Macroscopic materials assembled from nanoparticle superlattices.

Nanoparticle assembly has been proposed as an ideal means to program the hierarchical organization of a material by using a selection of nanoscale components to build the entire material from the bottom up. Multiscale structural control is highly desirable because chemical composition, nanoscale ordering, microstructure and macroscopic form all affect physical properties1,2. However, the chemical interactions that typically dictate nanoparticle ordering3-5 do not inherently provide any means to manipulate structure at larger length scales6-9. Nanoparticle-based materials development therefore requires processing strategies to tailor micro- and macrostructure without sacrificing their self-assembled nanoscale arrangements. Here we demonstrate methods to rapidly assemble gram-scale quantities of faceted nanoparticle superlattice crystallites that can be further shaped into macroscopic objects in a manner analogous to the sintering of bulk solids. The key advance of this method is that the chemical interactions that govern nanoparticle assembly remain active during the subsequent processing steps, which enables the local nanoscale ordering of the particles to be preserved as the macroscopic materials are formed. The nano- and microstructure of the bulk solids can be tuned as a function of the size, chemical makeup and crystallographic symmetry of the superlattice crystallites, and the micro- and macrostructures can be controlled via subsequent processing steps. This work therefore provides a versatile method to simultaneously control structural organization across the molecular to macroscopic length scales.

Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).

Rationally Designing the Supramolecular Interfaces of Nanoparticle Superlattices with Multivalent Polymers.

In supramolecular materials, multiple weak binding groups can act as a single collective unit when confined to a localized volume, thereby producing strong but dynamic bonds between material building blocks. This principle of multivalency provides a versatile means of controlling material assembly, as both the number and the type of supramolecular moieties become design handles to modulate the strength of intermolecular interactions. However, in materials with building blocks significantly larger than individual supramolecular moieties (e.g., polymer or nanoparticle scaffolds), the degree of multivalency is difficult to predict or control, as sufficiently large scaffolds inherently preclude separated supramolecular moieties from interacting. Because molecular models commonly used to examine supramolecular interactions are intrinsically unable to examine any trends or emergent behaviors that arise due to nanoscale scaffold geometry, our understanding of the thermodynamics of these massively multivalent systems remains limited. Here we address this challenge via the coassembly of polymer-grafted nanoparticles and multivalent polymers, systematically examining how multivalent scaffold size, shape, and spacing affect their collective thermodynamics. Investigating the interplay of polymer structure and supramolecular group stoichiometry reveals complicated but rationally describable trends that demonstrate how the supramolecular scaffold design can modulate the strength of multivalent interactions. This approach to self-assembled supramolecular materials thus allows for the manipulation of polymer-nanoparticle composites with controlled thermal stability, nanoparticle organization, and tailored meso- to microscopic structures. The sophisticated control of multivalent thermodynamics through precise modulation of the nanoscale scaffold geometry represents a significant advance in the ability to rationally design complex hierarchically structured materials via self-assembly.

A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers.

BACKGROUND: There is accumulating evidence supporting the clinical use of circulating tumor DNA (ctDNA) in solid tumors, especially in different types of gastrointestinal cancer. As such, appraisal of the current and potential clinical utility of ctDNA is needed to guide clinicians in decision-making to facilitate its general applicability. CONTENT: In this review, we firstly discuss considerations surrounding specimen collection, processing, storage, and analysis, which affect reporting and interpretation of results. Secondly, we evaluate a selection of studies on colorectal, esophago-gastric, and pancreatic cancer to determine the level of evidence for the use of ctDNA in disease screening, detection of molecular residual disease (MRD) and disease recurrence during surveillance, assessment of therapy response, and guiding targeted therapy. Lastly, we highlight current limitations in the clinical utility of ctDNA and future directions. SUMMARY: Current evidence of ctDNA in gastrointestinal cancer is promising but varies depending on its specific clinical role and cancer type. Larger prospective trials are needed to validate different aspects of ctDNA clinical utility, and standardization of collection protocols, analytical assays, and reporting guidelines should be considered to facilitate its wider applicability.

Reversible Diffusionless Phase Transitions in 3D Nanoparticle Superlattices.

Nanocomposite tectons (NCTs), polymer brush-grafted nanoparticles that use supramolecular interactions to drive their assembly, form ordered nanoparticle superlattices (NPSLs) with well-defined unit cell symmetries when thermally annealed. In this work, we demonstrate that appropriate assembly and processing conditions can also enable control over the microstructure of NCT lattices by balancing the enthalpic and entropic factors associated with ligand packing and supramolecular bonding during crystallization. Unary systems of NCTs are assembled via the addition of a small molecule capable of binding to multiple nanoparticle ligands; these NCTs initially form face-centered-cubic (FCC) structures in solvents that are favorable for the particles' polymer brushes. However, the FCC lattices undergo a reversible, diffusionless phase transition to body-centered-cubic (BCC) lattices when transferred to a solvent that induces polymer brush collapse. The BCC superlattices maintain the same crystal habit as the parent FCC phase but exhibit significant transformation twinning similar to that seen in martensitic alloys. This previously unseen diffusionless phase transformation in NPSLs enables unique microstructural features in the resulting assemblies, suggesting that NPSLs could serve as models for the investigation of microstructural evolution in crystalline systems and extend our understanding of NPSLs as atomic material analogues.

The Characteristics and Ethics of Sham Surgeries: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: We sought to perform a large-scale systematic review across all sham-controlled studies currently present in the literature to better characterize the ethical considerations of these studies. BACKGROUND: Innovative surgical procedures are often introduced into the clinical setting without the robust clinical trials required for medicinal treatments. Sham surgeries serve as placebos by performing all steps of a surgical intervention aside from those deemed therapeutically necessary. Yet, sham trials are underutilized because of ethical controversy. METHODS: Ovid MEDLINE was queried through April 2022 with combinations of the Medical Subject (MeSH) headings and keywords including, but not limited to, "surgery," "endoscopy," "randomized controlled trial," and "sham procedure." Primary outcomes were surgical indications and characteristics, outcome measurements, and whether the investigational treatment was offered to the sham cohort. RESULTS: One hundred seventy-two articles fit our inclusion criteria, with gastrointestinal pathologies being the most common surgical indication. Participants, personnel, and outcome assessment were all blinded in 8.7% of trials (n=15). Study populations included adult subjects (age ≥18) in 170 studies (98.8%), and two involved children. The most common level of dissection and type of anesthesia were deep (n=66, 38.4%) and general (n=49, 28.5%), respectively. An open surgical approach was utilized in 20.9% of studies (n=36). Primary outcomes were objective in 75 studies (43.6%) and subjective in 97 (56.4%), 62 of which used validated outcome measures (36.0%). Four trials explicitly did not offer the surgery to the sham arm (2.3%), whereas 106 had no mention of whether the intervention was offered (61.6%). CONCLUSIONS: Our systematic review of 172 randomized, sham-controlled trials highlights the ethical considerations that must be considered in these studies, namely the importance of transparent study design and objective outcome reporting, the difficulty of informed consent, and the inherent risks associated with surgical interventions.

Improving nanoparticle superlattice stability with deformable polymer gels.

The self-assembly of colloidal nanoparticles into ordered superlattices typically uses dynamic interactions to govern particle crystallization, as these non-permanent bonds prevent the formation of kinetically trapped, disordered aggregates. However, while the use of reversible bonding is critical in the formation of highly ordered particle arrangements, dynamic interactions also inherently make the structures more prone to disassembly or disruption when subjected to different environmental stimuli. Thus, there is typically a trade-off between the ability to initially form an ordered colloidal material and the ability of that material to retain its order under different conditions. Here, we present a method for embedding colloidal nanoparticle superlattices into a polymer gel matrix. This encapsulation strategy physically prevents the nanoparticles from dissociating upon heating, drying, or the introduction of chemicals that would normally disrupt the lattice. However, the use of a gel as the embedding medium still permits further modification of the colloidal nanoparticle lattice by introducing stimuli that deform the gel network (as this deformation in turn alters the nanoparticle lattice structure in a predictable manner). Moreover, encapsulation of the lattice within a gel permits further stabilization into fully solid materials by removing the solvent from the gel or by replacing the solvent with a liquid monomer that can be photopolymerized. This embedding method therefore makes it possible to incorporate ordered colloidal arrays into a polymer matrix as either dynamic or static structures, expanding their potential for use in responsive materials.

Compliance with Therapeutic Goods Association prescribing information: weekly or second weekly cetuximab for the treatment of metastatic colorectal cancer.

BACKGROUND: Treatment with cetuximab provides a survival benefit for patients with RAS wild-type metastatic colorectal cancer (mCRC). Practice-defining cetuximab studies utilised weekly (q1w) administration. More convenient second weekly (q2w) administration is supported by pharmacokinetic data and a recent meta-analysis, but large head-to-head studies have not been conducted. Therapeutic Goods Association (TGA) prescribing information states cetuximab be administered q1w for all indications. AIM: To assess the real-world use of q1w versus q2w cetuximab schedule and any difference in outcomes. METHODS: We analysed data from a prospective mCRC database at seven Melbourne hospitals from January 2010 to August 2019. Characteristics and outcomes for cetuximab-treated patients were examined, comparing q1w versus q2w schedules. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. RESULTS: Of 214 eligible patients, 103 (48%) received q1w and 111 (52%) received q2w cetuximab. Q2w cetuximab has been used in >70% of patients from 2015. Q2w was more commonly used in public patients (70% vs 13% in private, P < 0.001), in left-sided primary tumours (83% vs 68%, P = 0.025) and in combination with chemotherapy (73% q2w vs 40% q1w, P < 0.001). Q2w treatment was less common in BRAFV600E mutated tumours (4% vs 13%, P = 0.001). PFS was similar across all lines of therapy, including when analyses were limited to a left-sided primary and there was no difference in OS in multivariate analysis. CONCLUSION: This real-world analysis shows q2w cetuximab has become the dominant method of administration, despite TGA guidance. Our outcome data adds to other data supporting the use of q2w cetuximab as the standard option. Consideration could be given to modifying current TGA advice.

An investigation of vascular anomalies centers' transition of care practices.

This study aims to examine transition of care (TOC) practices of multidisciplinary vascular anomalies centers (VACs). Thirty-seven of 71 VAC leaders to whom the survey was sent completed the questionnaire. TOC and transfer practices varied with only 16% of VACs having TOC programs. The most frequently cited barriers to developing a TOC program were lack of resources and difficulty finding expert adult providers.

Identifying Systemic Factors when Counseling Black Women of Christian Faith in the USA.

When Black women of Christian faith in the USA receive secular help for psychological symptoms, their spiritual and religious communities often view the decision negatively. The women may feel shamed, ostracized, and condemned. They often experience emotional, physical, and spiritual trauma from the rejection that increases the frequency, duration, and intensity of their psychological symptoms. This article identifies specific community-based and systemic factors that exacerbate mental health issues in Black women of Christian faith. The authors discuss the influence of such factors on mental health and provide evidence-based practices for mental health clinicians working with Black women of Christian faith.

Nanoparticle Assembly as a Materials Development Tool.

Nanoparticle assembly is a complex and versatile method of generating new materials, capable of using thousands of different combinations of particle size, shape, composition, and ligand chemistry to generate a library of unique structures. Here, a history of particle self-assembly as a strategy for materials discovery is presented, focusing on key advances in both synthesis and measurement of emergent properties to describe the current state of the field. Several key challenges for further advancement of nanoparticle assembly are also outlined, establishing a roadmap of critical research areas to enable the next generation of nanoparticle-based materials synthesis.

Nanocomposite tectons as unifying systems for nanoparticle assembly.

Nanocomposite tectons (NCTs) are nanocomposite building blocks consisting of nanoparticle cores functionalized with a polymer brush, where each polymer chain terminates in a supramolecular recognition group capable of driving particle assembly. Like other ligand-driven nanoparticle assembly schemes (for example those using DNA-hybridization or solvent evaporation), NCTs are able to make colloidal crystal structures with precise particle organization in three dimensions. However, despite the similarity of NCT assembly to other methods of engineering ordered particle arrays, the crystallographic symmetries of assembled NCTs are significantly different. In this study, we provide a detailed characterization of the dynamics of hybridizations through universal (independent of microscopic details) parameters. We perform rigorous free energy calculations and identify the persistence length of the ligand as the critical parameter accounting for the differences in the phase diagrams of NCTs and other assembly methods driven by hydrogen bond hybridizations. We also report new experiments to provide direct verification for the predictions. We conclude by discussing the role of non-equilibrium effects and illustrating how NCTs provide a unification of the two most successful strategies for nanoparticle assembly: solvent evaporation and DNA programmable assembly.

Food insecurity, housing instability, and dietary quality among children with sickle cell disease: Assessment from a single urban center.

BACKGROUND: Food insecurity and housing instability, both social determinants of health (SDoH), disproportionately affect economically unstable, under-resourced US communities in which children with sickle cell disease (SCD) live. Association between these SDoH markers and dietary quality among children with SCD is unknown. PROCEDURES: We assessed a cross-sectional sample of dyadic parent-child patients and young adult patients up to age 21 from one pediatric SCD center. Food insecurity, housing instability, and dietary quality were measured using validated US instruments and a food frequency questionnaire. Better dietary quality was defined using US dietary guidelines. Multivariate regression assessed for associations among dietary quality and food insecurity with or without (±) housing instability and housing instability alone. RESULTS: Of 100 enrolled participants, 53% were Black and 43% Hispanic; mean age 10.6 ± 5.6 years. Overall, 70% reported less than or equal to one economic instability: 40% housing instability alone and 30% both food insecurity and housing instability. Eighty percent received more than or equal to one federal food assistance benefit. Compared to no economic instability, food insecurity ± housing instability was significantly associated with higher intake of higher dairy and pizza, while housing instability alone was significantly associated with higher dairy intake. Food insecurity ± housing instability was significantly associated with lower intake of whole grains compared to housing instability alone. CONCLUSIONS: Our sample reported high frequencies of both food insecurity and housing instability; having more than or equal to one SDoH was associated with elements of poorer diet quality. Screening families of children with SCD for food insecurity and housing instability may identify those with potential nutrition-related social needs.

Mismatch epitope load predicts de novo-DSA-free survival in pediatric liver transplantation.

BACKGROUND: Our knowledge of de novo anti-HLA donor-specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA-DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression. METHODS: A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre-transplant diagnosis, biopsy-proven T-cell-mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmaker™ 3.1. All statistical analyses were conducted using R software version 3.40. RESULTS: There were 99 dnDSA-negative patients and 73 dnDSA-positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan-Meier curves and log-rank tests showed high eplet mismatch load was associated with shorter dnDSA-free survival (log-rank p = .001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA-free survival (p < .001 and p = .036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 - 61.19; p < .001). Patients without TCMR were more likely to have dnDSA to HLA-DQ7 and less likely to have dnDSA to HLA-DQ2 (p = .03, p = .080). CONCLUSIONS: Mismatched epitope load predicts dnDSA-free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome.

SARS-CoV-2 Infection in Pediatric Solid Organ Transplant Recipients: A Single Center Observation.

OBJECTIVES: This is a descriptive study to characterize rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in pediatric SOT recipients. METHODS: We queried Organ Transplant Tracking Record (OTTR) for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 and June 30, 2021. Patients were tested by polymerase chain reaction (PCR): prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (1) acute infection versus convalescence; (2) acute infection versus SOT recipients without infection (called healthy controls); (3) liver transplant (LT) versus small bowel (SB)/multivisceral transplant (MVT); (4) positive versus negative test result. RESULTS: Of 257 LT recipients, 99 were tested: 6 were PCR positive, 13 were antibody positive. Of 150 SB/MVT recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs 10.0 years; P = 0.017). We observed a rapid decline in viral load within 96 hours without a change in immunosuppression. Antibody lasted >8 months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 T EM cell frequency ( P = 0.04, P = 0.03, respectively), decreased interferon (IFN)-γ production from T-cells (2.8% vs 11.3%; P = 0.006), and decreased CD8 TEMRA frequency (4.56% vs 11.70%; P = 0.006). CONCLUSIONS: Early in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.

Sickle cell disease in the new era: advances in drug treatment.

Sickle cell disease is an inherited blood disorder afflicting an estimated 100,000 individuals in the United States and over 20 million people worldwide. The disease is heralded as the first molecular disease. However, despite its genetic simplicity, the pathophysiologic processes leading to its clinical sequelae are complex, heterogeneous and interrelated, making drug development to treat the disease challenging. For over two decades only one drug, hydroxyurea, had been used as disease-modifying therapy. New pharmacologic agents are rapidly evolving with three new drugs, with different mechanisms of action, approved by the United States Food and Drug Administration in recent years (L-glutamine, crizanlizumab and voxelotor). Several therapeutic approaches targeting different pathways in the disease pathophysiology are being investigated. These include inhibition of hemoglobin S polymerization such as by fetal hemoglobin induction or by increasing hemoglobin oxygen affinity, as well as intervention of downstream pathways including inhibiting cellular adhesion, reducing inflammation and oxidant stress, modulating platelet activation and coagulation abnormalities, and targeting nitric oxide signaling. This review will provide an overview of these therapeutic strategies, discuss the four currently approved drugs in detail, and summarize ongoing clinical trials of new drugs or drug indications for the treatment of sickle cell disease in different phases of development excluding those related to cellular therapies.

Use and outcomes of chemotherapy for metastatic pancreatic cancer in Australia.

BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is highly lethal. Combination chemotherapy regimens improve overall survival (OS). Historically, only one-third of mPDAC patients in Victoria received chemotherapy. AIM: To describe current Australian chemotherapy utilisation and outcomes in patients with mPDAC using the multi-site PURPLE (Pancreatic cancer: Understanding Routine Practice and Lifting End Results) registry. METHODS: PURPLE collects longitudinal data on consecutive patients with pancreatic cancer seen since January 2016. Data were collated for patients with mPDAC from six Victorian sites, and analysed descriptively. RESULTS: Three hundred and sixty-three patients with mPDAC were identified. Median age was 70 years (range 20-94 years). First-line chemotherapy was administered in 195 (54%) patients. Prevalent regimens included gemcitabine-nab-paclitaxel (71%), gemcitabine alone (10%) and FOLFIRINOX (6%). Sixty-two of 195 (32%) patients who received first line treatment have proceeded to second-line chemotherapy. Chemotherapy-treated patients were younger (69 versus 73 years; P < 0.01), with better Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1 89 vs 66%; P < 0.01) and lower median Charlson comorbidity index (3 vs 4; P < 0.01) compared with untreated patients. Median OS of the entire cohort from diagnosis of metastases was 5.1 months. Median OS was 9.3 months in the chemotherapy treated patients, and 2.5 months in chemotherapy-untreated patients (P < 0.01). CONCLUSIONS: A substantial proportion of patients with mPDAC still do not receive active treatment, which may in part by explained by age, poor performance status and comorbidity. Gemcitabine-nab-paclitaxel was the preferred first-line chemotherapy regimen. Median OS for treated patients in this cohort was comparable to that of recent published clinical trials.

Impact of a Comfortable in our Skin interactive workshop on social media awareness and self-confidence in adolescents.

Social media use contributes to body dissatisfaction and reduced quality of life among adolescents. This study examines the impact of social media use and skin conditions on body image and suggests that a Comfortable in Our Skin (CIOS) pilot community-based workshop may promote healthier body image and social media usage among urban adolescents.

The pediatric dermatology psychosocial screen: Promoting psychosocial coping and early identification of mental illness in pediatric dermatology patients.

BACKGROUND/OBJECTIVES: The psychosocial impact of pediatric skin conditions can be difficult to assess accurately. There is currently no way to formally screen and provide stepped care specifically for psychosocial dysfunction or mental illness during dermatology clinics. The Psychosocial Screening Tool for Pediatric Dermatology (PDPS) was designed to identify patients in need of psychosocial support and to promote multidisciplinary care. METHODS: The PDPS was studied at Boston Children's Hospital outpatient dermatology clinics. A pilot study was conducted with 16 participants to assess language and applicability. The validation study included 105 participants aged 8-19 years. Participants completed the PDPS, the Children's Depression Index 2 Short (CDI-2 Short), and three subscales of the Behavior Assessment System for Children 2 (BASC-2) to assess content validity. Model fit from confirmatory factor analysis was evaluated using the root-mean-square error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI). RESULTS: Proper model fit and criterion validity were demonstrated through positively correlating the PDPS and the CDI-2 Short (CFI = 0.972, TLI = 0.969, RMSEA 5.3%) and BASC-2 subscales (RMSEA = 7.2%, CFI = 0.975, TLI = 0.969). Patient resilience was positively correlated with higher scores in each psychosocial domain. CONCLUSIONS: The PDPS is an effective screening tool for resilience versus need for early behavioral/mental health intervention in dermatology patients aged 8-19. The PDPS identifies psychosocial dysfunction and problems patients may not disclose otherwise (bullying, self-harm, social supports, neurodermatitis, and body dysmorphic disorder). Additionally, patients can directly indicate interest in various psychosocial health resources on the PDPS, guiding practitioners in providing comprehensive care.

Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies.

Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design. We combined individual patient data from three independent cohort studies of nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks after surgery. Mutations in ctDNA were assayed using a massively parallel sequencing technique called SafeSeqS. We analyzed 485 CRC patients (230 Stage II colon, 96 Stage III colon, and 159 locally advanced rectum). ctDNA was detected after surgery in 59 (12%) patients overall (11.0%, 12.5% and 13.8% for samples taken at 4-6, 6-8 and 8-10 weeks; P = .740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P < .001) and overall survival (64.6% vs 89.4%; P < .001). The predictive accuracy of postsurgery ctDNA for recurrence was higher than that of individual clinicopathologic risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele frequency (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1%, 0.5% and 1%). Postsurgery ctDNA was detected in 3 of 20 (15%) patients with locoregional and 27 of 60 (45%) with distant recurrence (P = .018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across nonmetastatic CRC, where ctDNA outperforms other clinicopathologic risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant vs locoregional recurrence.