Occurrence of premature battery depletion in a large multicentre registry of subcutaneous cardioverter-defibrillator patients.

AIMS: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have become established in preventing sudden cardiac death, with some advantages over transvenous defibrillator systems, including a lower incidence of lead failures. Despite technological advancements, S-ICD carriers may suffer from significant complications, such as premature battery depletion (PBD), that led to an advisory for nearly 40 000 patients. This multicentre study evaluated the incidence of PBD in a large set of S-ICD patients. METHODS AND RESULTS: Data from patients implanted with S-ICD models A209 and A219 between October 2012 and July 2023 across nine centres in Europe and the USA were reviewed. Incidence and implications of PBD, defined as clinically observed sudden drop in battery longevity, were analysed and compared to PBD with the definition of battery depletion within 60 months. Prospectively collected clinical data were obtained retrospectively from medical records, device telemetry, and manufacturer reports. This registry is listed on ClinicalTrials.gov (NCT05713708). Of the 1112 S-ICD devices analysed, 547 (49.2%) were equipped with a potentially affected capacitor linked to PBD occurrence, currently under Food and Drug Administration advisory. The median follow-up time for all patients was 46 [inter-quartile range (IQR) 24-63] months. Clinically suspected PBD was observed in 159 (29.1%) of cases, with a median time to generator removal or replacement of 65 (IQR 55-72) months, indicative of significant deviations from expected battery lifespan. Manufacturer confirmation of PBD was made in 91.7% of devices returned for analysis. No cases of PBD were observed in devices that were not under advisory. CONCLUSION: This manufacturer-independent analysis highlights a notable incidence of PBD in patients equipped with S-ICD models under advisory, and the rate of PBD in this study corresponds to the rate currently estimated by the manufacturer. To the best of our knowledge, this provides the largest contemporary peer-reviewed study cohort investigating the actual incidence of PBD in S-ICD patients. These findings emphasize the importance of post-market registries in collaboration between clinicians and the manufacturer to optimize safety and efficacy in S-ICD treatment.

Incidence, implications, and management of sense-B-noise failure in subcutaneous cardioverter-defibrillator patients: insights from a large multicentre registry.

AIMS: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) offer potentially distinct advantages over transvenous defibrillator systems. Recent randomized trials showed significantly lower lead failure rates than transvenous ICD. Still, S-ICDs remain associated with the risk of inappropriate shocks (IAS). While previous studies have reported varying causes of IAS, this study explores a rare cause of IAS, referred to as 'sense-B-noise.' It was recently described in case series, but its incidence has not been studied in a large cohort of S-ICD patients. METHODS AND RESULTS: We retrospectively reviewed data from patients implanted with S-ICD models 1010, A209, and A219 between October 2009 and July 2023 across nine centres in Europe and the USA. The analysis concentrated on determining the incidence and understanding the implications of sense-B-noise events. Sense-B-noise represents a rare manifestation of distinct electrogram abnormalities within the primary and alternate sensing vectors. Data were collected from medical records, device telemetry, and manufacturer reports for investigation. This registry is registered on clinicaltrials.gov (NCT05713708). Subcutaneous implantable cardioverter-defibrillator devices of the 1158 patients were analysed. The median follow-up time for all patients was 46 (IQR 23-64) months. In 107 patients (9.2%) ≥1 IAS was observed during follow-up. Sense-B-noise failure was diagnosed in six (0.5 and 5.6% of all IAS) patients, in all patients, the diagnosis was made after an IAS episode. Median lead dwell time in the affected patients was 23 (2-70) months. To resolve the sense-B-noise defect, in three patients reprogramming to the secondary vector was undertaken, and two patients underwent system removal with subsequent S-ICD reimplantation due to low amplitude in the secondary vector. In one patient, the secondary vector was initially programmed, and subsequently, an S-ICD system exchange was performed due to T-wave-oversensing IAS episodes. CONCLUSION: This multicentre analysis' findings shed light on a rare but clinically highly significant adverse event in S-ICD therapy. To our knowledge, we provide the first systematic multicentre analysis investigating the incidence of sense-B-noise. Due to being difficult to diagnose and limited options for resolution, management of sense-B-noise is challenging. Complete system exchange may be the only option for some patients. Educating healthcare providers involved in S-ICD patient care is crucial for ensuring accurate diagnosis and effective management of sense-B-noise issues.

Role of routine investigations post cardiac devices implants in detecting peri-procedural complications: A retrospective analysis from a tertiary UK center.

BACKGROUND: Peri-procedural complications associated with cardiac implantable electronic devices are not uncommon. European Society of Cardiology guidelines recommend device checks of all devices within 72 h of implant. European Heart Rhythm Association expert practical guide on Cardiac implantable electronic devices (CIEDs) recommend that a chest x-ray (CXR) should be performed within 24 h to rule out pneumothorax and document lead positions. First, the rate of peri-procedural complications associated with CIED implants at our center, as well as patient and/or procedural-related factors that are associated with higher rates of complications, is analyzed. Second, the yield of the guideline-recommended measures in the early detection of peri-procedural complications is examined. MATERIALS AND METHODS: Consecutive de novo transvenous device implants at our center in 2019 were retrospectively analyzed. Patients' demographics, types and indications for device therapy, procedural reports, device checks, and CXRs were obtained from the hospital electronic records. RESULTS: A total of 578 patients (Age 74 ± 16 years, 68% male) were included. All patients had routine post-procedure CXRs and device checks. There were 16 (2.8%) complications; 7 (1.2%) pneumothoraxes, 6 (1%) pericardial effusions, and 3 (0.5%) lead displacements. Procedure time correlated significantly with complications; in uncomplicated cases it was 99 ± 43 min versus 127 ± 50 min in procedures associated with complications (p = .02). CONCLUSIONS: Routine post CIED implantation CXRs can detect early peri-procedural complications, while repeat post mobilization device checks has low yield of detection of complications. The only statistically significant predictor of peri-procedural complications is the duration of the procedure; longer procedures were associated with higher rates of complications.

A cluster of inappropriate shocks in a pediatric S-ICD patient - how to troubleshoot?

We present the case of a 16-year-old male pediatric patient diagnosed with hypertrophic cardiomyopathy (HCM, identified as having a high risk of sudden cardiac death (SCD), who underwent a successful subcutaneous implantable cardiac defibrillator (S-ICD) implantation as a primary prevention measure in 2018. His past medical history included ADHD, Autism, and panic attacks. The patient experienced appropriate shocks that successfully terminated VF episodes. However, he also experienced multiple inappropriate shocks from the S-ICD, triggered by anxiety-induced tachycardia during panic episodes. Meticulous assessment of S-ICD tracings and electrocardiograms (ECGs) revealed the erroneous classification of sinus tachycardia as sustained ventricular tachycardia, leading to unwarranted therapeutic interventions. Clinical intervention involved reprogramming of the S-ICD, emphasizing the pivotal role of personalized device configuration in pediatric cases where fine margins matter. While literature on S-ICD use in pediatric populations remains limited, emerging registries underscore the efficacy and safety of S-ICDs in preventing sudden cardiac death while reducing complications associated with intravascular leads. This case underscores the critical nature of customized device programming in pediatric patients, underscoring S-ICDs as a practical defibrillation alternative that addresses distinct concerns within this cohort of patients.

Using artificial intelligence and deep learning to optimise the selection of adult congenital heart disease patients in S-ICD screening.

INTRODUCTION: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening. METHODS: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test. RESULTS: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p < 0.001). There was also a significant difference in the standard deviation of T: R between both groups (p = 0.04). CONCLUSIONS: T:R ratio, a main determinant for S-ICD eligibility, is significantly higher with more tendency to fluctuate in ACHD patients when compared to a population with normal hearts. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio, reducing the risk of TWO and inappropriate shocks in the ACHD patient cohort.

Role of deep learning methods in screening for subcutaneous implantable cardioverter defibrillator in heart failure.

INTRODUCTION: S-ICD eligibility is assessed at pre-implant screening where surface ECG traces are used as surrogates for S-ICD vectors. In heart failure (HF) patients undergoing diuresis, electrolytes and fluid shifts can cause changes in R and T waves. Subsequently, T:R ratio, a major predictor of S-ICD eligibility, can be dynamic. METHODS: This is a prospective study of patients with structurally normal hearts and HF patients undergoing diuresis. All patients were fitted with Holters® to record their S-ICD vectors. Our deep learning model was used to analyze the T:R ratios across the recordings. Welch two sample t-test and Mann-Whitney U were used to compare the data between the two groups. RESULTS: Twenty-one patients (age 58.43 ± 18.92, 62% male, 14 HF, 7 normal hearts) were enrolled. There was a significant difference in the T:R ratios between both groups. Mean T: R was higher in the HF group (0.18 ± 0.08 vs 0.10 ± 0.05, p < .001). Standard deviation of T: R was also higher in the HF group (0.09 ± 0.05 vs 0.07 ± 0.04, p = .024). There was no difference between leads within the same group. CONCLUSIONS: T:R ratio, a main determinant for S-ICD eligibility, is higher and has more tendency to fluctuate in HF patients undergoing diuresis. We hypothesize that our novel neural network model could be used to select HF patients eligible for S-ICD by better characterization of T:R ratio reducing the risk of T-wave over-sensing (TWO) and inappropriate shocks. Further work is required to consolidate our findings before applying to clinical practice.

Correlation analysis of deep learning methods in S-ICD screening.

BACKGROUND: Machine learning methods are used in the classification of various cardiovascular diseases through ECG data analysis. The concept of varying subcutaneous implantable cardiac defibrillator (S-ICD) eligibility, owing to the dynamicity of ECG signals, has been introduced before. There are practical limitations to acquiring longer durations of ECG signals for S-ICD screening. This study explored the potential use of deep learning methods in S-ICD screening. METHODS: This was a retrospective study. A deep learning tool was used to provide descriptive analysis of the T:R ratios over 24 h recordings of S-ICD vectors. Spearman's rank correlation test was used to compare the results statistically to those of a "gold standard" S-ICD simulator. RESULTS: A total of 14 patients (mean age: 63.7 ± 5.2 years, 71.4% male) were recruited and 28 vectors were analyzed. Mean T:R, standard deviation of T:R, and favorable ratio time (FVR)-a new concept introduced in this study-for all vectors combined were 0.21 ± 0.11, 0.08 ± 0.04, and 79 ± 30%, respectively. There were statistically significant strong correlations between the outcomes of our novel tool and the S-ICD simulator (p < .001). CONCLUSION: Deep learning methods could provide a practical software solution to analyze data acquired for longer durations than current S-ICD screening practices. This could help select patients better suited for S-ICD therapy as well as guide vector selection in S-ICD eligible patients. Further work is needed before this could be translated into clinical practice.

Personalized subcutaneous implantable cardioverter-defibrillator sensing vectors generated by mathematical rotation increase device eligibility whilst preserving device performance.

AIMS: Approximately 5.7% of potential subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients are ineligible by virtue of their vector morphology, with higher rates of ineligibility observed in some at-risk groups. Mathematical vector rotation is a novel technique that can generate a personalized sensing vector, one with maximal R:T ratio, using electrocardiogram (ECG) signal recorded from the present S-ICD location. METHODS AND RESULTS: A cohort of S-ICD ineligible patients were identified through ECG screening of ICD patients with no ventricular pacing requirement and their personalized vectors were generated using ECG signal from a Holter monitor. Subcutaneous ICD eligibility in this cohort was then recalculated. In a separate cohort, episodes of arrhythmia were recorded in patients undergoing arrhythmia induction, and arrhythmia detection in standard S-ICD vectors was compared to rotated vectors using an S-ICD simulator. Ninety-two participants (mean age 64.9 ± 2.7 years) underwent screening and 5.4% were found to be S-ICD ineligible. Personalized vector generation increased the R:T ratio in these vectors from 2.21 to 7.21 (4.54-9.88, P < 0.001) increasing the cohort eligibility from 94.6% to 100%. Rotated S-ICD vectors also showed high ventricular fibrillation (VF) detection sensitivity (97.8%), low time to VF detection (6.1 s), and excellent tachycardia discrimination (sensitivity 96%, specificity 88%), with no significant differences between rotated and standard vectors. CONCLUSION: In S-ICD ineligible patients, mathematical vector rotation can generate a personalized vector that is associated with a significant increase in R:T ratio, resulting in universal device eligibility in our cohort. Ventricular fibrillation detection efficacy, time to VF detection, and tachycardia discrimination were not affected by vector rotation.

A leadless pacemaker matched with a vasovagal syncope: how long can it last?

BACKGROUND: Guidelines recommend that cardiac pacing should be considered in patients suffering from frequent vasovagal syncopal (VVS) episodes. Studies have demonstrated the safety and efficacy of leadless pacemakers (LP) in cardioinhibitory vasovagal populations specifically, rendering them a reasonable alternative to transvenous pacing in these patients. However, due to the paucity of data on extraction and the number of concomitant LPs that can be safely implanted, there are concerns regarding LPs' battery longevity, especially in younger patients who may require decades of pacing therapy. METHODS: This is a retrospective analysis of the first 100 LPs implanted at a tertiary cardiac centre in the UK. Demographical data and device parameters at implant and follow-ups were obtained from the hospital's medical records. The battery life of the LPs in the VVS patients was compared to that of patients with other pacing indications. RESULTS: Ninety patients were included in the analysis. 14 patients (15.6%) had VVS, and 76 patients (84.4%) had other indications for pacing. Mean ages were 34 ± 13 years and 62 ± 20 years for the VVS and the other group, respectively. The estimated total battery life was 15.22 ± 0.35 and 13.65 ± 2.97 years in the VVS and the other indications group respectively (p = .04). There were no complications in the VVS group. CONCLUSION: LPs provide a promising treatment for patients with vasovagal syncope with reassuring battery performance at the short/intermediate term. Further longer-term follow-up data are needed to identify the true battery potential in this patient cohort.

S-ICD screening revisited: do passing vectors sometimes fail?

INTRODUCTION: Pre-implant ECG screening is performed to ensure that S-ICD recipients have at least one suitable sensing vector, yet cardiac over-sensing remains the commonest cause of inappropriate shock therapy in the S-ICD population. One explanation would be the presence of dynamic variations in ECG morphology that result in variations in vector eligibility. METHODS: Adult ICD patients had a 24-h ambulatory ECG performed using a digital Holter positioned to record all three S-ICD vectors. Using an S-ICD simulator, automated screening was then performed at one-minute intervals. In vectors with a mean vector score > 100 (the accepted value for a passing vector when screened on a single occasion), the percentage of all screening assessments that passed, eligible vector time (EVT), was calculated. EVT was compared statistically to QRS duration, corrected time to peak T (pTc) and mean vector score. RESULTS: Ambulatory monitoring was performed in 14 patients (mean age 63.7 ± 5.2 years, 71.4% male) with 42 vectors analysed. In 19 vectors the mean vector score was > 100. Within this "passing" cohort EVT varied between 42.7% and 100%. In 7/19 (37%) the EVT was <75%. A negative correlation was found between QRS duration and EVT (Pearson correlation -.60, p = .007). No correlation was found between EVT and mean vector score or pTc. CONCLUSION: Vector eligibility is dynamic. When "passing" vectors are subjected to repeated screening, 37% are found to be ineligible, more than a quarter of the time. Further investigation is required to determine the clinical significance of these findings.

Electrocardiographic changes during haemodialysis and the potential impact on subcutaneous implantable cardioverter defibrillator eligibility.

INTRODUCTION: Haemodialysis patients who require defibrillator therapy are expected to benefit from the entirely avascular subcutaneous defibrillator (S-ICD), but haemodialysis is associated with dynamic changes in R and T wave amplitude which can impact S-ICD eligibility. A continuous assessment of S-ICD eligibility during haemodialysis has not previously been performed. MATERIAL AND METHODS: Continuous surface ECG recordings were obtained from a cohort of patients undergoing maintenance haemodialysis, but without an indication for an ICD. Automated vector screening was retrospectively performed at one-minute intervals throughout the dialysis session. Variations in S-ICD eligibility were calculated and in vectors with high degrees of variation, the underlying mechanism was identified. RESULTS: 72 vector recordings (mean duration 254.1 ± 6.0 min) were obtained from 24 patients (mean age 64.3 ± 5.5 years, 68% male). At the start of haemodialysis 47 vectors were S-ICD eligible (65.2%). At the end of session, all of these vectors had remained eligible, and an additional 6 vectors had also become eligible (73.6%). High vector score variability was observed in 7 patients and the commonest cause was a progressive change in R:T ratio (71.5%). CONCLUSION: In a haemodialysis population, a single haemodialysis session can be associated with a potential change in S-ICD eligibility in 8.4% of vectors, with up to 12.5% of vectors showing high degrees of variability, most commonly due to variations in R:T ratio. In an S-ICD population with similar characteristics S-ICD screening prior to haemodialysis would be expected to more accurately identify vectors that retain eligibility.

An Unusual Cause of Cardioembolic Stroke: Paradoxical Embolism Due to Thrombus Formation on the Eustachian Valve.

Cardioembolism is an important cause of ischemic stroke, with several studies showing worse outcome than following other stroke subtypes. Paradoxical embolism is a rare cause of cardioembolic stroke. We report a case of a patient with presumed paradoxical cardioembolic stroke secondary to thrombus formation on the eustachian valve remnant in the right atrium. The patient was anticoagulated with resolution of the mass upon follow-up assessment. The diagnostic, investigative and management strategies are discussed for patients with suspected paradoxical embolism causing stroke. Physicians are reminded of the utility of echocardiography for identifying potential cardioembolic etiologies, including both transthoracic and transesophageal echocardiography.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

The application of fluoroscopic criteria to define leadless pacemakers implant position and the effect of location on device performance.

OBJECTIVE: Leadless pacemakers (LPs) were designed to avoid complications associated with transvenous pacing. To minimise risk of perforations, there is preference towards implanting LPs into the septum rather than the apex or free wall.An objective yet feasible way of characterising the LP location is currently lacking. We report a simple radiological method of defining LP position and our analysis of the impact of implantation site on performance of LPs. METHODS: The first 100 LPs implanted at our UK centre were reviewed and the devices' positions in fluoroscopy images and X-rays based on conventional criteria for lead positions and conventional practice for LPs positioning were assessed. The devices' electrical parameters at implant and at the latest device follow-up were used to compare performance between implantation sites. RESULTS: 35.6% of implants were in the apex. 31.1% in mid-septum, 16.7% in apical septum, 15.5% on the septal right ventricular inflow and 1.1% in the septal RV outflow tract. We had no major complications.Thresholds, R-wave amplitudes, and impedance averaged at 0.67 ± 0.41 V, 10.64 ± 5.30 mV, and 777.67 ± 201.67 Ohms, respectively, at the time of implantation, and 0.66 ± 0.39 V, 14.08 ± 6.14 mV, and 564.29 ± 96.76 Ohms at the last device check. There was no difference in the pacing thresholds or impedance between implant sites. CONCLUSIONS: We propose a simple, reproducible way of defining the LP location which can help standardise the assessment of the device location sites across LP implantation centres. ADVANCES IN KNOWLEDGE: Emphasis on the safety and reliability of the leadless pacemakers in a real-world setting.Establishing the variation in the implantation sites for leadless pacemakers and reporting the effect of the implantation sites on the devices' performance.We propose a simple, reproducible way of defining the LP location which can help standardise the assessment of the device location sites across LP implantation centres.

Tamarindus indica Extract as a Promising Antimicrobial and Antivirulence Therapy.

The worldwide crises from multi-drug-resistant (MDR) bacterial infections are pushing us to search for new alternative therapies. The renewed interest in medicinal plants has gained the attention of our research group. Tamarindus indica L. (T. indica) is one of the traditional medicines used for a wide range of diseases. Therefore, we evaluated the antimicrobial activities of ethanolic extract of T. indica. The inhibitions zones, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and fractional inhibitor concentration indices (FICI) against Gram+ve and -ve pathogens were detected. The bioactive compounds from T. indica extract were identified by mass spectroscopy, thin-layer chromatography, and bio-autographic assay. We performed scanning electron microscopy (SEM) and molecular docking studies to confirm possible mechanisms of actions and antivirulence activities, respectively. We found more promising antimicrobial activities against MDR pathogens with MIC and MBC values for Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), i.e., (0.78, 3.12 mg/mL) and (1.56, 3.12 mg/mL), respectively. The antimicrobial activities of this extract were attributed to its capability to impair cell membrane permeability, inducing bacterial cell lysis, which was confirmed by the morphological changes observed under SEM. The synergistic interactions between this extract and commonly used antibiotics were confirmed (FICI values < 0.5). The bioactive compounds of this extract were bis (2-ethylhexyl)phthalate, phenol, 2,4-bis(1,1-dimethylethyl), 1,2-benzenedicarboxylic acid, and bis(8-methylnonyl) ester. Additionally, this extract showed antivirulence activities, especially against the S. aureus protease and P. aeruginosa elastase. In conclusion, we hope that pharmaceutical companies can utilize our findings to produce a new formulation of T. indica ethanolic extract with other antibiotics.

Irradiation as a Promising Technology to Improve Bacteriological and Physicochemical Quality of Fish.

Fish is an excellent source of protein and other essential minerals and vitamins; nevertheless, several food-borne disease outbreaks have been linked to the consumption of different types of fish. Therefore, we aimed to overcome these health threats by evaluating gamma radiation as a good fish preservation method. The aerobic plate count (APC), identification of most common pathogenic bacteria, organoleptic properties, proximate composition, and other chemical evaluations were detected in both untreated and gamma-treated fish. The overall grades of organoleptic evaluations ranged from good to very good. Fortunately, the overall chemical analysis of all examined fish samples was accepted. For the untreated fish samples, the APC was within and above the permissible limit (5 × 107 CFU/g). Pathogenic bacteria were detected with a high prevalence rate, especially S. aureus, which was found in high percentages among examined untreated fish samples. Regarding the treated fish samples, APC and pathogenic bacterial counts were reduced in a dose-dependent manner, and the irradiation at dose 5 KGy resulted in complete eradication of the aerobic plate count (not detectable) with a mean reduction percentage equal to 100%. However, gamma irradiation has no significant effect on proximate composition; particularly, carbohydrates, proteins, and lipids were not significantly affected by low and medium doses of radiation. Therefore, gamma irradiation is a highly effective fish preservation method without any effect on fish quality. Additionally, gamma irradiation as a cold process is an attractive technology for solving the problem arising from fish-borne pathogens, and it has been purposed in this study as a cheap and safe method for reducing microbial contamination of fish.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Incidence of premature battery depletion in subcutaneous cardioverter-defibrillator patients: insights from a multicenter registry.

BACKGROUND: The subcutaneous ICD established its role in the prevention of sudden cardiac death in recent years. The occurrence of premature battery depletion in a large subset of potentially affected devices has been a cause of concern. The incidence of premature battery depletion has not been studied systematically beyond manufacturer-reported data. METHODS: Retrospective data and the most recent follow-up data on S-ICD devices from fourteen centers in Europe, the US, and Canada was studied. The incidence of generator removal or failure was reported to investigate the incidence of premature S-ICD battery depletion, defined as battery failure within 60 months or less. RESULTS: Data from 1054 devices was analyzed. Premature battery depletion occurred in 3.5% of potentially affected devices over an observation period of 49 months. CONCLUSIONS: The incidence of premature battery depletion of S-ICD potentially affected by a battery advisory was around 3.5% after 4 years in this study. Premature depletion occurred exclusively in devices under advisory. This is in line with the most recently published reports from the manufacturer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04767516 .