Complications Of Disease Research Articles

Gliflozins as remedies for correction of neurological complications of non-alcoholic fatty liver disease. Part 1

Gliflozins as remedies for correction of neurological complications of non-alcoholic fatty liver disease. Part 1

Acute Kidney Injury in Patients with Chronic Liver Disease: A Review

Introduction: Acute kidney injury (AKI) is a frequent complication of chronic liver disease (CLD) contributing to high morbidity and mortality worldwide. While liver transplantation (LT) has shown favorable outcomes, early identification and management of AKI is imperative for survival. This review aims to highlight the epidemiology, pathophysiology, management, and prognosis of AKI in CLD. Methods: An extensive literature search was performed using PubMed, Medline, and Google Scholar to identify literature related to epidemiology, burden, clinical presentations, prognosis, and management of AKI in CLD. Results: The identified studies highlighted a wide range of prevalence of AKI in hospitalized patients with CLD. The etiology and pathophysiology are multifactorial and include prerenal AKI, acute tubular injury, sepsis, gastrointestinal bleeding, bacterial translocation from the gut, and hepatorenal syndrome (HRS). AKI is associated with a higher risk of morbidity and mortality and progression to chronic kidney disease following LT. Management of AKI in CLD varies based on the underlying etiology. While vasoconstrictors like terlipressin have shown great potential in the treatment of HRS-AKI and is widely used in Europe and United States, LT remains the definitive therapy of choice. In most cases, kidney replacement therapy serves as a bridge to liver transplant. Conclusion: AKI is a serious complication of CLD and early identification is essential. Diagnosis and management, particularly HRS is challenging and requires a high index of suspicion. More research is required to identify novel therapies to improve outcomes of AKI in patients with CLD.

From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance

AbstractBackgroundThe natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex‐vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease.MethodsColonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents.Key ResultsCompared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction‐relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF‐1 was detected in both muscle and mucosa.Conclusion & InferencesThe different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.

Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this study was to gain insights into the molecular pathogenesis of neurological manifestations in this mouse model. To analyze differentially expressed genes (DEGs) in the brains of mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, and 6 days post-infection. We identified the DEGs by comparing them to animals that were not infected with the virus. We found that genes upregulated at day 6 post-infection were mainly associated with Toll-like receptor (TLR) signaling, RIG-I-like receptor (RLR) signaling, and cell death pathways. However, downregulated genes were associated with neurodegeneration and synaptic signaling pathways. In correlation with gene expression profiles, a multiplexed immunoassay showed the upregulation of multiple cytokines and chemokines involved in inflammation and cell death in SARS-CoV-2-infected brains. Furthermore, the pathway analysis of DEGs indicated a possible link between TLR2-mediated signaling pathways and neuroinflammation, as well as pyroptosis and necroptosis in the brain. In conclusion, our work demonstrates neuroinflammation-associated gene expression profiles, which can provide key insight into the severe disease observed in COVID-19 patients.

Surgical and non-operative treatment of acute complicated diverticulitis in a COVID hospital

Surgical treatment of acute abdomen during the SARS-CoV-2 pandemic was accompanied by an extremely high mortality rate, however, only a few studies have presented the results of acute inflammatory complications of diverticular disease (AICDD).AIM: analysis of treatment of AICDD in a COVID-19 hospital.PATIENTS AND METHODS: the retrospective study included 78 patients with acute diverticulitis (AD) from a COVID hospital, confirmed by CT or intraoperative revision. Assessment of COVID pneumonia, comorbidities, organ dysfunction, CT findings, peritonitis, treatment methods, and in-hospital mortality among patients was performed.RESULTS: organ dysfunction of ≥ 1 point on the qSOFA scale was detected in 59.0% of the patients. According to CT data, abdominal distant gas was detected in 48 (61.5%) patients, and pericolic gas in 14 (17.9%) patients. Segmental colon resection was performed in 60 (76.9%) patients, laparoscopic lavage (LL) of the abdominal cavity — in 3, non-operative treatment (NOT) with drainage of fluid collections — in 6, and only NOT in 10 patients. Most patients with distant or pericolic gas were operated on within an average time of 1 [0; 3.5] hours after admission. Diffuse peritonitis was detected during surgery in 45 (75%) of them. After resection, organ dysfunction of ≥ 2 points on the SOFA scale developed or progressed in 52 (86.7%) patients. The overall mortality rate was 48.7%, and the postoperative mortality was 63.3%. All patients (n = 38) died after segmental colon resection. Successful NOT was achieved in 4 patients with pericolic gas and 3 patients with distant gas.CONCLUSION: surgery for AICDD in patients with COVID-19 is associated with extremely high mortality, therefore, in the absence of obvious signs of diffuse peritonitis, initial non-operative treatment may be life-saving.

Managing Symptoms of Systemic Sclerosis for the Allergist-Immunologist.

Systemic sclerosis (SSc) is a chronic, multisystem, autoimmune disease characterized by fibrosis, vasculopathy and immune system dysregulation. We provide a comprehensive review of features of systemic sclerosis that can potentially present to the allergist. A thorough understanding of the management options is crucial for clinicians involved in the care of patients with SSc to optimize clinical outcomes. Management of systemic sclerosis has drastically changed in the last decade and continues to evolve. This review provides an overview of management strategies for the various symptoms including skin, upper and lower airway, gastrointestinal and vascular manifestations. Institution of treatment early in the disease, including referral to rheumatology or specialized scleroderma centers, can help to both prevent and manage disease complications, and improve patient quality-of-life. While the landscape of systemic sclerosis management has evolved, we continue to recognize that there is still a need for better biomarkers and targeted therapies.

Type 2 Diabetes Mellitus Patients’ Knowledge About Disease Complications and Management Targets for Glucose, Lipids, Blood Pressure, and Body Weight

Type 2 Diabetes Mellitus Patients’ Knowledge About Disease Complications and Management Targets for Glucose, Lipids, Blood Pressure, and Body Weight

Inflammatory Bowel Disease-Associated Arthritis Is Associated with Concomitant Autoimmune and Inflammatory Disorders.

Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.

Secondary hyperparathyroidism in chronic kidney disease: pathophysiology, Current treatments and investigational drugs.

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). It begins as an adaptive increase in parathyroid hormone levels to prevent calcium and phosphate derangements. Over time, this condition becomes maladaptive and is associated with increased morbidity and mortality. Current therapies encompass phosphate-lowering strategies, vitamin D analogues, calcimimetics and parathyroidectomy. These approaches harbor inherent limitations, stimulating interest in the development of new drugs for SHPT to overcome these limitations and improve survival and quality of life among CKD patients. This review delves into the main pathophysiological mechanisms involved in SHPT, alongside the treatment options that are currently available and under active investigation. Data presented herein stem from a comprehensive search conducted across PubMed, Web of Science, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) spanning from 2000 onwards. The advancements in investigational drugs for SHPT hold significant promise for enhancing treatment efficacy while minimizing side effects associated with conventional therapies. Although several challenges still hinder their adoption in clinical practice, ongoing research will likely continue to expand the available therapeutic options, refine treatment strategies, and tailor them to individual patient profiles.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

Enteric neuropathy in diabetes: Implications for gastrointestinal function

Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

Reply to the comments on "Coffee bean sign, steel pan sign and whirl sign in sigmoid volvulus".

We thank Prof. Atamanalp and colleagues for their interest and valuable comments on our article. The authors have highlighted important considerations in the diagnosis of sigmoid volvulus (SV). We would like to respond to their comments. Firstly, although we agree with their opinion that CT, MRI, and endoscopy are more reliable diagnostic tools than plain radiography, we still emphasize that diagnostic imaging for SV is initially based on plain radiography, as recommended by the WSES consensus guidelines. Since SV is the third most common cause of colonic obstruction worldwide, the accessibility of plain radiography is crucial. Among the many plain radiographic signs of SV, Levsky et al. reported that the most sensitive signs were absence of rectal gas, followed by inverted-U appearance and coffee bean sign. Understanding these signs may lead to early detection of SV and further CT evaluation for ischemia or perforation. Despite the high value of plain radiography, there is a global tend to use CT instead from the outset. Secondly, we agree with their opinion that endoscopy is not only a therapeutic, but also a diagnostic procedure to assess mucosal viability. In addition, we believe that endoscopy is also useful in ruling out other obstructive lesions, including colorectal neoplasia and complicated sigmoid diverticular disease. In the clinical setting, endoscopy is performed after the diagnosis of SV by plain radiography or CT and serves as the first line of decompression of SV when ischemia or perforation is not suspected. Finally, we congratulate Prof. Atamanalp and colleagues for their dedicated contribution to the large-scale SV studies in Eastern Anatolia, Turkey, where SV is endemic.

Network analysis combined with experimental assessment to explore the therapeutic mechanisms of New Shenqi Pills formula targeting mitochondria on senile diabetes mellitus

BackgroundThe escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM’s renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics.AimsThe objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment.MethodsNetwork analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet β cells.ResultsIn this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, β-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3β protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet β cells.ConclusionOur findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3β pathway plays an important regulatory role in this process.

Cavitating Mesenteric Lymph Node Syndrome in a Patient with Celiac Disease: Differential Diagnosis Based on Radiological Findings

Mesenteric lymph node syndrome is a rare condition characterized by cystic or cavitating changes in mesenteric lymph nodes. It is commonly associated with celiac disease. We present a case of a 59-year-old woman with known celiac disease who presented with abdominal pain, abdominal swelling, and weight loss, ultimately diagnosed with mesenteric lymph node syndrome. This case highlights the importance of radiological findings when considering rare complications of celiac disease in the differential diagnosis.

Post-Diarrheal Acute Kidney Injury During an Epidemic in Monsoon – A Retrospective Study from a Tertiary Care Hospital

Background: Acute kidney injury (AKI) is a severe complication of acute diarrheal diseases; however, there is limited data on post-diarrheal AKI (PD-AKI) epidemiology and outcomes. This study aimed to investigate the clinicodemographic profile and outcomes of PD-AKI in our hospital. Materials and Methods: We retrospectively analyzed data from 93 patients admitted with PD-AKI during a diarrheal illness epidemic. Patients were stratified based on the Kidney Disease: Improving Global Outcomes (KDIGO) AKI stage and quick Sequential Organ Failure Assessment (qSOFA) score. Clinicodemographic data and outcomes were recorded and analyzed. Results: The mean age of the patients was 45.7 ± 11.9 years, with a majority being men (n = 55, 59%). All patients presented with watery diarrhea, 85% (n = 79) had vomiting, and 66% (n = 61) presented in shock. At presentation, 59% were oliguric, while 32% were anuric. KDIGO stage 3 AKI was observed in 71% (n = 66) of patients. Dialytic support was required in 29% (n = 27) of cases. The mortality rate was 6.5% (n = 6), mostly due to refractory shock, while the remaining patients recovered. Risk factor analysis demonstrated a higher qSOFA score, and peak serum creatinine levels were associated with an increased likelihood of requiring renal replacement therapy and delayed renal recovery. Conclusion: This study provides valuable insights into the clinicodemographic characteristics and outcomes of PD-AKI. The high prevalence of severe AKI emphasizes the importance of early recognition and appropriate management strategies for these patients.

Construction of Zwitterionic Coatings with Lubricating and Anti-Adhesive Properties for Invisible Aligner Applications.

Invisible aligners have been widely used in orthodontic treatment but still present issues with plaque formation and oral mucosa abrasion, which can lead to complicated oral diseases. To address these issues, hydrophilic poly(sulfobetaine methacrylate) (polySBMA) coatings with lubricating, antifouling, and anti-adhesive properties have been developed on the aligner materials (i.e., polyethylene terephthalate glycol, PETG) via a simple and feasible glycidyl methacrylate (GMA)-assisted coating strategy. Poly(GMA-co-SBMA) was grafted onto the aminated PETG surface via the ring-opening reaction of GMA (i.e., "grafting to" approach to obtain G-co-S coating), or a polySBMA layer was formed on the GMA-grafted PETG surface via free radical polymerization (i.e., "grafting from" approach to obtain G-g-S coating). The G-co-S and G-g-S coatings significantly reduced the friction coefficient of PETG surface. Protein adsorption, bacterial adhesion, and biofilm formation on the G-co-S- and G-g-S-coated surfaces were significantly inhibited. The performance of the coatings remained stable after storage in air or artificial saliva for 2 weeks. Both coatings demonstrated good biocompatibility in vitro and did not cause irritation to the oral mucosa of rats in vivo over 2 weeks. This study proposed a promising strategy for the development of invisible aligners with improved performance, which is beneficial for oral health treatment. This article is protected by copyright. All rights reserved.

Safety and efficacy of unilateral focused ultrasound pallidotomy on motor complications in Parkinson's disease (PD): a systematic review and meta-analysis.

To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in Parkinson's disease (PD) patients. A comprehensive search strategy was implemented through August 15, 2023, and updated on February 13, 2024, across six databases, identifying studies relevant to unilateral focused ultrasound pallidotomy and PD. Eligibility criteria included observational studies, clinical trials, and case series reporting on the impact of the intervention on motor complications in PD patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment utilized appropriate tools for different study designs. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. Five studies were included in our study, involving 112 PD patients undergoing FUS pallidotomy. UPDRS-II analysis revealed a significant improvement from baseline (mean difference (MD): -3.205, 95% CI: -4.501, -1.909, P < 0.001). UPDRS-III overall change was significant (MD: -10.177, 95% CI: [-12.748, -7.606], P < 0.001). UPDRS-IV showed a significant change from baseline (MD: -5.069, 95% CI: [-5.915, -4.224], P < 0.001). UDysRS demonstrated a significant overall improvement (MD: -18.895, 95% CI: [-26.973, -10.818], P < 0.001). The effect of FUS pallidotomy on motor complications in PD patients was effective, with a significant decrease in the UPDRS and UDysRS, reflecting improvement. The incidence of adverse events (headaches, pin-site pain, difficulty walking, and sonication-related head pain) of the FUS pallidotomy was not statistically significant, indicating its safety.

Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease.

Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), but the precise mechanism by which it occurs is incompletely understood hampering the development of effective therapeutic strategies. Here, we aimed at inducing and characterizing an inflammation-mediated fibrosis in patient-derived organoids (PDOs) issued from crypts isolated from colonic mucosal biopsies of IBD pediatric patients and age matched-control subjects (CTRLs). Inflammatory-driven fibrosis was induced by exposing CTRL-, CD- and UC-PDOs to the pro-inflammatory cytokine TNF-α for one day, followed by a co-treatment with TNF-α and TGF-β1 for three days. Fibrotic response was proven by analyzing inflammatory and fibrotic markers by RT-qPCR and immunofluorescence. Transcriptomic changes were assessed by RNA-sequencing. Co-treatment with TNF-α and TGF-β1 caused in CTRL- and IBD-PDOs morphological changes towards a mesenchymal-like phenotype and up-regulation of inflammatory, mesenchymal, and fibrotic markers. Transcriptomic profiling highlighted that in all intestinal PDOs, regardless of the disease, the co-exposure to TNF-α and TGF-β1 regulated EMT genes and specifically increased genes involved in positive regulation of cell migration. Finally, we demonstrated that CD-PDOs display a specific response to fibrosis compared to both CTRL- and UC-PDOs, mainly characterized by upregulation of nuclear factors controlling transcription. This study demonstrates that intestinal PDOs may develop an inflammatory-derived fibrosis thus representing a promising tool to study fibrogenesis in IBD. Fibrotic PDOs show increased expression of EMT genes. In particular, fibrotic CD-PDOs display a specific gene expression signature compared to UC and CTRL-PDOs.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway.

Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-β1 (TGF-β1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-β1 and p-Smad3. TL1A promotes TGF-β1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

A Nationwide Analysis of the Impact of Cardiopulmonary Anomalies on Cleft Palate Surgical Outcomes.

To increase awareness and improve perioperative care of patients with cleft palate (CP) and coexisting cardiopulmonary anomalies. Retrospective cohort. Multi-center. Patients who underwent surgical repair of CP between 2012-2020 identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric Data File. Chi-squared analysis and Student's t-test were implemented to make associations between congenital heart disease (CHD) and congenital pulmonary disease (CPD) and postoperative complications. Multiple logistic regression was performed to identify associations between CP and CHD/CPD while controlling for age, gender, and ASA class. C2 values were used to assess the logistic regressions, with a significance level of 0.05 indicating statistical significance. Length of stay (LOS), perioperative complications (readmission, reoperation, reintubation, wound dehiscence, cerebrovascular accidents, and mortality). 9 96 181 patients were identified in the database, 17 786 of whom were determined to have CP, of whom 16.0% had congenital heart defects (CHD) and 13.2% had congenital pulmonary defects (CPD). Patients with CHD and CPD were at a significantly greater risk of increased LOS and all but one operative complication rate (wound dehiscence) relative to patients with CP without a history of CHD and CPD. This study suggests that congenital cardiopulmonary disease is associated with increased adverse outcomes in the setting of CP repair. Thus, heightened clinical suspicion for coexisting congenital anomalies in the presence of CP should prompt referring providers to perform a comprehensive and multidisciplinary evaluation to ensure cardiopulmonary optimization prior to surgical intervention.