Relationship between ablation index and myocardial biomarkers after radiofrequency catheter ablation for atrial fibrillation

BackgroundFurther in-vivo evidence is needed to support the usefulness of ablation index (AI) in guiding atrial fibrillation (AF) ablation. We aimed at evaluating the relationship between AI and other lesion indicators and the release of myocardial-specific biomarkers following radiofrequency AF ablation.MethodsForty-six patients underwent a first-time radiofrequency AF ablation and were prospectively enrolled in this study. Pulmonary vein isolation was performed by six experienced electrophysiologists with a point-by-point approach, guided by strict Visitag criteria and consistent AI target values. Myocardial-specific biomarkers troponin T and creatine kinase myocardial band were measured after 6 (TnT6 and CKMB6) and 20 h (TnT20 and CKMB20) following sheath removal. Ablation duration, impedance drop (ID), force-time integral (FTI) and AI were registered automatically and analyzed offline.ResultsTnT release was 985 ± 495 ng/L and 1038 ± 461 ng/L (p = ns) while CKMB release was 7.3 ± 2.7 μg/L and 6.5 ± 2.1 μg/L (p < 0.001) at 6 and 20 h respectively. Ablation duration, ID, FTI and AI were all significantly correlated with the release of myocardial-specific biomarkers both at 6 and 20 h. Ablation index showed the highest degree of correlation with TnT6, TnT20, CKMB6 and CKMB20 (Pearson's R 0.69, 0.69, 0.61, 0.64 respectively, p < 0.001). Multiple regression analysis demonstrated that AI had the strongest association with TnT6, TnT20, CKMB6 and CKMB20 (β 0.43, β 0.71, β 0.44 and β 0.43 respectively).ConclusionAblation index appears as the strongest lesion indicator as measured by the release of myocardial-specific biomarkers following radiofrequency catheter ablation for AF.     

Epicardial fat pad within the transverse sinus mimicking a left atrial appendage thrombus

The presence of left atrial thrombus is a contraindication to cardioversion or catheter ablation in patients with atrial fibrillation, due to the increased risk of systemic thromboembolism. Management of this situation includes changes in the anticoagulation regimen and repeat imaging tests. Accurate diagnosis of left atrial appendage thrombus is therefore essential but can sometimes be challenging. Multiple imaging modalities may sometimes be required in the setting of anatomical variations of the left atrial appendage and surrounding structures.We present the case of a patient awaiting ablation for atypical atrial flutter, who underwent a transthoracic echocardiogram that showed an echodense, mobile structure within the vicinity of the left atrial appendage, suggesting a possible thrombus. A cardiac CT demonstrated the image to correlate with an epicardial fat pad within the transverse sinus.     

Mechanical suppression of premature ventricular complexes during catheter ablation procedures

IntroductionMechanical suppression of premature ventricular complexes (PVCs) is not a well-known observation. We retrospectively reviewed this phenomenon in the Ventricular Arrhythmia (VA) ablation procedures performed at Richard L. Roudebush Veterans Health Administration (VHA) center.MethodsData from 40 consecutive patients who underwent VA ablation at VHA, Indianapolis, IN, with 44 VA was included in the study. Demographic and electrophysiological parameter data was collected.ResultsOverall the mean age of the population was 64 ± 11 years. The phenomenon of mechanical suppression was seen in 11 PVCs. The mean age was 59 ± 15 years in the group in which mechanical suppression was seen. Of the 11 cases, the site of earliest activation was seen in the coronary sinus in 8 and in the pulmonary artery in 3. In one case catheter ablation was not performed because of proximity to the left coronary artery system. However, sustained pressure at the site with earliest electrograms (?35 ms) and 95% pacematch resulted in long-term suppression of PVCs. In the cases in which mechanical suppression was seen, there was a statistically significant reduction in PVC burden compared to pre ablation PVC load (1.1% ± 1.50% (post ablation) versus 24.04% ± 13.07% (pre ablation) versus p < 0.05).In all the 11 cases the site of mechanical suppression was also the site with earliest electrograms.ConclusionThis case series illustrates phenomenon of mechanical suppression of PVCs as an indication for good site for successful ablation in unique veteran patient population.     

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review

ObjectiveThe impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT.MethodsA systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included.ResultsFrom 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration.ConclusionsThe results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT.Systematic Review RegistrationPROSPERO, identifier CRD42022323757.     

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis

BackgroundAmong many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin.AimsThis meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19.MethodsA comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio.ResultsA total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59–17.82%, I² – 92%), 10.22% (6.01–16.85%, I² – 79%), and 0.72% (0.34–1.51, I² – 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22–15.52, I² – 59%) and 8.61% (4.52–15.79, I² – 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77–1.93, I² – 0%) & 1.51 (0.79–2.87, I² – 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition).ConclusionThe use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.     

Sympathetic tone dictates the impact of lipolysis on FABP4 secretion

Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGL^AdpKO). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGL^AdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGL^fl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4^AdpKO) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGL^AdpKO mice was indeed from the adipocytes. ATGL^AdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGL^AdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling.     

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.     

Autoantibodies against red blood cell antigens are common in a malaria endemic area

Plasmodium falciparum malaria can cause severe anemia. Even after treatment, hematocrit can decrease. The role of autoantibodies against erythrocytes is not clearly elucidated and how common they are, or what they are directed against, is still largely unknown.We have investigated antibodies against erythrocytes in healthy adult men living in a highly malaria endemic area in Uganda. We found antibodies in more than half of the individuals, which is significantly more than in a non-endemic area (Sweden). Some of the Ugandan samples had a broad reactivity where it was not possible to determine the exact target of the autoantibodies, but we also found specific antibodies directed against erythrocyte surface antigens known to be of importance for merozoite invasion such as glycophorin A (anti-En^a, anti-M) and glycophorin B (anti-U, anti-S). In addition, several autoantibodies had partial specificities against glycophorin C and the blood group systems Rh, Diego (located on Band 3), Duffy (located on ACKR1), and Cromer (located on CD55), all of which have been described to be important for malaria and therefore of interest for understanding how autoantibodies could potentially stop parasites from entering the erythrocyte.In conclusion, specific autoantibodies against erythrocytes are common in a malaria endemic area.     

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

BackgroundCardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn’t been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.MethodsThis is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).ResultssP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.ConclusionOur study supports the previous researches’ results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.     

The Risk Factors for Developing Clustered Vertebral Compression Fractures: A Single-Center Study

ObjectiveVertebral compression fractures (VCFs) are common among elderly individuals, but clustered VCFs (C-VCFs) are rare and more severe. The risk factors for C-VCFs remain unclear. Thus, we investigated the clinical characteristics of C-VCFs to identify the imminent fracture risk and improve the treatment for such patients.MethodsWe reviewed the records of patients with VCF at a single medical center between January 2011 and September 2020. Patients who had 4 or more VCFs within 1 year were categorized into the C-VCF group, and the remaining patients were paired into the control group at a ratio of 2:1. We collected demographic, clinical, laboratory, and radiologic information regarding these patients. Univariate analyses, stratified analyses, and multivariate logistic regression were performed to identify the risk factors for C-VCFs.ResultsA total of 156 patients were enrolled, of whom 52 were patients with C-VCF. Patients with C-VCF had more severe fractures and pain, with fractures occurring at uncommon sites of the spine. The independent risk factors for C-VCFs included glucocorticoid (GC) treatment (P < .001; hazard ratio [HR], 12.7), recent fracture history (P = .021; HR, 5.5), and lower trabecular bone score (TBS) (P = .044; HR, 1.6). TBS and bone mineral density had greater predictive values in patients without GC treatment (P < .001). Sex, age, and bone turnover biomarkers were not independent risk factors for C-VCFs.ConclusionC-VCFs are rare adverse consequences of severe osteoporosis, for which GC treatment, recent fracture history, and lower TBS are unique risk factors that are valuable for the early identification and prevention of C-VCFs.     

Hormonal influences on women's extra-pair sexual interests: The moderating impact of partner attractiveness

Based on the idea that women are especially attracted to ancestral markers of male genetic quality when conceptive in their cycle, scholars have conjectured that increases in women's extra-pair sexual interests during the conceptive phase of the cycle are moderated by their primary partners' sexual attractiveness. Multiple studies have examined this prediction, with largely supportive but mixed results. The current study is the first to examine whether hormonal influences—thought to mediate cycle shifts—on women's extra-pair sexual interests are moderated by partner attractiveness. 213 naturally cycling, romantically involved women (181 attending multiple sessions) participated in up to four sessions over about a month. Estrogen and progesterone levels were measured multiple times across women's cycles. Male partner attractiveness moderated associations between progesterone levels (though not estrogen levels) and women's extra-pair sexual interests. A negative association between progesterone levels and extra-pair sexual interests, a composite measure, was observed for women with relatively unattractive partners. For women with relatively attractive partners, no clear association emerged. The interaction between progesterone and partner attractiveness was robust for women's interest in extra-pair sex, a component preregistered as exploratory. The interaction effect was also significant for the absolute intensity of women's extra-pair attraction (a component item referenced in the preregistration) but was non-significant for the frequency of women's extra-pair attraction relative to typical days (a composite component specified in the preregistration). These findings inform theoretical understandings of women's sexuality.     

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions

ObjectiveThe objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.MethodsA literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.ResultsMinimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.ConclusionSurgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.     

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.     

Expression profiles and functional characterization of common carp (Cyprinus carpio) T2Rs

Bitter taste perception is mediated by a family of G protein-coupled receptors (T2Rs) in vertebrates. Common carp (Cyprinus carpio), which has experienced an additional round of whole genome duplication during the course of evolution, has a small number of T2R genes similar to zebrafish, a closely related cyprinid fish species, and their expression pattern at the cellular level or their cognate ligands have not been elucidated yet. Here, we showed through in situ hybridization experiments, that three common carp T2R (ccT2R) genes encoding ccT2R200-1, ccT2R202-1, and ccT2R202-2, were specifically expressed in the subsets of taste receptor cells in the lips and gill rakers. ccT2R200-1 was co-expressed with genes encoding downstream signal transduction molecules, such as PLC-β2 and Gαia. Heterologous expression system revealed that each ccT2R showed narrowly, intermediately, or broadly tuned ligand specificity, as in the case of zebrafish T2Rs. However, ccT2Rs showed different ligand profiles from their orthologous zebrafish T2Rs previously reported. Finally, we identified three ccT2Rs, namely ccT2R200-1, ccT2R200-2, and ccT2R203-1, to be activated by natural bitter compounds, andrographolide and/or picrotoxinin, which elicited no response to zebrafish T2Rs, in a dose-dependent manner. These results suggest that some ccT2Rs may have evolved to function in the oral cavity as taste receptors for natural bitter compounds found in the habitats in a species-specific manner.     

A Novel Spectral Annotation Strategy Streamlines Reporting of Mono-ADP-ribosylated Peptides Derived from Mouse Liver and Spleen in Response to IFN-γ

Mass-spectrometry-enabled ADP-ribosylation workflows are developing rapidly, providing researchers a variety of ADP-ribosylome enrichment strategies and mass spectrometric acquisition options. Despite the growth spurt in upstream technologies, systematic ADP-ribosyl (ADPr) peptide mass spectral annotation methods are lacking. HCD-dependent ADP-ribosylome studies are common, but the resulting MS2 spectra are complex, owing to a mixture of b/y-ions and the m/p-ion peaks representing one or more dissociation events of the ADPr moiety (m-ion) and peptide (p-ion). In particular, p-ions that dissociate further into one or more fragment ions can dominate HCD spectra but are not recognized by standard spectral annotation workflows. As a result, annotation strategies that are solely reliant upon the b/y-ions result in lower spectral scores that in turn reduce the number of reportable ADPr peptides. To improve the confidence of spectral assignments, we implemented an ADPr peptide annotation and scoring strategy. All MS2 spectra are scored for the ADPr m-ions, but once spectra are assigned as an ADPr peptide, they are further annotated and scored for the p-ions. We implemented this novel workflow to ADPr peptides enriched from the liver and spleen isolated from mice post 4 h exposure to systemic IFN-γ. HCD collision energy experiments were first performed on the Orbitrap Fusion Lumos and the Q Exactive, with notable ADPr peptide dissociation properties verified with CID (Lumos). The m-ion and p-ion series score distributions revealed that ADPr peptide dissociation properties vary markedly between instruments and within instrument collision energy settings, with consequences on ADPr peptide reporting and amino acid localization. Consequentially, we increased the number of reportable ADPr peptides by 25% (liver) and 17% (spleen) by validation and the inclusion of lower confidence ADPr peptide spectra. This systematic annotation strategy will streamline future reporting of ADPr peptides that have been sequenced using any HCD/CID-based method.     

Bioactive lipid lysophosphatidic acid species are associated with disease progression in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality. Prognostic biomarkers to identify rapid progressors are urgently needed to improve patient management. Since the lysophosphatidic acid (LPA) pathway has been implicated in lung fibrosis in preclinical models and identified as a potential therapeutic target, we aimed to investigate if bioactive lipid LPA species could be prognostic biomarkers that predict IPF disease progression. LPAs and lipidomics were measured in baseline placebo plasma of a randomized IPF-controlled trial. The association of lipids with disease progression indices were assessed using statistical models. Compared to healthy, IPF patients had significantly higher levels of five LPAs (LPA16:0, 16:1, 18:1, 18:2, 20:4) and reduced levels of two triglycerides species (TAG48:4-FA12:0, -FA18:2) (false discovery rate < 0.05, fold change > 2). Patients with higher levels of LPAs had greater declines in diffusion capacity of carbon monoxide over 52 weeks (P < 0.01); additionally, LPA20:4-high (≥median) patients had earlier time to exacerbation compared to LPA20:4-low (<median) patients (hazard ratio (95% CI)): 5.71 (1.17–27.72) (P = 0.031). Higher baseline LPAs were associated with greater increases in fibrosis in lower lungs as quantified by high-resolution computed tomography at week 72 (P < 0.05). Some of these LPAs were positively associated with biomarkers of profibrotic macrophages (CCL17, CCL18, OPN, and YKL40) and lung epithelial damage (SPD and sRAGE) (P < 0.05). In summary, our study established the association of LPAs with IPF disease progression, further supporting the role of the LPA pathway in IPF pathobiology.     

The effect of redox signaling on extracellular matrix changes in diabetic wounds leading to amputation

Introduction& Objectives: Redox signaling is a critical regulator in the process of wound healing. This signaling pathway can be effective in the development or healing of diabetic ulcers through the ECM.In this study, the structure of extracellular matrix investigated in relation to redox signaling in the tissue of patients with diabetic ulcers that lead to organ amputation.Materials and methodsThe case-control design on diabetic patients ulcers as case group and non-diabetic limb ischemia as control were used.Hematoxylin-eosin, trichrome, and elastin staining methods were used for pathological evaluations of ECM. MDA, total thiol, and SOD levels were measured using ELISA kits to assess the oxidative stress level. Also, NO level was measured by using ELISA kits in both groups. Expression levels of genes MMP2, MMP9, and HIF were detected using real-time PCR with SYBR-green assay.ResultsThe pathological results showed an increase in the thickness of collagen and elastin fibers. Lipids atrophy was visible in the tissue isolated from the diabetic wound group. The amount of MAD to evaluate the level of lipid oxidation in patients with diabetic Ulcer was significantly higher than the control group(p < 0.01). Thiol level was significantly lower in the diabetic ulcer group than in the control group(p < 0.0001). The expression of metalloproteinases 2 and 9 genes in the tissues isolated from diabetic ulcers was lower than the control group(p < 0.0001). While the expression of the HIF gene in this group was higher than the control group(p < 0.0001).ConclutionIn the diabetic wound, the HIF secretion due to hypoxic conditions is beneficial for matrix deposition and prevents protease activity, but if the hypoxia persists, it can lead to ECM deposition subsequently increases the tissue pressure, increases of the collagen I-to-collagen III ratio in collagen accumulation that due to more hypoxia , lipidsAtrophy and eventually amputation.     

The Prevalence of Metabolic and Endocrine Disturbances on Fracture Nonunion

ObjectiveThis study aims to determine the prevalence of metabolic disturbance in all fracture nonunion cases and identify the most common endocrine abnormalities seen using a simple screening algorithm.MethodsA retrospective review study was performed evaluating patients who underwent operative intervention for nonunion from January 2010 to December 2018 at 2 level-1 trauma centers. Preoperative laboratory values were recorded for a 9-test “nonunion panel.” A metabolic or endocrine abnormality, specifically an abnormality in the thyroid or parathyroid axis, was evaluated.Results42% of patients had an undiagnosed metabolic laboratory abnormality. When multiple tests were used, the rate of metabolic dysfunction was between 60% and 75%, depending on the definition of vitamin D insufficiency vs deficiency used.ConclusionResults indicate a relatively high prevalence of metabolic disturbance in patients with nonunion and suggest metabolic screening for all nonunion patients not only those without a mechanical or infectious cause.Level of EvidenceIV, retrospective case series.     

Decreased Mortality After Long-Term Treatment With Dipeptidyl Peptidase-4 Inhibitors: A Retrospective Study of U.S. Veterans With Type 2 Diabetes

ObjectiveThe prevalence of chronic kidney disease (CKD) in the United States is 13% of the general population. Among those with CKD, diabetic nephropathy is the leading cause of end-stage renal disease. This is a retrospective study examining the effect of long-term use of dipeptidyl peptidase-4 (DPP-4) inhibitors on all-cause mortality and progression of renal disease in the veteran population.MethodsData was extracted using the Veterans Administration Informatics and Computing Infrastructure. A large cohort of veterans diagnosed with type 2 diabetes mellitus were used to identify patients on DPP-4 inhibitors and without DPP-4 inhibitors. Groups were compared to determine the effect of DPP-4 inhibitors on the progression of CKD and all-cause mortality. Data were analyzed using SAS.ResultsSubjects in the treatment group (n = 40 558) had baseline variables (age, body mass index, race) similar to the control group (n = 40 558). Diabetes control improved in the treatment group (HgbA1c, 8.3% [67 mmol/mol] to 7.8% [62 mmol/mol]; P < .001) but not in the control group (HgbA1c, 7.4% [57 mmol/mol] to 7.3% [56 mmol/mol]). New diagnoses of heart failure and coronary artery bypass grafts were clinically significant (odds ratios = 0.66 and 0.52). No change in progression of CKD was seen in either group. All-cause mortality was reduced by 59%.ConclusionWe conclude that DPP-4 inhibitors are associated with a significant reduction in all-cause mortality independent of glucose control, albeit with no clear cause, including obtainable cardiovascular outcomes. Our data is consistent with prior trials in that DPP-4 inhibitors did not show a significant change in serum creatinine or microalbuminuria.