Search

Assessing the volume status in critically ill patients is the key to maintain the stability of the hemodynamics; however, it can be challenging to view the complexity of cases and the diversity of shock etiology. Multiple noninvasive means have been used to study the effectiveness of volume resuscitation, but none of them have been used as gold standard. We aim to illustrate the most used techniques: left ventricular outflow tract velocity time integral versus inferior vena cava compressibility index, and highlight their limitations and strengths. These tools are both operator-dependent and might be affected by several factors including ventilator settings., Competing Interests: The authors declare that there is no conflict of interest., (Copyright 2024, Asogwa et al.)

Background: Endocarditis is more common in patients with cardiac prostheses. A Bentall procedure entails surgical replacement of the aortic valve, aortic root, and ascending aorta with re-implantation of coronary arteries into the graft., Case: 65-year-old male with history of atrial fibrillation on rivaroxaban, bicuspid aortic valve, and ascending aortic aneurysm with a history of a Bentall procedure two years prior, presented with headache and dysarthria for one day. National Institutes of Health Stroke Scale was 3 and CT head showed 2.7 cm left frontal hematoma with extension into the subarachnoid space. Andexanet alfa was given for rivaroxaban reversal followed by cerebral angiogram which showed 5 mm intracranial inferior MCA aneurysm and embolization and coil placement was done. Blood cultures grew Lactococcus garvieae and transesophageal echocardiogram revealed aortic valve thickening and vegetation on the non-coronary cusp. He was subsequently treated with six weeks of IV ceftriaxone and Gentamycin., Conclusion: With increasing use of bioprosthetic valves, the possibility of infective endocarditis with uncommon pathogens should be kept in mind. Lactococcus commonly affects native valves, however it can affect bioprosthetic valves and can present with mycotic aneurysms., (© 2023 The Authors. Published by Elsevier Ltd.)

Skull base osteomyelitis is an aggressive infection involving bones of the skull. It is a rare complication of malignant otitis externa, caused by the contiguous spread of the infection. Patients are mostly elderly with comorbidities that compromise immunity. It is atypical for Streptococcus species to be encountered in basilar skull osteomyelitis. Here we present the case of an 80-year-old male with multiple comorbidities including diabetes mellitus with a two-month history of right ear pain associated with occasional discharge and diminished hearing who was found to have bacteremia and basilar skull osteomyelitis with Streptococcus pneumoniae isolated from blood and otorrhea fluid cultures. This unusual presentation of S. pneumoniae related skull base osteomyelitis could be attributed to an undiagnosed pancreatic cancer at the time of presentation. Malignant otitis externa can progress into invasive disease in the head and neck; almost all cases tend to be caused by Pseudomonas aeruginosa but unusual cases, such as this, can be caused by Streptococcus pneumoniae., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Wahbah Makhoul et al.)

We herein report the case of a previously healthy 26-year-old male patient who presented to our hospital with chest pain and fevers. Investigations revealed oxacillin-resistant Staphylococcus aureus (ORSA) osteomyelitis of the manubrium, for which no inciting event or background was identified, classifying it as primary sternomanubrial osteomyelitis (PSO). The patient was appropriately treated with intravenous antibiotics, resulting in clinical improvement. The sternomanubrial site without trauma has rarely been described in the literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Assaad et al.)

The use of stem cells to repair the heart after a myocardial infarction (MI) remains promising, yet clinical trials over the past 20 years suggest that cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function. Here, we demonstrate the cardioprotective potential of a composite inserting human amniotic stromal mesenchymal stem cells (ASMCs) in a chitosan and hyaluronic acid (C/HA) based hydrogel in a rat MI model. Mechanical characterization of the C/HA platform indicated a swift elastic conversion at 40°C and a rapid sol-gel transition time at 37°C. Cell viability assay presented active and proliferating AMSCs in the C/HA. The ASMCs + C/HA injected composite significantly increased left ventricular ejection fraction, fractional shortening, and neovessel formation. The encapsulated AMSCs were abundantly detected in the infarcted myocardium 6 weeks post-administration and co-expressed cardiac proteins and notably proliferative markers. Proteomic profiling revealed that extracellular vesicles released from hypoxia preconditioned ASMCs contained proteins involved in cytoprotection, angiogenesis, cardiac differentiation and non-canonical Wnt-signaling. Independent activation of non-canonical Wnt-signaling pathways in ASMCs induced cardiogenesis. Despite a low injected cellular density at baseline, the encapsulated AMSCs were abundantly retained and increased cardiac function. Furthermore, the C/HA hydrogel provided an active milieu for the AMSCs to proliferate, co-express cardiac proteins, and induce new vessel formation. Hence, this novel composite of AMSCs + C/HA scaffold is a conceivable candidate that could restore cardiac function and reduce remodeling., (© 2021 John Wiley & Sons Ltd.)

Background: Rate of cesarean section (CS), including elective CS has globally increased. Studies have found that term elective CS before 39 weeks of gestation is associated with increased risk of adverse respiratory outcomes., Objective: To determine the rate of elective CS and examine the association between timing of elective term CS and adverse neonatal outcomes in a large population of Lebanese women., Methods: A Multi-Center Study was conducted using data from the National Collaborative Perinatal Neonatal Network database. Simple and multivariable logistic regression models were used to examine the association between timing of term elective CS and adverse neonatal outcomes. Some of the neonatal adverse outcomes we examined included respiratory distress syndrome, admission to the NICU, and a composite of respiratory outcomes., Results: A total of 28,997 low risk mothers who delivered through primary and repeat elective CS were included in the study. Uncomplicated elective planned term CS constituted 25% of all CS deliveries in Lebanon. Primary and repeat CS at 37 weeks of gestation increased the odds of most of the studied adverse neonatal outcomes. There were few associations between CS and adverse neonatal outcomes at 38 weeks of gestation., Conclusions: Term primary and repeat cesarean delivery prior to 39 weeks of gestation is associated with respiratory and other adverse neonatal outcomes. Delaying birth 1-2 weeks till 39 weeks of gestation can prevent 64-77% of adverse respiratory outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute myocardial infarction (MI) remains one of the leading causes of death worldwide with no curative therapy available. Stem cell therapies have been gaining interest as a means to repair the cardiac tissue after MI and prevent the onset of heart failure. Many in vivo reports suggest that the use of stem cells is promising, yet clinical trials suggest that the cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function and repair. To battle this limitation, the combination of using stem cells embedded in a bioactive scaffold that promotes cell retention is growing in interest. Yet, a systematic review of the literature on the use of stem cells embedded in bioactive scaffolds for cardiac repair has not yet been performed. In this protocol, we outline a systematic review and meta-analysis of preclinical trials in animal MI models that utilize stem cell-embedded scaffolds for cardiac repair and compare their effects to stem cell-treated animals without the use of a scaffold., Methods/design: We will search the following electronic databases: Cochrane Library, MEDLINE, Embase, PubMed, Scopus and Web of Science, and gray literature: Canadian Agency for Drugs and Technologies in Health and Google Scholar. We will only include randomly controlled preclinical trials that have directly investigated the effects of stem cells embedded in a scaffold for cardiac repair in an animal MI model. Two investigators will independently review each article included in the final analysis. The primary endpoint that will be investigated is left ventricular ejection fraction. Secondary endpoints will include infarct size, end systolic volume, end diastolic volume, fractional shortening and left ventricular wall thickness. Pooled analyses will be conducted using the DerSimonian-Laird random effects and Mantel-Haenszel fixed-effect models. Between-studies heterogeneity will be quantified and determined using the Tau 2 and I 2 statistics. Publication bias will be assessed using visual inspection of funnel plots and complemented by Begg's and Egger's statistical tests. Possible sources of heterogeneity will be assessed using subgroup-meta analysis and meta-regression., Discussion: To date, the use of scaffolds in myocardial repair has not yet been systematically reviewed. The results of this meta-analysis will aid in determining the efficacy of stem cell-embedded scaffolds for cardiac repair and help bring this therapy to the clinic.

Background and Aims: Aortic valve stenosis (AVS) affects a significant percentage of our elderly population and younger subjects with familial hypercholesterolemia. Lipoprotein(a) [Lp(a)] has been associated with AVS in recent genetic studies. The purpose of this study was to determine the effects of Lp(a) on human aortic valve interstitial cells (HAVICs), and to identify apolipoproteins and phospholipids in diseased human aortic valves., Methods: We examined the effects of Lp(a) on HAVICs mineralization and oxidant formation. Proteomic analyses were used to determine the effects of Lp(a) on downstream intracellular markers. We also used mass spectroscopy to identify the different lipoproteins and oxidized phospholipids in calcified aortic valves., Results: HAVICs incubated with either LDL or Lp(a) had significantly higher calcium deposition, compared to control (p<0.001), with Lp(a) having the most significant effect (p<0.01) compared to LDL. Proteomic analysis after 10 days of treatment with Lp(a) resulted in enrichment of proteins involved in calcium deposition and vesicle biogenesis. Treatment of HAVICs with Lp(a) significantly increased ROS formation (p<0.05). Patients with calcific aortic stenosis had higher plasma Lp(a) concentrations compared to non-CAD individuals (p<0.001). LC-MS/MS revealed the presence of apolipoproteins and phospholipids in calcified human aortic valves., Conclusions: The present study outlines an association between Lp(a) and AVS, and suggests that Lp(a) may serve as a potential target for therapeutic purposes to manage the progression of AVS., (Copyright © 2018. Published by Elsevier B.V.)

Background: Poor viability and retention of transplanted bone marrow mesenchymal stem cells (BM-MSC) remains an obstacle in promoting healing after myocardial infarction (MI). This study aimed to understand the migratory, angiogenic, and cardioprotective effects induced by tumor necrosis factor (TNF)-α and hypoxia through rat BM-MSC (rBM-MSC) paracrine secretions, collectively referred to as secretome, after MI., Methods: Secretome from rBM-MSC cultures treated with various combinations of H9c2 cardiomyoblast-conditioned medium, TNF-α, and hypoxia was initially collected. Immunocytochemistry, Western blot analyses, and transwell cell migration assays were conducted. In vivo, echocardiography was performed on rats with induced MI after their treatment with TNF-α and hypoxia-induced secretome., Results: Immunocytochemistry confirmed the presence of TNF receptors 1 and 2 on rBM-MSCs. Western blot analyses of rBM-MSCs treated with TNF-α and hypoxia showed an overall increasing trend in the expression of antiinflammatory proteins and angiogenic and migratory cytokines (transforming growth factor-β, fibroblast growth factor-2, angiopoietin-2, vascular endothelial growth factor-1). In addition, the TNF-α and hypoxia-induced secretome significantly increased the in vitro rBM-MSCs migration. In the rat MI model, the rats treated with the TNF-α and hypoxia-induced secretome had a significantly higher left ventricular fractional shortening than the control group., Conclusions: Our data suggest that after MI, rBM-MSCs secrete paracrine factors in response to TNF-α and hypoxia that work together to manipulate the microenvironment and decrease inflammation. In addition, these signaling factors trigger angiogenic and migratory effects at the site of the infarct to promote myocardial healing and improve the cardiac function., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: For more than a decade, stem cells isolated from different tissues have been evaluated in cell therapy. Among them, the human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were investigated extensively in the treatment of myocardial infarction. Recently, the human placenta-derived mesenchymal stem cells (hPD-MSCs), which are readily available from a biological waste, appear to be a viable alternative to hBM-MSCs., Methods: C-X-C chemokine receptor type 4 (CXCR4) gene expression and localization were detected and validated in hPD-MSCs and hBM-MSCs via polymerase chain reaction and immunofluorescence. Subsequently, cell culture conditions for CXCR4 expression were optimized in stromal-derived factor-1 alpha (SDF1-α), glucose, and cobalt chloride (CoCl 2 ) by the use of cell viability, proliferation, and migration assays. To elucidate the cell signaling pathway, protein expression of CXCR4, hypoxia-inducible factor-1α, interleukin-6, Akt, and extracellular signal-regulated kinase were analyzed by Western blot. CXCR4-positive cells were sorted and analyzed by florescence-activated cell sorting., Results: CXCR4 was expressed on both hPD-MSCs and hBM-MSCs at the basal level. HPD-MSCs were shown to have a greater sensitivity to SDF-1α-dependent cell migration compared with hBM-MSCs. In addition, CXCR4 expression was significantly greater in both hPD-MSCs and hBM-MSCs with SDF-1α or CoCl 2 -induced hypoxia treatment. However, CXCR4 + hPD-MSCs population increased by 10-fold in CoCl 2 -induced hypoxia. In contrast, only a 2-fold increase was observed in the CXCR4 + hBM-MSCs population in similar conditions. After CoCl 2 -induced hypoxia, the CXCR4/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway was activated prominently in hPD-MSCs, whereas in hBM-MSCs, the CXCR4/phosphatidylinositol 3-kinase/Akt pathway was triggered., Conclusions: Our current results suggest that hPD-MSCs could represent a viable and effective alternative to hBM-MSCs for translational studies in cardiocellular repair., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiomyocytes are understood to possess a limited regenerative capacity. Any myocardial insult leads to an irreversible injury. Mesenchymal stem cell differentiation into cardiomyocyte-like cells stands as one of the leading experimental therapies. However, a candidate cell source has yet to be defined. Here, we examined the in vitro and in vivo cardiac differentiation potential of human placenta derived stem cells (hPDSCs); a unique, abundant, and non-immunogenic cell source., Main Methods: H9c2 cell culture medium was applied to hPDSCs at different ratios for a period of 4weeks. In parallel, hPDSCs, human bone marrow stem cells, or cell free culture medium was injected in peri-infarcted regions induced in rat hearts., Key Findings: In vitro, hPDSCs pre-conditioned with H9c2 cell culture medium proportionally over-expressed alpha sarcoplasmic actinin and displaced connexin 43 from the cytoplasm to the cell membrane. Additionally, pre-conditioning promoted hPDSCs survival and triggered vascular endothelial growth factor (VEGF) dependent angiogenesis by activating the pAkt and p38MAPK/pSTAT3 pathways. In vivo, echocardiography analysis showed a significant improvement in cardiac parameters in the rats injected with hPDSCs, similar to the human bone marrow stem cells injected group. Moreover, hPDSCs detected within rat cardiac tissues expressed troponin I and myosin heavy chain. In accordance with the pre-conditioning findings, VEGF positive neovessels were observed in hearts injected with hPDSCs., Significance: hPDSCs have the potential to differentiate into cardiac-like cells and induce angiogenesis via paracrine effects. With the advantages of easy availability and young age, these cells could be more suitable for clinical translation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodically exuberant heterotopic ossification (HO), whereby skeletal muscle is abnormally converted into misplaced, but histologically normal bone. This HO leads to progressive immobility with catastrophic consequences, including death by asphyxiation. FOP results from mutations in the intracellular domain of the type I BMP (bone morphogenetic protein) receptor ACVR1; the most common mutation alters arginine 206 to histidine (ACVR1(R206H)) and has been thought to drive inappropriate bone formation as a result of receptor hyperactivity. We unexpectedly found that this mutation rendered ACVR1 responsive to the activin family of ligands, which generally antagonize BMP signaling through ACVR1 but cannot normally induce bone formation. To test the implications of this finding in vivo, we engineered mice to carry the Acvr1(R206H) mutation. Because mice that constitutively express Acvr1[R206H] die perinatally, we generated a genetically humanized conditional-on knock-in model for this mutation. When Acvr1[R206H] expression was induced, mice developed HO resembling that of FOP; HO could also be triggered by activin A administration in this mouse model of FOP but not in wild-type controls. Finally, HO was blocked by broad-acting BMP blockers, as well as by a fully human antibody specific to activin A. Our results suggest that ACVR1(R206H) causes FOP by gaining responsiveness to the normally antagonistic ligand activin A, demonstrating that this ligand is necessary and sufficient for driving HO in a genetically accurate model of FOP; hence, our human antibody to activin A represents a potential therapeutic approach for FOP., (Copyright © 2015, American Association for the Advancement of Science.)

Injectable hydrogels are extensively used in drug delivery and tissue engineering to administer drugs, genes, growth factors and live cells. We report a method to produce tough, in-situ thermogelling, non-toxic, injectable hydrogels made of chitosan and hyaluronic acid co-crosslinked with β-glycerophophate and genipin. The gels are highly homogeneous and form within 32 min, i.e., faster than gels crosslinked with either genipin or β-glycerophophate. The shear strength of co-crosslinked hydrogels is 3.5 kPa, higher than any chitosan-based gel reported. Chondrocytes and nucleus pulposus cells thrive inside the gels and produce large amounts of collagen II. Injection in rats shows that the gels form in-vivo within a short time and remain well localized for more than one week while the rats remain healthy and active. The excellent mechanical properties, fast in-situ gelation, good biocompatibility and the ability to encapsulate live cells at physiological conditions make these hydrogels ideal for tissue engineering, especially cartilage regeneration., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: The use of stem cells in cardiac regeneration is still limited due to low cellular integration and engraftment rates. Consequently, there has been a spurt in research on developing alternative regenerative therapies. Hyaluronic acid (HA) is a major component of the extracellular matrix that is non-immunogenic, and has been implicated in various wound-healing functions such as angiogenesis and inflammation modulation, making it an ideal candidate for regenerative biomaterials. In this study, we examine the potential of acellular hyaluronic acid-based hydrogel in improving cardiac function post-myocardial infarction in a rat model., Methods: Hyaluronic acid-based hydrogel was injected into the peri-infarct region post-myocardial infarction induction in Lewis rats. Cardiac function in control (n = 10) and gel-injected groups (n = 10) was evaluated up to 4 weeks post-myocardial infarction. Evaluation of cardiac function was conducted using transthoracic echocardiography. Histological analysis of scar area was evaluated via haematoxylin and eosin (H & E), and Sirius red staining. Neovascularization was detected using vascular endothelial growth factor (VEGF) staining., Results: Evaluation of cardiac function using transthoracic echocardiography revealed a 18.2% (P < 0.01) increase in ejection fraction in gel-injected groups when compared with the control group, almost returning the ejection fraction to baseline levels (preop). Histological analysis of scar area by haematoxylin and eosin (H&E), and Sirius red staining demonstrated decreased scarring, and a 22.6% (P < 0.01) decrease in collagen deposition in the gel-injected group compared with the control group. VEGF staining indicated a significant increase in novel vasculature formation in hydrogel-injected groups when compared with control., Conclusions: Due to its regenerative potential, hyaluronic acid-based hydrogel provides a promising novel therapy to be used alone, or as a scaffold delivering a variety of drugs or cells to combat heart disease in a multifaceted approach.

In coronary heart disease, the use of stem cells for regeneration purposes has been broadly studied. Whereas bone marrow mesenchymal stem cells remain the most extensively investigated, other cell sources have been reported. Here we discuss and compare the characteristics of placenta-derived mesenchymal stem cells as a novel alternative cell source for cellular cardiomyoplasty. These cells are isolated from the human term placenta, which is normally discarded post partum. With their lack of ethical conflicts and young age, the readily available placenta-derived mesenchymal stem cells could be more suitable for myocardial regenerative therapy., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This study aims at modifying the synthesis method of preparing N-isopropylacrylamide (NIPAAM)/N-vinyl-2-pyrrolidone (VP)/Polyethylene glycol monoacrylate (PEG-A) polymeric nanoparticles encapsulating curcumin as a model drug. The optimal concentration of nanoparticle reagents was determined using Fourier Transform Infrared Spectroscopy. Curcumin nanoparticles mean hydrodynamic size was found to be 104 nm with zeta potential of 3 ± 13 mV. The release kinetic study of curcumin nanoparticles indicates that a maximum release of curcumin at 24 h positively correlates with increase in temperature; however, change in pH did not produce any substantial drug release. In vitro cell viability assay performed on cancer cells exposed to various concentrations of model compound displayed the IC50 ranging between 100 and 200 μg/mL for human prostate cancer cells (PC3 cells) and 50 and 200 μg/mL for epidermoid carcinoma (A431 cell line). The Hoechst staining and phase contrast micrographs for 48 h exposure of curcumin nanoparticles at a concentration of 400 μg/mL resulted in almost 92% of cells death in both cell lines. This study concludes that the physiochemical characteristics of NIPAAM/VP/PEG-A polymer with key features of water solubility, sustained drug release, small particle size make these nanoparticles a prominent drug delivery device.

Objective: Docusate sodium (Colace) is an off-label ceruminolytic agent used to soften ear wax and relieve ear canal obstruction. At present, its effect on hearing in the presence of tympanic membrane (TM) perforation is not clear. The present study aimed to assess the safety of ototopic docusate sodium on hearing in the presence of TM perforation., Study Design: A prospective, randomized, controlled trial in a guinea pig animal model., Materials and Methods: Ten guinea pigs underwent bilateral myringotomy. In each animal, one ear received docusate sodium, serving as the experimental ear, and the other received normal saline as the control. Auditory brain response (ABR) was performed at baseline and then 1, 7, and 14 days following the application., Results: At day 14 following application, there was no significant change in ABR thresholds at 8, 12, 16, 20, or 25 kHz., Conclusion: In guinea pigs with perforated TMs, docusate sodium does not seem to cause ototoxicity. Future clinical studies are required.

The independent effect of consanguinity on the prevalence of congenital heart defects (CHDs), all and specific types, was investigated in newborns admitted to nine hospitals located in Beirut, Lebanon and members of the National Collaborative Perinatal Neonatal Network (NCPNN). Cases were 173 newborns admitted to the Neonatal Intensive Care Units (NICU) of participating hospitals during the 3-year period from January 1, 2000 to December 31, 2002 and diagnosed during their hospital stay as having one or more CHD. Cases with chromosomal abnormalities were excluded. Cases with more than one CHD were assigned one principal malformation. Controls consisted of a random sample of 865 newborns without a CHD admitted to the NICU during the same period. After controlling for confounders, first cousin consanguinity remained significantly associated with an increased risk of CHD: infants born to first cousin marriages had a 1.8 times higher risk of having a CHD diagnosed at birth compared to those born to unrelated parents (95% CI: 1.1-3.1). In particular, first-cousin marriage was a significant risk factor for ventricular septal defect (VSD), atrial septal defect (ASD), hypoplastic left heart (HLH), and single ventricle (SV). No association was found with d-transposition of the great arteries, coarctation, pulmonary atresia (PA), atrioventricular septal defect (AVSD), and tetralogy of Fallot (TOF). The results of this study suggest a familial factor in the multifactorial etiology of CHDs. Additional epidemiologic and family-based genetic studies are needed to understand the complex cause of CHDs., (Copyright 2006 Wiley-Liss, Inc.)