SARS-CoV-2 Omicron Neutralization After Heterologous Vaccine Boosting

As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming followed by boosting with 100-μg or 50-μg mRNA-1273, Ad26.COV2.S single-dose priming followed by Ad26.COV2.S booster and BNT162b2 two-dose priming followed by BNT162b2 boosting; and two heterologous primary-booster combinations: BNT162b2 followed by Ad26.COV2.S and Ad26.COV2.S followed by BNT162b2. Neutralizing antibody (Nab) titers to D614G on the day of boost (baseline) were detected in 85-100% of participants, with geometric mean titers (GMT) of 71-343 in participants who received an mRNA vaccine series versus GMTs of 35-41 in participants primed with Ad26.OV2.S. Baseline NAb titers to Omicron were detected in 50-90% of participants who received an mRNA vaccine series (GMT range 12.8-24.5) versus 20-25% among participants primed with Ad26.COV2.S. The booster dose increased the neutralizing GMT in most combinations to above 1000 for D614G and above 250 for Omicron by Day 29. Homologous prime-boost Ad26.COV2.S had the lowest NAb on Day 29 (D614G GMT 128 and Omicron GMT 45). Results were similar between age groups. Most homologous and heterologous boost combinations examined will increase humoral immunity to the Omicron variant.

Incidence of Head and Neck Cancers before and after 9/11 in New York City and New York State

<b><i>Introduction:</i></b> The incidence of cancers in New York State (NYS) before and after 9/11 including lung, colorectal, and renal cancers has been previously described. To date, the incidence of head and neck cancers (HNCs) before and after 9/11 has not been described. <b><i>Methods:</i></b> Cancers involving the oral cavity and oropharynx; the nose, nasal cavity, nasopharynx, and middle ear; larynx; and thyroid were identified using the New York State Cancer Registry (NYSCR). Age-adjusted incidence and rates per 100,000 residents from 1987 to 2015 were analyzed using joinpoint regression. Trends in incidence using annual percent changes are presented. <b><i>Results:</i></b> The overall rate of HNC increased slightly by 0.7% (<i>p</i> &#x3c; 0.001) from 1987 to 2003 in NYS. From 2003 to 2008, the rate increased by 5.73% (<i>p</i> &#x3c; 0.001), and from 2008 to 2015, the rate increased by 1.68% (<i>p</i> &#x3c; 0.001). The rate of thyroid cancer increased by 6.79% (<i>p</i> &#x3c; 0.001) from 1987 to 2003, by 9.99% (<i>p</i> &#x3c; 0.001) from 2003 to 2009, and by 2.41% (<i>p</i> = 0.001) from 2009 to 2015. The rate of thyroid cancer was higher in women at all time points. In a subset analysis of HNCs excluding thyroid cancer, the rate decreased by 2.02% (<i>p</i> &#x3c; 0.001) from 1991 to 2001, followed by a nonsignificant increase of 0.1% (<i>p</i> = 0.515) from 2001 to 2015. The rate of oropharyngeal (OP) cancer significantly increased from 1999 to 2015 (2.65%; <i>p</i> &#x3c; 0.001). The rate of oral cavity cancer significantly decreased from 1987 to 2003 (1.97%; <i>p</i> &#x3c; 0.001), with no significant change after 2003. The rate of laryngeal cancer decreased significantly by 2.43% (<i>p</i> &#x3c; 0.001) from 1987 to 2015, as did the rate of nasal cavity/nasopharyngeal cancer (0.33%; <i>p</i> = 0.03). <b><i>Conclusions:</i></b> In NYS, OP cancer and thyroid cancer rates increased significantly during the study period. The rate of thyroid cancer was higher in women. The rate of combined HNC increased significantly after 9/11 compared to before 9/11; however, in a subset analysis of all HNC patients excluding thyroid cancer, the rate decreased significantly prior to 9/11 and then nonsignificantly increased afterward. This suggests that the increase in thyroid cancer accounts for the increase in combined HNC in NYS. The impact of 9/11 on rates of HNC requires further research.

Daratumumab-based therapies in transplant-ineligible patients with untreated multiple myeloma and hepatic dysfunction: A systematic review of subgroup analyses

Introduction There is subgroup analysis suggesting a lack of benefit of daratumumab use in multiple myeloma (MM) and hepatic disease (HD). The objectives of this study were to conduct a systematic review and interpretation of daratumumab-based regimen efficacy in transplant-ineligible patients with untreated MM and HD. Methods A systematic search in Pubmed® database about randomized clinical trials (RCTs) with subgroup analysis regarding hepatic function for overall survival (OS) or progression-free survival (PFS) were developed. Two methodologies were applied. One of them considered statistical interaction, prespecification, biological support and consistency of subgroup results. Second methodology was two-part validated tool: preliminary questions to reject subset analysis without minimal relevance, and a checklist relating a recommendation for applicability in clinical practice. Results It was included three records. About first methodology, statistical interaction among subgroups was found for PFS in one RCT. Subsets were prespecified in all RCTs. Biological support of efficacy differences could be reasonable. Inconsistent results were found. Second methology directly rejected applicability of subset analysis in two records. Checklist recommended “null” application of results in the remaining RCT. Conclusions No consistent heterogeneity for daratumumab-based regimen efficacy was observed among subgroups regarding hepatic function in transplant-ineligible patients with untreated MM. Patients with normal hepatic function and HD could benefit from these treatments.

Early Fresh Frozen Plasma Transfusion: Is It Associated With Improved Outcomes of Patients With Sepsis?

Background: So far, no study has investigated the effects of plasma transfusion in the patients with sepsis, especially in the terms of prognosis. Therefore, we aimed to explore the association of early fresh frozen plasma (FFP) transfusion with the outcomes of patients with sepsis.Methods: We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care III database (v1.4). External validation was obtained from the First Affiliated Hospital of Wenzhou Medical University, China. We adopted the Sepsis-3 criteria to extract the patients with sepsis and septic shock. The occurrence of transfusion during the first 3-days of intensive care unit (ICU) stay was regarded as early FFP transfusion. The primary outcome was 28-day mortality. We assessed the association of early FFP transfusion with the patient outcomes using a Cox regression analysis. Furthermore, we performed the sensitivity analysis, subset analysis, and external validation to verify the true strength of the results.Results: After adjusting for the covariates in the three models, respectively, the significantly higher risk of death in the FFP transfusion group at 28-days [e.g., Model 2: hazard ratio (HR) = 1.361, P = 0.018, 95% CI = 1.054–1.756] and 90-days (e.g., Model 2: HR = 1.368, P = 0.005, 95% CI = 1.099–1.704) remained distinct. Contrarily, the mortality increased significantly with the increase of FFP transfusion volume. The outcomes of the patients with sepsis with hypocoagulable state after early FFP transfusion were not significantly improved. Similar results can also be found in the subset analysis of the septic shock cohort. The results of external validation exhibited good consistency.Conclusions: Our study provides a new understanding of the rationale and effectiveness of FFP transfusion for the patients with sepsis. After recognizing the evidence of risk-benefit and cost-benefit, it is important to reduce the inappropriate use of FFP and avoid unnecessary adverse transfusion reactions.

Clinical Use of Lymphocyte Subset Analysis: As a Prognostic Marker for Dogs with Pyometra

BackgroundLymphocyte subset analysis is clinically applied in human medicine. However, lymphocyte subset analysis is rarely used in small animal practice. We hypothesized that lymphocyte subsets analysis was useful in small animal practice as a biomarker for evaluating immune competence and predicting the disease prognosis. Lymphocyte subset analysis was performed prospectively for pyometra, a common disease in dogs, to assess its clinical usefulness in small animal practice.ResultsThis study included 29 dogs diagnosed with pyometra. They were classified into group 1 and group 2 on the basis of clinical course postoperatively. Sixteen dogs were classified in group 1 with no adverse events postoperatively. Thirteen dogs experienced adverse events such as increase in C-reactive protein concentration and white blood cell count, discharge from operation site, and hypoglycemia. These dogs were classified as group 2. Nine dogs were below the reference interval for the lymphocyte subset, eight of which were in group 2. Group 2 included significantly more dogs with lymphocyte subset abnormalities (p = 0.005). In the multivariable logistic regression analysis, only the result of lymphocyte subset analysis was significantly associated with adverse events (p = 0.02, 95% confidence interval = 1.68–192). Most dogs in group 2 were successfully treated.ConclusionsThese results indicate that lymphocyte subset analysis is useful as a prognostic tool for pyometra. Further studies are necessary for evaluating the clinical usefulness of lymphocyte subset analysis in pyometra and other diseases.

Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy

Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

How to Effectively Decrease Patient Co-Payments of High-Cost Drugs Through Innovation: Lessons From the Karmanos Specialty Pharmacy

PURPOSE: High-cost drugs impose a financial burden on patients with cancer. Karmanos Specialty Pharmacy (KSP) developed a process to automate financial assistance (FA) applications to decrease patient drug cost. We evaluate the outcomes of this program on cost to patients and payers. METHODS: This is an observational, retrospective study of the KSP claims data set from January to December 2019, accessed by 13 statewide cancer centers within Michigan. Drug cost of patients, payers, FA (funds to lower patient drug cost), and types of FA were obtained. A subset analysis was performed to determine drug delivery times. RESULTS: In 2019, 869 prescriptions and 1,722 prescription fills were provided to 463 patients through KSP. The total cost of drug claims was approximately $10 million US dollars (USD) among Medicare patients (58%), approximately $3.4 million USD for privately insured patients (20%), and approximately $3.7 million USD for Medicaid patients (22%). Twenty-seven percent of patients (22% of all prescription fills) required additional FA with initial total co-payment claims of $335,216 USD. $280,988 USD of FA was obtained, which substantially lowered total patient costs by 81%. $250,818 USD of FA obtained was from foundation grants (327 fills), and $21,441 USD from manufacturer co-pay cards (47 fills). An additional $12,260 USD (12 fills) from a Karmanos Patient Assistance Fund was used. There was high dependence on foundation grant assistance among Medicare patients (33% of claims). In a subset analysis, the median time from prescription written to delivery to the patient was < 7 days (0-56 days). CONCLUSION: Twenty-seven percent of patients (22% of prescriptions fills) in 2019 required additional FA for high-cost drugs. KSP substantially reduced patient cost by implementing an efficient process using additional pharmacy assistants to obtain FA.