Development of Takotsubo cardiomyopathy following spontaneous coronary artery dissection in a patient with fibromuscular dysplasia.

New-onset Takotsubo cardiomyopathy following spontaneous coronary artery dissection (SCAD) is rare. We report a middle-aged woman without significant cardiovascular risk factors, who initially presented with non-ST-elevation myocardial infarction (NSTEMI) with angiography showing sudden 'pruning' of the coronary artery consistent with SCAD. One week later, the patient returned with recurrent NSTEMI. Repeat coronary angiogram showed no change in SCAD, but ventriculogram revealed new-onset apical ballooning beyond the SCAD-affected territory, consistent with Takotsubo cardiomyopathy. Further head-to-pelvis angiogram revealed an irregular beaded appearance of the left vertebral artery consistent with fibromuscular dysplasia. The patient was managed conservatively with aspirin, carvedilol and escitalopram with complete resolution of cardiac and mood symptoms. Our case supports an association between SCAD and Takotsubo cardiomyopathy in a potentially mutually aggravating process. Clinical vigilance is therefore required to rule out the other condition when one of the two entities is diagnosed.

Optimal approach for ultrasound-guided transversus abdominis plane (TAP) blocks for abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.

Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Excretory/secretory products from Trichinella spiralis adult worms ameliorate myocardial infarction by inducing M2 macrophage polarization in a mouse model.

BACKGROUND: Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. METHODS: The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. RESULTS: We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. CONCLUSIONS: Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases.

Factors that predict compliance in a virtual cardiac rehabilitation program.

BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States. METHODS: We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05. RESULTS: Age was the single strongest predictor for virtual CR compliance (adjusted R2 = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R2 = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R2 = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance. CONCLUSIONS: Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.

Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases.

Caspases are evolutionarily conserved cysteine proteases that are essential for regulating cell death and are involved in multiple development and disease processes, including immunity. Here, we show that the bacterial type III secretion system (T3SS) effector CopC (Chromobacterium outer protein C) from the environmental pathogen Chromobacterium violaceum attacks caspase-3/-7/-8/-9 by ADPR-deacylization to dysregulate programmed cell death, including apoptosis, necroptosis, and pyroptosis. This modification involves ADP-ribosylation- and deamination-mediated cyclization on Arg207 of caspase-3 by a mechanism that requires the eukaryote-specific protein calmodulin (CaM), leading to inhibition of caspase activity. The manipulation of cell death signaling by CopC is essential for the virulence of C. violaceum in a mouse infection model. CopC represents a family of enzymes existing in taxonomically diverse bacteria associated with a wide spectrum of eukaryotes ranging from humans to plants. The unique activity of CopC establishes a mechanism by which bacteria counteract host defenses through a previously unrecognized post-translational modification.

Endothelial ARHGEF26 is an angiogenic factor promoting VEGF signalling.

AIMS: Genetic studies have implicated the ARHGEF26 locus in the risk of coronary artery disease (CAD). However, the causal pathways by which DNA variants at the ARHGEF26 locus confer risk for CAD are incompletely understood. We sought to elucidate the mechanism responsible for the enhanced risk of CAD associated with the ARHGEF26 locus. METHODS AND RESULTS: In a conditional analysis of the ARHGEF26 locus, we show that the sentinel CAD-risk signal is significantly associated with various non-lipid vascular phenotypes. In human endothelial cell (EC), ARHGEF26 promotes the angiogenic capacity, and interacts with known angiogenic factors and pathways. Quantitative mass spectrometry showed that one CAD-risk coding variant, rs12493885 (p.Val29Leu), resulted in a gain-of-function ARHGEF26 that enhances proangiogenic signalling and displays enhanced interactions with several proteins partially related to the angiogenic pathway. ARHGEF26 is required for endothelial angiogenesis by promoting macropinocytosis of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) on cell membrane and is crucial to Vascular Endothelial Growth Factor (VEGF)-dependent murine vessel sprouting ex vivo. In vivo, global or tissue-specific deletion of ARHGEF26 in EC, but not in vascular smooth muscle cells, significantly reduced atherosclerosis in mice, with enhanced plaque stability. CONCLUSIONS: Our results demonstrate that ARHGEF26 is involved in angiogenesis signaling, and that DNA variants within ARHGEF26 that are associated with CAD risk could affect angiogenic processes by potentiating VEGF-dependent angiogenesis.

Development of Models to Predict Postoperative Complications for Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Surgical treatment remains the best option for patients with hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV) infection. However, there is no optimal tool based on readily accessible clinical parameters to predict postoperative complications. Herein, our study aimed to develop models that permitted risk of severe complications to be assessed before and after liver resection based on conventional variables. METHODS: A total of 1,047 patients treated by hepatectomy for HCC with HBV infection at three different centers were recruited retrospectively between July 1, 2014, and July 1, 2018. All surgical complications were recorded and scored by the Comprehensive Complication Index (CCI). A CCI ≥26.2 was used as a threshold to define patients with severe complications. We built two models for the CCI, one using preoperative and one using preoperative and postoperative data. Besides, CCI and other potentially relevant factors were evaluated for their ability to predict early recurrence and metastasis. All the findings were internally validated in the Hangzhou cohort and then externally validated in the Lanzhou and Urumqi cohorts. RESULTS: Multivariable analysis identified National Nosocomial Infections Surveillance (NNIS) index, tumor number, gamma-glutamyltransferase (GGT), total cholesterol (TC), potassium, and thrombin time as the key preoperative parameters related to perioperative complications. The nomogram based on the preoperative model [preoperative CCI After Surgery for Liver tumor (CCIASL-pre)] showed good discriminatory performance internally and externally. A more accurate model [postoperative CCI After Surgery for Liver tumor (CCIASL-post)] was established, combined with the other four postoperative predictors including leukocyte count, basophil count, erythrocyte count, and total bilirubin level. No significant association was observed between CCI and long-term complications. CONCLUSION: Based on the widely available clinical data, statistical models were established to predict the complications after hepatectomy in patients with HBV infection. All the findings were extensively validated and shown to be applicable nationwide. Such models could be used as guidelines for surveillance follow-up and the design of post-resection adjuvant therapy.

MiR-770 promotes oral squamous cell carcinoma migration and invasion by regulating the Sirt7/Smad4 pathway.

Oral squamous cell carcinoma (OSCC) is a common malignant cancer with unfavorable prognosis, and the epithelial-to-mesenchymal transition (EMT) is a critical contributor to OSCC metastasis. Recently, we have shown that sirtuin 7 (Sirt7) is associated with EMT and OSCC metastasis by acetylating small mother against decapentaplegic 4 (Smad4). Nonetheless, the mechanism of Sirt7 downregulation in OSCC cells remains unknown. This study analyzed the potential microRNAs that were predicted to regulate Sirt7 expression by online databases. We identified miR-770 as an upstream regulator of Sirt7 that targets its 3'-untranslated region. The expression of miR-770 was observed to be negatively correlated with the mRNA expression of Sirt7 in metastatic OSCC tumors, and higher miR-770 expression was correlated with poorer OSCC patient survival. Our in vitro data indicated that miR-770 promoted OSCC cell migration and invasion, and this process was dependent on Sirt7/Smad4 signaling. Furthermore, in vivo metastasis experiments indicated that miR-770 overexpression led to more prominent OSCC metastasis and downregulated Sirt7 expression. Collectively, our results revealed a new role of Sirt7 downregulation in metastatic OSCC and suggested that miR-770 is a potential target in counteracting OSCC metastasis.

Assessment of Quality of Life of Free Anterolateral Thigh Flap for Reconstruction of Tissue Defects of Total or Near-Total Glossectomy.

BACKGROUND: The aim of this study was to evaluate quality of life of free anterolateral thigh flap (ALTFF) for reconstruction of tissue defects of total or near-total glossectomy. METHODS: Quality of life was assessed by means of the University of Washington Quality of Life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14), after 12 months postoperatively. RESULTS: 65 of 79 questionnaires were returned (82.27%). In the UW-QOL, the best-scoring domain was "shoulder," whereas the lowest scores were for "chewing" and "pain." In the OHIP-14, the lowest-scoring domain was "handicap," followed by "Social disability" and "Psychological disability." CONCLUSION: Free anterolateral thigh perforator flaps for reconstruction of total or near-total glossectomy defects after cancer resection would have significantly influenced the patients' oral functions and quality of life.