Drug Eluting Research Articles

Late Catch-up In-Stent Restenosis and Stent Thrombosis for 2nd Generation Biodegradable Polymer Drug Eluting Stents

Second generation drug-eluting stents (DES) have reduced the rate of in-stent restenosis (ISR) to < 10% [1, 2] in patients undergoing PCI. However, late catch-up in-stent restenosis remains an issue despite the advent in drug-eluting stent technology from 1st to 2nd generation drug eluting stents. The late catch-up phenomenon has been associated with serious consequences and adverse events and remains an important issue in modern practice, despite medical advances with more biocompatible and biodegradable polymers, as well as new therapeutic agents and thinner scaffolds in the development of 2nd generation DES polymer systems. The idea behind biodegradable polymers has been to provide a more controlled elution profile for DES drugs, allowing for long-term therapeutic, but sub-toxic, drug levels in the arterial tissue to prevent ISR and stent thrombosis. However, the late catch-up phenomenon remains an issue resulting in 2ndary revascularization beyond the first year of primary PCI, as it is defined as ISR >1 year. Late stent thrombosis (<1 year) and very late stent thrombosis (>1 year) also remain an issue for biodegradable polymer systems. A long-term presence of the polymer can cause inflammation and thrombogenesis, which is dependent upon polymer degradation kinetics in case of biodegradable polymer DES systems. However, the cause of late catch-up restenosis and stent thrombosis is multi-factorial from a drug-in-polymer formulation perspective of drug release kinetics, e.g., drug elution profile, drug physiochemical properties, and polymer degradation kinetics. It appears that the focus should be on controlling burst release for both late catch-up restenosis and stent thrombosis phenomena.

Slow-flow phenomena following lower limb paclitaxel- and sirolimus-coated balloon angioplasty in the setting of chronic limb threatening ischaemia—a case series

The Achilles heel of plain old balloon angioplasty (POBA) is neointimal hyperplasia (NIH) and restenosis, caused from the barotrauma of ballooning. Drug-coated balloons using a paclitaxel-based platform (PCB) have been shown to retard the restenotic process, using the anti-proliferative effects of paclitaxel, and give longer vessel patency. This is important in the setting of chronic limb threatening ischemia (CLTI) and for the protracted wound healing process in these frail patients. However, during PCB application, more than 50% of the drug is lost downstream, a phenomenon termed particulate embolization. This is thought to account for the slow- or no-flow phenomenon encountered after PCB use. Recent data suggest that slow-flow phenomenon was associated with a lower target lesion revascularisation rate and worse amputation free survival (AFS). The use of sirolimus coated balloons (SCB) to impede the NIH cascade has been less well studied but recent data suggested excellent short-term efficacy and found no slow flow phenomenon with their use in the tibial arteries in CLTI patients. Aim of this case series is to highlight the difference in flow phenomena using PCB and SCB elution in the setting of CLTI. We evaluated the use of parametric colour coding and time attenuation curves (TAC) as a quantitative measure of blood flow. SCB may have an advantage over PCB use in the peripheral vasculature because of a reduced incidence of slow flow phenomenon following drug elution.

Case series of coronary artery aneurysms after Everolimus eluting stent implantation and comparison with Sirolimus eluting stents

BackgroundCoronary artery aneurysms after drug eluting stents are rare. We present a case series of type II coronary aneurysms after implantation of Everolimus eluting stents including patients developing giant aneurysms with a toxic course.Case presentationOver a span of 3.5 years at our center 2572 patients were implanted Everolimus eluting stents out of which 4 patients developed coronary type II aneurysms an incidence of 0.00156 whereas 5838 patients were implanted Sirolimus eluting 2nd generation stents out of which 2 patients developed similar aneurysms with an incidence of 0.00034. The slight increase in incidence in Everolimus stents does not reach statistical significance (p = 0.054) and is limited by single centre non randomized study. We also propose a hypothesis that the slight increase in the incidence maybe due to allergy to Methacrylate present in Everolimus eluting Xience stent’s primer which is absent in other Sirolimus eluting stents used at our center but that needs to be further investigated. We also found some patients who developed giant aneurysms including Left main aneurysms. In our series operative repair of these patients had better outcomes than covered stent deployment but larger trials maybe needed to confirm the same.ConclusionsCoronary artery aneurysms after stent implantation are rare but occasionally giant aneurysms are formed with a toxic course. The incidence and morphology of aneurysms after Everolimus and Sirolimus eluting stent deployment do not differ much.

Comparison of diagnostic accuracy of immediate angiography derived residual quantitative flow ratio after bioresorbable scaffold and drug eluting stent implantation.

Quantitative flow ratio (QFR) is a novel angiography derived fractional flow reserve (FFR) technique. However, its diagnostic accuracy has only be validated in native coronary lesions but not in vessels after bioresorbable scaffold (BRS) implantation. This study aims to evaluate the diagnostic accuracy of residual QFR in coronary vessels immediately post-BRS implantation. This is a retrospective, two center, validation cohort study. 73 stable angina patients who received at least one de novo lesion of an everolimus eluting stent (EES)/BRS implantation with subsequent residual FFR assessment were screened. Patients with aorta-ostial stenoses, bridge vessels at the distal segment of targeted vessels, acute coronary syndrome, previous coronary artery bypass grafting, age <18 years, lack of ≥2 final angiographic projections were excluded. Contrast QFR assessment was performed blinded to FFR assessment. A good correlation (r = 0.680, p < 0.001) was found between residual QFR and FFR. In the EES implantation cohort, a good correlation (r = 0.769, p < 0.001) was found between residual QFR and FFR, and a moderate correlation (r = 0.446, p = 0.038) in the BRS cohort. The area under the Receiver operator characteristic (ROC) curve for detecting FFR ≤0.86 was 0.883 for all patients. Residual QFR assessment after BRS implantation is feasible, and has a moderate correlation and agreement with residual FFR. QFR may be a promising tool similar to FFR to evaluate post-BRS effect.

Target and non-target vessel related events at 10 years post percutaneous coronary intervention

AimsTo define the incidence of events related to the stented vessel (target vessel related events: TVRE) and events related to non-stented vessels (non-target vessel related events: NTVRE) through to 10-year follow-up in patients post-PCI with newer generation drug eluting stents (DES).Methods and resultsThe current study is a post-hoc analysis of patient level data from two randomised controlled trials in Germany. Patients older than 18 years with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% de novo stenosis located in the native coronary vessels were considered eligible. The endpoints of interest were TVRE (a composite of first target vessel myocardial infarction or target vessel revascularization) and NTVRE (a composite of first non-target vessel MI or non-target vessel revascularization) through to 10 years post PCI.We included 4953 patients in this analysis. Through to 10-years post-PCI, TVRE occurred in 1238 of 4953 patients (cumulative incidence: 25.8%) and NTVRE occurred in 1442 of 4953 patients (cumulative incidence: 30.3%). The majority of TVRE and NTVRE were revascularization events. From 0 to 1 years, the cumulative incidence of TVRE was 15.9% and of NTVRE was 12.3%. From 1 to 10 years, the cumulative incidences of TVRE and NTVRE were 11.2% and 22.4%, respectively.ConclusionAt 10-year post-PCI with new generation drug eluting stents, events related to remote vessel disease progression account for a higher proportion of events than events related to the stented vessel.Trial registrationISAR TEST 4 ClinicalTrials.gov Identifier: NCT00598676. ISAR TEST 5 ClinicalTrials.gov Identifier: NCT00598533.Graphical abstract

Relationship between atherogenic index of plasma and stent thrombosis in patients with acute coronary syndrome.

Stent thrombosis (ST) is an uncommon but serious complication in patients undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the effect of atherogenic index of plasma (AIP) on ST. Among the 10,258 patients who underwent coronary angiography between January 2018 and December 2020, 239 patients who underwent PCI with the diagnosis of acute coronary syndrome (ACS) due to ST were included as the study group (ST group) and 459 patients who underwent percutaneous intervention for ACS and did not have any in-stent lesion as the control group (non-ST group). ST classification was done according to the Academic Research Consortium definition. The mean age of the patients was 63.3±10.6 years (483 male, 69.2%). The groups were similar in terms of characteristic properties, comorbidities, and the drugs being used (p>0.05 for all). Drug eluting stents were used in 86.5% of the patients. In the ST group, the median time from stent implantation to thrombosis was 285 days. Mean AIP and the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) were statistically significantly higher in the ST group than in the controls (p<0.001 and p=0.018, respectively), and a positive correlation was observed between time from stent implantation to thrombosis and AIP and TG/HDL-C (rS=0.229, p=0.010 and rS=0.222, p=0.010, respectively). Multivariate logistic regression analysis revealed that stent length, prior ST elevation myocardial infarction, TG/HDL-C, and AIP were independent predictors of ST. AIP is an easy calculable biomarker, and the performance of AIP to predict ST is better than TG/HDL-C.

Intravascular lithotripsy during percutaneous coronary intervention for calcified coronary lesions: analysis of patient and procedural characteristics and clinical outcomes

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Coronary artery calcification is frequently encountered during percutaneous coronary intervention (PCI). It can reduce PCI success and increase intra-procedural and post-procedural complications, including stent embolization, under-expansion and mal-apposition. Intravascular lithotripsy (IVL) is a new tool developed to treat calcified coronary lesions. Purpose Retrospective analysis of all cases of intravascular lithotripsy performed within our local health district to examine patient and procedural characteristics and clinical outcomes. Methods All patients undergoing PCI with intravascular lithotripsy between September 2019-August 2021 within our local health district were analysed. Patient and procedural characteristics and clinical outcomes were recorded. Results 67 patients (50 men) were included with mean age 71.4 ± 8.7years. Risk factors prevalence included smoking (34%), hypertension (82%), dyslipidaemia (69%) and diabetes (46%). Trans-radial artery access was used in 38 patients (57%). IVL was performed most commonly in the left anterior descending artery (52%),[Figure 1]. IVL was utilised in 9 chronic total occlusions and 12 bifurcation lesions. Intracoronary (IC) imaging was performed in 59 patients (88%), intravascular ultrasound in 41(61%) and optical coherence tomography in 18 (27%). 41 (69%) patients had imaging performed pre and post IVL and post PCI. IC imaging identified 14 cases with 270º calcification arc and 45 cases with 360º arc. Nine cases (13.4%) required rotational atherectomy prior to IVL (most commonly 1.75mm burr). Mean reference vessel diameter was 3.2 ± 0.3mm. Mean lesion length was 36.3 ± 16.5mm. Mean pre-PCI stenosis was 85.5 ± 10.8%. Drug eluting stents were successfully deployed in 57 cases (85%), 10 had balloon angioplasty alone. Mean stent length was 39.2 ± 17.8mm. Mean post-PCI stenosis was 4.5 ± 13.3% (median 0%). Figure 2 shows a statistically significant increase in minimum lumen diameter and minimum lumen area post-IVL and minimal-stent-area (MSA) post-PCI. Mean stent expansion was 83%. Mean screening time 35.8 ± 17.8 minutes with mean contrast used 207.3 ± 78.7mL. No sustained arrhythmias or side-branch loss occurred. Vessel rupture was recorded in one patient necessitating urgent cardiac surgery (due to oversized balloon) and in 4 cases the IVL balloon could not cross the lesion. Conclusion Our experience shows that IVL is safe and effective and facilitates stent delivery and expansion. Intracoronary imaging is important to determine the need for calcium modification and evaluate its success prior to stent delivery and to confirm optimised stent expansion. Abstract Figure. Breakdown of PCI Artery Abstract Figure. IC Dimensions Pre/Post IVL/Post PCI

Endovascular treatment of common hepatocellular carcinoma: the experience of one center

Objective ‒ to determine the place of transarterial chemoembolization of the liver (TACE) in the modern protocol for treating patients with common hepatocellular carcinoma and by optimizing indications and contraindications to improve the results of complex treatment of these patients.Materials and methods. During the period 2011‒2021 242 TACE procedures were performed on 112 patients with inoperable hepatocellular carcinoma. Conventional lipidol embolization (c-TACE) was performed in 53 patients, procedures with drug eluting beads (DEB-TACE) ‒ in 58. All patients underwent a minimum of 1, a maximum of 5 TACE procedures. The decision to re-TACE was made individually, according the prevalence of the lesion (for bilobar lesions performed at least 2 unilobar TACE) and the tumor’s response to the intervention. Results. TACE results were evaluated according to mRECIST criteria: complete tumor response (CR) was noted in 3 (2.7 %) cases, partial (PR) ‒ in 68 (60.7 %) cases, process stabilization (SD) ‒ in 29 (25.9 %), progression (PD) ‒ 12 (10.7 %) cases. According by the obtained results, convincing data for the superiority of any of the applied TACE methods were not found. Repeated TACE courses increase the overall effectiveness of the treatment. Conclusions. The use of TACE in patients with inoperable hepatocellular carcinoma allows with minimal invasiveness to reduce or stabilize tumor growth in 89.3 % of cases. Repeated performance of the procedure allows to increase the treatment efficiency by 21.2 %.

Tirofiban and Rivaroxaban use in the management of right coronary artery thrombus as a primary manifestation of essential thrombocythemia

A 45 year old male with hypertension was presented to our centre with a recent inferior wall myocardial infarction (IWMI) and post infarction angina. Invasive coronary angiography revealed an occluded proximal right coronary artery (RCA) with high thrombus burden, in the absence of obstructive disease in the remaining coronary vasculature. Based on raised platelet counts of 923,000/microliter and positive Janus kinase (JAK 2- V617) mutations tested by polymerase chain reaction (PCR), a diagnosis of essential thrombocythemia (ET) was made. A therapeutic strategy of aspiration thrombectomy along with I/V Tirofiban was used for three days, followed by reassessed angiogram and percutaneous coronary intervention (PCI) with drug eluting stent (DES) placement was applied. In addition to dual antiplatelet and statin therapy, patient was treated with Rivaroxaban 15 mg once daily for a month and Hydroxyurea 500mg twice daily. At one month follow up, patient was asymptomatic, Continue...

In vitro study of elution kinetics and biological activity of piperacillin/tazobactam and gentamicin in acrylic bone cement

BackgroundAntibiotics differ in their elution characteristics from bone cement. But no such data is available on piperacillin and tazobactam. Therefore, we performed an in vitro observational study to examine (1) in vitro elution characteristics of piperacillin and tazobactam from bone cement, (2) their biological activity using minimum inhibitory concentration and (3) elution characteristics and biological activity when combined with gentamicin in bone cement. HypothesisThe null hypothesis was that piperacillin and tazobactam after elution from bone cement can achieve concentrations higher than minimum inhibitory concentration. Material and methodsForty milligrams bone cement was mixed with the following combination of antibiotics: without any antibiotic (sample A, control), 4g/0.50g piperacillin/tazobactam (sample B), 6g/0.75g piperacillin/tazobactam (sample C), 8g/1.0g piperacillin/tazobactam (sample D) and 4g/0.50g piperacillin/tazobactam and 400mg gentamicin (sample E). Samples were analysed on reverse-phase ultra-high-performance liquid chromatography. Antibacterial activity in the elute were tested against standard American Type Culture Collection (ATCC) strains. ResultsDetectable drug elution for piperacillin and tazobactam was seen till 21days. Peak drug levels for all formulations were seen at 48hours (140.8 & 297.5μg/mL for samples B of piperacillin and tazobactam respectively). About 0.83–1.24% of piperacillin and 23.17–29.17% of tazobactam were released from the samples. Gentamicin improved elution of piperacillin and tazobactam: 140.8 vs. 919.9μg/mL (p=0.000) for samples B & E of piperacillin respectively and 297.5 & 1138.4μg/mL (p=0.001) for samples B & E of tazobactam respectively at 2days. Sample E showed complete inhibition of tested microorganisms, while B sample was microbiologically less active compared to E on day 5. ConclusionsPiperacillin and tazobactam eluted successfully from bone cement and also retained antimicrobial activity after elution. Maximum elution was seen up to day 2 after which it reduced drastically. Antimicrobial action was seen up to 7days. Level of evidenceIII; comparative study.

Nivolumab (NIVO) and drug eluting bead transarterial chemoembolization (deb-TACE): Updated results from an ongoing phase 1 study of patients (pts) with liver limited hepatocellular carcinoma (HCC).

437 Background: TACE is a standard of care for liver limited HCC and impacts the immune microenvironment, potentially augmenting the effects of immune checkpoint inhibitors. Methods: This is a multicenter phase 1 study of NIVO and deb-TACE in unresectable HCC pts and Child Pugh A cirrhosis (NCT03143270). The primary objective is to assess safety. Secondary objectives include response rate by RECIST v1.1, progression-free and overall survival by Kaplan-Meier methodology, and blood/tumor immune correlates. A 3 + 3 design with expansion cohort sequentially evaluates 3 cohorts of differing schedules of NIVO relative to deb-TACE. Deb-TACE (75mg of doxorubicin) is administered on Day 0. NIVO is dosed at 240mg IV every 14 days for 1 year (Cohort 1: NIVO begins day +14 after deb-TACE; Cohort 2, interrupted NIVO dosing begins at Day -28 but is held on the Day 0 then restarted on Day +14; Cohort 3, continuous NIVO dosing begins on Day -28 without interruption). Results: As of September 2021, 19 pts were treated [median 67 years (range: 54-78), male (80%), ECOG PS 0 (47%), Child Pugh A (100%), 3 pts in each cohort 1 and 2, 13 pts in cohort 3]. No cases of treatment related liver failure or Grade 5 adverse events (AEs) were observed. 1 DLT of Grade 3 transaminitis was observed in cohort 3 and resolved without intervention and did not recur with drug rechallenge. Median ALT at baseline, day 28, day 56, and end of treatment (EOT) were 27, 43.5, 36.5, and 29 U/L. Median bilirubin at baseline, day 28, day 56, and EOT were 0.6, 0.6, 0.5, and 0.6 mg/dL. Mean ALBI score at baseline (N=19) and EOT (N=14) were -2.75 ± 0.48 vs. -2.55 ± 0.50. The most common treatment-related AEs of any grade were fatigue (53%), ALT/AST increase (42%), fever (37%), and pruritis (32%). The objective response rate by RECIST v 1.1 was 21% (Table). 5/19 pts remained on study with SD or better for ≥12 (range 12-43) months. Updated survival analysis will be presented at the meeting; correlatives at a separate venue. Conclusions: Nivolumab administered with deb-TACE is safe with antitumor activity. This study provides a needed benchmark for the safety of embolization along with anti-PD1 therapy in liver limited HCC. The clinical question of combining immunotherapy with embolization to improve outcome over embolization alone remains investigational and several, pivotal, phase 3 studies are ongoing. Clinical trial information: NCT03143270. [Table: see text]

Sustained Safety and Efficacy of Magnesium Reabsorbable Scaffold: 2-Year Follow-Up Analysis From First Magmaris Multicenter Italian Registry

BackgroundMagnesium Reabsorbable Scaffold (MRS), is the newest reabsorbable technology with low thrombogenicity, short scaffolding time and almost complete resorption at 12-months (95%). Preliminary 12-months data in selected patients has shown that safety and efficacy are comparable with second generation Drug Eluting Stent (DES). Magmaris Multicenter registry showed 1-and 2-years clinical outcome on the first patients suitable for MRS enrolled in 4 Italian centers. MethodsWe evaluated 12- and 24-months clinical results in “real world” experience with Magnesium Reabosrbable Scaffold in terms of Target Lesion Failure (TLF) and scaffold thrombosis (ST). TLF is the primary endpoint and was defined as composite of cardiac mortality, target vessel myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). 4P's strategy (Patient/lesion selection, Pre-dilatation, Proper scaffold sizing and Post-dilatation) was strongly recommended. Dual Antiplatelet Therapy (DAPT) has been recommended for 12 months. ResultsData from 207 patients, including initial experience, have been collected. Patients were 83% male, 20% diabetic and Acute Coronary Syndrome (ACS) in 23%. Lesion type were A-B1 in 54% and B2C in 46%. 4P's strategy was respected in 94%. Procedural success was 98% (2% peri-procedural MI). Compliance at 12-months follow up was 97.6%, TLF rate was 5.4% (including 1 case of myocardial infarction with late scaffold thrombosis (ST), all patients were successfully treated with in-scaffold segment DES implantation). At 24-months compliance was 92.8% (192 patients) and TLF was 7.4%. In the period between 13 and 24 months only 4 patients had TLF (including 1 case of myocardial infarction, all patients were successfully treated with in-scaffold segment DES implantation). None of the patients died for a cardiac reason. ConclusionOur 2-years results confirm safety and efficacy showed at 12-months, reinforcing long-term performance with only 2% rate of TLF increase and no ST after 1 year.

Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

Pharmacokinetics and biodistribution of supraparticle-delivered neurotrophin 3 in the guinea pig cochlea

Hearing loss is the most prevalent sensory disorder affecting nearly half a billion people worldwide. Aside from devices to assist hearing, such as hearing aids and cochlear implants, a drug treatment for hearing loss has yet to be developed. The neurotrophin family of growth factors has long been established as a potential therapy, however delivery of these factors into the inner ear at therapeutic levels over a sustained period of time has remained a challenge restricting clinical translation. We previously demonstrated that direct delivery of exogenous neurotrophin-3 (NT3) in the guinea pig cochleae via a bolus injection was rapidly cleared from the inner ear, with almost complete elimination 3 days post-treatment. Here, we explored the potential of suprapaticles (SPs) for NT3 delivery to the inner ear to achieve sustained delivery over time. SPs are porous spheroid structures comprised of smaller colloidal silica nanoparticles that provide a platform for long-term controlled release of therapeutics. This study aimed to assess the pharmacokinetics and biodistribution of SP-delivered NT3. We used a radioactive tracer (iodine 125: 125I) to label the NT3 to determine the loading, retention and distribution of NT3 delivered via SPs. Gamma measurements taken from 125I NT3 loaded SPs revealed high drug loading (an average of 5.3 μg of NT3 loaded per SP weighing 50 μg) and elution capacities in vitro (67% cumulative release over one month). Whole cochlear gamma measurements from SP-implanted cochleae harvested at various time points revealed detection of 125I NT3 in the guinea pig cochlea after one month, with 3.6 and 10% of the loaded drug remaining in the intracochlear and round window-implanted cochleae respectively. Autoradiography analysis of cochlear micro-sections revealed widespread 125I NT3 distribution after intracochlear SP delivery, but more restricted distribution with the round window delivery approach. Collectively, drug delivery into the inner ear using SPs support sustained, long-term availability and release of neurotrophins in the inner ear.

Integrated binary hologram to monitor cargo release from a drug-eluting film

Nowadays, holography translates from a pure technical tool for recording the phase and amplitude of the light wave to a widely applicable research-based method. Holographic devices are used for security enhancement, entertainment, 3D display technologies and augmented reality. Binary computer-generated holograms (amplitude or phase-based) are of specific interest. They are easy to compute and their manufacturing methods are fast and robust. In this work, a method of manufacturing amplitude-only binary holograms out of biopolymers films is proposed. Opaque cargo bits made out of different bioactive substances (antibiotics, dyes, etc.) absorb or scatter specific parts of the incoming light wave. Cargo release was conducted by submerging the produced holograms into the aqueous solution at specific pH and temperature levels. Drug elution from the film was traced out by the numerical analysis of the far-field diffraction pattern, which otherwise could only be measured post-factum using sophisticated spectroscopic or chromatography devices. This approach broadens the application of general holography over to the field of biomedical research relevant to quantitative monitoring of the drug elution.

A Warm Welcome to The First Issue of JSCAI

A Warm Welcome to The First Issue of JSCAI

Unknown Peaks and Spuriously Low Values of Glycated Haemoglobin by High Performance Liquid Chromatography: A Cross-sectional Survey

Introduction: Glycated haemoglobin (HbA1c) has humongous role both in diagnosis as well as in guiding the clinicians in making therapeutic decision in diabetic patients. There are various methods of laboratory estimation of glycated haemoglobin depending on charge and affinity. However, the methods are affected by a number of factors like haemoglobin variants, drugs and erythrocyte survival. Aim: To identify and evaluate abnormal peaks in chromatogram of High Performance Liquid Chromatography (HPLC) and compare it with boronate affinity chromatography and it also assessed the interference of elution of silent haemoglobin variants or drugs in exactness of HbA1c estimation by HPLC. Materials and Methods: A cross-sectional survey was conducted in the laboratory of Purwanchal Nagarik Samity, Kolkata, West Bengal, India, from November 2020 to August 2021, where 2500 samples were evaluated for HbA1c estimation. Abnormal variant window, unknown peaks or spuriously low HbA1c were identified in eight samples, where estimation was done by HPLC. These were processed further to investigate for the haemoglobin variants. The glycated haemoglobin in those samples was further estimated by Boronate affinity chromatography. Results: Out of the eight samples, three patients were Haemoglobin E trait, two were Haemoglobin E homozygous and one had sickel cell trait. However, two samples showed a normal chromatogram in HbA2/HbF mode. The glycated haemoglobin was affected by Haemoglobin E, sickel cell traits as well as other interferences that may cause inappropriate lowering of glycated haemoglobin. Conclusion: The results of this study and literature review suggests the progression of various micro/macrovascular complications in diabetic individuals can be arrested by maintaining normal HbA1c levels. Therefore, the laboratory consultant should meticulously take into consideration factors like plasma glucose concentration, drug history, biological variation or abnormal haemoglobinopathies. Thus, every laboratory catering to the huge burden of diabetic patients, where the prevalence of haemoglobinopathy is high, should individualise the method of HbA1c estimation.

Improved 3-Year Cardiac Survival After IVUS-Guided Long DES Implantation: A Patient-Level Analysis From 2 Randomized Trials.

The present study aimed to evaluate long-term cardiac survival benefit for intravascular ultrasound (IVUS)- versus angiography-guided long drug-eluting stent (DES) implantation. Although the long-term benefit of IVUS guidance for DES implantation has been reported from recent randomized trials, this benefit was primarily driven by the reduction in repeat revascularization. Thus, it remains uncertain whether IVUS guidance improved survival during long-term follow-up. We pooled the data of 2 randomized trials (IVUS-XPL [Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions] and ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions]) and compared IVUS guidance versus angiography guidance in 2,577 patients with long lesions treated with an implanted stent length≥28mm. The primary end point was cardiac death at 3 years. A 3-year clinical follow-up was completed in 96%. The primary end point of cardiac death occurred in 12 patients (1.0%) in the IVUS-guided group vs 28 patients (2.2%) in the angiography-guided group (HR: 0.43; 95% CI: 0.22-0.84; P=0.011). In addition, target lesion-related myocardial infarction occurred in 3 patients (0.2%) in the IVUS-guided group and in 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95%CI: 0.09-1.22; P=0.081), stent thrombosis developed in 3 patients (0.2%) in the IVUS-guided group and 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95%CI: 0.09-1.23; P=0.082), and ischemia-driven target lesion revascularization was observed in 47 patients (3.8%) in the IVUS-guided group and 80 patients (6.5%) in the angiography-guided group (HR: 0.57; 95%CI: 0.40-0.82; P=0.002). In this post hoc pooled patient-level analysis, the use of IVUS-guided long DES implantation compared with angiography-guided stent implantation improved long-term patient cardiac survival.

A viewpoint on material and design considerations for oesophageal stents with extended lifetime

Oesophageal stents are meshed tubular implants designed to maintain patency of the oesophageal lumen and attenuate the symptoms of oesophageal cancer. Oesophageal cancers account for one in twenty cancer diagnoses and can lead to dysphasia, malnutrition and the diminishment of patient quality of life (QOL). Self-expanding oesophageal stents are the most common approach to attenuate these symptoms. Recent advances in oncological therapy have enabled patient survival beyond the lifetime of current devices. This introduces new complications for palliation, driving the need for innovation in stent design. This review identifies the factors responsible for stent failure. It explores the challenges of enhancing the longevity of stent therapies and outlines solutions to improving clinical outcomes. Discussions focus on the role of stent materials, construction methods, and coatings upon device performance. We found three key stent enhancement strategies currently used; material surface treatments, anti-migratory modifications, and biodegradable skeletons. Furthermore, radioactive and drug eluting stent designs were identified as emerging novel treatments. In conclusion, the review offers an overview of remaining key challenges in oesophageal stent design and potential solutions. It is clear that further research is needed to improve the clinical outcome of stents and patient QOL.

Importance of myocardial perfusion scintigraphy for early detection of coronary artery disease in patients with positive family history of premature CAD -case study

Background: Acute coronary syndrome refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non-STEMI or unstable angina. Case presentation: We present a case of a 36-year-old female who visited cardiac outdoor patient department with continuous left arm pain. She was then referred to nuclear cardiology for screening of coronary artery disease (CAD). A pharmacological stress study was planned but the rest study was done instead due to the patient having persistent pain in the left arm. The rest study showed a large perfusion defect in left anterior descending artery (LAD) territory. As the patient was not having any previous history of CAD except for positive family history of premature CAD, she was immediately referred to an interventional cardiologist where her primary percutaneous coronary revascularization to LAD (3 × drug eluting stent) got done and she was saved from impending MI. Conclusion: Regular follow-up and monitoring should be fine in young adults with a positive family history of premature CAD. This may help in early detection leading to time management and acute coronary events in young adults may be avoided. This will eventually reduce mortality and morbidity.