Nevin Manimala

J Allergy Clin Immunol. 2024 Aug 13:S0091-6749(24)00817-0. doi: 10.1016/j.jaci.2024.07.024. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5 and IL-13 cytokines produced by T_H2 lymphocytes or type 2 innate lymphoid cells (ILC2s). Interleukin-2 family cytokines play a key role in the differentiation, homeostasis and effector function of innate and adaptive lymphocytes.

OBJECTIVE: IL-9 and IL-21 boost the activation and proliferation of T_H2 and ILC2s, but the relative importance and potential synergism between these γc cytokines is currently unknown.

METHODS: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination, in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human allergic asthmatics in comparison to non-asthmatic controls. Here, we also measured IL-21 in both groups.

RESULTS: IL-9 played a central role in controlling innate IL-33 induced lung inflammation by promoting proliferation and activation of ILC2s, in an IL-21 independent manner. Conversely, chronic house dust mite induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, that controlled T_H2 activation, eosinophilia, total serum IgE and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, since combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage (BAL) samples we measured elevated IL-21 protein within the allergic asthmatic group, compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets.

CONCLUSION: IL-9 and IL-21 play important and non-redundant roles in allergic asthma by boosting ILC2s and T_H2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.

PMID:39147327 | DOI:10.1016/j.jaci.2024.07.024

J Shoulder Elbow Surg. 2024 Aug 14:S1058-2746(24)00466-X. doi: 10.1016/j.jse.2024.05.020. Online ahead of print.

ABSTRACT

BACKGROUND: Proximal humerus nonunion is a challenging complication of fractures that can be treated surgically with either open reduction internal fixation (ORIF) or reverse total shoulder arthroplasty (RTSA). The few studies published on this subject have shown high rates of complications and revision surgery when RTSA has been performed for proximal humerus nonunion. The purpose of this study was to determine the rates of complications and revision of this procedure at our institution, as well as to identify any variables that may impact risks of complications and reoperations.

METHODS: A single-institution retrospective review of all patients who underwent RTSA for proximal humerus nonunion between 2005 and 2021 was performed. Nonunion was defined as imaging evidence of lack of union, at least 90 days after the index fracture. Patients with less than one year of clinical follow-up were excluded. Fifty patients were included, with the majority being female (78%). The mean age at time of RTSA was 71 (range: 54-86) years and most patients were initially treated nonoperatively (74%). Mean total follow-up was 49 (range: 11-130) months. Demographic and surgical variables were recorded. Primary outcomes were complications and reoperations. Complications were divided into surgical (those directly related to RTSA), or other (those unrelated to RTSA). Secondary outcomes included VAS pain scores and range of motion.

RESULTS: A total of 17 shoulders (34%) sustained complications after RSA, with 10 (20%) requiring reoperation. Six patients (12%) sustained dislocations and 5 (10%) had radiographic evidence of humeral loosening. No variables examined, including nonoperative vs surgical management of the index fracture, prosthesis type, or management of tuberosities, influenced the risk of dislocation. Survivorship free from reoperation at 2 years was 73%. Younger age at time of RTSA and the presence of diabetes mellitus both increased the risk of reoperation significantly (p=0.013 and p=0.037, respectively). There was a trend towards increased risk of reoperation in patients who were treated with initial ORIF (HR=2.95); however, this did not reach statistical significance (p=0.088). Three patients (6%) sustained a periprosthetic fracture after a fall.

CONCLUSION: RTSA provides improved pain and function for properly selected patients with proximal humerus nonunion. Dislocation, humeral loosening, and reoperation rates remain high when RTSA is performed for nonunion compared to other diagnoses. In this study, younger age and diabetes mellitus increased the odds of reoperation. Every effort must be made to optimize implant stability and humeral component fixation when RTSA is performed for proximal humerus nonunion.

PMID:39147268 | DOI:10.1016/j.jse.2024.05.020

Int J Radiat Oncol Biol Phys. 2024 Aug 13:S0360-3016(24)03230-9. doi: 10.1016/j.ijrobp.2024.08.007. Online ahead of print.

ABSTRACT

PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here.

METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed.

RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 – 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0.

CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

PMID:39147209 | DOI:10.1016/j.ijrobp.2024.08.007

Int J Radiat Oncol Biol Phys. 2024 Aug 13:S0360-3016(24)03206-1. doi: 10.1016/j.ijrobp.2024.07.2335. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: Ependymomas are the third most common brain tumors in children. Standard of care is surgery followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. We completed a systematic review and meta-analysis to determine the optimal dose for local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients.

MATERIALS & METHODS: We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science through January 2024. We included cohort studies that compared adjuvant radiotherapy of ≤54Gy to >54Gy in pediatric patients (≤22 years) with non-metastatic intracranial ependymomas. We assessed study quality using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and assessed statistical heterogeneity via I². When HRs were unavailable, we transformed risks using established methods. We narratively summarized qualitative outcomes.

RESULTS: Seven studies met our inclusion criteria, covering a combined 1321 patients. Studies included a range of doses from 45-66.6Gy. Compared with >54Gy, we found no difference in LC for those receiving ≤54Gy (HR=0.83, 95% CI 0.56-1.24, I²=49.1%), in EFS (HR=1.02, 95% CI 0.95-1.09, I²=0.00%), and OS (HR=0.99, 95% CI 0.82-1.20, I²=37.5%). Two studies reported on subtotal resection by radiotherapy dose, neither study reporting statistical differences in LC, EFS, or OS, though the number of patients was small (n≤30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequent. Overall study quality was high, though lower scores were consistently seen in comparability of cohorts. No studies reported on molecular subgroups.

CONCLUSIONS: We found no difference in LC, EFS, or OS for those treated with ≤54Gy compared to >54Gy. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on extent of resection or molecular subgroups.

PMID:39147207 | DOI:10.1016/j.ijrobp.2024.07.2335

J Hypertens. 2024 Aug 14. doi: 10.1097/HJH.0000000000003824. Online ahead of print.

ABSTRACT

OBJECTIVE: A high office blood pressure (BP) is associated with cognitive decline. However, evidence of 24-h ambulatory BP monitoring is limited, and no studies have investigated whether longitudinal changes in 24-h BP are associated with cognitive decline. We aimed to test whether higher longitudinal changes in 24-h ambulatory BP measurements are associated with cognitive decline.

METHODS: We included 437 dementia-free participants from the Maracaibo Aging Study with prospective data on 24-h ambulatory BP monitoring and cognitive function, which was assessed using the selective reminding test (SRT) and the Mini-Mental State Examination (MMSE). Using multivariate linear mixed regression models, we analyzed the association between longitudinal changes in measures of 24-h ambulatory BP levels and variability with cognitive decline.

RESULTS: Over a median follow-up of 4 years (interquartile range, 2-5 years), longitudinal changes in 24-h BP level were not associated with cognitive function (P ≥ 0.09). Higher longitudinal changes in 24-h and daytime BP variability were related to a decline in SRT-delayed recall score; the adjusted scores lowered from -0.10 points [95% confidence interval (CI), -0.16 to -0.04) to -0.07 points (95% CI, -0.13 to -0.02). We observed that a higher nighttime BP variability during follow-up was associated with a decline in the MMSE score (adjusted score lowered from -0.08 to -0.06 points).

CONCLUSION: Higher 24-h BP variability, but not BP level, was associated with cognitive decline. Prior to or in the early stages of cognitive decline, 24-h ambulatory BP monitoring might guide strategies to reduce the risk of major dementia-related disorders including Alzheimer’s disease.

PMID:39146553 | DOI:10.1097/HJH.0000000000003824

Neurol Neuroimmunol Neuroinflamm. 2024 Sep;11(5):e200282. doi: 10.1212/NXI.0000000000200282. Epub 2024 Aug 15.

ABSTRACT

BACKGROUND AND OBJECTIVES: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.

METHODS: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage.

RESULTS: MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor’s degree or higher (OR 0.42, 95% CI 0.22-0.80, p = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; p = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS.

DISCUSSION: Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.

PMID:39146511 | DOI:10.1212/NXI.0000000000200282

Am J Manag Care. 2024 Aug;30(8):381-386. doi: 10.37765/ajmc.2024.89589.

ABSTRACT

OBJECTIVES: To examine characteristics of Medicare Advantage (MA) enrollees who use their plan’s customer service to help plans understand how to better meet members’ needs.

STUDY DESIGN: National sample of 259,533 respondents to MA Consumer Assessment of Healthcare Providers and Systems survey enrolled in any of the 559 MA contracts in 2022.

METHODS: We assessed the association between self-reported customer service use in the prior 6 months and enrollee demographic, coverage, health, and health care utilization characteristics. We used weighted linear regression models to test for bivariate and multivariate associations between customer service use and enrollee characteristics.

RESULTS: Forty-two percent of MA enrollees reported using customer service in the prior 6 months. Use was 20 percentage points (PP) higher for those in poor vs excellent/very good general health, 13 PP higher for those in poor vs excellent/very good mental health, and 14 PP higher for those reporting 3 or more vs no chronic conditions. Those using customer service more often had lower educational attainment, had limited income and assets, preferred another language to English, and had greater health care utilization.

CONCLUSIONS: MA customer service supports a less healthy, higher-need population with greater-than-average barriers to health care, and so should be designed and staffed to effectively serve medically complex, high-need patients. Commercial plan evidence suggests that continuity in customer service support for a member or a given issue may be helpful. Customer service is an important mechanism for improving quality and addressing health equity.

PMID:39146487 | DOI:10.37765/ajmc.2024.89589

Am J Manag Care. 2024 Aug;30(8):374-379. doi: 10.37765/ajmc.2024.89588.

ABSTRACT

OBJECTIVE: To determine the geographic variability of Medicaid acceptance among allergists in the US.

STUDY DESIGN: Geospatial analysis predicted Medicaid acceptance across space, and a multivariable regression identified area-level population demographic variables associated with acceptance.

METHODS: We used the National Plan & Provider Enumeration System database to identify allergists. Medicaid acceptance was determined from lists or search engines from state Medicaid offices and calls to provider offices. Spatial analysis was performed using the empirical Bayesian kriging tool. Multivariate logistic regression was used to identify county-level characteristics associated with provider Medicaid acceptance.

RESULTS: Of 5694 allergists, 55.5% accepted Medicaid. Acceptance in each state ranged from 13% to 90%. Washington, Arizona, and the Northeast had lowest predicted proportion of both Medicaid acceptance and Medicaid acceptance per 10,000 enrollees. Overall, county-level characteristics were not associated with the likelihood of accepting Medicaid in multivariate analyses. Only the percentage of individuals living in poverty was associated with a higher likelihood of providers accepting Medicaid (OR, 1.245; 95% CI, 1.156-1.340; P < .001).

CONCLUSIONS: A barrier to accessing allergy-related health care is finding a provider who accepts a patient’s insurance, which is largely variable by state. Lack of access to allergy care likely affects health outcomes for children with prevalent atopic conditions such as food allergy.

PMID:39146486 | DOI:10.37765/ajmc.2024.89588

Am J Manag Care. 2024 Aug;30(8):365-371. doi: 10.37765/ajmc.2024.89587.

ABSTRACT

OBJECTIVES: To discuss the social, psychological, and access barriers that inhibit weight loss, and to propose steps and initiatives for addressing the growing obesity epidemic.

STUDY DESIGN: Narrative review of the obesity epidemic in the US and associated racial/ethnic and socioeconomic disparities.

METHODS: An internet search of relevant studies and government reports was conducted.

RESULTS: Obesity is a significant health crisis affecting more than 123 million adults and children/adolescents in the US. An estimated 1 in 5 deaths in Black and White individuals aged 40 to 85 years in the US is attributable to obesity. Obesity puts individuals at elevated risk for type 2 diabetes, cardiovascular disease, chronic kidney disease, gastrointestinal disorders, nonalcoholic fatty liver disease, cancer, respiratory ailments, dementia/Alzheimer disease, and other disorders. In the US, significantly more Black (49.9%) and Hispanic (45.6%) individuals are affected by obesity than White (41.4%) and Asian (16.1%) individuals. Health care costs for obesity account for more than $260 billion of annual US health care spending-more than 50% greater in excess annual medical costs per person than individuals with normal weight.

CONCLUSIONS: Addressing the obesity epidemic will require a multifaceted approach that focuses on prevention, treatment, and reducing the impact of stigma. Continued advocacy and education efforts are necessary to make progress and improve the health and well-being of individuals affected by obesity.

PMID:39146485 | DOI:10.37765/ajmc.2024.89587

Am J Manag Care. 2024 Aug;30(8):353-358. doi: 10.37765/ajmc.2024.89559.

ABSTRACT

OBJECTIVES: To examine a 12-month dementia care management program’s effect on health care cost, utilization, and overall return on investment in a Medicare managed care population.

STUDY DESIGN: Pre-post analysis of participants (n = 121) enrolled in Ochsner’s Care Ecosystem program from 2019 through 2021 compared with propensity-matched controls (n = 121). The primary outcome comparison was total cost of care. Secondary outcomes included components of total cost of care (eg, inpatient, outpatient, emergency department [ED] costs), health care utilization (eg, number of ED visits), and differences in Hierarchical Condition Category (HCC) risk scores.

METHODS: Difference-in-differences analyses were conducted from baseline through 12 months comparing various financial metrics and utilization between groups.

RESULTS: Care Ecosystem participants had significantly lower total cost of care at 12 months, mean savings of $475.80 per member per month compared with controls. Care Ecosystem participants had fewer ED, outpatient, and professional visits. HCC risk scores were also better relative to matched controls.

CONCLUSIONS: A collaborative dementia care program demonstrated significant financial benefit in a managed Medicare population.

PMID:39146484 | DOI:10.37765/ajmc.2024.89559