Blood-based biomarkers have been proposed as an alternative to liver biopsy for non-invasive liver disease assessment (NILDA) in chronic liver disease (CLD). Our aims for this systematic review were ...to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4) and cirrhosis (F4), as compared to biopsy in CLD.
We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in hepatitis B virus (HBV) and C virus (HCV), HIV-HCV/HBV co-infection, and nonalcoholic fatty liver disease (NAFLD). Positive (LR+) and negative (LR) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86 respectively; LR+ and LR for NAFLD F2-4, F3-4 and F4 were 2-65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15 respectively. Overall, proportional odds ratio indicated FIB-4 <1.45 was better than APRI <0.5 for F2-4. FIB-4 >3.25 was also better than APRI >1.5 for F3-4 and F4. There was limited data for combined tests.
Blood-based biomarkers are associated with small-to-moderate change in pre-test probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV co-infection, and NAFLD, with limited comparative or combination studies for other CLD.
To compare effectiveness and safety of large-bore aspiration thrombectomy (LBAT) with catheter-directed thrombolysis (CDT) for treatment of acute massive and submassive pulmonary embolism (PE).
This ...retrospective review included patients with acute PE treated with LBAT or CDT using tissue plasminogen activator (tPA) between December 2009 and May 2020. A propensity score based on Pulmonary Embolism Severity Index class and PE severity (massive vs submassive) was calculated, and 26 LBAT cases (age 60.2 y ± 17.1, 14/26 women) were matched with 26 CDT cases (age 59.7 y ± 14.2, 14/26 women).
The CDT group had 22.1 mg ± 8.1 tPA infused over 21.2 h ± 6.6. Both groups demonstrated similar initial and final systolic pulmonary artery pressure (PAP) (LBAT: 54.5 mm Hg ± 12.9 vs CDT: 54.5 mm Hg ± 16.3, P = .8, and LBAT: 42.5 mm Hg ± 14.1 vs CDT: 42.6 mm Hg ± 12.1, P = .8, respectively) and similar reductions in heart rate (LBAT: -5.4 beats/min ± 19.2 vs CDT: -9.6 beats/min ± 15.8, P = .4). CDT demonstrated a higher reduction in Miller score (-10.1 ± 3.9 vs -7.5 ± 3.8, P = .02). LBAT resulted in 1 minor hemorrhagic complication and 2 procedure-related mortalities, and CDT resulted in 1 minor and 1 major hemorrhagic complication.
LBAT and CDT resulted in similar reductions of PAP and heart rate when used to treat acute PE. CDT reduced thrombus burden to a greater degree. Although hemorrhagic complications rates were not significantly different, the LBAT group demonstrated a higher rate of procedure-related mortality. Larger studies are needed to compare the safety of these techniques.
Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize ...bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.
Background and Aims: Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied ...imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). Approach and Results: A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. Conclusions: LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in ...resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To identify factors that increase the risk of gastrointestinal-related (GI-related) hospitalization of infants with cystic fibrosis (CF) during the first year of life.
The Baby Observational and ...Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post-hoc assessment of the frequency and indications for GI-related admissions during the first year of life.
Sixty-five participants had at least one admission in the first 12 months of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000 lipase units/kg per meal; hazard ratio HR = 14.75, P = 0.0005) and use of acid suppressive medications (HR = 4.94, P = 0.01) during the study period were positively associated with subsequent GI-related admissions. High levels of fecal calprotectin (fCP) (>200 μg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI-related admissions (HR = 2.64, P = 0.033 and HR = 4.49, P = 0.002, respectively). During the first 12 months of life, participants with any admission had lower weight-for-length z scores (WLZ) (P = 0.01). The impact of admission on WLZ was particularly evident in participants with a GI-related admission (P < 0.0001).
Factors associated with a higher risk for GI-related admission during the first 12 months include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI-related hospitalization had lower WLZ at 12 months of age than those not admitted as well as those admitted for non-GI-related indications.
Purpose: To present the results of rheolytic pharmacomechanical thrombectomy (PMT) for the management of acute limb ischemia (ALI) as reported in the PEARL Registry (PEripheral Use of AngioJet ...Rheolytic Thrombectomy with a variety of catheter Lengths). Methods: A total of 283 patients (mean age 65±13 years; 170 men) presenting with ALI undergoing treatment with the AngioJet System at participating institutions were enrolled in the registry. Rutherford ALI categories included 26% with viable limbs, 38% with marginally threatened limbs, 35% with immediately threatened limbs, and <1% with irreversible damage. Procedure and follow-up data were collected for the calculation of outcomes. To control for patient selection bias, propensity score matching was used to compare outcomes for patients undergoing PMT with or without catheter-directed thrombolysis (CDT). Results: Procedure success was achieved in 235 (83%) of 283 patients. Half of the procedures (147, 52%) were completed without the need for adjunctive CDT. At 12-month follow-up, amputation-free survival and freedom from mortality were 81% and 91%, respectively; 12-month freedom from bleeding requiring transfusion was 91%, and freedom from renal failure was 95%. Subgroup analysis revealed significantly better outcomes in patients without infrapopliteal involvement and those who underwent PMT without CDT. In the matched cohorts, higher rates of procedure success, 12-month amputation-free survival, and 12-month freedom from amputation were observed in the PMT without CDT group (88% vs 74%, p=0.021; 87% vs 72%, p=0.028; 96% vs 81%, p=0.01, respectively). Conclusions: The results support the use of PMT as a first-line treatment for ALI, providing a rapid reperfusion to the extremity, reduced procedure time, and an acceptable risk profile without compromising limb salvage.
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