failure of primary ETV were deemed suitable for analysis. A data set of 663 patients was analyzed. Re-ETV was done in 220 patients (33.18%) and VPS Placement was done in 443 patients (66.81%). The primary ETV failure rates ranged from 16.6 to 60.89%. There was a higher failure rate of Re-ETV (74.98%) compared to VPS (22.26%) indicating that VPS is generally more successful as a secondary intervention. The presence of hemorrhage during primary ETV suggested more benefit from VPS placement rather than Re-ETV (P < 0.05). Conclusion: Our systematic review suggests that VPS placement is the more prevalent choice after primary ETV failure, likely due to its higher overall success rate and the nature of complications. The wide variability in failure rates and follow-up durations suggests that treatment outcomes can differ greatly between patients and studies. Decisions regarding secondary interventions should be individualized, considering patient-specific factors such as age, complications, and timing of intervention.

BACKGROUND AND OBJECTIVES: Aneurysm risk prediction remains an imprecise science that places patients at risk for either over or undertreatment. Machine learning (ML) models may improve clinical practice by adding precision to risk assessment. This study aims to comprehensively assess the current landscape of ML applications in predicting the risk of aneurysm rupture and compare the performance with the widely used PHASES score. METHODS: A systematic review of PubMed, Scopus, and Web of Science was conducted. All studies using ML tools to predict the rupture risk of intracranial aneurysms were included. Meta-analysis was conducted with consideration to the ML algorithms and compared with the PHASES score. RESULTS: Thirty-six studies involving 22 462 patients were included in the final analysis. ML techniques, including 124 models using 25 algorithms, were employed. Among various ML models, while they had comparable diagnostic performance, deep learning exhibited a slightly better performance profile (sensitivity = 0.792, specificity = 0.788, and accuracy = 0.778 in external validation). Based on our analysis, ML, regardless of the algorithm, provides comparable sensitivity (0.743 vs 0.771, P = .60) and higher specificity (0.763 vs 0.507, P < .01) compared with the PHASES score. Consistently, pooling the area under the receiver operating characteristic curve (AUC) for 60 ML models and 5 PHASES score data, ML models exhibited higher AUC (0.84 vs 0.64, P < .01). Using hemodynamic parameters as input for models improved specificity ( P < .01) in the test sets without any significant changes in the sensitivity. The later improvement was not observed in the external validation sets. CONCLUSION: ML techniques have the potential to enhance the prediction of intracranial aneurysm rupture compared with traditional approaches, like the PHASES score. Incorporating hemodynamic parameters may further enhance the accuracy of ML models. Feature prospective studies are required to validate the utility of ML models for clinical integration.

Abstract Background Radiofrequency ablation (RFA) of neuromas has emerged as a potential treatment option for refractory neuroma‐associated postamputation pain (PAP). Objective To evaluate the feasibility of using internally cooled radiofrequency ablation (C‐RFA) for treating neuroma‐associated PAP. Design Prospective single‐arm pilot study. Setting Tertiary academic medical center. Participants Eight participants with neuroma‐associated PAP (mean age 56.5 [ interquartile range, 50.5–68.5] years; mean body mass index 30.2 [ interquartile range, 26.3–34.8] kg/m 2 ). Intervention Participants were recruited and treated with C‐RFA between 2019 and 2023. Main Outcome Measures Pain and functional outcomes were assessed at 1, 3, 6, and 12 months after C‐RFA using Numeric Rating Scale (NRS), Groningen Activity Restriction Scale (GARS), Patient Global Impression of Change (PGIC), and Medication Quantification Scale III (MQS‐III). Responder definitions for each outcome measure were ≥50% NRS reduction, ≥30% GARS improvement, ≥6 on PGIC, and ≥6.8‐point MQS‐III reduction. Results NRS responder rates at 1, 3, 6, and 12 months were 25.0% (95% CI, 7.0%–59.1%), 50.0% (95% CI, 21.5%–78.5%), 37.5% (95% CI, 13.7%–69.4%), and 50.0% (95% CI, 21.5%–78.5%), respectively. Responder rates for GARS were 25.0% (95% CI, 7.1%–59.1%) at 1 month and 12.5% (95% CI, 2.2%–47.1%) at 3, 6, and 12 months. The proportion of PGIC responders was 37.5% (95% CI, 13.7%–69.4%) at 1 and 3 months and 12.5% (95% CI, 2.2%–47.1%) at 6 and 12 months. MQS‐III responder rates were 25.0% (95% CI, 7.1%–59.1%) at 1 month, 12.5% (95% CI, 2.2%–47.1%) at 3 months, and 37.5% (95% CI, 13.7%–69.4%) at 6 and 12 months. There were no complications associated with the C‐RFA procedure. Conclusions These findings indicate the feasibility of neuroma C‐RFA as a treatment for refractory neuroma‐associated PAP but also suggest that further patient selection and C‐RFA technique optimization are warranted before investigating this treatment paradigm in a larger prospective study.