Engineering Wet-Resistant and Osteogenic Nanocomposite Adhesive to Control Bleeding and Infection after Median Sternotomy.

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.

Development of preeclampsia in pregnant women with white-coat hypertension: a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a hypertensive disease characterized by an increased clinic blood pressure but normal home or workplace blood pressure. Due to variable prevalence, a subset of women with WCH may be incorrectly diagnosed with chronic hypertension, highlighting the need for accurate diagnosis. Little is known about the role of WCH in pregnancy, but a meta-analysis aims to determine whether WCH increases the likelihood of developing preeclampsia. METHODS: A systematic review and meta-analysis was conducted to determine whether there is an association between WCH and the incidence of preeclampsia in pregnant women. The search included PubMed, Embase, and Scopus databases until February 2023, using PRISMA guidelines. Pregnant women with apparent office hypertension throughout pregnancy who underwent 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring were included. Meta-analysis was performed using RevMan. RESULTS: This study included 12 studies with a total of 4,672 pregnant women and found that women with WCH have a higher risk of developing preeclampsia compared to normotensive women (RR: 2.29, 95% CI [1.18,4.43], P = 0.01). However, when compared with pregnant women with gestational hypertension or chronic hypertension, women with WCH had a significantly lower risk of developing preeclampsia ((RR: 0.39, [0.20,0.80], p=0.009) and (RR: 0.41, [0.27,0.62], P<0.001), respectively). CONCLUSION: The study recommends incorporating 24-hour ABPM into clinical practice to differentiate between chronic hypertension and WCH in early pregnancy and focus on special management for those who need it. The findings may guide future research on ABPM's role in diagnosing WCH and its effects on pregnancy outcomes.

A realistic approach to evaluating the effect of baseline lipid profile in postcoronary artery bypass grafting surgery.

BACKGROUND: There are still many uncertainties in the association between lipid profile and postcoronary artery bypass grafting (CABG) outcomes. Although simplifying the association to linear equations makes it understandable but cannot explain many findings. HYPOTHESIS: There is a nonlinear associatin between lipid profile indices and adverse outcomes after CABG. METHODS: A total of 17 555 patients who underwent isolated CABG between 2005 and 2016 were evaluated. During the median follow-up of 75.24 months, the Restricted Cubic Splines (RCS) estimated from the Cox regression model adjusted for all possible confounders was applied to show a nonlinear relationship of lipid profile contents with the "ln hazard ratio" of mortality and major cerebro-cardiac events (MACCE). RESULTS: The relationship between LDL-C and HDL-C with all-cause mortality was nonlinear (nonlinear p were .004 and <.001, respectively). The relationship between remnant cholesterol and all-cause mortality was linear (linearity p = .023). Among men, those in the highest LDL-C level (Q4, LDL-C > 114) and those in the lowest HDL-C level (Q1, HDL-C < 30) showed a significantly higher risk of all-cause mortality compared to other groups (compared with Q3, LDL-C Q4, HR = 1.16, 95% confidence interval [CI]:1.02-1.26, p = .014; HDL-C Q1, HR = 1.14, 95% CI: 1.01-1.31, p = .041). Female patients in the lowest HDL-C level (Q1, HDL-C < 30) showed a significantly higher (compared with Q3, HR = 1.14, 95% CI:1.01-1.31, p = .028) and those in the highest HDL-C level (Q4, HDL-C > 43) showed a significantly lower (compared with Q3, HR = 0.74, 95% CI:0.58-0.98, p = .019) risk of all-cause mortality. CONCLUSION: Determining a universal cut off for components of lipid profile may be misleading and should better be revised. Extreme values (very low or very high) for HDL-C and LDL-C have different effects on cardiovascular outcomes.

The prevalence of permanent pacemaker implantation after open-heart surgeries; eight years of experience in Tehran heart center.

BACKGROUND: We aimed to evaluate the prevalence of permanent pacemaker implantation (PPI) among open-heart surgery patients. METHODS: We reviewed data from 23 461 patients undergoing open-heart surgeries between 2009 and 2016 in our heart center in Iran. A total of 18 070 patients (77%) had coronary artery bypass grafting (CABG), 3 598 (15.3%) valvular surgeries, and 1 793 (7.6%) congenital repair procedures. Finally, 125 patients who received PPI following open-heart surgeries were enrolled in our study. We defined the demographic and clinical characteristics of all these patients. RESULTS: PPI was required in 125 (0.53%) patients with an average age of 58 ± 15.3 years. The average hospitalization time after surgery and waiting time for PPI were 19.7 ± 10.2 and 11.4 ± 6.5 days, respectively. Atrial fibrillation was the dominant pre-operative cardiac conduction abnormality (29.6%). Also, the primary indication for PPI was complete heart block in 72 patients (57.6%). Patients in the CABG group were significantly older (P = 0.002) and were more likely to be male (P = 0.030). The valvular group longer bypass and cross-clamp times and had more left atrial abnormalities. In addition, the congenital defect group was younger and had longer ICU stay times. CONCLUSIONS: Based on our study findings, PPI was required in 0.53% of patients following open-heart surgery due to damage to the cardiac conduction system. The current study paves the way for future investigations to identify possible predictors of PPI in patients undergoing open-heart surgeries.

Advanced micro-/nanotechnologies for exosome encapsulation and targeting in regenerative medicine.

Exosomes, a subset of vesicles generated from cell membranes, are crucial for cellular communication. Exosomes' innate qualities have been used in recent studies to create nanocarriers for various purposes, including medication delivery and immunotherapy. As a result, a wide range of approaches has been designed to utilize their non-immunogenic nature, drug-loading capacity, or targeting ability. In this study, we aimed to review the novel methods and approaches in exosome engineering for encapsulation and targeting in regenerative medicine. We have assessed and evaluated each method's efficacy, advantages, and disadvantages and discussed the results of related studies. Even though the therapeutic role of non-allogenic exosomes has been demonstrated in several studies, their application has certain limitations as these particles are neither fully specific to target tissue nor tissue retainable. Hence, there is a strong demand for developing more efficient encapsulation methods along with more accurate and precise targeting methods, such as 3D printing and magnetic nanoparticle loading in exosomes, respectively.

Strong and bioactive bioinspired biomaterials, next generation of bone adhesives.

The bone adhesive is a clinical requirement for complicated bone fractures always articulated by surgeons. Applying glue is a quick and easy way to fix broken bones. Adhesives, unlike conventional fixation methods such as wires and sutures, improve healing conditions and reduce postoperative pain by creating a complete connection at the fractured joint. Despite many efforts in the field of bone adhesives, the creation of a successful adhesive with robust adhesion and appropriate bioactivity for the treatment of bone fractures is still in its infancy. Because of the resemblance of the body's humid environment to the underwater environment, in the latest decades, researchers have pursued inspiration from nature to develop strong bioactive adhesives for bone tissue. The aim of this review article is to discuss the recent state of the art in bone adhesives with a specific focus on biomimetic adhesives, their action mechanisms, and upcoming perspective. Firstly, the adhesive biomaterials with specific affinity to bone tissue are introduced and their rational design is studied. Consequently, various types of synthetic and natural bioadhesives for bone tissue are comprehensively overviewed. Then, bioinspired-adhesives are described, highlighting relevant structures and examples of biomimetic adhesives mainly made of DOPA and the complex coacervates inspired by proteins secreted in mussel and sandcastle worms, respectively. Finally, this article overviews the challenges of the current bioadhesives and the future research for the improvement of the properties of biomimetic adhesives for use as bone adhesives.

Aortic dissection in the first trimester; is it a dead end? A narrative review of recent articles.

INTRODUCTION: Acute-type aortic dissection (AD) during pregnancy is considered a rare and potentially fatal complication for both mother and fetus. Although the definite treatment for an acute-type AD is considered to be open-heart surgery, the decision to perform such a surgery during pregnancy requires a multidisciplinary approach and carries significant risks. METHODS: In the present review of the literature, we have discussed various challenges in the management of acute-type AD during pregnancy, including therapeutic approaches, choosing the preferred imaging modalities, surgical techniques, and medication challenges. We have also reported an 8-week pregnant woman with Marfan syndrome who presented with chest pain and was diagnosed with acute AD. RESULTS: The patient underwent a Bentall operation and was discharged in good condition with her fetus alive. The medical team's various decisions during preoperative, operative, and postoperative treatments were discussed. CONCLUSIONS: Type A AD is considered infrequent in the second and third trimester of pregnancy and rare in the first trimester. Performing a CMR study without contrast in stable patients can help evaluate the extension of the flap. Urgent surgery in the hands of a skilled surgeon may prove lifesaving for the mother while maximizing the likelihood of preserving the fetus.

A review of gene- and cell-based therapies for familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. A rare form of autosomal recessive FH has been also described due to LDLr adaptor protein 1 (LDLRAP1) gene mutations. FH is characterized by very high levels of plasma LDL cholesterol associated with the high incidence of premature atherosclerotic cardiovascular disease (CVD). Despite heterozygous FH (HeFH) patients are still poorly recognized and treated, there is today a large availability of drugs (i.e., statins, ezetimibe and PCSK9 inhibitors) allowing theoretically the normalization of plasma LDL cholesterol levels in this population. Homozygous FH patients (HoFH) have a more severe form of FH, characterized by low responsiveness to the conventional lipid-lowering treatment and often associated with unfavorable prognosis in the young age. Inspired by promising outcomes obtained by orthotopic liver transplantation (OLT), scientists are investigating the possibility of correcting the defective LDLr in these patients by using gene therapy approaches to achieve a novel therapeutic solution with high efficiency. In this article, we tried to review the in vitro, ex vivo, and in vivo attempts conducted to correct FH-causing LDLr gene mutations by using different methods of gene delivery, gene editing, and stem cell manipulation. We also discussed some clinical trials performed in this context.

Functional biological pacemaker generation by T-Box18 protein expression via stem cell and viral delivery approaches in a murine model of complete heart block.

Despite recent advances in the treatment of cardiac arrhythmia, the available options are still limited and associated with some complications. Induction of biological pacemakers via Tbx18 gene insertion in the heart tissue has been suggested as a promising therapeutic strategy for cardiac arrhythmia. Following a previous in vitro study reporting the production of Tbx18-expressing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), we aimed to investigate the efficacy of these engineered cells to generate pacemaker rhythms in a murine model of complete heart block. We also attempted to generate a functional pacemaker by Tbx18 overexpression in native cardiac cells of rat heart. The hiPSC-derived pacemaker cells were produced by lentiviral delivery of Tbx18 gene to stem cells during a small molecule-based differentiation process. In the present study, 16 male albino Wistar rats were randomly assigned to Tbx18-lentivirus (n = 4) and Tbx18-pacemaker cells (n = 4) administered via injection into the left ventricular anterolateral wall. The control rats received GFP-lentiviruses (n = 4) and GFP-pacemaker cells (n = 4). Fourteen days after the injection, the rats were sacrificed and analyzed by electrocardiography (ECG) recording using a Langendorff-perfused heart model following complete heart block induced by hypokalemia and crashing. Immunofluorescence staining was used to investigate the expression of Tbx18, HCN4 and connexin 43 (Cx43) proteins in Tbx18-delivered cells of heart tissues. The heart rate was significantly reduced after complete heart block in all of the experimental rats (P < 0.05). Heart beating in the Tbx18-transduced hearts was slower compared with rats receiving Tbx18-pacemaker cells (P = 0.04). The duration of ventricular fibrillation (VF) was higher in the lentiviral Tbx18 group compared with the GFP-injected controls (P = 0.02) and the Tbx18-pacemaker cell group (P = 0.02). The ECG recording data showed spontaneous pacemaker rhythms in both intervention groups with signal propagation in Tbx18-transduced ventricles. Immunostaining results confirmed the overexpression of HCN4 and downregulation of Cx43 as a result of the expression of the Tbx18 gene and spontaneously contracting myocyte formation. We confirmed the formation of a functional pacemaker after introduction of Tbx18 via cell and gene therapy strategies. Although the pacemaker activity was better in gene-received hearts since there were longer VF duration and signal propagation from the injection site, more data should be gathered from the long-term activity of such pacemakers in different hosts.

Cell laden hydrogel construct on-a-chip for mimicry of cardiac tissue in-vitro study.

Since the leading cause of death are cardiac diseases, engineered heart tissue (EHT) is one of the most appealing topics defined in tissue engineering and regenerative medicine fields. The importance of EHT is not only for heart regeneration but also for in vitro developing of cardiology. Cardiomyocytes could grow and commit more naturally in their microenvironment rather than traditional cultivation. Thus, this research tried to develop a set up on-a-chip to produce EHT based on chitosan hydrogel. Micro-bioreactor was hydrodynamically designed and simulated by COMSOL and produced via soft lithography process. Chitosan hydrogel was also prepared, adjusted, and assessed by XRD, FTIR and also its degradation rate and swelling ratio were determined. Finally, hydrogels in which mice cardiac progenitor cells (CPC) were loaded were injected into the micro-device chambers and cultured. Each EHT in every chamber was evaluated separately. Prepared EHTs showed promising results that expanded in them CPCs and work as an integrated syncytium. High cell density culture was the main accomplishment of this study.

Unusual Presentation of Interventricular Hydatid Cyst: A Case Report.

Echinococcus infection typically affects liver and lungs while rarely occur through heart. Cardiac hydatidosis can be fatal or lead to major complications if it is not treated. The majority of patients with cardiac hydatid cysts complain from cardiac problems as their first presentation. However, this article reports an unusual case suffers from an interventricular hydatid cyst presented by abdominal pain on 2013. After the patient transferred to Tehran Heart Center, surgical cyst excision with removing germinal layer and concurrent albendazole therapy was prescribed for the management of this Iranian 15 year old female.