[DDQM][HSO4]/TBHP as a Multifunctional Catalyst for the Metal Free Tandem Oxidative Synthesis of 2-Phenylquinazolin-4(3H)-ones.

A bifunctional ionic liquid (IL) [DDQM][HSO4] has been designed and explored as a three-way catalyst for the synthesis of 2-phenylquinazolin-4(3H)-ones from anthranilamide and benzyl alcohol in 3.5 min incorporating microwave irradiation. Photochemically the reaction proceeds for 4 h at room temperature and thermally for 8 h at 120 °C. Further IL-assisted metal, solvent, and base free in situ oxidation of benzyl alcohols to aldehydes shows its task specificity. The multifunctionality of the IL was reestablished with the synthesis of two Wnt pathway antagonists.

Versatile surface-active ionic liquid: construction of microemulsions and their applications in light harvesting.

This article outlines a sustainable method towards the synthesis of advanced materials such as core/shell Quantum Dots (QDs) and their in situ stabilization using microemulsions (MEs). QDs are versatile materials which show unusual optical properties. We have constructed MEs consisting of an Ionic Liquid (IL) based surfactant i.e. choline dioctylsulfosuccinate, [Cho][AOT] as an emulsifier, toluene as a nonpolar phase and water as a polar phase. The system forms a large single-phase region in the phase diagram without any co-surfactant. Spontaneous formation of micelles has been observed and studied through tensiometry and fluorescence and isothermal titration calorimetry (ITC). The exceptional swelling behaviour of the MEs was studied using Dynamic Light Scattering (DLS) and small angle neutron scattering (SANS). In ME droplets, i.e. Reverse Micelles (RMs), we successfully synthesized spherical core/shell QDs (size ∼3 to ∼6 nm) with precise control over the size and morphology. The QDs have been characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Powder X-ray Diffraction (PXRD). QDs stabilized in MEs exhibited excellent optical properties and can be suitably used as light harvesting materials for diverse applications.

Vascular Complications of Percutaneous Transradial Cardiac Catheterization.

The percutaneous transradial approach for coronary angiography and percutaneous coronary intervention is increasing in the United States. Although its vascular safety profile is better than the traditional femoral approach, it is important to learn about potential complications. In this article, we present two cases of vascular complications, namely, pseudoaneurysm and radial artery occlusion, after transradial cardiac catheterization, along with a review of the relevant literature.

Outcomes of operative intervention for ulcers over hemodialysis arteriovenous access.

INTRODUCTION: The native arteriovenous fistula (AVF) is the gold standard for long-term hemodialysis access. When native vein options are exhausted, arteriovenous graft (AVG) becomes the next choice. An ulcer over an AVF or AVG is a serious condition with the potential for life-threatening hemorrhage. OBJECTIVES: This study aims to present our experience with surgical management of ulcers over AVFs or AVGs. MATERIALS AND METHODS: Electronic records of 26 patients who underwent 27 consecutive surgical procedures for ulcers over AVFs or AVGs from December 31, 2016 to December 31, 2021 at the Royal Liverpool University Hospital were retrospectively analyzed. RESULTS: The majority were males (14/26, 53.8%) and the median age was 64.5 years. Operative repair was required for 25 ulcers over 24 AVFs and 2 ulcers over 2 AVGs. Ten patients (37%) presented with bleeding. Seventeen (63%) had impending bleeding suggested by a thin soft tissue covering or a false aneurysm at the site of the ulcer. Previous endovascular intervention for fistula outflow stenosis was a significant predictor for presenting with bleeding (p = 0.031). All ulcers (27/27, 100%) underwent excision and primary skin closure. Fistula wall defects were directly repaired in 18/27 (66.7%). Four/26 (14.8%) fistulas had to be ligated and 2 (7.4%) had end-to-end re-anastomosis after excision of damaged segments. Three/26 (11.53%) fistulas thrombosed immediately after the intervention. The overall fistula salvage rate was 73.08% (19/26). There was 1 (3.7%) patient mortality due to bleeding from wound breakdown after surgery. CONCLUSIONS: An acceptable fistula salvage rate can be expected following surgical repair of ulcers over AVFs and AVGs. A history of previous endovascular interventions for fistula outflow stenosis was a predictor of bleeding from these ulcers.

Emerging therapies for residual risk.

The role of statins in reducing the risk of coronary artery disease is well established. The use of statins in patients at high risk for cardiovascular disease has reduced the incidence of major clinical events by 25% to 40%. However, despite aggressive statin therapy and the achievement of target low-density lipoprotein cholesterol levels, the residual risk of cardiovascular events remains high. This review investigates emerging therapies to target the residual risk of cardiovascular events with concurrent statin therapy.

Endovascular Treatment for Transplant Renal Artery Stenosis Improves the Short- and Long-Term Graft and Patient Outcomes.

OBJECTIVES: Transplant renal artery stenosis is the commonest vascular complication after kidney transplant. This study aimed to evaluate the efficacy of endovascular treatment for patients with clinically significant transplant renal artery stenosis. MATERIALS AND METHODS: Electronic patient records of kidney transplant recipients who received transplants from October 1, 2010, to July 31, 2021, at the Royal Liverpool University Hospital were retrospectively reviewedtoidentify thosewhounderwent endovascular treatment for transplant renal artery stenosis. Analysis of variance and paired sample t tests were respectively used to compare serum creatinine and the mean number of antihypertensive medications before and aftertreatment. RESULTS: During the period of analysis, there were 1211 kidney transplant recipients, with 33 (2.72%) who received endovascular treatment for transplant renal artery stenosis. Mostofthesepatientsweremen(25/33), and the median age was 59 years (range, 27-83 y). The mean follow-up duration was 69.82 months. As primary treatment, 19/33 patients (57.6%) were treated with percutaneous balloon angioplasty and 14/33 (42.4%) received stents. Procedure-related complications occurred in 3 patients (9.1%; 2 had false aneurysms, 1 had renal artery dissection). Significant improvements in mean serum creatinine levels were shown up to 4 years after the procedure (P = .019). A significant difference in the mean number of antihypertensive drugs before and after treatment was noted in those who had resistant hypertension as a presentation for transplantrenal artery stenosis (P = .016). At the end of follow-up, 7 patients (21.1%) had graft failure, with 1 patient (3.0%) having graft failure as a direct consequence of transplant renal artery stenosis. There was no reported incidence of patient mortality. CONCLUSIONS: Endovascular treatment for transplant renal artery stenosis provides a sustained improvement in graft function and a significant reduction in antihypertensive drug requirement.

Outcomes of Nonstandard Donor Kidney Transplants in Recipients Aged 70 Years or More: A Single-Center Experience.

OBJECTIVES: There is a global increase in the prevalence of end-stage kidney disease among the elderly. As a result, more elderly recipients are being considered for kidney transplants. Because of the scarcity of donor organs, such patients are more likely to receive transplants from nonstandard donor kidneys.Here, we examined the outcomes of kidney transplants with a nonstandard donor allograftin recipients ≥70 years of age. MATERIALS AND METHODS: Records of patients who received transplants at a single UK centerfrom April 1, 2015, through March 31, 2021, were retrospectively analyzed to identify those who were ≥70 years old at the time of surgery. Outcomes ofthose who received a kidney transplantfrom a nonstandard donor (group 1) were compared to those who received a kidney transplant from a standard criteria donor or living donor (group 2). RESULTS: During the study period, of 670 kidney transplant procedures, 67 recipients (10%) were ≥70 years of age at the time of surgery, with 54 (80.6%) identified in group 1 and 13 (19.4%) identified in group 2. Cold ischemia time (P = .001) and incidence of delayed graft function (P = .044) were significantly higherin group 1. Duration of graft survival atthe end of follow-up was not different between the groups (log rank = 0.218), butthe mean serum creatinine values at 2 years (P = .016) and 3 years (P = .048) years were significantly higherin group 1. Patients in group 1 had shorter survival time (log rank = 0.037). CONCLUSIONS: Nonstandard donor kidneys should be used cautiously in elderly recipients as patient survival was shown to be comparatively poor compared with elderly recipients who received a kidney transplant from a standard criteria donor or a living donor.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Coronary artery calcium scoring.

Numerous clinical studies have shown that coronary artery calcium scoring provides substantial incremental risk prediction beyond conventional coronary risk factors for coronary heart disease events. About half of all patients with coronary artery disease (CAD) present initially with unexpected myocardial infarction or sudden death. Early identification of this subgroup of patients is vital for institution of intensive, early preventive measures to decrease morbidity and mortality due to CAD.

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

UNLABELLED: Study Type - Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation. Post-transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre-transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre-transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy. OBJECTIVE: To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation. PATIENTS AND METHODS: A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken. RESULTS: There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43-65). Twenty patients were in the pre-transplant nephrectomy group, 12 in the post-transplant group, and three underwent the sandwich technique. Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety). Seven individuals in the pre-transplant group and three in the post-transplant group required critical care admission after nephrectomy. Transient renal graft dysfunction occurred in two post-transplant bilateral nephrectomy patients. Two patients in the bilateral nephrectomy pre-transplant group and one in the bilateral nephrectomy post-transplant group died in the immediate post-operative period. No complications were noted in the sandwich technique group. CONCLUSION: Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre-transplant group. Post-transplant unilateral nephrectomy appears to be the safest approach with fewest complications.

Ionic Liquid-Based Colloidal Formulations for the Synthesis of Nano-MOFs: Applications in Gas Adsorption and Water Desalination.

Microemulsions (MEs) comprising choline dioctylsulfosuccinate [Cho][AOT], a biobased ionic liquid (IL) surfactant as an emulsifier, (R)-(+)-limonene (RL) as a nonpolar phase, and ethylene glycol (EG)/ethanolammonium formate (EOAF) as an organic solvent/low-viscosity IL polar component were constructed. Spontaneous aggregation of [Cho][AOT] was observed with a negative ΔH form using isothermal titration calorimetry. The aggregates of [Cho][AOT] in RL showed a critical micellar concentration (cmc) of ∼5.49 mM, EG (cmc ∼3.99 mM), and EOAF (cmc ∼1.56 mM), and these are further characterized by various techniques. These novel IL-based MEs have been used as nanoreactors for the sustainable synthesis of uniform nanosized metal-organic frameworks (N-MOFs), such as MIL-53(Al), HKUST-1, UIO-66-NH2, and ZIF-8, with a precise control over size and morphology at room temperature. Characterization of N-MOFs has been performed using scanning electron microscopy, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The synthesized N-MOFs have been used to prepare stable and uniform thin film nanocomposite nanofiltration membranes, suitable for desalination of brackish water with excellent flux (31.8 LMH/bar) and rejection (99.0%) of divalent salts.

Negative pressure wound therapy used to heal complex urinary fistula wounds following renal transplantation into an ileal conduit.

Transplantation into an ileal conduit is an established option for patients with end-stage renal failure and a nonfunctioning urinary tract. Urinary fistulae are more common following these complex transplants. Urinary fistula in this scenario can cause substantial morbidity and even result in graft loss. The management options depend on the viability of the transplant ureter, the level of local sepsis and the overall condition of the patient. Urinary diversion with a nephrostomy and ureteric stents has been described in aiding the healing of urinary leaks in renal transplants into a functioning urinary tract. We describe the successful use of negative wound pressure therapy to eradicate the local sepsis and help the healing of a recurrent urinary fistula following kidney transplantation into an ileal conduit. To our knowledge these are the first such cases reported in the literature.

Update on cardiac risk stratification of renal transplant candidates.

Numerous modifiable and unmodifiable risk factors have been identified that contribute to increased cardiovascular risk in renal transplant recipients. We reviewed several clinical studies and journal articles to identify these risk factors in an attempt to risk stratify chronic kidney disease patients who are candidates for renal transplantation. Cardiovascular disease has been identified as the leading cause of death with graft function among renal transplant recipients. No single test or diagnostic modality has been found to provide complete diagnostic and prognostic information. Hence, a combination of clinical, biochemical, and radiographic data is essential to risk stratify renal transplantation candidates.

Investigating the relationship between class I HLA-specific immunoglobulin-G subclasses, Pan-IgG single antigen bead assays and complement mediated interference in sera from renal transplant recipients.

INTRODUCTION: Antibody mediated rejection is the leading cause of kidney transplant failure. Not all antibodies are harmful and some may be protective. Immunoglulin Gs, of which there are four subtypes, are detected by single antigen bead testing. The aims of this study were to characterise the IgG subclass profiles for class I HLA-specific antibodies in an uncensored post-transplant population and to determine the underlying relationship between reactivity patterns and MFI cut-offs with the pan-IgG assay. METHODS: Patients were recruited to the study who were transplanted in our centre between 2009 and 2014. Prospectively stored post-transplant serum initially underwent a Labscreen Mixed assay and those positive for class I HLA-specific antibody underwent standard SAB testing, EDTA, 1 in 10 dilution and IgG subclass modifications using the Luminex platform. A total of 4947 bead reactions from 51 patients were analysed. RESULTS: A 1 in 10 dilution was used as a comparator pan-IgG assay for summed subclass and individual subclass linear regression analyses. Using a dilution to standard assay ratio we characterised all reactions for prozone potential i.e. how likely there is to be inhibition related to complement complex formation. We stratified samples into degrees of association and were able to determine suggested MFI thresholds of Log 5.35 for the dilution assay and Log 5.05 for the summed subclass assay when considering a Log MFI of 6.9 (1000) in the standard assay. Using individual subclass dominant reactions (>70%) we were able to determine linear relationships between the 1 in 10 dilution pan-IgG assay and the individual subclass assays (excluding prozone potential reactions for IgG1/3) enabling us to suggest Log MFI thresholds of 5.03, 3.58, 4.3 and 4.05 respectively for IgG1-4. DISCUSSION: We recommend a 1 in 10 dilution as the optimum pan-IgG comparator assay for a subclass analysis. We advocate the utilisation of the summed subclass assay to determine overall relationships and potential subclass failures. Following others, we recommend serum pre-treatment of the subclass assays to mitigate prozone. We suggest cut-offs for each IgG subclass which should be used with caution given the many inhibitory influences which may include competitive inhibition for bead binding, IgM and IgA interference and under-representation of specific subclasses on the bead panel.

Investigating complement mediated interference in class I HLA-specific antibodies following renal transplantation.

INTRODUCTION: Single antigen bead testing (SAB) for HLA-specific antibody enables efficient organ allocation and aids in the diagnosis of antibody mediated rejection. In this retrospective cohort study, a population of kidney transplant recipients possessing HLA Class I antibodies was used to evaluate the best method for resolving complement interference, the so called "prozone" effect. The aim was to compare the use of EDTA versus a Biotin-Streptavidin Complex as methodological approaches for abating the prozone effect using a fixed 1 in 10 dilution as validation. METHODS: One hundred and seventeen patients transplanted in our centre between 2009 and 2014 were identified as having class I HLA-specific antibody(-ies) using a Labscreen® Mixed assay. Positive sera underwent class I HLA-specific SAB testing; for comparison a standard SAB with and without EDTA, BSC and dilution (1 in 10) modifications were utilised. Samples were processed on the Luminex platform generating 11,349 bead reactions for analysis. RESULTS: We identified sera from 23 patients giving rise to 170 bead reactions showing complement interference. Using linear modelling, we observed slightly higher MFIs on average in both EDTA and BSC modifications when compared to the standard assay, allowing the nominal threshold MFI of 2000 in the standard assay to be adjusted to 2097 and 2033 in the EDTA and BSC assays respectively. We calculated 99% prediction intervals to establish outlier bead reactions for each assay. The 1 in 10 dilution was used as a crosscheck for determining which prozone reactions were overcome by EDTA and BSC. Using ROC curve analysis, EDTA was found to be ~90% sensitive and 100% specific compared to BSC which was ~60% sensitive and 100% specific in ameliorating prozone positive reactions at the thresholds defined by linear models. DISCUSSION: Our data indicates that both EDTA and BSC are suitable assays in overcoming CMI. We recommend that all clinical laboratories adopt a validated assay designed specifically to abrogate CMI for all potential renal transplant recipients, as the standard assay is inhibited in nearly 20% of a post-transplant cohort.

Implantable Cardioverter-Defibrillator Shock after Stenting Across the Device Leads.

A 45-year-old man with nonischemic cardiomyopathy and end-stage renal disease had lived uneventfully with a cardiac resynchronization therapy defibrillator (CRT-D) for 5 years. Less than a month before presenting at our institution, he had undergone stenting of his partially occluded subclavian vein, to relieve stenosis of the ipsilateral arteriovenous fistula that was used for his hemodialysis. The CRT-D subsequently discharged. Device interrogation revealed that electrical noise originating from leads damaged by the stent had caused the inappropriate shock and intermittent electrical discharges thereafter. The patient was highly traumatized by these events and insisted upon device removal, which deprived him of a potentially life-saving intervention. He later had a cardiac arrest that resulted in sustained profound hypoxic ischemic encephalopathy with minimal neurologic recovery: his family placed him in a long-term care facility on ventilator support, with a tracheostomy and feeding tube. This situation might have been avoided through collaboration between the interventional radiologist and the electrophysiologist. To our knowledge, this is the first report of a patient with nonischemic cardiomyopathy and end-stage renal disease who presented with inappropriate defibrillator discharge caused by lead damage secondary to stenting across the leads.