A Risk Tool for Evaluating Overuse Injury and Return-to-Play Time Periods in Youth and Collegiate Athletes: Preliminary Study.

BACKGROUND: Overuse injuries in youth athletes are associated with risks, including sports specialization, biological maturation, female sex, and workload measures. As no assessment tool exists to evaluate risk accumulation, we developed a novel risk factor scoring system (Sport Training Assessment of Risk [STAR]) to assess participants' risk of overuse injury and explore association with return-to-play (RTP) time periods. HYPOTHESIS: (1) STAR will reach an acceptable predictive threshold in the assessment of overuse injury in youth athletes. (2) Higher STAR scores will be associated with increased RTP time periods after injury. STUDY DESIGN: Longitudinal cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Youth athletes with an injury sustained during competitive sport completed questionnaires. Association of questionnaire variables with injury risk type was evaluated via logistic regression analyses, and unweighted and weighted versions of a total risk score were developed. RTP was defined by physician clearance per electronic medical record review. Mantel-Haenszel chi-square tests and Kendall's rank correlation coefficients were used to assess the relationship between weighted total risk score and RTP time periods. The weighted STAR model was analyzed with receiver operating characteristic (ROC) curves. RESULTS: The weighted STAR model trended toward an acceptable level of prediction for overuse (nonserious + serious) injury (area under the ROC curve [AUC], 0.66; 95% CI, 0.61-0.71), but was less predictive for serious overuse injury (AUC, 0.63; 95% CI, 0.55-0.71). Weighted total risk score was weakly associated with return to full play (ρ = 0.11; P < 0.01), and potentially with return to modified play (ρ = -0.08; P = 0.04). CONCLUSION: STAR may be a feasible tool for assessing overuse injury risk and RTP time periods in youth athletes but requires further development, as it did not reach an acceptable predictive threshold in this preliminary study. CLINICAL RELEVANCE: Clinicians can use STAR to assess overuse injury risk in youth athletes.

The Effects of Injury Type on Health-Related Quality of Life in Youth Athletes: A Cross-Sectional Analysis.

OBJECTIVE: The relationship between health-related quality of life (HRQoL) and injury type has not been analyzed for young athletes. We hypothesized that there would be no difference in HRQoL between injured athletes, injured nonathletes, and normative data for healthy youth (NDHY) or among athletes with acute, overuse, or concussion injuries. DESIGN: Cross-sectional clinical cohort. SETTING: Primary care sports medicine clinics at 3 academic institutions. PARTICIPANTS: Patients aged 8 to 18 years presenting with injury. INDEPENDENT VARIABLES: Injury type and athletic participation. MAIN OUTCOME MEASURES: Health-related quality of life measured 1 month after injury through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric-25 v2.0 assessed pain interference, peer relationships, depression, fatigue, anxiety, and mobility. One-way analysis of variance was performed with P values of <0.05 considered significant. Concussion Learning Assessment and School Survey (CLASS) evaluated academic performance. RESULTS: Three hundred fifty-seven patients (36% male), with average age of 14.2 years, completed HRQoL and CLASS surveys following injury. There were 196 overuse injuries (55%), 119 acute injuries (33%), and 42 concussions (12%). Ninety-four percent were athletes. Six percent were nonathletes; 90.5% of concussed patients reported grades worsening. Concussed athletes reported more fatigue (P = 0.008) compared with other injury types but no worse than NDHY. Athletes with overuse injuries had lower mobility (P = 0.005) than other injury types and NDHY. Patients with lower HRQoL were female, older age, or required surgery. No other domains had significant differences by injury type nor did HRQoL differ between the athletes, nonathletes, and NDHY. CONCLUSIONS: With the exception of injuries requiring surgery, HRQoL of injured young athletes was similar to NDHY in most domains.

Three-year Outcomes After Conversion From Monthly to Every 2-month Belatacept Maintenance Therapy in Kidney Transplant Recipients: Results From a Randomized Controlled Trial.

Maintenance immunosuppression with belatacept following kidney transplantation results in improved long-term graft function as compared with calcineurin inhibitors. However, broad application of belatacept has been limited, in part related to logistical barriers surrounding a monthly (q1m) infusion requirement. Methods: To determine whether every 2-mo (q2m) belatacept is noninferior to standard q1m maintenance, we conducted a prospective, single-center randomized trial in low-immunologic-risk, stable renal transplant recipients. Here, post hoc analysis of 3-y outcomes, including renal function and adverse events, are reported. Results: One hundred sixty-three patients received treatment in the q1m control group (n = 82) or q2m study group (n = 81). Renal allograft function as measured by baseline-adjusted estimated glomerular filtration rate was not significantly different between groups (time-averaged mean difference of 0.2 mL/min/1.73 m2; 95% confidence interval: -2.5, 2.9). There were no statistically significant differences in time to death or graft loss, freedom from rejection, or freedom from donor-specific antibodies (DSAs). During the extended 12- to 36-mo follow-up, 3 deaths, 1 graft loss occurred in the q1m group, compared with 2 deaths, and 2 graft losses in the q2m group. In the q1m group, 1 patient developed DSAs and acute rejection. In the q2m group, 3 patients developed DSAs and 2 associated with acute rejection. Conclusions: Based on the similar renal function and survival at 36 mo compared with q1m, q2m belatacept is a potentially viable maintenance immunosuppressive strategy in low immunologic risk kidney transplant recipients that may facilitate increased clinical utilization of costimulation blockade-based immunosuppression.

Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization.

BACKGROUND: After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. OBJECTIVES: We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. METHODS: Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP-)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. RESULTS: The extent of M1CL reorganization was related to greater lesion volume in the MEP- group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP- but not MEP+ participants. Absence of an MEP (MEP-), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. CONCLUSIONS: In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence.ClinicalTrials.gov Identifier: NCT02544503.

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.

Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy.

Interleukin-10 (IL-10) is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper (Tfh) cell differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph nodes (LNs) were induced by infection and not normalized with antiretroviral therapy (ART). During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including Tfh cells, and predicted the frequency of CD4+ Tfh cells and their cell-associated SIV-DNA content during ART, respectively. In ART-treated rhesus macaques, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B cell follicle in proximity to IL-10. Finally, we demonstrated that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques reduced B cell follicle maintenance and, by extension, LN memory CD4+ T cells, including Tfh cells and those expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.

Prospective comparison of dysphagia following anterior cervical discectomy and fusion (ACDF) with and without rhBMP-2.

BACKGROUND CONTEXT: Previous studies have called into question the safety of using rhBMP-2 in anterior cervical fusion due to the possibility of airway compromise and dysphagia. A retrospective chart review identified a significant increase in the severity of dysphagia after II-level ACDF with rhBMP-2 compared to patients who did not receive rhBMP-2. To date, this topic has not been studied prospectively. PURPOSE: Compare the incidence of dysphagia following anterior cervical discectomy and fusion (ACDF) when recombinant human bone morphogenetic protein-2 (rhBMP-2) is used with allograft compared to allograft alone. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: A total of 114 patients completed a baseline SWAL-QOL survey and met the inclusion criteria. Thirty-nine patients underwent I- or II-level ACDF with allograft plus 0.5mg rhBMP-2/level. 44 patients underwent ACDF with allograft alone. Thirty-one patients undergoing a lumbar decompression were enrolled in a third cohort to control for dysphagia secondary to intubation. OUTCOME MEASURES: The primary outcome measure was the 14-point SWAL-QOL dysphagia questionnaire. Other patient factors obtained from anesthesia and operative records were examined to evaluate their potential relationship to postoperative dysphagia. METHODS: The 14-point SWAL-QOL questionnaire was administered at multiple time points (pre-op, post-op 7 days, 6 weeks, 6 months, and at least 1 year). Multivariable repeated-measures analysis was applied to data. RESULTS: Baseline adjusted SWAL-QOL means 7 days after surgery were significantly different between the three study groups. These differences resolved by 6 weeks postoperative, beyond which point there were no differences. At final follow-up, baseline adjusted SWAL-QOL means at 1 year were similar for the three study groups. CONCLUSIONS: This single-center study of anterior cervical surgery demonstrated that the addition of rhBMP-2 to an ACDF increased postoperative dysphagia at 7 days after surgery, but these patients recover to levels comparable to those who underwent ACDF without rhBMP-2 or lumbar surgery within 6 weeks.

Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion.

Importance: There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions. Objective: To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. Design, Setting, and Participants: This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020. Exposures: Donor sex and mean donor age. Main Outcomes and Measures: The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. Results: In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. Conclusions and Relevance: These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.

A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.

IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques.

Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy, nonpathogenic infections in natural hosts, such African green monkeys, are characterized by a lack of gut microbial translocation and robust secondary lymphoid natural killer cell responses resulting in an absence of chronic inflammation and limited SIV dissemination in lymph node B-cell follicles. Here we report, using the pathogenic model of antiretroviral therapy-treated, SIV-infected rhesus macaques that sequential interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells (NKG2a/clowCD16+) with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides. This is in contrast to control macaques, where less differentiated, interferon gamma-producing natural killer cells predominate. The frequency and activity of terminally differentiated NKG2a/clowCD16+ natural killer cells correlates with a reduction of replication-competent SIV in lymph node during antiretroviral therapy and time to viral rebound following analytical treatment interruption. These data demonstrate that African green monkey-like natural killer cell differentiation profiles can be rescued in rhesus macaques to promote viral clearance in tissues.

Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.

Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIVmac239-infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <104 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs.IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy.

Observational study of cytomegalovirus from breast milk and necrotising enterocolitis.

OBJECTIVE: To evaluate the relationship between cytomegalovirus (CMV) exposure from breast milk and risk of necrotising enterocolitis (NEC). DESIGN: Secondary analysis of a multicentre, observational cohort study. Maternal breast milk and infant serum or urine were serially evaluated by nucleic acid testing at scheduled intervals for CMV. Infants with evidence of congenital infection were excluded. Competing-risks Cox models, with adjustment for confounders, were used to evaluate the relationship between breast milk CMV exposure or postnatal CMV infection and NEC. SETTING: Three neonatal intensive care units in Atlanta, Georgia. PATIENTS: Infants with a birth weight≤1500 grams. EXPOSURES: Maximal CMV viral load in breast milk in the first 14 days after birth or postnatal CMV infection. Two different approaches were used to assess the timing of onset of CMV infection (midpoint or early). MAIN OUTCOME MEASURES: NEC, defined as Bell stage II or greater. RESULTS: Among 596 enrolled infants, 457 (77%) were born to CMV seropositive mothers and 33 developed postnatal CMV infection (cumulative incidence 7.3%, 95% CI 5.0% to 10.1%). The incidence of NEC was 18% (6/33) among infants with CMV infection, compared with 7% (37/563) among infants without infection (adjusted cause-specific HR (CSHR): 2.81; 95% CI 0.73 to 10.9 (midpoint); 6.02; 95% CI 1.28 to 28.4 (early)). Exposure to higher breast milk CMV viral load was associated with a higher risk of NEC (adjusted CSHR per twofold increase 1.28; 95% CI 1.06 to 1.54). CONCLUSIONS: CMV exposure from breast milk may be associated with the development of NEC in very low birth weight infants.

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.

The effects of roux en y gastric bypass surgery on neurobehavioral symptom domains associated with severe obesity.

BACKGROUND: Neurobehavioral symptoms and cognitive dysfunction related to mood disorders are present in individuals with severe obesity. We sought to determine acute improvements in these symptoms and relationships with adiposity, inflammation, and insulin sensitivity after roux-en-y gastric bypass (RYGB) surgery. METHODS: The self-report Zung Depression Rating (ZDRS) and Neurotoxicity Rating (NRS) scales were administered before, and at 6-months after RYGB surgery in severely obese women (body mass index > 35 kg/m2; N = 19). Symptom domains corresponding to depressed mood/suicide ideation, anxiety, cognitive, somatic, and neurovegetative symptoms were assessed. Biologic measures were of adiposity [leptin, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue], inflammation [IL-6, C-reactive protein (CRP)], and insulin sensitivity (Si). Spearman correlations and linear regression (adjusted for biologic measures) assessed relationships between changes in biologic measures and changes in neurobehavioral domains. RESULTS: By 6-months after RYGB, VAT, SAT, Si, CRP, and IL-6 had improved (p < .05). Anxiety, somatic, and neurovegetative symptoms domains improved (p < .05), but depressed mood/suicidal ideation and cognitive domains did not. Reductions in VAT were associated with decreases in neurovegetative symptoms (beta = 295 ±â€¯85, p < .01). We also found significant positive longitudinal associations between IL-6 concentrations and minor changes in cognitive symptoms. CONCLUSION: Anxiety, somatic and neurovegetative symptoms, improved within 6 months after RYGB, but depressed mood/suicidal ideation and cognitive symptoms did not improve. Associations between visceral adiposity, IL-6 concentrations and neurovegetative and cognitive symptoms support links between obesity, inflammation and distinct neurobehavioral symptoms.

Platelet transfusions and mortality in necrotizing enterocolitis.

BACKGROUND: Prior studies have suggested an association between platelet transfusions (PTXs) and worse outcomes among infants with necrotizing enterocolitis (NEC), potentially mediated by proinflammatory factors released by platelets. However, the effects of storage on platelet proinflammatory factor release and the confounding role of illness severity on NEC outcomes have not been determined. STUDY DESIGN AND METHODS: First, neuropeptide Y (a potent splanchnic vasoconstrictor released by platelets) was measured by enzyme-linked immunosorbent assay in fresh frozen plasma and in the supernatant of leukoreduced apheresis-derived platelets at different times during storage. Next, we evaluated the relationship between PTX rates and death in a multicenter cohort of very-low-birth-weight infants with NEC, adjusting for illness severity. RESULTS: Neuropeptide Y levels increased over time in the supernatant of leukoreduced apheresis-derived platelets and were 4.4-fold and 8.9-fold higher than in fresh frozen plasma on Days 2 and 3 of storage, respectively (p < 0.001). Among 598 very-low-birth-weight infants, 44 developed NEC. In unadjusted analysis, PTX rate was 30.3 (95% confidence interval [CI], 11.5-80.1) per 100 infant-days among infants who died, compared to 6.0 (95% CI, 3.2-11.2) among survivors (incidence rate ratio, 5.1; 95% CI, 1.6-16.2; p = 0.006). In multivariable analysis, there was no association between PTX rate and mortality (incidence rate ratio, 3.0; 95% CI, 0.6-15.0; p = 0.18), although estimation was imprecise. CONCLUSION: Proinflammatory mediators accumulate in platelet suspensions during storage. Although PTX rates were not associated with increased mortality among infants with NEC in our study, our estimates suggest the potential for such an association that needs evaluation in larger studies.

Medicaid Payer Status Is Associated with Increased 90-Day Morbidity and Resource Utilization Following Primary Total Hip Arthroplasty: A Propensity-Score-Matched Analysis.

BACKGROUND: Medicaid payer status has been shown to affect risk-adjusted outcomes and resource utilization across multiple medical specialties. The purpose of this study was to examine resource utilization via readmission rates, length of stay, and total cost specific to Medicaid payer status following primary total hip arthroplasty. METHODS: The Nationwide Readmissions Database (NRD) was utilized to identify patients who underwent total hip arthroplasty in 2013 as well as corresponding "Medicaid" or "non-Medicaid" payer status. Demographic data, 14 individual comorbidities, readmission rates, length of stay, and direct cost were evaluated. A propensity-score-based matching model was utilized to control for baseline confounding variables between payer groups. Following propensity-score matching, the chi-square test was used to compare readmission rates between the 2 payer groups. The relative risk (RR) with 95% confidence interval (CI) was estimated to quantify readmission risk. Length of stay and total cost comparisons were evaluated using the Wilcoxon signed-rank test. RESULTS: A total of 5,311 Medicaid and 144,814 non-Medicaid patients managed with total hip arthroplasty were identified from the 2013 NRD. A propensity score was estimated for each patient on the basis of the available baseline demographics, and 5,311 non-Medicaid patients were matched by propensity score to the 5,311 Medicaid patients. Medicaid versus non-Medicaid payer status yielded significant differences in overall readmission rates of 28.8% versus 21.0% (p < 0.001; RR = 1.37 [95% CI, 1.28 to 1.46]) and 90-day hip-specific readmission rates of 2.5% versus 1.8% (p = 0.01; RR = 1.38 [95% CI, 1.07 to 1.78]). Mean length of stay was greater in the Medicaid group than in the non-Medicaid group at 4.5 versus 3.3 days (p < 0.0001), as was the mean total cost at $71,110 versus $65,309 (p < 0.0001). CONCLUSIONS: This study demonstrates that Medicaid payer status is independently associated with increased resource utilization, including readmission rates, length of stay, and total cost following primary total hip arthroplasty. Providers may have a disincentive to treat patient populations who require increased resource utilization following surgery. Risk adjustment models accounting for Medicaid payer status are necessary to avoid decreased access to care for this patient population and to avoid financial penalty for physicians and hospitals alike. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

High-resolution plasma metabolomics analysis to detect Mycobacterium tuberculosis-associated metabolites that distinguish active pulmonary tuberculosis in humans.

INTRODUCTION: Pulmonary tuberculosis (TB) is a major worldwide health problem that lacks robust blood-based biomarkers for detection of active disease. High-resolution metabolomics (HRM) is an innovative method to discover low-abundance metabolites as putative blood biomarkers to detect TB disease, including those known to be produced by the causative organism, Mycobacterium tuberculosis (Mtb). METHODS: We used HRM profiling to measure the plasma metabolome for 17 adults with active pulmonary TB disease and 16 of their household contacts without active TB. We used a suspect screening approach to identify metabolites previously described in cell culture studies of Mtb based on retention time and accurate mass matches. RESULTS: The association of relative metabolite abundance in active TB disease subjects compared to their household contacts predicted three Mtb-associated metabolites that were significantly increased in the active TB patients based on accurate mass matches: phosphatidylglycerol (PG) (16:0_18:1), lysophosphatidylinositol (Lyso-PI) (18:0) and acylphosphatidylinositol mannoside (Ac1PIM1) (56:1) (p<0.001 for all). These three metabolites provided excellent classification accuracy for active TB disease (AUC = 0.97). Ion dissociation spectra (tandem MS/MS) supported the identification of PG (16:0_18:1) and Lyso-PI (18:0) in the plasma of patients with active TB disease, though the identity of Ac1PIM1 could not be definitively confirmed. CONCLUSIONS: Presence of the Mtb-associated lipid metabolites PG (16:0_18:1) and Lyso-PI (18:0) in plasma accurately identified patients with active TB disease. Consistency of in vitro and in vivo data suggests suitability for exploring these in future studies for possible development as TB disease biomarkers.

Medicaid is associated with increased readmission and resource utilization after primary total knee arthroplasty: a propensity score-matched analysis.

BACKGROUND: Medicaid payer status has been shown to affect resource utilization across multiple medical specialties. There is no large database assessment of Medicaid and resource utilization in primary total knee arthroplasty (TKA), which this study sets out to achieve. METHODS: The Nationwide Readmissions Database was used to identify patients who underwent TKA in 2013 and corresponding "Medicaid" or "non-Medicaid" payer statuses. Demographics, 15 individual comorbidities, readmission rates, length of stay, and direct cost were evaluated. A propensity score-based matching model was then used to control for baseline confounding variables between payer groups. A chi-square test for paired proportions was used to compare readmission rates between the 2 groups. Length of stay and direct cost comparisons were evaluated using the Wilcoxon signed-rank test. RESULTS: A total of 8372 Medicaid and 268,261 non-Medicaid TKA patients were identified from the 2013 Nationwide Readmissions Database. A propensity score was estimated for each patient based on the baseline demographics, and 8372 non-Medicaid patients were propensity score matched to the 8372 Medicaid patients. Medicaid payer status yielded a statistically significant increase in overall readmission rates of 18.4% vs 14.0% (P < .0001, relative risk = 1.31, 95% confidence interval [1.23-1.41]) with non-Medicaid status and 90-day readmission rates of 10.0% vs 7.4%, respectively (P < .001, relative risk = 1.35, 95% confidence interval [1.22-1.48]). The mean length of stay was longer in the Medicaid group compared with the non-Medicaid group at 4.0 days vs 3.3 days (P < .0001) as well as the mean total cost of $64,487 vs $61,021 (P < .0001). CONCLUSIONS: This study demonstrates that Medicaid payer status is independently associated with increased resource utilization, including readmission rates, length of stay, and total cost after TKA.

Social Capital, Depressive Symptoms, and HIV Viral Suppression Among Young Black, Gay, Bisexual and Other Men Who Have Sex with Men Living with HIV.

Social capital, the sum of an individual's resource-containing social network connections, has been proposed as a facilitator of successful HIV care engagement. We explored relationships between social capital, psychological covariates (depression, stigma and internalized homonegativity), and viral suppression in a sample of young Black gay, bisexual and other men who have sex with men (YB-GBMSM). We recruited 81 HIV-positive YB-GBMSM 18-24 years of age from a clinic setting. Participants completed a cross-sectional survey, and HIV-1 viral load (VL) measurements were extracted from the medical record. Sixty-five percent (65%) were virally suppressed (HIV-1 VL ≤ 40 copies/ml). Forty-seven percent (47%) had a positive depression screen. Depressive symptoms affected viral suppression differently in YB-GBMSM with lower vs. higher social capital (p = 0.046, test for statistical interaction between depression and social capital). The odds of viral suppression among YB-GBMSM with lower social capital was 93% lower among those with depressive symptoms (OR 0.07, p = 0.002); however, there was no association between depressive symptoms and viral suppression among those with higher social capital. Our results suggest that social capital may buffer the strong negative effects of depressive symptoms on clinical outcomes in YB-GBMSM living with HIV. In addition to treating depression, there is a role for interventions to augment social capital among YB-GBMSM living with HIV as a strategy for enhancing care engagement.