We sought to estimate the incidence, prevalence, and racial-ethnic distribution of physician-diagnosed inflammatory bowel disease (IBD) in the United States.
The study used 4 administrative claims ...data sets: a 20% random sample of national fee-for-service Medicare data (2007 to 2017); Medicaid data from Florida, New York, Pennsylvania, Ohio, and California (1999 to 2012); and commercial health insurance data from Anthem beneficiaries (2006 to 2018) and Optum’s deidentified Clinformatics Data Mart (2000 to 2017). We used validated combinations of medical diagnoses, diagnostic procedures, and prescription medications to identify incident and prevalent diagnoses. We computed pooled age-, sex-, and race/ethnicity-specific insurance-weighted estimates and pooled estimates standardized to 2018 United States Census estimates with 95% confidence intervals (CIs).
The age- and sex-standardized incidence of IBD per 100,000 person-years was 10.9 (95% CI, 10.6–11.2). The incidence of IBD peaked in the third decade of life, decreased to a relatively stable level across the fourth to eighth decades, and declined further. The age-, sex- and insurance-standardized prevalence of IBD was 721 per 100,000 population (95% CI, 717–726). Extrapolated to the 2020 United States Census, an estimated 2.39 million Americans are diagnosed with IBD. The prevalence of IBD per 100,000 population was 812 (95% CI, 802–823) in White, 504 (95% CI, 482–526) in Black, 403 (95% CI, 373–433) in Asian, and 458 (95% CI, 440–476) in Hispanic Americans.
IBD is diagnosed in >0.7% of Americans. The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans.
Display omitted
Approximately 2.4 to 2.7 million Americans are diagnosed with inflammatory bowel diseases. The prevalence of inflammatory bowel diseases was highest among non-Hispanic Whites and residents of the Northeast.
Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. ...Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4
and CD8
T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria-two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8
T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4
T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.
Rising anthropogenic carbon emissions have dire environmental consequences, necessitating remediative approaches, which includes use of solid sorbents. Here, aminopolymers (poly(ethylene imine) (PEI) ...and poly(propylene imine) (PPI)) are supported within solid mesoporous MIL-101(Cr) to examine effects of support defect density on aminopolymer-MOF interactions for CO2 uptake and stability during uptake-regeneration cycles. Using simulated flue gas (10 % CO2 in He), MIL-101(Cr)-ρhigh (higher defect density) shows 33 % higher uptake capacity per gram adsorbent than MIL-101(Cr)-ρlow (lower defect density) at 308 K, consistent with increased availability of undercoordinated Cr adsorption sites at missing linker defects. Increasing aminopolymer weight loadings (10-50 wt.%) within MIL-101(Cr)-ρlow and MIL-101(Cr)-ρhigh increases amine efficiencies and CO2 uptake capacities relative to bare MOFs, though both incur CO2 diffusion limitations through confined, viscous polymer phases at higher (40-50 wt.%) loadings. Benchmarked against SBA-15, lower polymer packing densities (PPI>PEI), weaker and less abundant van der Waals interactions between aminopolymers and pore walls, and open framework topology increase amine efficiencies. Interactions between amines and Cr defect sites incur amine efficiency losses but grant higher thermal and oxidative stability during uptake-regeneration cycling. Finally, >25 % higher CO2 uptake capacities are achieved for aminopolymer/MIL-101(Cr)-ρhigh under humid conditions, demonstrating promise for realistic applications.
Rising anthropogenic carbon emissions have dire environmental consequences, necessitating remediative approaches, which includes use of solid sorbents. Here, aminopolymers (poly(ethylene imine) (PEI) ...and poly(propylene imine) (PPI)) are supported within solid mesoporous MIL-101(Cr) to examine effects of support defect density on aminopolymer-MOF interactions for CO
uptake and stability during uptake-regeneration cycles. Using simulated flue gas (10 % CO
in He), MIL-101(Cr)-ρ
(higher defect density) shows 33 % higher uptake capacity per gram adsorbent than MIL-101(Cr)-ρ
(lower defect density) at 308 K, consistent with increased availability of undercoordinated Cr adsorption sites at missing linker defects. Increasing aminopolymer weight loadings (10-50 wt.%) within MIL-101(Cr)-ρ
and MIL-101(Cr)-ρ
increases amine efficiencies and CO
uptake capacities relative to bare MOFs, though both incur CO
diffusion limitations through confined, viscous polymer phases at higher (40-50 wt.%) loadings. Benchmarked against SBA-15, lower polymer packing densities (PPI>PEI), weaker and less abundant van der Waals interactions between aminopolymers and pore walls, and open framework topology increase amine efficiencies. Interactions between amines and Cr defect sites incur amine efficiency losses but grant higher thermal and oxidative stability during uptake-regeneration cycling. Finally, >25 % higher CO
uptake capacities are achieved for aminopolymer/MIL-101(Cr)-ρ
under humid conditions, demonstrating promise for realistic applications.
ABSTRACT
Introduction: X‐linked myotubular myopathy (XLMTM), characterized by severe hypotonia, weakness, respiratory distress, and early mortality, is rare and natural history studies are few. ...Methods: RECENSUS is a multicenter chart review of male XLMTM patients characterizing disease burden and unmet medical needs. Data were collected between September 2014 and June 2016. Results: Analysis included 112 patients at six clinical sites. Most recent patient age recorded was ≤18 months for 40 patients and >18 months for 72 patients. Mean (SD) age at diagnosis was 3.7 (3.7) months and 54.3 (77.1) months, respectively. Mortality was 44% (64% ≤18 months; 32% >18 months). Premature delivery occurred in 34/110 (31%) births. Nearly all patients (90%) required respiratory support at birth. In the first year of life, patients underwent an average of 3.7 surgeries and spent 35% of the year in the hospital. Discussion: XLMTM is associated with high mortality, disease burden, and healthcare utilization. Muscle Nerve 57: 550–560, 2018
Tumor metastases are responsible for death in the majority of cancer patients. Here we have explored the role of the ectonucleotidase CD39 in select models of tumor metastases and further tested the ...therapeutic anticancer activity of the NTPDase inhibitor sodium polyoxotungstate (POM-1). CD39 was expressed on tumor-infiltrating regulatory T cells (Treg), myeloid cells and some NK cells, and it was upregulated on these cells within tumors early after inoculation in vivo. NK cell numbers and effector functions were increased in globally CD39-deficient mice and also in WT mice treated with POM-1. Dosing with POM-1 suppressed experimental and spontaneous metastases in four different tumor models and was well tolerated. This anti-metastatic activity was completely abrogated in mice, that were depleted of NK cells, had IFNγ neutralized or were deficient in CD39 expression in bone marrow-derived cells. POM-1 was highly effective in suppressing metastases when used in combination with BRAFi/MEKi or anti-PD-1/anti-CTLA-4 or IL-2. These data highlight the importance of the CD39 pathway in suppressing NK cell-mediated anti-tumor immunity and validate further the development of CD39-based therapies in the clinic.
We describe long-term functional, neurodiagnostic, and psychosocial outcomes of a cohort of 12 children from Colorado diagnosed with acute flaccid myelitis (AFM) in 2014.
Children were assessed every ...3 months for 1 year or until clinical resolution. Assessments included neurologic examination, MRI, EMG/nerve conduction studies (NCS), functional measures (Assisting Hand Assessment, Hammersmith Functional Motor Scale), and Patient-Reported Outcomes Measurement Information System questionnaires.
Eight of 12 children completed the study. Six of 8 had persistent motor deficits at 1 year; 2 demonstrated full recovery. Four were not enrolled, 2 of whom reported full recovery. The 6 affected were weakest in proximal muscles, showing minimal to no improvement and significant atrophy at 1 year. All patients improved in distal muscle groups. Cranial nerve dysfunction resolved in 2 of 5 and improved in all. Four of 5 showed progressive functional improvement at 6 and 12 months. Two of 8 reported pain at 1 year. Three of 8 reported depressive symptoms. Repeat MRI was performed in 7 of 8 children a median of 7 months after onset and showed significant improvement or normalization in all but one child. Repeat EMG/NCS was performed on 4 children a median of 8 months after onset and showed ongoing denervation and chronic reinnervation in 3 children with persistent deficits.
At 1 year, children with AFM demonstrated functional gains but weakness persisted. EMG changes correlated with persistent deficits better than imaging. Despite improvements, AFM had substantial long-term functional effects on affected children.
The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer ...passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.
PDF
