End of Life Care for Unplanned Vascular Admissions.

BACKGROUND: Unplanned vascular admissions have a high mortality. Previous studies have indicated that end of life care (EoLC) among this group of patients is low but there exist limited data on EoLC in the United Kingdom. The aim of this study was to evaluate the quality and predictors of EoLC for unplanned vascular admissions to a tertiary center in the United Kingdom. METHODS: This was a retrospective single-center cohort study of unplanned vascular surgery admissions from August 1, 2019 to January 22, 2020. Data on patient demographics, markers of quality of palliative care, mortality, and cause of death of unplanned admission to the vascular surgery department were collected from hospital and general practitioner records and evaluated against EoLC to evaluate predictors and efficacy of EoLC. Quality of palliative care markers included documentation of preferred place of death and care priorities, time spent in hospital and the intensive care unit toward the end of life, and realization of documented care objectives. EoLC input was defined as a dedicated palliative care consultation (PCC) by a palliative care professional, medical doctor, surgeon, or advanced care practitioner. We also conducted a subgroup analysis of patients within this group with chronic limb-threatening ischemia (CLTI), diabetic foot, and ruptured aortic aneurysms, as all patients in this group should be offered EoLC according to international guidelines. RESULTS: One-hundred and fifty patients were included. Median age at presentation was 70.5 years, and the cohort consisted of mostly men (72%). CLTI (31%) was the most common reason for admission. Surgical intervention was carried out in 60% of patients. Two-year mortality was 36%, and pneumonia (22%) was the most common cause of death. Seven percent of patients received PCC, which occurred a median of 10 days before death. Only a minority of patients had preferred place of care/death (14%), care priorities (37%), and family involvement during advance care planning (17%) documented in their notes; 29% of patients had Recommended Summary Plan for Emergency Care and Treatment forms in place. A diagnosis of left ventricular systolic dysfunction, chronic kidney disease, and increasing age predicted Recommended Summary Plan for Emergency Care and Treatment form completion. Patients with PCC were more likely to have advance care planning, but this did not translate into improvements in the other markers of quality of palliative and, consequently, EoLC. CONCLUSIONS: EoLC was insufficient and of low quality despite a high mortality in this group. Clinical guidelines and pathways are needed to ensure these patients are considered for EoLC and those with CLTI, diabetic foot sepsis or ruptured abdominal aortic aneurysms are offered it by default. Further research is needed to help identify vascular patients who would benefit from EoLC earlier to improve quality at end of life.

End-of-life care and advance care planning for outpatients with inoperable aortic aneurysms.

OBJECTIVE: A significant proportion of patients with abdominal and thoracic aortic aneurysms (AA) do not proceed to intervention after reaching treatment threshold diameter due to a combination of poor cardiovascular reserve, frailty, and aortic morphology. This patient cohort has a high mortality; however, until this study, there exist no studies on the end-of-life care conservatively managed patients receive. METHODS: This is a retrospective multicenter cohort study of 220 conservatively managed patients with AA referred to Leeds Vascular Institute (UK) and Maastricht University Medical Centre (the Netherlands) for intervention between 2017 and 2021. Demographic details, mortality, cause of death, advance care planning and palliative care outcomes were analysed to examine predictors of palliative care referral and efficacy of palliative care consultation. RESULTS: A total of 1506 patients with AA were seen over this time period, giving a nonintervention rate of 15%. There was a 3-year mortality rate of 55%, a median survival of 364 days, and rupture was the reported cause of death in 18% of the decedents. Median follow-up was 34 months. Only 8% of all patients and 16% of decedents received a palliative care consultation, which took place a median of 3.5 days before death. Patients >81 years of age were more likely to have advance care planning. Only 5% and 23% of conservatively managed patients had documentation of preferred place of death and care priorities respectively. Patients with a palliative care consultation were more likely to have these services in place. CONCLUSIONS: Only a small proportion of conservatively treated patients had advance care planning and this was far below international guidelines on end-of-life care for adults, which recommends it for each of these patients. Pathways and guidance should be implemented to ensure patients not offered AA intervention receive end-of-life care and advance care planning.

Analyzing Sex Differences in Intensity of Cardiovascular Disease Prevention Medications in Patients With Abdominal Aortic Aneurysms-A Single-Center Cross-Sectional Study.

BACKGROUND: Patients with abdominal aortic aneurysm (AAA) are at a significant risk of cardiovascular events, similar to that of patients who have already experienced a major cardiac event. The European Society for Vascular Society AAA guidelines suggest that antiplatelet therapy and lipid-lowering therapy (LLT) should be considered in all patients with AAA. This study explores the overall prevalence and intensity of antithrombotic therapy and LLT, and lipid profile monitoring in a single center AAA surveillance cohort alongside any sex differences. METHODS: This was a retrospective, single center, cross-sectional study of 614 patients enrolled in the AAA surveillance program of a tertiary vascular surgery unit. All patients undergoing at least 1 surveillance scan from January 1, 2018, to December 31, 2020, were assessed. Electronic hospital records linked to real-time primary care records were interrogated for data on demographics, comorbidities, antiplatelet and LLT prescriptions, and serum cholesterol laboratory results. An analysis of covariance test was used to account for the effects of confounding comorbidities. RESULTS: Twenty-one percent of patients were not on antithrombotic therapy, and 20% of patients were not on LLT which reflects a group of patients receiving sub-optimal clinical care. In total, 47% of the cohort were on low/moderate intensity statin therapy which reflects a group of patients where care can be improved upon. Female sex was independently associated with a reduced likelihood of being prescribed LLT (P = 0.008, eta squared (ηp2) = 0.012, small effect size) but not antithrombotic therapy (P = 0.202). Fewer women underwent low-density lipoprotein cholesterol (LDL-C) monitoring (mean difference 9%, P = 0.040) and achieved the European Society of Cardiology-European Atherosclerosis Society- LDL-C target of <1.4 mmol/L (mean difference 9%, P = 0.040). CONCLUSIONS: Overall, there is room for improvement in these aspects of cardiovascular risk prevention for both sexes. Sex differences in the prescription of LLT, the prevalence of lipid profile monitoring, and likelihood of achieving LDL-C targets exist among patients with AAA, with a lower prevalence in women.

Digitizing Chemical Synthesis in 3D Printed Reactionware.

Chemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well-defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well-defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki-Miyaura coupling reaction, and synthesis of the drug sulfanilamide.

Four novel suture-sealing techniques to repair varying size paravalvular leaks.

BACKGROUND: Paravalvular leak (PVL) is a well-known complication of aortic valve replacement. Currently, there is no consensus on optimal intraoperative management of patients with mild-to-moderate or moderate PVL. TECHNIQUE: In this paper we present four novel surgical techniques, each combining suturing with sealing technique, to repair aortic PVLs, nullifying the need to replace the prosthesis. CONCLUSION: These techniques will offer cardiac surgeons new alternatives to the repair techniques currently used.

Modified band annuloplasty technique for functional tricuspid regurgitation repair in patients with grossly dilated annuli: The three-suture junctional continuous suture band annuloplasty technique.

Functional tricuspid regurgitation (FTR) is the most common of all tricuspid dysfunctions. Ring annuloplasty is an effective treatment strategy for FTR. Currently, the most commonly used suture method for tricuspid ring annuloplasty is the interrupted U-shaped suture method. However, when tricuspid annuli are grossly dilated (septal segments > 60 mm), interrupted sutures are insufficient in avoiding the folding over of the annulus or the tearing of sutures. Therefore, we recommend a new band suture technique; namely, the three-suture junctional continuous suture band annuloplasty technique.

Right atrium hemangioma in patient with history of mixed-thrombus surgery.

Primary cardiac neoplasms are rare, cardiac hemangiomas are even rarer, and a mixed thrombus followed by a primary cardiac hemangioma is exceptionally rare epidemiology. Here, we report the case of a man with a right atrium mixed-thrombus surgical history who went on to develop a cardiac hemangioma.

Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats.

BACKGROUND/AIMS: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI). This study investigated the potential for poly (lactic-co-glycolic acid) (PLGA) complex inoculated with olfactory ensheathing cells (OECs) to treat spinal cord injury in a rat model. METHODS: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR) p75. The Basso, Beattie, and Bresnahan (BBB) score, together with an inclined plane (IP) test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB) staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP) and the microtubule-associated protein-2 (MAP-2), representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. RESULTS: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05). CONCLUSION: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

Autophagy upregulation and apoptosis downregulation in DAHP and triptolide treated cerebral ischemia.

It has previously been demonstrated that ischemic stroke activates autophagy pathways; however, the mechanism remains unclear. The aim of this study is to further investigate the role that autophagy plays in cerebral ischemia. 2, 4-diamino-6-hydroxy-pyrimidine (DAHP), for its nitric oxide synthase (NOS) inhibiting neuroprotective effect, and triptolide (TP), for its anti-inflammatory property, were selected to administer pre middle cerebral artery occlusion (MCAO). The drugs were administered 12 hours prior to MCAO. Both magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that the drugs reduce the area of infarction. Immunoblotting analysis revealed increases in Beclin-1 and myeloid cell leukelia-1(Mcl-1) in treated rats. This could be a contributing factor to the reduction in autophagy induced damage. Immunochemistry and western blot showed that mTOR expression in treated rats was marginally different 24 h after injury, and this could also be significant in the mechanism. Furthermore, terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) staining proved that the drugs are effective in reducing apoptosis. The upregulation of Beclin-1 and Mcl-1 and downregulation of Bcl-2, caspase-3, and the Bcl-2/Beclin-1 ratio infer that the neuroprotective effect of DAHP and TP act via the mediation of autophagy and apoptosis pathways.

The effect of highly active antiretroviral therapy on liver function in human immunodeficiency virus-infected pediatric patients with or without hepatitis virus co-infection.

BACKGROUND: Co-infection of hepatitis virus is common in human immunodeficiency virus (HIV) infected adults in China. But little is known about hepatitis virus co-infection in pediatric HIV-infected subjects. The study aimed to investigate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection and highly active antiretroviral therapy (HAART) on liver function of pediatric HIV-infected subjects. MATERIALS AND METHODS: A cohort study including 101 pediatric HIV-infected subjects with HBV/HCV co-infection and 44 pediatric comparators with HIV mono-infection was carried out in Henan Province of China from September 2011 to September 2012. All patients received HAART for 1-year. HBV and HCV infection was determined by antibody tests. HIV RNA load, CD4(+) T-cell counts and liver function were determined before and after HAART. The Student's t-test or a one-way ANOVA was used for normally distributed values and A Mann-Whitney U-test was performed for values without normal distribution using SPSS statistical package 18.0 (SPSS Inc.). RESULTS: After HAART for 1-year, the median levels of viral load were decreased to lower limit of detection in 90.34% pediatric HIV-infected subjects with/without HBV/HCV co-infection (P < 0.001), and CD4(+) T-cell counts increased significantly (P < 0.001). Compared with the pre-HAART, mean level of alanine aminotransferase (ALT) in each group had a significant increase after HAART (P < 0.01). The mean levels of ALT and aspartate aminotransferase (AST) in nevirapine (NVP) based HAART group increased significantly after HAART (P < 0.01). Mean change values of ALT and AST were significantly higher in the NVP based regimen group than in the efavirenz (EFV) based regimen group (P < 0.01). For HIV/HBV/HCV co-infected patients, mean change values of ALT and AST in NVP-based HAART group was significantly higher than that in EFV-based HAART group (P < 0.01). CONCLUSION: Highly active antiretroviral therapy can damage liver function in pediatric HIV-infected subjects, especially in those with HBV/HCV co-infection. NVP was more harmful to liver function of pediatric HIV-infected subjects than EFV.

Mifepristone: a potential clinical agent based on its anti-progesterone and anti-glucocorticoid properties.

Nowadays, unwanted pregnancy is a major globe tragedy for millions of women, associated with significant direct and indirect costs, no matter for individuals or society. The progesterone receptor antagonist steroid, mifepristone has been widely and effectively using throughout the world for medical abortion, but to a lesser extent for emergency contraception. In this review, we hope to explore the role of mifepristone as a contraceptive, particularly for emergency contraception. Studies of mifepristone have also been expanding to the fields of endometriosis and uterine fibroids. Furthermore, this initially considered reproductive medicine has been investigated in some psychotic diseases and various disorders of hypercortisolism, because of its glucocorticoid receptor antagonism. Mifepristone was approved suitable for patients with hyperglycemia secondary to Cushing's syndrome by the United States Food and Drug Administration (FDA) in 2012. The aim of this article is to review published reports on the anti-progesterone and anti-glucocorticoid properties of mifepristone as a clinical agent. There is a new insight into systematically describing and evaluating the potential efficiency of mifepristone administrated in the field of endocrine and neuroendocrine, not only in obstetrics and gynecology.

Systematic hypothesis for post-stroke depression caused inflammation and neurotransmission and resultant on possible treatments.

Post-stroke depression (PSD) is a prevalent complex psychiatric disorder that causes delay to functional recovery from rehabilitation and also increases cognitive impairment. The etiology of PSD remains controversial and appears to be physical and psycho-social in origin, alone or in combination. The causes of PSD as well as the mechanisms conferring beneficial antidepressant effects in the context of ischemic brain injury are still unknown. In addition, appropriate treatment strategies for therapy to prevent stroke-induced depression-like behavior remain to be developed. This paper, therefore, proposes two hypotheses for post-stroke depression: The inflammatory hypothesis, which is the increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas causing the pathogenesis of post-stroke depression and the glutamate hypothesis, where the excess glucocorticoids released from stress-induced over-activation of hypothalamus-pituitary-adrenal (HPA) lead to dysfunction of glutamatergic transmission. Neurotrophins, especially brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) both play various roles in the central nervous system (CNS), attenuate apoptosis in cultured neurons, stimulate neurogenesis and increase survival and protect neuronal tissues from cell death induced by ischemia or depression. We also touch upon recent treatment strategies including inhibition of pro-inflammatory cytokines, SSRI, neurotrophins and cell-based therapies. In the present review, we provide an overview of recent evidence concerning the mechanisms of post-stroke depression and propose four prospective treatment strategies so as to provide references for clinical evidence-based medications.

Dose-dependent anti-inflammatory and neuroprotective effects of an ανß3 integrin-binding peptide.

Previous studies have shown that prevention of leukocyte infiltration by targeting integrins involved in transendothelial migration may suppress the clinical and pathological features of neuroinflammatory disease. This study was designed to investigate the effects of C16, an ανß3 integrin-binding peptide, in an acute experimental allergic encephalomyelitis (EAE) rat model. Multiple histological and immunohistochemical staining, electron microscopy observation, ELISA assay, Western blot, and magnetic resonance imaging (MRI) were employed to assess the degree of inflammation, axonal loss, neuronal apoptosis, white matter demyelination, and extent of gliosis in the brain and spinal cord of differently treated EAE models. The results showed that C16 treatment could inhibit extensive leukocyte and macrophage accumulation and infiltration and reduce cytokine tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) expression levels. A significantly lower clinical score at the peak time of disease was also demonstrated in the C16 treated group. Moreover, astrogliosis, demyelination, neuronal death, and axonal loss were all alleviated in C16 treated EAE animals, which may be attributed to the improvement of microenvironment. The data suggests that C16 peptide may act as a protective agent by attenuating inflammatory progression and thus affecting the expression of some proinflammatory cytokines during neuroinflammatory disease.

Evaluation of national institute for health and care excellence guidance for ruptured abdominal aortic aneurysms by emulating a hypothetical target trial.

Objective: This retrospective study evaluates the performance of UK National Institute for Health and Care Excellence (NICE) Guidelines on management of ruptured abdominal aortic aneurysms in a "real world setting" by emulating a hypothetical target trial with data from two European Aortic Centers. Methods: Clinical data was retrospectively collected for all patients who had undergone ruptured endovascular aneurysm repair (rEVAR) and ruptured open surgical repair (rOSR). Survival analysis was performed comparing NICE compliance to usual care strategy. NICE compliers were defined as: female patients undergoing rEVAR; male patients >70 years old undergoing rEVAR; and male patients ≤70 years old undergoing rOSR. Hemodynamic instability was considered additionally. Results: This multicenter study included 298 patients treated for rAAA. The majority of patients were treated with rOSR (186 rOSR vs. 112 rEVAR). Overall, 184 deaths (68 [37%] with rEVAR and 116 [63%] with rOSR) were observed during the study period. Overall survival under usual care was 69.2% at 30 days, 56.5% at one year, and 42.4% at 5 years. NICE compliance gave survival outcomes of 73.1% at 30 days, 60.2% at 1 year and 42.9% at 5 years. The risk ratios at these time points, comparing NICE-compliance to usual care, were 0.88, 0.92 and 0.99, respectively. Conclusions: We support NICE recommendations to manage men below the age of 71 years and hemodynamic stability with rOSR. There was a slight survival advantage for NICE compliers overall, in men >70 years and women of all ages.

A novel bidirectional side exiting pledgetted suture for valve replacement surgery.

The pledgetted mattress suture is one of the most widely used suture techniques for valve replacement surgery. However, the traditional pledgetted suture has several defects including intertwining of the sutures and the pledget flipping over. Here we present a novel side exiting pledgetted suture that can overcome these defects. It offers cardiac surgeons a new alternative for valve replacement surgeries.

Palliative Care Interventions for Peripheral Artery Disease: A Systematic Review and Narrative Synthesis.

Background: Peripheral artery disease (PAD) encompasses conditions with poor outcome and severe suffering, both mentally and physically, yet utilization and research into palliative care interventions remain sparse. Objective: The purpose of this study is to identify existing evidence on palliative care intervention for chronic limb threatening ischaemia (CLTI) and abdominal aortic aneurysm (AAA). Design: We conducted a PROSPERO-registered systematic review of studies published between 1991 and 2020 in which people with PAD received palliative care interventions and at least one patient outcome was recorded. For the purpose of this study, a palliative care intervention was defined as one which aims primarily to reduce negative impact of PAD on patients' and/or caregivers' physical, emotional, psychological, social, or spiritual condition. Results: A total of 8 studies involving 87,024 patients met the inclusion criteria (4 cohort studies and 4 cross-sectional studies). Methodological quality ranged from low to moderate. The small number of studies and study heterogeneity precluded meta-analysis. Regarding our primary outcomes, only two articles recorded patient-reported outcomes. Five articles found an association between palliative care and reduction in health care utilization, a secondary outcome of the study. Most of the studies reported that palliative care was likely underused. Only two of the studies included non-hospital patients. Conclusion: Despite high mortality and morbidity associated with PAD, evidence of the effectiveness of palliative care in this group of patients is lacking. There are only a handful of articles on palliative care for people with PAD, and the majority are small, methodologically flawed and lack meaningful patient-reported outcomes. High-quality research of palliative care interventions in patients with PAD is urgently needed to better understand the impact of palliative care on quality of end of life and to develop and evaluate service-level interventions.

Automatic Generation of 3D-Printed Reactionware for Chemical Synthesis Digitization using ChemSCAD.

We describe a system, ChemSCAD, for the creation of digital reactors based on the chemical operations, physical parameters, and synthetic sequence to produce a given target compound, to show that the system can translate the gram-scale batch synthesis of the antiviral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anticancer agent Lomustine (batch yield 65% over two steps) in purities greater than or equal to 96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a database repository, with the information necessary to critically evaluate and improve upon reactionware syntheses being easily shared and versioned.

The effect of ifosfamide, epirubicin, and recombinant human endostatin therapy on a cardiac angiosarcoma: A case report.

RATIONALE: Cardiac angiosarcoma is a rare malignant tumor, for which only surgery has been proven to be effective to date. Currently there are no reports as to whether a postoperative regimen of ifosfamide, epirubicin, and recombinant human endostatin is effective. PATIENT CONCERN: The patient presented to us with chest pain and dyspnea. DIAGNOSIS: Enhanced computerized tomography (CT) and positron emission tomography-computerized tomography (PET-CT) suggested pericarditis and an atrial perforation, but malignancy was suspected, so the patient underwent an operation to resect the tumor and repair. Pathology of the tumor reseccted at operation showed the tumor to be an angiosarcoma. INTERVENTION: After the surgery, the patient was stared on a paclitaxel chemotherapy regimen (135 mg/m once every 3 weeks). However, 2 cycles later, pulmonary and hepatic metastases were found. Chemotherapy was then changed to ifosfamide, epirubicin (ifosfamide 2000 mg/m days 1-3, epirubicin 70 mg/m days 1-2) and recombinant human endostatin (7.5 mg/m days 1-14) in 3 weekly cycles. OUTCOME: Three cycles later, follow-up showed that chemotherapy had delayed progression of the pulmonary metastases, but that the hepatic node was still growing. The patient has now survived 8 months post surgery and is still on follow-up. LESSONS: This case shows us that operation on late stage cardiac angiosarcomas can alleviate a patient's symptoms; postoperative paclitaxel monotherapy was insufficient and ifosfamide and epirubicin plus recombinant human endostatin has a limited effect on late stage cardiac angiosarcoma. Studies with a larger sample size are needed for verification of these findings.