Association between dysglycemia and the Charlson Comorbidity Index among hospitalized patients with diabetes

AimInpatient dysglycemia has been linked to short-term mortality, but longer-term mortality data are lacking. Our aim was to evaluate the association between inpatient dysglycemia and one-year mortality risk.MethodsRetrospective chart review of adults with diabetes hospitalized between 2015 and 2019. The Charlson Comorbidity Index (CCI) was used to estimate 1-year mortality risk, stratified into low (CCI ≤ 5) and high risk (CCI ≥6). Simple and multivariable logistic regression was used to evaluate the association between dysglycemic measures and high mortality risk.ResultsAmong 22,639 unique admissions, BG ≥ 180, ≥300, ≤70, <54 and <40 mg/dL were associated with adjusted odds of 1.43 (95 % CI, 1.33, 1.54), 1.58 (95 % CI, 1.48, 1.68), 2.16 (95 % CI, 2.01, 2.32), 2.58 (95 % CI, 2.32, 2.86), and 2.56 (95 % CI, 2.19, 2.99) for high mortality risk, respectively. Older age and Black race were positively associated with hyperglycemia and hypoglycemia. Myocardial infarction, congestive heart failure (CHF), and moderate to severe liver disease were most strongly associated with hyperglycemia, while renal disease, CHF, peripheral vascular disease, and peptic ulcer disease were most strongly associated with hypoglycemia.ConclusionsInpatient hypoglycemia and hyperglycemia were both positively associated with higher one-year mortality risk, with stronger magnitude of association observed for hypoglycemia. The association appears to be mediated mainly by presence of diabetes-related complications.     

Long-term survival and postoperative complications of pre-liver transplantation transarterial chemoembolisation in hepatocellular carcinoma: A systematic review and meta-analysis

ObjectivesThe aim of this meta-analysis was to conduct a contemporary systematic review of high quality non-randomised controlled trials to determine the effect of pre-liver transplantation (LT) transarterial chemoembolisation (TACE) on long-term survival and complications of hepatocellular carcinoma (HCC) patients.BackgroundTACE is used as a neoadjuvant therapy to mitigate waitlist drop-out for patients with HCC awaiting LT. Previous studies have conflicting conclusions on the effect of TACE on long-term survival and complications of HCC patients undergoing LT.MethodsCINAHL, Cochrane Controlled Register of Trials, Embase, PubMed, and Web of Science were systematically searched. Baseline characteristics included number of patients outside Milan criteria, tumour diameter, MELD score, and time on the waiting list. Primary outcomes included 3- and 5-year overall and disease-free survival. Secondary outcomes included tumour recurrence, 30-day postoperative mortality, and hepatic artery and biliary complications.ResultsTwenty-one high-quality NRCTs representing 8242 patients were included. Tumour diameter was significantly larger in TACE patients (3.49 cm vs 3.15 cm, P = 0.02) and time on the waiting list was significantly longer in TACE patients (4.87 months vs 3.46 months, P = 0.05), while MELD score was significantly higher in non-TACE patients (10.81 vs 12.35, P = 0.005). All primary and secondary outcomes displayed non-significant differences.ConclusionPatients treated with TACE had similar survival and postoperative outcomes to non-TACE patients, however, they had worse prognostic features compared to non-TACE patients. These findings strongly support the current US and European clinical practice guidelines that neoadjuvant TACE can be used for patients with longer expected waiting list times (specifically >6 months). Randomised controlled trials would be needed to increase the quality of evidence.     

Skin3D: Detection and longitudinal tracking of pigmented skin lesions in 3D total-body textured meshes

We present an automated approach to detect and longitudinally track skin lesions on 3D total-body skin surface scans. The acquired 3D mesh of the subject is unwrapped to a 2D texture image, where a trained objected detection model, Faster R-CNN, localizes the lesions within the 2D domain. These detected skin lesions are mapped back to the 3D surface of the subject and, for subjects imaged multiple times, we construct a graph-based matching procedure to longitudinally track lesions that considers the anatomical correspondences among pairs of meshes and the geodesic proximity of corresponding lesions and the inter-lesion geodesic distances.We evaluated the proposed approach using 3DBodyTex, a publicly available dataset composed of 3D scans imaging the coloured skin (textured meshes) of 200 human subjects. We manually annotated locations that appeared to the human eye to contain a pigmented skin lesion as well as tracked a subset of lesions occurring on the same subject imaged in different poses. Our results, when compared to three human annotators, suggest that the trained Faster R-CNN detects lesions at a similar performance level as the human annotators. Our lesion tracking algorithm achieves an average matching accuracy of 88% on a set of detected corresponding pairs of prominent lesions of subjects imaged in different poses, and an average longitudinal accuracy of 71% when encompassing additional errors due to lesion detection. As there currently is no other large-scale publicly available dataset of 3D total-body skin lesions, we publicly release over 25,000 3DBodyTex manual annotations, which we hope will further research on total-body skin lesion analysis.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Trained immunity of alveolar macrophages requires metabolic rewiring and type 1 interferon signaling

Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred to as trained immunity. Here, we investigated whether a ubiquitous microbial compound has the potential to induce AM training in vivo. We discovered that intranasal exposure to ambient amounts of lipopolysaccharide (LPS) induced a pronounced AM memory response, characterized by enhanced reactivity upon pneumococcal challenge. Exploring the mechanistic basis of AM training, we identified a critical role of type 1 interferon signaling and found that inhibition of fatty acid oxidation and glutaminolysis significantly attenuated the training effect. Notably, adoptive transfer of trained AMs resulted in increased bacterial loads and tissue damage upon subsequent pneumococcal infection. In contrast, intranasal pre-exposure to LPS promoted bacterial clearance, highlighting the complexity of stimulus-induced immune responses, which likely involve multiple cell types and may depend on the local immunological and metabolic environment. Collectively, our findings demonstrate the profound impact of ambient microbial exposure on pulmonary immune memory and reveal tissue-specific features of trained immunity.