Citations

AbstractContextIndividuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures.MethodsWe searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence.ResultsWe included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty).ConclusionThe certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.

7571 Background: In clinical trials of CAR T-cell therapies and real-world studies published to date, there is a paucity of data on outcomes by race and ethnicity. Here, we examined outcomes by race and ethnicity among LBCL pts who received axi-cel in the real-world setting. Methods: A total of 1389 pts with LBCL were identified from a non-interventional post-authorization safety study with pts receiving commercial axi-cel between 10/2017 and 08/2020. Race (African American or Asian vs White) and ethnicity (Hispanic vs non-Hispanic) were self-reported by pts. Pts with rescinded consent, enrolled in trials, having prior non-HCT cellular therapy, primary CNS lymphoma, unknown comorbidity or data in query were excluded. Median follow-up was 12.7 mo. Outcomes included ORR, CR rate, DOR, PFS and OS, grade ≥ 3 CRS (Lee 2014 criteria) and ICANS (ASTCT consensus grade). ORR and CR were evaluated in pts with ≥ 180 days of follow-up. Kaplan-Meier estimates were calculated for PFS and OS. Multivariable analyses comparing race and ethnicity were conducted via logistic and Cox regression. Results: Among all, 1127 (81%) were White, 70 (5%) African American and 81 (6%) Asian; 152 (11%) were Hispanic including 104 White, 2 Black, and 1 Asian Hispanic. African Americans, compared to White, were younger (median age 55.5 vs 62.8 years), more likely to have pulmonary impairment (41% vs 28%) and tended to have longer time from diagnosis (≥ 12 mo 71% vs 59%). Hispanic pts were younger (median age 58.5 vs 62.6 years) than non-Hispanic pts. ORR was 74% (CR 57%, 12-mo PFS and OS 48% and 63%) for White, 57% (CR 45%, 12-mo PFS and OS 36% and 62%) for African American, 67% (CR 53%, 12-mo PFS and OS 55% and 65%) for Asian and 73% (CR 55%, 12-mo PFS and OS 50% and 65%) for Hispanic pts. Grade ≥ 3 CRS and ICANS occurred in 7% and 18% of African American, 10% and 19% of Asian, and 8% and 27% of White pts, respectively. Hispanic pts had lower rates of grade ≥ 3 CRS and ICANS (4% and 15%) vs non-Hispanic (9% and 27%). African American race was associated with inferior ORR (OR 0.40; 95% CI, 0.24-0.69) and CR rate (OR 0.55; 95% CI 0.32-0.93) vs White. Asian pts had favorable DOR compared to both White (HR 0.46; 95% CI 0.24-0.87) and African American (HR 0.39; 95% CI 0.17-0.88). No statistical differences were found in OS and PFS across races, nor in any efficacy outcome between Hispanic and non-Hispanic pts. Asian (OR 0.52; 95% CI 0.29-0.96 vs White) and Hispanic pts (OR 0.51; 95% CI 0.31-0.85 vs non-Hispanic) had lower risk of grade ≥ 3 ICANS. Conclusions: Overall, axi-cel showed favorable OS, PFS and safety profile regardless of race and ethnicity in the real-world setting. No notable differences in outcomes were observed for Hispanic or Asian pts. Lower response rates in African American pts noted here warrant further investigation including any underrepresentation not explained by a lower incidence rate for DLBCL (SEER), access to care, and disease burden.

Abstract MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I 2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I 2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

Introduction: Theobromine is a naturally occurring substance found in cocoa products. Theobromine may have beneficial cardiovascular effects through various mechanisms. We used the NHANES database to analyze associations between theobromine consumption and cardiovascular health outcomes. Methods: The NHANES database represents a nationally representative population which was used to construct the study population from 1996-2016. We assessed multiple demographic factors and compared differences amongst those who consumed various amounts of theobromine to those who did not. The primary outcome measures were hypertension and lipid profiles. Results: Among 42,038 NHANES survey participants, 37569 and 4469 of the participants reported never consuming theobromine and consuming theobromine, respectively. Table 1 demonstrates baseline characteristics of those reporting no theobromine consumption in comparison to the theobromine consuming participants (100-400md/g and 400-850mg/d). Moderate to high amounts of theobromine consumption was observed in participants who were older with higher BMI and more education and were more likely to be tobacco users in comparison to those with no theobromine consumption (all p-values <0.05). Moderate to high theobromine consumption was also observed to be associated with a higher hemoglobin level, higher LDL cholesterol, lower HDL cholesterol, and prevalence of hypertension (all p-values <0.05). Conclusions: We observed that individuals who consumed moderate to high amounts of theobromine had associated improvements in lipid profile parameters as well as reduced blood pressure. Theobromine may represent a complementary non-pharmacologic supplementation to typical lifestyle modifications to improve cardiovascular outcomes. Further prospective studies are needed to better clarify this potential association.

Abstract Objective Leucocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of leucocyte receptors. Our previous study reported LILRA3 transcripts were markedly upregulated in neutrophils from patients with APS. We undertook this study to investigate clinical implications of LILRA3 in APS and its potential role in APS-associated thrombosis. Methods Two independent cohorts were studied. The first consisted of 294 APS patients, 48 asymptomatic aPL carriers and 150 healthy controls (HCs) from Peking University People’s Hospital. The second included 99 APS patients, 25 aPL carriers and 40 HCs from United States APS centres. Serum or plasma concentrations of LILRA3 and MPO-DNA complexes were measured. Additionally, 35 patients with thrombotic APS (tAPS) were evaluated to determine potential effects of immunosuppressive therapy on serum concentrations of LILRA3 and MPO-DNA complexes. Results Both positivity and serum concentration of LILRA3 were significantly increased in APS patients, especially in those with tAPS. LILRA3-positive tAPS patients displayed more severe thrombotic manifestations. Serum LILRA3 was positively correlated with MPO-DNA complexes in LILRA3-positive tAPS. After immunosuppressive treatment, LILRA3 and MPO-DNA complexes were consistently decreased in tAPS patients. Key findings from the Peking cohort were confirmed in the United States cohort. Conclusion Our study provides first evidence that LILRA3 is aberrantly expressed in APS, especially in patients with tAPS. Serum LILRA3 correlated with MPO-DNA complexes, and the two indices were consistently decreased in tAPS patients after treatment. LILRA3 may play a role in thrombosis of APS and may serve as a biomarker and/or therapeutic target in tAPS.

Introduction: Current proposed Dietary Guidelines for Americans, 2015 suggested replacing refined grains (e.g., white rice) with whole grains (e.g., brown rice) for improved health outcomes; however, the association between white rice consumption and risk of cardiovascular disease (CVD) was not fully investigated. The purpose of this study was to explore the associations between rice consumption, metabolic syndrome and cardiovascular disease. Methods: We conducted a comprehensive search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through May 2015. Observational studies were included if the studies reported hazard ratios (HRs) or odd ratios (ORs) of the associations between rice consumption, metabolic syndrome and cardiovascular disease. Data were extracted by one reviewer and then reviewed by two independent reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled HRs and pooled ORs with 95% confidence intervals (95% CIs). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: Out of 343 retrieved articles, we identified 6 cross-sectional and 9 prospective studies with a total of 575,852 individuals with 24,649 total CVD events and 4,409 metabolic syndrome cases. The highest category of white rice consumption (≥5 times/week) was associated with a 37% higher risk of metabolic syndrome (pooled OR, 1.37; 95% CI: 1.03-1.84; p<0.001; I 2 = 78.7%) but not a higher risk of cardiovascular disease (pooled HR, 1.01; 95% CI: 0.95-1.08; p=0.65; I 2 = 0%), compared to the lowest category (≤1 time/month). Conclusions: Higher white rice consumption has not been shown to increase the risk of cardiovascular diseases but may be associated with increased risk of metabolic syndrome.

Introduction: Obesity is a growing global health problem associated with substantial morbidity and mortality. The risk of obesity on incident new-onset heart failure is controversial. The aim of this systematic review and meta-analysis was to explore the association between overweight, obesity and incident new-onset heart failure. Methods: We systematically searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through April 2015. Prospective cohort studies were included if the studies reported hazard ratios (HRs) of the association between overweight or obesity and new-onset heart failure (HF) relative to individuals with normal weight. Data were extracted by one reviewer followed by independent screening and extraction of study characteristics and outcome data by two other reviewers. Conflicts were resolved through consensus. Random-effects meta-analyses were used to pool the hazard ratio from the included studies. Subgroup analyses were performed to explore the potential sources of heterogeneity. Results: Out of 1,865 retrieved articles, we identified 10 relevant studies. Median follow-up was 12 years with a total of 82,167 individuals and 4,570 total HF events. Compared to normal body weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) was associated with 27% higher risk of new-onset heart failure events (pooled HR, 1.27; 95% confidence intervals (95% CI): 1.15-1.41; p<0.001; I 2 = 0%) and obesity (BMI ≥30 kg/m2) was associated with a two-fold increased risk for new-onset heart failure events (pooled HR, 2.09; 95% CI, 1.68-2.60; p<0.001; I 2 = 67.8%). Conclusions: Compared with normal-weight individuals, both overweight and obesity were independently associated with significantly higher incidence of heart failure. These results highlight the need for better understanding of mechanisms of obesity and heart failure.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.