Emerging From the Haze™: Pilot Feasibility Study Comparing Two Virtual Formats of a Cognitive Rehabilitation Intervention.

OBJECTIVES: To gather feasibility and preliminary data comparing two virtual delivery methods for providing Emerging From the Haze™ (Haze) to cancer survivors compared to waitlist control (WLC). SAMPLE & SETTING: Eligible participants (N = 93) reported cancer-related cognitive impairment following chemotherapy for stage I-III solid tumors, Hodgkin lymphoma, or non-Hodgkin lymphoma. METHODS & VARIABLES: A three-arm randomized design was used to compare virtual live group presentation of Haze sessions, virtual prerecorded Haze group sessions, and WLC. Data were collected at baseline, week 10, and week 14. RESULTS: Feasibility was demonstrated. Significant cognitive function improvement at week 10 versus WLC was reported for the live group, and clinical improvement was reported for the prerecorded group. The prerecorded group reported significant improvement at week 14 versus WLC in physical activity, sleep, and health-related quality of life. IMPLICATIONS FOR NURSING: Additional pilot and feasibility evidence for cognitive rehabilitation interventions was demonstrated. Prerecorded Haze delivery shows potential for clinical effectiveness and scalability. Future multisite research is warranted.

Hospital-Initiated Smoking Cessation Among Patients Admitted with Behavioral Health Conditions.

BACKGROUND: Smoking rates among people living with behavioral health conditions (BHC) range from 30 to 65% and are 2-4 times higher than rates found in the general population. Starting tobacco treatment during a hospital stay is effective for smoking cessation, but little is known regarding treatment response among inpatients with BHC. OBJECTIVE: This study pooled data across multiple clinical trials to determine the relative success in quitting among participants with BHC compared to other study participants. PARTICIPANTS: Adults who smoke (≥ 18 years old) from five hospital-based smoking cessation randomized clinical trials. DESIGN: A retrospective analysis using data from the electronic health record to identify participants with primary diagnoses related to BHC. Recruitment and data analysis were conducted from 2011 to 2016. We used propensity score matching to pair patients with BHC to those with similar characteristics and logistic regression to determine differences between groups. MEASURES: The main outcome was self-reported 30-day abstinence 6 months post-discharge. RESULTS: Of 6612 participants, 798 patients had a BHC-related primary diagnosis. The matched sample included 642 pairs. Nearly 1 in 3 reported using tobacco medications after hospitalization, with no significant difference between patients with and without BHC (29.3% vs. 31.5%; OR (95% CI) = 0.90 (0.71, 1.14), p = 0.40). Nearly 1 in 5 patients with BHC reported abstinence at 6 months; however, their odds of abstinence were 30% lower than among people without BHC (OR (95% CI) = 0.70 (0.53,0.92), p = 0.01). CONCLUSION: When offered tobacco treatment, hospitalized patients with BHC were as likely as people without BHC to accept and engage in treatment. However, patients with BHC were less likely to report abstinence compared to those without BHC. Hospitals are a feasible and promising venue for tobacco treatment among inpatients with BHC. More studies are needed to identify treatment approaches that help people with BHC achieve long-term abstinence.

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. METHODS: The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2. RESULTS: ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/ß-catenin pathway. CONCLUSION: ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/ß-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.

Randomized singular value decomposition for integrative subtype analysis of 'omics data' using non-negative matrix factorization.

Integration of multiple 'omics datasets for differentiating cancer subtypes is a powerful technic that leverages the consistent and complementary information across multi-omics data. Matrix factorization is a common technique used in integrative clustering for identifying latent subtype structure across multi-omics data. High dimensionality of the omics data and long computation time have been common challenges of clustering methods. In order to address the challenges, we propose randomized singular value decomposition (RSVD) for integrative clustering using Non-negative Matrix Factorization: intNMF-rsvd. The method utilizes RSVD to reduce the dimensionality by projecting the data into eigen vector space with user specified lower rank. Then, clustering analysis is carried out by estimating common basis matrix across the projected multi-omics datasets. The performance of the proposed method was assessed using the simulated datasets and compared with six state-of-the-art integrative clustering methods using real-life datasets from The Cancer Genome Atlas Study. intNMF-rsvd was found working efficiently and competitively as compared to standard intNMF and other multi-omics clustering methods. Most importantly, intNMF-rsvd can handle large number of features and significantly reduce the computation time. The identified subtypes can be utilized for further clinical association studies to understand the etiology of the disease.

An Updated Systematic Review and Meta-Analysis of Tissue Oximetry Versus Conventional Methods for Postoperative Monitoring of Autologous Breast Reconstruction.

BACKGROUND: Tissue oximetry monitoring has shown superior outcomes to conventional monitoring methods for autologous breast reconstruction in retrospective studies with consecutive cohorts. A recent study used consecutive cohorts with tissue oximetry as the earlier cohort and found that tissue oximetry was nonsuperior. We hypothesize that improvement in microsurgical outcomes with institutional experience confounds the superiority of tissue oximetry demonstrated in prior studies. This study aimed to perform a systematic review and meta-analysis of the outcomes of tissue oximetry monitoring compared with conventional monitoring. METHODS: Relevant studies were found using PubMed, Embase, and Web of Science searches for keywords such as near-infrared spectroscopy or tissue oximetry and microsurgery. Studies included compared tissue oximetry and conventional monitoring in autologous breast reconstruction patients. Studies were excluded if they did not contain a comparison group. Random-effective models were used to analyze early returns to the operating room, the total number of partial or complete flap loss, and late fat necrosis. RESULTS: Six hundred sixty-nine studies were identified; 3 retrospective cohort studies met the inclusion criteria. A total of 1644 flaps were in the tissue oximetry cohort, and 1387 flaps were in the control cohort. One study contained tissue oximetry as the former cohort; 2 had tissue oximetry as the latter. Neither technique was superior for any measured outcomes. The estimated mean differences between tissue oximetry and conventional monitoring method were early returns, -0.06 (95% confidence interval [CI], -0.52 to 0.410; P = 0.82); partial flap loss, -0.04 (95% CI, -0.86 to 0.79; P = 0.93); complete flap loss, -1.29 (95% CI, -3.45 to 0.87; P = 0.24); and late fat necrosis -0.02 (95% CI, -0.42 to, 0.39; P = 0.94). CONCLUSIONS: In a systematic review and meta-analysis of mixed timeline retrospective cohort studies, tissue oximetry does not provide superior patient outcomes and shifts our current understanding of postoperative breast reconstruction monitoring. Prospective studies and randomized trials comparing monitoring methods need to be included in the existing literature.

A nomogram model for predicting distant metastasis of newly diagnosed colorectal cancer based on clinical features.

Objective: Colorectal cancer is one of the most common primary malignancies and the third most common cause of cancer death in both men and women in the United States. Among people diagnosed with initial colorectal cancer, 22% had metastatic colorectal cancer, while the 5-year survival rate was less than 20%. The purpose of this study is to develop a nomogram for predicting distant metastasis in newly diagnosed colorectal cancer patients and to identify high-risk groups. Methods: We retrospectively reviewed the data of patients who were diagnosed with colorectal cancer at Zhong nan Hospital of Wuhan University and People's Hospital of Gansu Province between January 2016 and December 2021. Risk predictors for distant metastasis from colorectal patients were determined by the univariate and multivariate logistic regression analyses. Nomograms were developed to predict the probabilities of distant metastatic sites of colorectal cancer patients and evaluated by calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA). Results: A total of 327 cases were included in this study: 224 colorectal cancer patients from Zhong nan Hospital of Wuhan University were incorporated into the training set, and 103 colorectal cancer patients from Gansu Provincial People's Hospital were incorporated into the testing set. By univariate logistic regression analysis, platelet (PLT) level (p = 0.009), carcinoembryonic antigen (CEA) level (p = 0.032), histological grade (p < 0.001), colorectal cancer tumor markers (p < 0.001), N stage (p < 0.001), and tumor site (p = 0.005) were associated with distant metastasis in colorectal cancer patients. Multivariate logistic regression analysis showed that N stage (p < 0.001), histological grade (p = 0.026), and colorectal cancer markers (p < 0.001) were independent predictors of distant metastasis in patients initially diagnosed with colorectal cancer. The above six risk factors were used to predict distant metastasis of newly diagnosed colorectal cancer. The C-indexes for the prediction of the nomogram were 0.902 (95% confidence interval (CI), 0.857-0.948). Conclusion: The nomogram showed excellent accuracy in predicting distant metastatic sites, and clinical utility may facilitate clinical decision-making.

Diet was less significant than physical activity in the prognosis of people with sarcopenia and metabolic dysfunction-associated fatty liver diseases: Analysis of the National Health and Nutrition Examination Survey III.

Background: Sarcopenia is prevalent in metabolic dysfunction-associated fatty liver diseases (MAFLD), and the primary treatment for both diseases is lifestyle modification. We studied how dietary components and physical activity affect individuals with sarcopenia and MAFLD. Materials and methods: We conducted a study utilizing National Health and Nutrition Examination Survey (NHANES) III (1988-1994) data with Linked Mortality file (through 2019). The diagnosis of fatty liver disease (FLD) was based on ultrasound images revealing moderate and severe steatosis. Using bioelectrical measures, sarcopenia was assessed. Using self-report data, dietary intake and physical activity levels were evaluated. Results: Among 12,259 participants, 2,473 presented with MAFLD, and 290 of whom had sarcopenia. Higher levels of physical activity (odds ratio [OR] = 0.51 [0.36-0.95]) and calorie (OR = 0.58 [0.41-0.83]) intake reduced the likelihood of sarcopenia in MAFLD patients. During a median follow-up period of 15.3 years, 1,164 MAFLD and 181 MAFLD patients with sarcopenia perished. Increased activity levels improved the prognosis of patients with sarcopenia (Insufficiently active, HR = 0.75 [0.58-0.97]; Active, HR = 0.64 [0.48-0.86]), which was particularly pronounced in older patients. Conclusion: In the general population, hyperglycemia was highly related to MAFLD prognosis. Physical inactivity and a protein-restricted diet corresponded to sarcopenia, with physical inactivity being connected to poor outcomes. Adding protein supplements would be beneficial for older people with sarcopenia who are unable to exercise due to frailty, while the survival benefits were negligible.

Sample size calculation for the combination test under nonproportional hazards.

For sample size calculation in clinical trials with survival endpoints, the logrank test, which is the optimal method under the proportional hazard (PH) assumption, is predominantly used. In reality, the PH assumption may not hold. For example, in immuno-oncology trials, delayed treatment effects are often expected. The sample size without considering the potential violation of the PH assumption may lead to an underpowered study. In recent years, combination tests such as the maximum weighted logrank test have received great attention because of their robust performance in various hazards scenarios. In this paper, we propose a flexible simulation-free procedure to calculate the sample size using combination tests. The procedure extends the Lakatos' Markov model and allows for complex situations encountered in a clinical trial, like staggered entry, dropouts, etc. We evaluate the procedure using two maximum weighted logrank tests, one projection-type test, and three other commonly used tests under various hazards scenarios. The simulation studies show that the proposed method can achieve the target power for all compared tests in most scenarios. The combination tests exhibit robust performance under correct specification and misspecification scenarios and are highly recommended when the hazard-changing patterns are unknown beforehand. Finally, we demonstrate our method using two clinical trial examples and provide suggestions about the sample size calculations under nonproportional hazards.

Combined Exercise and Game-Based Cognitive Training Intervention: Correlative Pilot Study of Neurotrophic and Inflammatory Biomarkers for Women With Breast Cancer.

BACKGROUND: Interventions that increase neuroprotective factors and/or decrease inflammatory biomarkers may be effective in improving cognitive function for cancer survivors. Concurrent investigation of potential mechanism(s) to fully understand and refine effective interventions is needed. OBJECTIVE: This correlative prospective substudy was conducted to investigate biomarkers related to potential mechanism(s) for a combined exercise and game-based brain training intervention designed to improve cognitive function in breast cancer survivors. INTERVENTIONS/METHODS: Fingerstick bloodspot samples were collected at 3 time points during the randomized, wait-list controlled interventional parent study. Samples were analyzed for neuroprotective factors and inflammatory biomarker levels. RESULTS: Insulinlike growth factor 1 (IGF-1) levels significantly increased (P < .01) for the intervention group from baseline to 4 and 16 weeks postintervention. Insulinlike growth factor 1 levels correlated with neurocognitive test performace improvement for Trail Making Test B (r = 0.31, P = .02). This association was not significant in the mixed model. No significant correlation was seen between IGF-1 levels and changes in self-report of cognitive function, activity level, or intervention dose. CONCLUSIONS: Further investigation of IGF-1 levels is warranted as related to potential mechanisms for the Combined Exercise and Game-based Cognitive Training intervention. Future investigations should involve a larger sample cohort and incorporate objective measures of physical activity and prescribed sampling time in relationship to the most recent performance of the intervention. IMPLICATIONS FOR PRACTICE: Fingerstick bloodspot sample collection is feasible, acceptable, and effective for conducting biomarker research. This methodology minimizes participant burden and discomfort; increases clinical trial access for home, off-site, or rural settings; and facilitates research efforts during times of pandemic restrictions.

Psycholinguistic Assessment of Cognitive Function in Breast Cancer Survivors.

OBJECTIVES: To gather preliminary data on correlations among psycholinguistic measures, self-report of cognitive function, and performance on neurocognitive tests in breast cancer survivors. SAMPLE & SETTING: Participants were breast cancer survivors who reported issues with cognitive function after completion of chemotherapy. This secondary analysis used data from participants in parent studies at two National Cancer Institute-designated cancer centers. METHODS & VARIABLES: Qualitative interview transcripts (N = 52) underwent psycholinguistic analyses for grammatical and semantic complexity. Relationships among six psycholinguistic variables, self-report of cognitive function, and performance on neurocognitive tests were examined. RESULTS: Three grammatical complexity variables had a significant positive correlation to self-report of cognitive function. One semantic complexity variable had a significant positive correlation to delayed recall neurocognitive tests. IMPLICATIONS FOR NURSING: Results suggest that psycholinguistic analysis may be used to assess cognitive function among breast cancer survivors. Confirmatory studies are needed to establish the correlation between psycholinguistic measures, self-report of cognitive function, and domain-specific tests of neurocognitive performance, as well as to evaluate longitudinal sensitivity to change.

Sleep quality in individuals with chronic low back pain and central sensitization.

BACKGROUND AND PURPOSE: Sleep problems are common in individuals with chronic low back pain (CLBP). Central sensitization (CS) is present in a subgroup of individuals with CLBP. However, our knowledge about whether sleep quality varies between the subgroups of CLBP is limited. Therefore, we sought to examine whether the subgroup of CLBP with CS has poorer sleep quality than the subgroup without CS. METHODS: 2011 Fibromyalgia Survey (2011 FM survey) was used as a surrogate measure of CS to divide the CLBP participants into two subgroups: CLBP with CS and CLBP without CS. We also created a CS index comprising a set of quantitative sensory testing measures (i.e., pressure pain thresholds, conditioned pain modulation) to evaluate pain sensitivity. Sleep quality was assessed with Pittsburgh Sleep Quality Index (PSQI). Group differences about PSQI and CS index and associations between sleep quality and CS across the groups were analyzed. RESULTS: We included 60 participants with CLBP and 23 healthy controls (HCs). Overall, 80% of the participants with CLBP presented with poor sleep quality. Participants with CLBP with CS showed significantly higher PSQI scores (poorer sleep) than participants with CLBP without CS and HCs (p < 0.05). Both the 2011 FM survey and CS index were significantly correlated with sleep quality (r = 0.5870, p < 0.001 and r = -0.264, p = 0.04). Logistic regression models revealed that the FM status (odds ratio (OR) = 6.00, p = 0.02 [95% confidence interval: 1.31-42.1]), but not the CS index (OR = 1.11, p = 0.79 [95% CI: 0.48-2.71]) was associated with PSQI. After adjusting covariates, the results remained similar but became non-significant for the FM status. DISCUSSION: We found that sleep problems were more common and severe in those who exhibited signs of CS. Thus, clinicians may consider using 2011 FM survey to identify those with CS and co-existing sleep problems.

Impact of pharmacy services on time to elexacaftor-tezacaftor-ivacaftor initiation.

BACKGROUND: The approval of elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) expanded highly effective cystic fibrosis transmembrane receptor modulator therapy to approximately 90% of persons aged 12 years and older with cystic fibrosis. Clinical pharmacists and pharmacy technicians played a key role in planning for ELX/TEZ/IVA initiation prior to US Food and Drug Administration approval as well as initiating therapy after approval. OBJECTIVE: To evaluate the impact of pharmacy services on time to ELX/TEZ/IVA initiation. METHODS: A retrospective chart review evaluated 146 patients aged at least 12 years with cystic fibrosis qualifying for ELX/TEZ/IVA at a single health system between October 21, 2019, and April 1, 2020. RESULTS: Patients filling ELX/TEZ/IVA at an integrated health system specialty pharmacy (HSSP) vs an outside specialty pharmacy (SP) started on therapy an average of 10.8 days sooner (10.8 days ± 14.0 vs 21.6 days ± 18.8, respectively; P = 0.006). More patients filling at an HSSP received ELX/TEZ/IVA within 14 days of the prescription being written compared with outside SPs (82.0% vs 41.4%, respectively; P = 0.001). Before ELX/TEZ/IVA initiation, patients were hospitalized for a cystic fibrosis-related complication for an average of 6.26 days (range = 0-183) compared with 1.16 days (range = 0-91) after ELX/TEZ/IVA initiation. Lastly, an estimated $134,810 was saved in hospitalization dollars in the 105 patients that were able to fill ELX/TEZ/IVA at an HSSP by initiating the drug an average of 10.8 days sooner than outside SPs. CONCLUSIONS: The results of this study demonstrate the value of an integrated HSSP model. The ability to fill specialty medications at an integrated HSSP may optimize medication access, control costs, and improve patient outcomes for patients receiving care within a health system. DISCLOSURES: Dr Loucks has accepted payment for reviewing content of Lexicomp through Wolters Kluwer Consulting and for presenting and attending the American Society of Health System Pharmacists (ASHP) Summer Meeting in June 2022. Dr Loucks is also a Workgroup Chair for the ASHP Pharmacist Section of Specialty Pharmacy Practitioners - Section Advisory Group on Outcomes and Value. Dr Simonsen was a participant in the Vertex Pharmaceuticals Advisory Board in April 2019 and accepted payment for travel and expenses. The remaining authors have no conflicts of interest or financial interests to disclose. This work is in part supported by the Statistical Expertise and Network (StatNet) Award of Cystic Fibrosis Foundation.

Early Vitamin A Supplementation for Prevention of Short-Term Morbidity and Mortality in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis.

Background: Vitamin A plays an important role in the development and maintenance of the normal function of organs and systems. Premature infants have low levels of vitamin A, which may be associated with an increased risk of developing disease. This study aimed to evaluate the effects of vitamin A supplementation on short-term morbidity and mortality in very-low-birth-weight (VLBW) infants. Methods: We used PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science to conduct a literature search of studies published before January 1, 2022, to be included in our meta-analysis. The analysis included randomized controlled trials that compared the effects of vitamin A supplementation on VLBW infants (birth weight <1,500 g) and controls given a placebo or no treatment. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Results: Twelve randomized controlled trials were included in the meta-analysis, and 2,111 infants were pooled and analyzed. The overall risk of bias was not serious in the included studies. Vitamin A supplementation for reducing the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age seems to be limited [risk ratio (RR):0.85; 95% confidence intervals (CI): 0.70-1.04; 8 studies, 1,595 infants, very-low-certainty evidence], which is different from the previous systematic review. Length of hospital stay (mean difference: -12.67, 95% CI: -23.55 to -1.79; 6 studies, 739 infants, low-certainty evidence), and the incidence of vitamin A deficiency at 28 days postnatal age (RR: 0.08; 95% CI: 0.02-0.38; 3 studies, 358 infants, low-certainty evidence) were reduced in the vitamin A group. Besides, vitamin A supplementation seems to reduce the incidence of periventricular leukomalacia (RR: 0.68; 95% CI: 0.47-0.97; 4 studies, 1,224 infants, low-certainty evidence) and retinopathy of prematurity of any grade (RR: 0.61; 95% CI: 0.48-0.76; 4 studies, 463 infants, moderate-certainty evidence). Conclusions: There is no sufficient evidence regarding vitamin A supplementation preventing BPD in VLBW infants. Vitamin A supplementation can reduce the incidence of vitamin A deficiency and retinopathy of prematurity of any grade, and may exert an effect of preventing periventricular leukomalacia. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020211070.

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes. Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT). Design, Setting, and Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose. Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines. Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]). Conclusions and Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.

Very low-dose recombinant Factor VIIa administration for cardiac surgical bleeding reduces red blood cell transfusions and renal risk: a matched cohort study.

Outcomes following administration of very-low-dose recombinant activated factor VIIa (vld-rFVIIa) for cardiac surgical bleeding remain debatable. We sought to determine the association of vld-rFVIIa and adverse surgical outcomes. Retrospective, cohort matching of patients undergoing cardiac surgery who received vld-rFVIIa (median 13.02 µg/kg) for perioperative bleeding were matched to cardiac surgical patients who had bleeding and received standard of care for bleeding without Factor VIIa administration. Of the 362 matched patients (182 in each group), patients who received rFVIIa required significantly less red blood cell transfusions [median 3 units (range 0--60, IQR = 4 units) versus 4 units (range 2-34, IQR = 4 units); P = 0.0004], decreased length of hospital stay (median 8 versus 9 days; P = 0.0158) and decreased renal risk (P < 0.0001). Incidence of renal failure, postoperative infection, postoperative thrombosis, prolonged ventilation, total ICU hours and 30-day mortality were not different between the two groups. Vld-rFVIIa for cardiac surgical bleeding was associated with decreased red blood cell transfusion, renal risk and length of hospital stay without increased thromboembolism or mortality when compared to patients who had cardiac surgical bleeding and received standard of care without Factor VIIa.

Lewis Pair Catalyzed Regioselective Polymerization of (E,E)-Alkyl Sorbates for the Synthesis of (AB)n Sequenced Polymers.

In this contribution, Lewis pairs (LPs) composed of N-heterocyclic olefins (NHOs) with different steric hindrance and nucleophilicity as Lewis bases (LBs) and Al-based compounds with comparable acidity but different steric hindrance as Lewis acids (LAs) were applied for 1,4-selective polymerization of (E,E)-methyl sorbate (MS) and (E,E)-ethyl sorbate (ES). The effects of steric hindrance, electron-donating ability, and acidity of LPs on MS and ES polymerization were systematically investigated. High catalytic activity and high initiation efficiency can be achieved, leading to the formation of PMS with 100 % 1,4-selectivity, tunable molecular weight (Mw up to 333 kg mol-1 ), and narrow molecular weight distribution (MWD). Block copolymerization of ES and methyl methacrylate (MMA) was also realized. Meanwhile, this system can be applied to other homologous conjugated diene substrates. Furthermore, simple chemical reactions can efficiently convert PMS to different polymers with strict (AB)n sequence structures, such as poly(sorbic acid), poly(propylene-alt-methyl acrylate), poly(propylene-alt-acrylic acid), poly(propylene-alt-allyl alcohol), and poly(ethylene-alt-2-butylene).

A framework for personalized mammogram screening.

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014). For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child. Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

Non-cancer clinical trials start-up metrics at an academic medical center: Implications for advancing research.

The primary goal for any clinical trial after it receives a funding notification is to receive regulatory approval and initiate the trial for recruitment. Every trial must go through documentation and regulatory process before it can start recruiting participants and collecting data; this initial process of review and approval is known as the study start-up process (SSU). We evaluated the average time taken for studies to receive approvals. Using data from clinical trials conducted at the University of Kansas Medical Center, various times to reach the start of the study were calculated based on the dates of individual study. The results of this analysis showed that chart review studies and investigator-initiated trials had a shorter time to activation than other types of studies. Additionally, single-center studies had a shorter activation time than multi-center studies. The analysis also demonstrated that the overall processing time consistently had been reduced over time.

Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. The relationship between CDI and acute graft-versus-host disease (aGVHD) has been a topic of interest, as these 2 conditions may influence each other. We studied the temporal relationship of CDI to aGVHD in the first 100 days post-transplantation in a large cohort of allo-HSCT recipients. We performed a retrospective cohort study of adult patients undergoing their first allo-HSCT at our tertiary care medical center between January 1, 2010, and December 31, 2016. Patients were followed for CDI diagnosis, development of aGVHD, and vital status up to day +100 post-transplantation. Descriptive statistics and multivariate Cox models with CDI as a time-varying covariate and aGVHD and high-grade aGVHD as outcomes were used for data analyses. A total of 656 allo-HSCT recipients were included in the analysis. Of these, 419 (64%) developed aGVHD, and 111 (17%) were diagnosed with CDI within the first 100 days post-transplantation. CDI developed before the onset of aGVHD in 72 of the 84 allo-HSCT recipients (85%) with both CDI and aGVHD. Fidaxomicin was used in the treatment of 57 of the 111 CDI cases (50%), whereas vancomycin was used in 52 (47%). Most of the CDI cases (88%) were diagnosed in the peritransplantation period (between day -10 and day +10). The median time to the development of CDI and aGVHD was 3.5 days (range, -7 to 95 days) and 33 days (range, 9 to 98 days) post-transplantation, respectively. Using multivariate Cox model, the following predictors were significantly associated with the development of aGVHD: CDI (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.17 to 1.97; P = .0018), transplantation from a matched related donor (MRD) compared with a matched unrelated donor (aHR, 0.68; 95% CI, 0.54 to 0.85; P = .0003), and myeloablative versus nonmyeloablative conditioning (aHR, 2.45; 95% CI, 1.80 to 3.34; P < .0001), adjusting for age, sex, race, underlying disease, cytomegalovirus CMV serostatus, transplant source, and receipt of antithymocyte globulin (ATG). There was no association between CDI and high-grade aGVHD after adjustment for age, underlying disease, transplant type, intensity of conditioning, and receipt of ATG (aHR, 1.59; 95% CI, 0.95 to 2.66; P = .0755). CDI after allo-HSCT is associated with increased risk of GVHD when no CDI prophylaxis was used. Further studies examining CDI preventive measures, including prophylaxis, as well as the preservation or reconstitution of the gastrointestinal microbiome in the setting of HSCT are warranted.