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Renal denervation (RDN) is an adjunct therapy for resistant hypertension, reducing blood pressure (BP) by inhibiting both afferent sensory and efferent sympathetic renal nerve activity. The resulting reduction in central sympathetic outflow including that directed toward the heart may beneficially impact cardiac remodeling, left ventricular hypertrophy (LVH) and atrial fibrillation (AF). RDN has been shown to reduce left ventricular mass and AF burden but long‐term data is sparse. Forty patients (72.5% male, 69.2 ± 9.6 years) underwent 12‐lead ECG at baseline prior to RDN and at a mean long‐term follow‐up (LTFU) of 8.3 ± 0.9 years post‐intervention. A 24‐h ambulatory blood pressure monitor (ABPM) was obtained at both time points. Cornell voltage indices were calculated at baseline and LTFU, then converted to left ventricular mass based on validated formulae accounting for sex. ECGs underwent cardiologist review for determination of AF at both time‐points. There was no difference in Cornell voltages or left ventricular mass index (LVMI) between baseline and long‐term follow‐up in neither males ( p  = 0.89) nor females ( p  = 0.91). BP lowering at LTFU was correlated with a more pronounced reduction in LVMI ( r  = 0.50, p  = 0.0011) No change was observed in the incidence of atrial fibrillation between baseline or long‐term follow‐up ( p  = 0.99). There was no reduction in mean Cornell voltage or LVMI across the cohort between baseline and long‐term follow‐up. However, changes in ambulatory systolic BP correlated with reduction in LVMI suggestive of an RDN‐induced BP dependent long‐term reduction in LVMI out to eight years post‐RDN.

Purpose of ReviewLoin pain hematuria syndrome (LPHS) frequently presents with severe chronic pain that poses a clinical challenge. Current treatment approaches are mostly empirical and include a wide range of therapeutic strategies such as physical therapy, local and systemic analgesia, interventional and surgical approaches usually flanked by psycho-behavioral therapy, and other strategies. LPHS often impacts negatively on quality of life particularly in patients who are refractory to treatment.Recent FindingsWith recent advances in catheter-based treatment approaches and better understanding of the pathophysiology of LPHS, intraluminal renal denervation (RDN) has been proposed as a valuable treatment option for kidney-related pain syndromes. The present review provides a brief overview of the clinical challenges associated with LPHS, highlights recent insights into its underlying mechanisms, and summarizes currently available data on the use of RDN in the context of LPHS and kidney-related pain syndromes.SummaryRenal denervation via various approaches including surgical and catheter-based techniques has shown promise in alleviating kidney-related pain syndromes. Randomized controlled trials are now required to better define its role in the management of these conditions.

Herein, we review interventional peripheral neuromodulatory approaches to reduce blood pressure (BP), specifically focusing on catheter-based renal denervation (RDN), as well as the latest data from recent clinical trials underpinning its clinical use. Given the apparent failure of established lifestyle measures and pharmacologic BP-lowering approaches to improve hypertension (HTN) control rates, the past decade has seen remarkable scientific efforts to explore the utility of interventional strategies for BP management. Experimental studies and human clinical trials have demonstrated the crucial role of the sympathetic nervous system in the development and mainenance of HTN - consequently, most recent interventional technologies aimed primarily at modulating neural pathways. Advanced approaches that were rigorously tested in human studies include RDN, endovascular baroreflex amplification, baroreflex activation therapy and cardiac neuromodulation stimulation.Amongst these, RDN is by far the most established technology. With recent robust evidence from clinical trials and real-world data showing the safety and efficacy of both ultrasound and radiofrequency-based approaches, a recent clinical consensus statement of the European Society of Cardiology Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions concludes that RDN represents an ancillary therapeutic option in patients with uncontrolled resistant HTN confirmed by ambulatory blood pressure measurement and in spite of attention to lifestyle changes and optimised pharmacological treatment. Furthermore, RDN could alos be considered for patienst unlikley to adhere to or tolerate long-term antihypertensive drug treatment. Very recent data indicate long-term safety and efficacy up to 10 years. Appropriate implementation of RDN into clinical practice is now warranted.For all other interventions additional data from adequately designed human studies are required to establish their safety and clinical utility for potential future use in routine practice.

Abstract Background Inadvertent lead malposition (ILM) in the left ventricle (LV) via the subclavian artery is a rare complication during the insertion of cardiac implantable electronic devices (CIED). If not identified, there is a risk of systemic thromboembolism. Transarterial pacing lead extraction often requires surgical removal and carries high risks of bleeding and thromboembolism, but percutaneous extraction has also been previously described. Case summary A 71-year-old female presented with left homonymous hemianopia on Day 1 post-insertion of a dual-chamber permanent pacemaker (PPM). A computed tomography (CT) angiogram of the brain and aortic arch revealed an acute occlusion of a branch of the right posterior circulating artery (PCA) and a malpositioned pacing lead in the left subclavian artery. Urgent percutaneous removal of the transarterial lead using the retained wire technique was successfully performed. Discussion Inadvertent lead malposition in the arterial system is rare and often requires lead extraction due to systemic thromboembolic complications. The retained wire technique has been previously described for percutaneous transvenous lead extraction and exchange, but to our knowledge, we are the first to report utilizing this technique for transarterial lead extraction. Using a case report, we highlight the utility, safety, and effectiveness of the retained wire technique in extracting a malposition lead in the subclavian artery and LV.

PurposeThis study aims to investigate the influence of different storage humidity conditions on crystallization and aerosol performance of inhalable spray dried amorphous powder formulations (Ciprofloxacin hydrochloride as the model drug).MethodsThe spray dried samples were stored at 20%, 55% and 75% relative humidity (RH). Crystallinity was monitored by Powder X-ray diffraction (PXRD), and particle morphology was measured by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Aerosol performance was evaluated using a multi-stage liquid impinger (MSLI).ResultsPXRD diffractograms showed the spray dried Ciprofloxacin stored at 20% RH for three weeks were amorphous; whereas those stored at 55% RH and 75% RH started crystallizing after one hour. Fine particle fraction (FPF) of the particles was improved from 28% to 42% after storage at 55% RH for three days. Such improvement was attributed to the crystallization of amorphous powders, which led to increased particle roughness and reduced particulate contact area, as visualized by SEM and quantified by AFM. A linear relationship was observed between degree of crystallinity/crystallite size and FPF (R2 = 0.94 and R2 = 0.96, respectively). However, deterioration in aerosol performance was observed after storage at 75% RH due to formation of inter-particulate liquid/solid bridges, as confirmed by SEM.ConclusionsThis study provides a fundamental understanding in moisture-induced physical and aerosol instability of the spray dried powder formulations.

Chikungunya fever (CHIKF) is endemic in India, with multiple outbreaks occurring across the country since its reemergence in 2005. Suspected CHIKF patients were recruited from four clinical sites during 2019–2022, with data collected on sociodemographic, clinical, and epidemiological aspects. Sera samples were screened for IgM, IgG antibodies and viral RNA along with their neutralizing capacity. Envelope genes of Chikungunya virus (CHIKV) isolated were sequenced and further analysed. A total of 1312 suspected patients were screened during the study period; 258 patients were laboratory-confirmed with CHIKV infection. Severe clinical manifestation was observed in the patients during the viremic phase of infection. The neutralization potential was found to be increasing proportionally with the onset of illness, coinciding with the rise of IgG antibodies. Three of the four clinical sites had reported CHIKF outbreaks at different time points during the study period, and a distinct pattern of clinical presentation was observed across the sites. Phylogenetic and network analyses of E1, E2 and E3 genes from 62 CHIKV isolates demonstrated their evolution within the country. This study provides preliminary evidence of spatial and temporal variation in the clinical presentation and molecular evolution of virus in CHIKF outbreaks across India.

Background: Emvolio is a non-medical device, indigenously developed portable refrigeration for maintaining the internal temperature 2-8˚C. The Indian Patent Office has granted patent for applications such as preservation and transport of medicines, vaccines, food, beverages, dairy etc. Further, use of Emvolio can be utilized in transport and store biologicals to preserve their biochemical and cellular integrity.  The objective of this study was to evaluate the biochemical and haematological integrity of biological samples such as rat blood, serum and liver. Methods: The steady temperature was maintained inside the Emvolio, and it was compared to that of thermocol and polypropylene boxes aided with frozen gel packs. The blood and liver samples were isolated from Wistar rats and kept in Emvolio, thermocol and polypropylene boxes for 10 hrs, and the temperature was monitored. The blood parameters, namely red blood cells (RBC), white blood cells (WBC), platelets, haematocrit, haemoglobin, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) and red cell distribution width (RDW), serum parameters like alanine transaminase, alkaline phosphatase, total protein, albumin, creatine kinase, blood urea nitrogen and liver parameters like superoxide dismutase (SOD), glutathione (GSH), catalase were estimated and compared. Results: Emvolio maintained a constant inner temperature range of 2-8˚C, whereas a significant temperature variation was seen in thermocol and polypropylene boxes. There was no significant deviation in the parameters tested when samples were kept in Emvolio for six hours compared to the zero hour readings. In contrast, there was a significant deviation among the parameters for the samples kept in thermocol and polypropylene boxes for six hours compared to zero hour parameters. Conclusions: Emvolio maintained constant temperature and preserved the biological integrity of rat blood, serum and liver. Thus, Emvolio can be efficiently used as a biological sample carrier, especially in preclinical studies.

PurposeDissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin.MethodsComposite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. The resultant formulations were characterized for particle size, morphology, surface composition, solid-state properties, solubility and dissolution.ResultsThe results demonstrate that surfaces composition has critical impacts on the dissolution of composite formulations. Colistin was shown to increase the solubility of azithromycin. For composite formulations with no surface colistin, azithromycin released at a similar dissolution rate as the spray-dried azithromycin alone. An increase in surface colistin concentration was shown to accelerate the dissolution of azithromycin. The dissolution of colistin from the composite formulations was significantly slower than the spray-dried pure colistin. In addition, FTIR spectrum showed intermolecular interactions between azithromycin and colistin in the composite formulations, which could contribute to the enhanced solubility and dissolution of azithromycin.ConclusionsOur study provides fundamental understanding of the effects of surface concentration of colistin on azithromycin dissolution of co-spray-dried composite powder formulations.

As a chronic illness, tuberculosis is known to negatively affect patients’ day-to-day functioning. Therefore, evaluating all aspects of their health is imperative to improve their quality of life. The current study was conducted to assess the quality of life of patients receiving tuberculosis therapy and to identify the associated risk factors. A prospective, cross-sectiol study of 6 months was planned and conducted in 66 Mycobacterium tuberculosis-infected patients who met the pre-defined inclusion criteria. All pertinent data about the patients were collected in a precisely created data collection form. Further, the brief version of the World Health Organization Quality of Life Questionire was used to evaluate the patient’s quality of life. Of the 66 patients who were enrolled, 42 (63.6%) were male, and 14 (21.2%) belonged to the age group of 61-70 years. The domains of physical, psychological, social relationships, and environment had mean scores of 46.76±20.15 standard deviation (SD), 55.02±16.12 SD, 54.83±13.91 SD, and 64.92±14.59 SD, respectively. All four quality-of-life domains were found to have statistically significant associations with a variety of sociodemographic and treatment-related variables. This study gives healthcare practitioners an insight into the need to evaluate patients’ health-related quality of life, particularly for individuals with chronic illnesses.