Use of Rounding Checklists to Improve Communication and Collaboration in the Adult Intensive Care Unit: An Integrative Review.

BACKGROUND: Intensive care units are complex settings that require effective communication and collaboration among professionals in many disciplines. Rounding checklists are frequently used during interprofessional rounds and have been shown to positively affect patient outcomes. OBJECTIVE: To identify and summarize the evidence related to the following practice question: In an adult intensive care unit, does the use of a rounding checklist during interprofessional rounds affect the perceived level of staff collaboration or communication? METHODS: An integrative review was performed to address the practice question. No parameters were set for publication year or specific study design. Studies were included if they were set in adult intensive care units, involved the use of a structured rounding checklist, and had measured outcomes that included staff collaboration, communication, or both. RESULTS: Seven studies with various designs were included in the review. Of the 7 studies, 6 showed that use of rounding checklists improved staff collaboration, communication, or both. These results have a variety of practice implications, including the potential for better patient outcomes and staff retention. CONCLUSIONS: Given the complexity of the critical care setting, optimizing teamwork is essential. The evidence from this review indicates that the use of a relatively simple rounding checklist tool during interprofessional rounds can improve perceived collaboration and communication in adult intensive care units.

Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length.

RNA-based therapeutics have gained traction for the prevention and treatment of a variety of diseases. However, their fragility and immunogenicity necessitate a drug carrier. Lipid nanoparticles (LNPs) have emerged as the predominant delivery vehicle for RNA therapeutics. An important component of LNPs is the ionizable lipid (IL), which is protonated in the acidic environment of the endosome, prompting cargo release into the cytosol. Currently, there is growing evidence that the structure of IL lipid tails significantly impacts the efficacy of LNP-mediated mRNA translation. Here, we optimized IL tail length for LNP-mediated delivery of three different mRNA cargos. Using C12-200, a gold standard IL, as a model, we designed a library of ILs with varying tail lengths and evaluated their potency in vivo. We demonstrated that small changes in lipophilicity can drastically increase or decrease mRNA translation. We identified that LNPs formulated with firefly luciferase mRNA (1929 base pairs) and C10-200, an IL with shorter tail lengths than C12-200, enhance liver transfection by over 10-fold. Furthermore, different IL tail lengths were found to be ideal for transfection of LNPs encapsulating mRNA cargos of varying sizes. LNPs formulated with erythropoietin (EPO), responsible for stimulating red blood cell production, mRNA (858 base pairs), and the C13-200 IL led to EPO translation at levels similar to the C12-200 LNP. The LNPs formulated with Cas9 mRNA (4521 base pairs) and the C9-200 IL induced over three times the quantity of indels compared with the C12-200 LNP. Our findings suggest that shorter IL tails may lead to higher transfection of LNPs encapsulating larger mRNAs, and that longer IL tails may be more efficacious for delivering smaller mRNA cargos. We envision that the results of this project can be utilized as future design criteria for the next generation of LNP delivery systems for RNA therapeutics.

Locally Advanced Adenocarcinoma of the Esophagus: Is Esophagectomy Associated with Improved Overall Survival?

BACKGROUND: Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined. STUDY DESIGN: The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004-2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score-matched to patients treated non-surgically. Kaplan-Meier analysis was used to compare five-year overall survival (OS). RESULTS: 3,703 patients met inclusion criteria. 541 (15%) underwent esophagectomy, 3,162 (85%) did not. Age ≤ 65 (aOR 1.69, [1.33, 2.14]), white race (aOR 2.98, [2.24, 3.96]), treatment in academic centers (aOR 1.64, [1.33, 2.02]), private insurance (aOR 1.88, [1.50, 2.36]), and tumors <6cm (aOR 1.86, [1.44, 2.40]) were associated with use of esophagectomy. Government/lack of insurance (HR 1.23, [1.12, 1.35]), income <$46,000 (HR 1.11, [1.03, 1.20]), treatment in non-academic centers (HR 1.16, [1.07, 1.25]), CCI ≥ 1 (HR 1.22, [1.12, 1.32]), and tumors ≥ 6 cm (HR 1.20, [1.09, 1.32]) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, [0.44, 0.56]) and systemic therapy (HR 0.40, [0.37, 0.43]) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p<0.0001) and longer median OS (24.71 vs. 10.09 months, p<0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p<0.0001) and longer median OS (25.53 vs. 11.01 months, p<0.0001). CONCLUSIONS: In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared to non-surgical treatment.

Assessing Discomfort in American Adult Intensive Care Patients.

BACKGROUND: While in the intensive care unit, critically ill patients experience a myriad of distressing symptoms and stimuli leading to discomfort, a negative emotional and/ or physical state that arises in response to noxious stimuli. Appropriate management of these symptoms requires a distinct assessment of discomfort-causing experiences. OBJECTIVES: To assess patient-reported discomfort among critically ill patients with the English-language version of the Inconforts des Patients de REAnimation questionnaire, and to explore relationships between demographic and clinical characteristics and overall discomfort score on this instrument. METHODS: This study had a cross-sectional, descriptive, single-cohort design. The convenience sample consisted of alert and oriented patients aged 18 years or older who had been admitted to intensive care units at a Midwestern tertiary referral hospital and were invited to participate. An 18-item questionnaire on physiological and psychological stimuli inducing discomfort was administered once. Each item was scored from 0 to 10, with the total possible discomfort score ranging from 0 to 100. Descriptive statistics were used to analyze participants' demographic and clinical characteristics and questionnaire responses. RESULTS: A total of 180 patients were enrolled. The mean (SD) overall discomfort score was 32.9 (23.6). The greatest sources of discomfort were sleep deprivation (mean [SD] score, 4.0 [3.4]), presence of perfusion catheters and tubing (3.4 [2.9]), thirst (3.0 [3.3]), and pain (3.0 [3.0]). CONCLUSIONS: Intensive care unit patients in this study reported mild to moderate discomfort. Additional research is needed to design and test interventions based on assessment of specific discomfort-promoting stimuli to provide effective symptom management.

Locally advanced pancreatic cancer: Is surgical palliation associated with improved clinical outcome relative to medical palliation?

BACKGROUND: The value of palliative surgery in pancreatic cancer is not well-defined. METHODS: We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage. Kaplan-Meier method was used to compare overall survival for matched cohorts. RESULTS: 9,107 patients met inclusion criteria: 3,567 (39 â€‹%) underwent curative intent surgery, 1608 (18 â€‹%) surgical palliation, 3932 (43 â€‹%) medical palliation. Patients undergoing resection and surgical palliation had significant hospitalizations (11.0 â€‹± â€‹0.4 vs. 10.0 â€‹± â€‹0.3 days; p â€‹= â€‹0.821) and rates of readmission (8.1 â€‹% vs. 2.0 â€‹%; p â€‹< â€‹0.001). Patients undergoing surgical palliation demonstrated marginal increases in survival relative to those undergoing medical palliation (8.54 vs. 7.36 months; p â€‹< â€‹0.0001). CONCLUSION: In patients undergoing care for locally advanced pancreatic cancer, palliative surgery is associated with marginal improvement in survival but significant lengths of hospitalization and risk of readmission.

Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer-killing cells is a complicated ex vivo process involving leukapheresis, artificial T cell activation, and CAR construct introduction. The activation step requires the engagement of CD3/TCR and CD28 and is vital for T cell transfection and differentiation. Though antigen-presenting cells (APCs) facilitate activation in vivo, ex vivo activation relies on antibodies against CD3 and CD28 conjugated to magnetic beads. While effective, this artificial activation adds to the complexity of CAR T cell production as the beads must be removed prior to clinical implementation. To overcome this challenge, this work develops activating lipid nanoparticles (aLNPs) that mimic APCs to combine the activation of magnetic beads and the transfection capabilities of LNPs. It is shown that aLNPs enable one-step activation and transfection of primary human T cells with the resulting mRNA CAR T cells reducing tumor burden in a murine xenograft model, validating aLNPs as a promising platform for the rapid production of mRNA CAR T cells.

Predictive High-Throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood-Brain Barrier Transfection and Crossing.

Lipid nanoparticle (LNP)-mediated nucleic acid therapies, including mRNA protein replacement and gene editing therapies, hold great potential in treating neurological disorders including neurodegeneration, brain cancer, and stroke. However, delivering LNPs across the blood-brain barrier (BBB) after systemic administration remains underexplored. In this work, we engineered a high-throughput screening transwell platform for the BBB (HTS-BBB), specifically optimized for screening mRNA LNPs. Unlike most transwell assays, which only assess transport across an endothelial monolayer, HTS-BBB simultaneously measures LNP transport and mRNA transfection of the endothelial cells themselves. We then use HTS-BBB to screen a library of 14 LNPs made with structurally diverse ionizable lipids and demonstrate it is predictive of in vivo performance by validating lead candidates for mRNA delivery to the mouse brain after intravenous injection. Going forward, this platform could be used to screen large libraries of brain-targeted LNPs for a range of protein replacement and gene editing applications.

A short-TR single-echo spin-echo breath-hold method for assessing liver T2.

OBJECTIVE: Conventional single-echo spin-echo T2 mapping used for liver iron quantification is too long for breath-holding. This study investigated a short TR (~100 ms) single-echo spin-echo T2 mapping technique wherein each image (corresponding to a single TE) could be acquired in ~17 s-short enough for a breath-hold. TE images were combined for T2 fitting. To avoid T1 bias, each TE acquisition incremented TR to maintain a constant TR-TE. MATERIALS AND METHODS: Experiments at 1.5T validated the technique's accuracy in phantoms, 9 healthy volunteers, and 5 iron overload patients. In phantoms and healthy volunteers, the technique was compared to the conventional approach of constant TR for all TEs. Iron overload results were compared to FerriScan. RESULTS: In phantoms, the constant TR-TE technique provided unbiased estimates of T2, while the conventional constant TR approach underestimated it. In healthy volunteers, there was no significant discrepancy at the 95% confidence level between constant TR-TE and reference T2 values, whereas there was for constant TR scans. In iron overload patients, there was a high correlation between constant TR-TE and FerriScan T2 values (r2 = 0.95), with a discrepancy of 0.6+/- 1.4 ms. DISCUSSION: The short-TR single-echo breath-hold spin-echo technique provided unbiased estimates of T2 in phantoms and livers.

Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review.

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.

MCT Nanoemulsions for the Efficient Delivery of siRNA.

In this study, an oil-in-water (o/w) nanoemulsion is used to deliver siRNA targeting Twist1, a protein that contributes to tumor metastasis in a variety of cancers. The FDA-approved oil, medium chain triglycerides (MCT), is used as the hydrophobic phase for the nanoemulsion. The siRNA is paired with dioleoyl-3-trimethylammonium-propane (DOTAP) to form a hydrophobic salt that is soluble at high concentrations in MCT. The resulting MCT/siRNA-DOTAP solution is formulated into a nanoemulsion with an average particle size of 140 nm. The nanoemulsion displays long term stability over the course of 195 days. In an in vivo murine tumor model, the nanoemulsion facilitates a 46% decrease in Twist1 mRNA after 48 h.

Fragmented care in localized pancreatic cancer: Is commission on cancer accreditation associated with improved overall survival?

BACKGROUND: Prior studies of fragmentation of care in pancreatic cancer have not adjusted for indicators of hospital quality such as Commission on Cancer accreditation. The effect of fragmentation of care has not been well defined. METHODS: We queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy and distal pancreatectomy with perioperative systemic therapy for clinical stages I-III pancreatic cancer between 2006 and 2019. Patients who received systemic therapy at a center different than the center performing surgery were categorized as having fragmentation of care. Patients having fragmentation of care were further categorized on the basis of whether (fragmentation of care Commission on Cancer) or not (fragmentation of care non-Commission on Cancer) systemic therapy was administered at a facility accredited by the Commission on Cancer. RESULTS: A total of 11,732 patients met inclusion criteria; 5,668 (48.3%) underwent fragmentation of care, and 3,426 (29.2%) fragmentation of care non-Commission on Cancer. Patients undergoing fragmentation of care non-Commission on Cancer were less likely to receive neoadjuvant systemic therapy than those undergoing fragmentation of care Commission on Cancer or non-fragmented care (27.7% vs 40.1% vs 36.8%, P < .001). On Cox analysis, advanced age, comorbid disease, node-positive disease, and facility type were associated with risk of overall survival. Fragmentation of care was not (adjusted hazard ratio = 0.99, 95% confidence interval [0.94-1.06], P = .8). On Kaplan-Meier analysis, there were no significant differences in 5-year overall survival between treatment cohorts. CONCLUSION: In patients undergoing fragmentation of care for localized pancreatic cancer, those treated with systemic therapy in Commission on Cancer accredited facilities are more likely to be given neoadjuvant therapy but demonstrate no significant improvement in survival relative to those undergoing non-fragmented care or those undergoing fragmentation of care but receiving systemic therapy in nonaccredited facilities.

Esophageal cancer: Does inaccuracy in clinical staging affect our ability to reach optimal outcomes?

BACKGROUND: Pretreatment clinical staging is used to decide the course of treatment in early-stage esophageal cancer. Few studies assess the effect of inaccurate clinical staging on oncologic outcomes. METHODS: We queried the National Cancer Database to identify patients undergoing esophagectomy for clinical stage cT1bN0 esophageal carcinoma between 2010 and 2019. Patients were categorized as being upstaged if, on final pathology, they had histopathologic disease that would have warranted treatment with neoadjuvant therapy. The textbook oncologic outcome was defined as margin-negative resection, 15 lymph nodes examined, a hospital stay of <21 days, no unplanned 30-day readmission or mortality, and stage-appropriate use of neoadjuvant therapy. RESULTS: In total, 916 patients met inclusion criteria; 378 (41.2%) had a pathologic stage that differed from their pretreatment clinical stage. By multivariable regression, factors associated upstaging included: presentation between 2015 and 2019 (odds ratio 1.92 95% confidence interval [1.19, 3.13]), delay to esophagectomy of >30 days (odds ratio 2.38 95% confidence interval [1.13, 5.57]), larger tumor size (>2 cm relative to <2 cm, odds ratio 2.73 95% confidence interval [1.72, 4.39]), and poorly differentiated histology (odds ratio 2.79 95% confidence interval [1.75, 4.49]). The rate of textbook oncologic outcome assuming reliable clinical staging was 43.8%; accounting for upstaging, the rate of textbook oncologic outcome was 22.5% (P < .001). CONCLUSION: In patients with cT1bN0 esophageal cancer, tumor size and histology are associated with the risk of inaccurate pretreatment clinical staging. Inaccuracies in clinical staging impact the rate at which providers achieve optimal oncologic outcomes.

Clinical stage T2N0M0 rectal adenocarcinoma: Is radical resection associated with improved overall survival in patients with low-risk histology?

BACKGROUND: Prior studies evaluating the efficacy of local excision compared to radical resection in the treatment of rectal adenocarcinoma lacked sufficient power to identify differences in outcomes for patients with cT2 disease but low-risk histopathology. We compared the outcomes of local excision and radical resection for low-risk histopathology and high-risk histology of patients with cT2N0M0 rectal adenocarcinoma to assess their outcomes. METHODS: We queried the National Cancer Database for patients presenting with cT2N0M0 rectal adenocarcinoma between 2004 and 2019 and categorized them as low-risk histopathology or high-risk histology. We used the Cox proportional hazards model to identify factors associated with the risk of all-cause mortality. We 1:1 propensity-matched patients who underwent local excision to patients who underwent radical resection and used the Kaplan-Meier method to compare overall survival for matched cohorts. RESULTS: Of the 4,446 patients selected, we classified 1,206 (27%) as high-risk histology and 3,240 (73%) as low-risk histopathology. Among the patients with high-risk histology, 121 (10%) underwent local excision and 1,085 (90%) underwent radical resection. Among the patients with low-risk histopathology, 340 (10%) underwent local excision and 2,900 (90%) radical resections. Whereas radical resection was associated with decreased risk of all-cause mortality and increased overall survival for patients with high-risk histology, it was not for patients with low-risk histopathology. CONCLUSION: The overall survival of patients with low-risk histopathology with cT2N0M0 rectal adenocarcinoma who undergo local excision is similar to those of patients with low-risk histopathology who undergo radical resection, suggesting local excision is a reasonable approach for these patients. In contrast, radical resection provides a significant survival advantage for patients with high-risk histology and should remain their treatment of choice.

Association between COVID-19 diagnosis and postoperative outcomes in sleeve gastrectomy and Roux-en-Y gastric bypass: A national cohort study.

BACKGROUND: We seek to determine the association between COVID-19 diagnosis and postoperative outcomes following bariatric surgery. METHODS: Using the Metabolic and Bariatric Surgery Accreditation Quality Improvement Project (MBSAQIP) database, patients undergoing sleeve gastrectomy and gastric bypass without a COVID-19 diagnosis were 2:1 propensity-score matched to those with COVID-19 infection pre or postoperatively. RESULTS: 1369 (0.74 â€‹%) and 1331 (0.72 â€‹%) patients had a COVID-19 diagnosis within 14 days prior to or 30 days after their operation, respectively. Patients with preoperative COVID-19 infection had equivalent outcomes to COVID-19 negative patients (all p â€‹> â€‹0.05). Postoperative COVID-19 diagnosis was associated with worse outcomes including increased risk of anastomotic/staple line leak (1.1 â€‹% vs 0.1 â€‹%, p â€‹< â€‹0.001), postoperative pneumonia (2.9 â€‹% vs 0.1 â€‹%, p â€‹< â€‹0.001), and 30-day reoperation (2.1 â€‹% vs 0.9 â€‹%, p â€‹= â€‹0.002). CONCLUSIONS: Postoperative diagnosis of COVID-19 after bariatric surgery is associated with worse outcomes; however, it is safe to perform these procedures on patients recently convalesced from COVID-19 infection.

Does commission on cancer (CoC) accreditation mitigate the effect of care fragmentation on clinical outcome in localized rectal cancer?

BACKGROUND: Studies of fragmented care (FC) in rectal cancer have not adjusted for indicators of hospital quality and may misrepresent the effects of FC. METHODS: We queried the National Cancer Database to identify patients undergoing care for clinical stage II and III rectal adenocarcinoma between 2006 and 2019. Those undergoing FC were sub-categorized based on whether (FC CoC) or not (FC non-CoC) they received systemic therapy at CoC accredited facilities. RESULTS: 44,339 patients met inclusion criteria; 23,921 (54 â€‹%) underwent FC, 16,929 (71 â€‹%) FC non-CoC. Differences in utilization of neoadjuvant therapy (92.3 â€‹% vs 89.7 â€‹% vs 89.5 â€‹%, p â€‹< â€‹0.01) and 5-year overall survival (76.1 vs 75.5 vs 74.1 %, p â€‹< â€‹0.01) between treatment cohorts were marginal. CONCLUSION: In patients undergoing multimodality therapy for rectal cancer, care fragmentation is not associated with long-term clinical outcome. Decisions regarding where these patients go for systemic therapy may be safely made on the basis of ease of access.

The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice.

Both excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or because of arsenic found directly in alcoholic beverages. This study aims to determine if co-exposure to alcohol and arsenic leads to worse outcomes in neurodegeneration and associated mechanisms that could lead to cell death. To study this, mice were exposed to a 10-day gavage model of alcohol-induced neurodegeneration with varying doses of arsenic (0, 0.005, 2.5, or 10 mg/kg). The following were examined after the last dose of ethanol: (1) microglia activation assessed via immunohistochemical detection of Iba-1, (2) reactive oxygen and nitrogen species (ROS/RNS) using a colorimetric assay, (3) neurodegeneration using Fluoro-Jade® C staining (FJC), and 4) arsenic absorption using ICP-MS. After exposure, there was an additive effect of the highest dose of arsenic (10 mg/kg) in the dentate gyrus of alcohol-induced FJC+ cells. This additional cell loss may have been due to the observed increase in microglial reactivity or increased arsenic absorption following co-exposure to ethanol and arsenic. The data also showed that arsenic caused an increase in CYP2E1 expression and ROS/RNS production in the hippocampus which could have independently contributed to increased neurodegeneration. Altogether, these findings suggest a potential cyclical impact of co-exposure to arsenic and ethanol as ethanol increases arsenic absorption but arsenic also enhances alcohol's deleterious effects in the CNS.

A C1qTNF3 collagen domain fusion chaperones diverse secreted proteins and anti-Aß scFvs: Applications for gene therapies.

Enhancing production of protein cargoes delivered by gene therapies can improve efficacy by reducing the amount of vector or simply increasing transgene expression levels. We explored the utility of a 126-amino acid collagen domain (CD) derived from the C1qTNF3 protein as a fusion partner to chaperone secreted proteins, extracellular "decoy receptor" domains, and single-chain variable fragments (scFvs). Fusions to the CD domain result in multimerization and enhanced levels of secretion of numerous fusion proteins while maintaining functionality. Efficient creation of bifunctional proteins using the CD domain is also demonstrated. Recombinant adeno-associated viral vector delivery of the CD with a signal peptide resulted in high-level expression with minimal biological impact as assessed by whole-brain transcriptomics. As a proof-of-concept in vivo study, we evaluated three different anti-amyloid Aß scFvs (anti-Aß scFvs), alone or expressed as CD fusions, following viral delivery to neonatal CRND8 mice. The CD fusion increased half-life, expression levels, and improved efficacy for amyloid lowering of a weaker binding anti-Aß scFv. These studies validate the potential utility of this small CD as a fusion partner for secretory cargoes delivered by gene therapy and demonstrate that it is feasible to use this CD fusion to create biotherapeutic molecules with enhanced avidity or bifunctionality.

Rectal neuroendocrine tumors: Can they be observed?

BACKGROUND: Studies comparing approaches to managing rectal neuroendocrine tumors are underpowered by institutional series. The efficacy of expectant management relative to local excision and radical resection is poorly defined. METHODS: We queried the National Cancer Database to identify patients presenting with non-metastatic rectal neuroendocrine tumors between 2004 and 2019. Multivariable regression was used to identify factors associated with expectant management. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing expectant management were 1:1:1 propensity score matched for demographics and comorbid disease to those undergoing radical resection and local excision. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts. RESULTS: A total of 6,316 patients met the inclusion criteria. Of these, 5,211 (83%) underwent local excision, 600 (9.5%) radical resection, and 505 (8%) expectant management. On multivariable regression, factors associated with expectant management included Black race, government insurance, and tumor size <2.0 centimeters. On Cox modeling, factors associated with mortality included age >65 years, male sex, government insurance, comorbidity score >0, tumor size >2 centimeters, and poorly differentiated histology. On comparison of matched cohorts: patients undergoing radical resection had longer hospitalizations and higher readmission rates than those undergoing local excision; there was no difference in overall survival between cohorts in patients with stage 1 disease; in stage 2 and 3 diseases, patients undergoing local excision and radical resection demonstrated improved rates of overall survival relative to those undergoing expectant management. CONCLUSION: Expectant management is a reasonable approach for patients with stage 1 rectal neuroendocrine tumors. Local excision should be the preferred treatment option for those presenting with stage 2/3 disease.

T2 mapping magnetic resonance imaging of cartilage in hemophilia.

Background: In hemophilia, recurrent hemarthrosis may lead to irreversible arthropathy. T2 mapping MRI may reflect cartilage changes at an earlier reversible stage of arthropathy as opposed to structural MRI. Objectives: To evaluate interval changes of T2 mapping compared with the International Prophylaxis Study Group (IPSG) structural MRI scores of ankle cartilage in boys with hemophilia receiving prophylaxis. Methods: Eight boys with hemophilia A (median age, 13; range, 9-17 years), 7 age- and sex-matched healthy boys (controls, median age, 15; range, 7-16 years). A multiecho spin-echo T2-weighted MRI sequence at 3.0T was used to obtain T2 maps of cartilage of boys with hemophilia and controls. Structural joint status was evaluated using the IPSG MRI score. Results: T2 relaxation times of ankle cartilage increased significantly over time in both persons with hemophilia and controls (P = .002 and P = .00009, respectively). Changes in T2 relaxation time strongly correlated with changes in IPSG cartilage scores (rs = 0.93 to rs = 0.78 [P = .0007 to P = .023]), but not with changes in age (P = .304 to P = .840). Responsiveness of T2 relaxation times were higher than that of IPSG cartilage scores, with standardized response means >1.4 for T2 mapping in all regions-of-interest compared with 0.84 for IPSG cartilage scores. Baseline T2 relaxation time strongly correlated with timepoint 2 IPSG cartilage score (rs = 0.93 to rs = 0.82 [P = .001 to P = .012]) and T2 relaxation time (rs = 0.98 to rs = 0.88 [P = .00003 to P = .004]) changes in most regions-of-interest. Conclusion: T2 mapping shows sensitivity to biochemical changes in cartilage prior to detectable damage using conventional MRI, offering potential for early detection of bleed-related cartilage damage in boys with hemophilia.