Characterization of the maternal serum inflammatory profile during pregnancy according to socioeconomic status.

PROBLEM: In pregnancy, lower socioeconomic status (SES) is associated with adverse outcomes, which is partly attributed to chronic inflammation. Our study compared the maternal serum cytokine profiles in patients with low and high SES. METHOD OF STUDY: This retrospective cohort study compared maternal serum cytokine profiles between Medicaid-insured patients who delivered at an urban safety-net hospital (low SES) and privately-insured patients who delivered at a community-based academic hospital (high SES) in Atlanta, GA (n = 32-33/group). Serum samples were obtained during prenatal venipuncture from 13 to 38 weeks' gestation and the cohorts were matched by gestational age. Interferon (IFN)-γ, Interleukin (IL)-10, IL-1ß, IL-4, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-α were assayed from maternal serum samples using a standard ELISA assay. RESULTS: Median concentrations of IL-6, a promotor of chronic inflammation, were higher in the low SES group (0.85 vs. 0.49 pg/mL, p < .001), while median levels of IL-1ß, a potent monocyte activator, and TNF-α, a master regulator of acute inflammation, were lower in the low SES group (0.09 vs. 0.46 pg/mL, p < .001, and 1.23 vs. 1.58 pg/mL, p = .002, respectively) as compared to the high SES group. After adjusting for maternal age, obesity, hypertensive disorders, and gestational age at delivery, the differences in IL-6 and IL-1ß by SES persisted (p = .0002 and p < .0001, respectively). CONCLUSIONS: In this retrospective cohort study, there were significant differences in levels of pro-inflammatory cytokines during pregnancy for groups defined by SES, even after adjustment for confounding variables. Our data are foundational for further research to investigate SES-associated inflammation that may contribute to adverse pregnancy outcomes.

Quality of dietary macronutrients is associated with glycemic outcomes in adults with cystic fibrosis.

Objective: Poor diet quality contributes to metabolic dysfunction. This study aimed to gain a greater understanding of the relationship between dietary macronutrient quality and glucose homeostasis in adults with cystic fibrosis (CF). Design: This was a cross-sectional study of N = 27 adults with CF with glucose tolerance ranging from normal (n = 9) to prediabetes (n = 6) to being classified as having cystic fibrosis-related diabetes (CFRD, n = 12). Fasted blood was collected for analysis of glucose, insulin, and C-peptide. Insulin resistance was assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). Subjects without known CFRD also underwent a 2-h oral glucose tolerance test. Three-day food records were used to assess macronutrient sources. Dietary variables were adjusted for energy intake. Statistical analyses included ANOVA, Spearman correlations, and multiple linear regression. Results: Individuals with CFRD consumed less total fat and monounsaturated fatty acids (MUFA) compared to those with normal glucose tolerance (p < 0.05). In Spearman correlation analyses, dietary glycemic load was inversely associated with C-peptide (rho = -0.28, p = 0.05). Total dietary fat, MUFA, and polyunsaturated fatty acids (PUFA) were positively associated with C-peptide (rho = 0.39-0.41, all p < 0.05). Plant protein intake was inversely related to HOMA2-IR (rho = -0.28, p = 0.048). Associations remained significant after adjustment for age and sex. Discussion: Improvements in diet quality are needed in people with CF. This study suggests that higher unsaturated dietary fat, higher plant protein, and higher carbohydrate quality were associated with better glucose tolerance indicators in adults with CF. Larger, prospective studies in individuals with CF are needed to determine the impact of diet quality on the development of CFRD.

Characterization of the inflammatory response to COVID-19 illness in pregnancy.

OBJECTIVE: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1ß, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease. STUDY DESIGN: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test. RESULTS AND DISCUSSION: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1ß, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

Human Immunodeficiency Virus (HIV) Care Continuum Outcomes After Transition to Adult Care Among a Prospective Cohort of Youth With HIV in Atlanta, Georgia.

BACKGROUND: Healthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting human immunodeficiency virus (HIV) care outcomes after healthcare transition. METHODS: We conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age, 24 years) were enrolled up to 3 months before the expected transition and were followed up to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at the baseline and at 6, 12, 18, and 24 months. RESULTS: The majority of our cohort (n = 70) was male (88.6%) and black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% confidence interval, 78%-94%) at 6 months, 76% (66%-86%) at 12 months, and 66% (55%-78%) at 18 and 24 months. Once in adult care, the proportion with viral suppression was stable (73% at baseline and 74%, 77%, 67%, and 78% at 6, 12, 18, and 24 months, respectively). CONCLUSIONS: Although most youth successfully linked to adult care, retention rates decreased over the 24-month follow-up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing this transition for youth with HIV.

Complication rate of overlapping versus nonoverlapping functional and stereotactic surgery: a retrospective cohort study.

OBJECTIVE: Overlapping surgery, in which one attending surgeon manages two overlapping operating rooms (ORs) and is present for all the critical portions of each procedure, is an important policy that improves healthcare access for patients and case volumes for surgeons and surgical trainees. Despite several studies demonstrating the safety and efficacy of overlapping neurosurgical operations, the practice of overlapping surgery remains controversial. To date, there are no studies that have investigated long-term complication rates of overlapping functional and stereotactic neurosurgical procedures. The primary objective of this study was to investigate the 1-year complication rates and OR times for nonoverlapping versus overlapping functional procedures. The secondary objective was to gain insight into what types of complications are the most prevalent and test for differences between groups. METHODS: Seven hundred eighty-three functional neurosurgical cases were divided into two cohorts, nonoverlapping (n = 342) and overlapping (n = 441). The American Society of Anesthesiologists (ASA) scale score was used to compare the preoperative risk for both cohorts. A complication was defined as any surgically related reason that required readmission, reoperation, or an unplanned emergency department or clinic visit that required intervention. Complications were subdivided into infectious and noninfectious. Chi-square tests, independent-samples t-tests, and uni- and multivariable logistic regressions were used to determine significance. RESULTS: There were no significant differences in mean ASA scale score (2.7 ± 0.6 for both groups, p = 0.997) or overall complication rates (8.8% nonoverlapping vs 9.8% overlapping, p = 0.641) between the two cohorts. Infections accounted for the highest percentage of complications in both cohorts (46.6% vs 41.8%, p = 0.686). There were no statistically significant differences between mean in-room OR time (187.5 ± 141.7 minutes vs 197.1 ± 153.0 minutes, p = 0.373) or mean open-to-close time (112.2 ± 107.9 minutes vs 121.0 ± 123.1 minutes, p = 0.300) between nonoverlapping and overlapping cases. CONCLUSIONS: There was no increased risk of 1-year complications or increased OR time for overlapping functional and stereotactic neurosurgical procedures compared with nonoverlapping procedures.

Performance of Modified ALMS and BLISS Criteria with Standard of Care Treatment in Two US Health Care Systems.

OBJECTIVE: A retrospective cohort study was undertaken in a predominantly Black population undergoing standard treatment for lupus nephritis (LN) to estimate the incidence of, and risk factors for, complete response (CR) according to modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Study in Lupus Nephritis (mBLISS) criteria by 12 months. METHODS: Patients with biopsy-proven LN class III or IV ± V, urine protein-to-creatinine ratio of ≥1gm/gm and estimated glomerular filtration rate of >50 ml/minute/1.73 m2 at the time of the incident LN flare were included. The clinical, treatment, and laboratory factors associated with CR were identified using multivariable Cox regression. RESULTS: Of 173 patients, 86.1% were women, 77.5% were Black, and over half (59.5%) had non-commercial insurance. By 12 months, 20.6% (95% confidence interval (95% CI) 14.6-28.6%) achieved mALMS CR and 33.7% (95% CI 26.4-42.4%) achieved mBLISS CR. Factors associated with mBLISS CR were commercial insurance (adjusted CR ratio = 3.5 [95% CI 1.9-6.7]; P < 0.001), albumin (adjusted CR ratio = 1.8 per 1 gm/dl increase in albumin; P = 0.02), and low C4 (adjusted CR ratio = 2.6; P = 0.03). Cumulative incidence of end-stage renal disease (ESRD) at 3 years was 23.1% (95% CI 15.7-31.3%) and 6.1% (95% CI 2.8-11.1%) for death. Patients with non-commercial insurance were more likely to develop ESRD, with cumulative incidence of 30.4% (95% CI 19.6-41.9%) compared to 12.7% (95% CI 5.0-24.2%) for patients with commercial insurance (P = 0.024). CONCLUSION: In a primarily Black, uninsured LN population, despite achieving similar CR rates at 12 months, the incidence of ESRD and death exceeded those observed in controlled clinical trials with placebo arms.

Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.

BACKGROUND: Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). METHODS: We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time. RESULTS: At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease. CONCLUSION: Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.

Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.

BACKGROUND: Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE: Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS: Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS: eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION: Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.

Ethanol Lock Therapy Markedly Reduces Catheter-Related Blood Stream Infections in Adults Requiring Home Parenteral Nutrition: A Retrospective Study From a Tertiary Medical Center.

BACKGROUND: The use of central venous catheter (CVC) access for home parenteral nutrition (HPN) is associated with catheter-related bloodstream infections (CRBSIs). There are limited data on the use of ethanol lock therapy (ELT) to prevent CRBSI in adult HPN patients. Our aim was to determine whether the routine institution of ELT decreased the incidence of CRBSI compared with historic controls at Emory University Hospital (EUH) in Atlanta, Georgia, USA. METHODS: EUH medical records of adult HPN patients discharged with a tunneled, silicone CVC on ELT were retrospectively studied during a pre-hoc determined 14-month observation period (n = 87; 13,386 catheter days) and compared with clinically similar HPN patients from the same institution before institution of the ELT protocol for all appropriate patients. The ELT protocol involved instilling 2 mL of 70% ethanol into each catheter lumen daily after the HPN cycle, following initial flushing with normal saline. RESULTS: Only 5 of 87 patients (5.7%) who received ELT were diagnosed with a CRBSI (0.45/1000 catheter days) during observation. We compared these data with our previously published clinically matched patient population from EUH (n = 22) receiving HPN via a silicone CVC without ELT. Of these historical controls, 45.5% were diagnosed with 1 or more CRBSIs (8.7/1000 catheter days) during observation (P < .001 vs the current ELT cohort). CONCLUSIONS: In this retrospective study with historical controls from the same academic center, institution of ELT in adults requiring HPN via a silicone CVC was associated with a marked (19-fold) reduction in CRBSI.

Enteral iron supplementation, red blood cell transfusion, and risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

BACKGROUND: Enteral iron supplementation and RBC transfusions are routinely administered to very-low-birth-weight (VLBW) infants, although the potential risks of these exposures have not been adequately quantified. This study evaluated the association between the cumulative dose of enteral iron supplementation, total volume of RBCs transfused, and risk of bronchopulmonary dysplasia (BPD) in VLBW infants. STUDY DESIGN AND METHODS: Retrospective, multicenter observational cohort study in Atlanta, Georgia. Cumulative supplemental enteral iron exposure and total volume of RBCs transfused were measured until the age at assessment of BPD. Multivariable generalized linear models were used to control for confounding, and the reliability of the factors was assessed in 1000 bootstrap models. RESULTS: A total of 598 VLBW infants were studied. In multivariable analyses, a greater cumulative dose of supplemental enteral iron exposure was associated with an increased risk of BPD (adjusted relative risk per 50-mg increase, 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.002). Similarly, a greater volume of RBCs transfused was associated with a higher risk of BPD (adjusted relative risk per 20-mL increase, 1.05; 95% CI, 1.02-1.07; p < 0.001). Both factors were reliably associated with BPD (>50%). Volume of RBCs transfused was similar to gestational age in reliability as a risk factor for BPD (present in 100% of models) and was more reliable than mechanical ventilation at 1 week of age. CONCLUSION: The cumulative dose of supplemental enteral iron exposure and total volume of RBC transfusion are both independently associated with an increased risk of BPD in VLBW infants.

Higher Mediterranean Diet Quality Scores and Lower Body Mass Index Are Associated with a Less-Oxidized Plasma Glutathione and Cysteine Redox Status in Adults.

Background: Both systemic redox status and diet quality are associated with risk outcomes in chronic disease. It is not known, however, the extent to which diet quality influences plasma thiol/disulfide redox status. Objective: The purpose of this study was to investigate the influence of diet, as measured by diet quality scores and other dietary factors, on systemic thiol/disulfide redox status. Methods: We performed a cross-sectional study of 685 working men and women (ages ≥18 y) in Atlanta, GA. Diet was assessed by 3 diet quality scores: the Alternative Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean Diet Score (MDS). We measured concentrations of plasma glutathione (GSH), cysteine, their associated oxidized forms [glutathione disulfide (GSSG) and cystine (CySS), respectively], and their redox potentials (EhGSSG and EhCySS) to determine thiol/disulfide redox status. Linear regression modeling was performed to assess relations between diet and plasma redox after adjustment for age, body mass index (BMI), sex, race, and history of chronic disease. Results: MDS was positively associated with plasma GSH (ß = 0.02; 95% CI: 0.003, 0.03) and total GSH (GSH + GSSG) (ß = 0.02; 95% CI: 0.003, 0.03), and inversely associated with the CySS:GSH ratio (ß = -0.02; 95% CI: -0.04, -0.004). There were significant independent associations between individual MDS components (dairy, vegetables, fish, and monounsaturated fat intake) and varying plasma redox indexes (P < 0.05). AHEI and DASH diet quality indexes and other diet factors of interest were not significantly correlated with plasma thiol and disulfide redox measures. Conclusion: Adherence to the Mediterranean diet was significantly associated with a favorable plasma thiol/disulfide redox profile, independent of BMI, in a generally healthy working adult population. Although longitudinal studies are warranted, these findings contribute to the feasibility of targeting a Mediterranean diet to improve plasma redox status.

T-cell receptor activator of nuclear factor-κB ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts.

OBJECTIVE: Higher incidence of osteopenia and osteoporosis underlie increased rates of fragility fracture in HIV infection. B cells are a major source of osteoprotegerin (OPG), an inhibitor of the key osteoclastogenic cytokine receptor activator of nuclear factor-κB ligand (RANKL). We previously showed that higher B-cell RANKL/OPG ratio contributes to HIV-induced bone loss. T-cell OPG production in humans, however, remains undefined and the contribution of T-cell OPG and RANKL to HIV-induced bone loss has not been explored. DESIGN: We investigated T-cell OPG and RANKL production in ART-naive HIV-infected and uninfected individuals in relation to indices of bone loss in a cross-sectional study. METHODS: T-cell RANKL and OPG production was determined by intracellular staining and flow cytometry, and plasma levels of bone resorption markers were determined by ELISA. RESULTS: We demonstrate for the first time in-vivo human T-cell OPG production, which was significantly lower in HIV-infected individuals and was coupled with moderately higher T-cell RANKL production, resulting in a significantly higher T-cell RANKL/OPG ratio. T-cell RANKL/OPG ratio correlated significantly with BMD-derived z-scores at the hip, lumbar spine and femur neck in HIV-infected individuals with CD4 T-cell counts at least 200 cells/µl but not in those with lower counts. CONCLUSION: Our data suggest that T cells may be a physiologically relevant source of OPG and T-cell RANKL/OPG imbalance is associated with HIV-induced bone loss in CD4 T-cell-sufficient patients. Both B and T lymphocytes may thus contribute to HIV-induced bone loss.

Peritransplantation Red Blood Cell Transfusion Is Associated with Increased Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day -7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.

The P-mJOA: A Patient-derived, Self-reported Outcome Instrument for Evaluating Cervical Myelopathy: Comparison with the mJOA.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: The objective of this study is to evaluate and validate a patient-derived version of the modified Japanese Orthopaedic Association (the "P-mJOA") that a patient can complete along with other patient-derived outcome measures. SUMMARY OF BACKGROUND DATA: The modified Japanese Orthopaedic Association (mJOA) is a validated instrument widely used in the assessment of cervical myelopathy; however, it is not a patient-derived outcome. If available and reliable, a patient-derived version of the mJOA (P-mJOA) could facilitate research because the data would be immediately available upon patient completion and also remove any potential physician bias. Currently, there is no patient-derived myelopathy survey with the widespread acceptance of the mJOA. METHODS: The P-mJOA was created by very slightly modifying the verbiage of the mJOA to make it possible for a patient to complete the instrument while maintaining the questionnaire's core structure. A total of 100 consecutive consenting patients with cervical myelopathy were enrolled. After the patient completed the P-mJOA, the mJOA was scored by a physician blinded to the P-mJOA result. RESULTS: The P-mJOA and the mJOA had identical mean scores of 14.7 (mean difference±SD: 0.0±1.5; P=0.89). Several measures of reliability demonstrated agreement between the 2 surveys, including strong agreement with the intraclass correlation coefficient and Spearman ρ (both 0.83) and moderate to substantial agreement with weighted κ values (0.55 to 0.66). In addition, 67% of patients preferred to fill out the P-mJOA themselves, suggesting low patient burden. CONCLUSIONS: The P-mJOA provided identical mean scores to the mJOA in assessing myelopathy with moderate to strong agreement. Comprised of the same 4 questions as the mJOA but slightly reworded for patient comprehension, the P-mJOA also demonstrated low patient burden in completing the survey. We believe the P-mJOA is a promising tool in cervical myelopathy research with the benefits of a patient-derived outcome measure and low patient burden. LEVEL OF EVIDENCE: Level II.

Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia.

BACKGROUND: This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. OBJECTIVE: The objective of this study was to assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. STUDY DESIGN: We conducted a 3+3 dose-escalation Phase I trial in a group of women aged 18-45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intravaginally daily for 14 days. The primary end point for this study was safety based on severe adverse events regarding laboratory toxicity, clinical findings, and colposcopic abnormalities. We administered an acceptability questionnaire to assess product experience and attributes. RESULTS: No dose-limiting toxicities (0/13) were experienced (95% confidence interval: 0.0%-22.8%) in this study. The pharmacokinetics data demonstrated that curcumin and curcumin conjugates were not measurable in the serum and negligible in the urine of the study participants. Although 23 adverse events occurred during the course of the trial, all events were grade I based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and were resolved by the end of the study in an average of 9 days. Fifty-six percent of the adverse events were related to the study drug, which included genital pruritus (23% of subjects), vaginal discharge (100%), vaginal dryness (15%), abnormal prothrombin (23%), and hypokalemia (8%). CONCLUSION: Intravaginal curcumin was well tolerated by all subjects and safe. In this Phase I trial, there were no severe adverse events observed at any of the administered dose levels. All adverse events were grade I and did not result in early termination of the study. There was no evidence of systemic absorption or significant local absorption of intravaginally administered curcumin.

Macronutrient intake and body composition changes during anti-tuberculosis therapy in adults.

BACKGROUND: Malnutrition is common in patients with active tuberculosis (TB), yet little information is available on serial dietary intake or body composition in TB disease. OBJECTIVE: To evaluate macronutrient intake and body composition in individuals with newly diagnosed TB over time. DESIGN: Adults with active pulmonary TB (n = 191; 23 with multidrug resistant TB (MDR-TB) and 36 culture-negative household contacts (controls) enrolled in a clinical trial of high-dose cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index (BMI; kg/m(2)) and bioelectrical impedance analysis (BIA) to estimate fat mass and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes over time and linear regression were used. RESULTS: At baseline, mean daily energy, protein, fat and carbohydrate (CHO) intakes were significantly higher, and body weight, BMI, fat-free mass and fat mass were significantly lower, between TB subjects and controls. These remained significant after adjusting for age, gender, employment status and smoking. In all TB subjects, baseline mean daily intakes of energy, fat and protein were adequate when compared to the US Dietary Reference Intakes and protein significantly increased over time (p < 0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB patients exhibited lower body weight and fat-free mass over time, despite similar daily intake of kcal, protein, and fat. CONCLUSIONS: Macronutrient intake was higher in TB patients than controls, but TB-induced wasting was evident. As macronutrient intake of TB subjects increased over time, there was a parallel increase in BMI, while body composition proportions were maintained. However, individuals with MDR-TB demonstrated concomitantly decreased body weight and fat-free mass over time versus drug-sensitive TB patients, despite increased macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient intake, likely reflecting the catabolic effects of TB.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Pattern of cardiac surveillance among patients with lymphoma receiving anthracycline-based chemotherapy.

OBJECTIVE: Anthracyclines are potent antineoplastic agents in the treatment of lymphoid malignancies, but their therapeutic benefit is limited by cardiotoxicity. The American Heart Association (AHA) recommends routine surveillance, early diagnosis and treatment of anthracycline-based chemotherapy (AC) induced cardiomyopathy (AC-CMP). We aimed to assess the prevalence of AC-CMP in patients with lymphoma, surveillance patterns of left ventricular ejection fraction (LVEF) in those receiving AC and management of patients with AC-CMP at an academic medical centre prior to the development of a comprehensive cardio-oncology programme. METHODS: We performed a retrospective cohort study examining 218 patients with aggressive B cell non-Hodgkin's lymphomas (B-NHL) who received AC 1992-2012 and had serial follow-up. AC-CMP was defined as LVEF decrease ≥10% with final LVEF≤50% or LVEF reduction ≥15% regardless of final LVEF. RESULTS: Of 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and after receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher cumulative all-cause mortality than those without AC-CMP (HR 2.35, p=0.03). Coronary artery disease (CAD) was an independent predictor of AC-CMP (p=0.048). Mean post-AC LVEF was lower in patients with CAD compared with those without CAD when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001) but was similar at 65% (p=0.33). Less than half of patients with AC-CMP received recommended heart failure medication therapy. CONCLUSIONS: Historically, one-third of patients with B-NHL treated with AC underwent surveillance according to AHA guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of patients with lymphoma receiving AC.

Can Preoperative Psychological Assessment Predict Outcomes After Temporomandibular Joint Arthroscopy?

PURPOSE: Psychological assessment has been used successfully to predict patient outcomes after cardiothoracic and bariatric surgery. The purpose of this study was to determine whether preoperative psychological assessment could be used to predict patient outcomes after temporomandibular joint arthroscopy. MATERIALS AND METHODS: Consecutive patients with temporomandibular dysfunction (TMD) who could benefit from arthroscopy were enrolled in a prospective cohort study. All patients completed the Millon Behavior Medicine Diagnostic survey before surgery. The primary predictor variable was the preoperative psychological scores. The primary outcome variable was the difference in pain between the pre- and postoperative periods. The Spearman rank correlation coefficient and the Pearson product-moment correlation were used to determine the association between psychological factors and change in pain. Univariable and multivariable analyses were performed using a mixed-effects linear model and multiple linear regression. A P value of .05 was considered significant. RESULTS: Eighty-six patients were enrolled in the study. Seventy-five patients completed the study and were included in the final analyses. The mean change in visual analog scale (VAS) pain score 1 month after arthroscopy was -15.4 points (95% confidence interval, -6.0 to -24.7; P < .001). Jaw function also improved after surgery (P < .001). No association between change in VAS pain score and each of the 5 preoperative psychological factors was identified with univariable correlation analyses. Multivariable analyses identified that a greater pain decrease was associated with a longer duration of preoperative symptoms (P = .054) and lower chronic anxiety (P = .064). CONCLUSIONS: This study has identified a weak association between chronic anxiety and the magnitude of pain decrease after arthroscopy for TMD. Further studies are needed to clarify the role of chronic anxiety in the outcome after surgical procedures for the treatment of TMD.

Dysregulated B cell expression of RANKL and OPG correlates with loss of bone mineral density in HIV infection.

HIV infection is associated with high rates of osteopenia and osteoporosis, but the mechanisms involved are unclear. We recently reported that bone loss in the HIV transgenic rat model was associated with upregulation of B cell expression of the key osteoclastogenic cytokine receptor-activator of NF-κB ligand (RANKL), compounded by a simultaneous decline in expression of its physiological moderator, osteoprotegerin (OPG). To clinically translate these findings we performed cross-sectional immuno-skeletal profiling of HIV-uninfected and antiretroviral therapy-naïve HIV-infected individuals. Bone resorption and osteopenia were significantly higher in HIV-infected individuals. B cell expression of RANKL was significantly increased, while B cell expression of OPG was significantly diminished, conditions favoring osteoclastic bone resorption. The B cell RANKL/OPG ratio correlated significantly with total hip and femoral neck bone mineral density (BMD), T- and/or Z-scores in HIV infected subjects, but revealed no association at the lumbar spine. B cell subset analyses revealed significant HIV-related increases in RANKL-expressing naïve, resting memory and exhausted tissue-like memory B cells. By contrast, the net B cell OPG decrease in HIV-infected individuals resulted from a significant decline in resting memory B cells, a population containing a high frequency of OPG-expressing cells, concurrent with a significant increase in exhausted tissue-like memory B cells, a population with a lower frequency of OPG-expressing cells. These data validate our pre-clinical findings of an immuno-centric mechanism for accelerated HIV-induced bone loss, aligned with B cell dysfunction.