Examining Concordance Between Self-Report and Biomedical HIV Viral Load Data: A Scoping Review.

Assessment of HIV viral load based on laboratory results is the gold standard in HIV care and research. However, blood assay or accessing medical records is not always possible due to research or service contexts and constraints. Self-report of viral load test results expands data resources, is a convenient method of collecting data in both research and service settings, and is useful for HIV surveillance. The purpose of this scoping review was to identify existing literature on the validity of self-reported viral load data compared to blood assay or medical record review. We found that the existing literature is limited, with varied data collection methods, self-report measures, and study designs, as well as predictors of accuracy. Concordance between self-reported viral load and biomedical data varied across studies but appeared to be more consistent among samples recruited from clinical populations that reported engagement in HIV care. While it is difficult to draw definitive conclusions about the validity of self-reported viral load across existing studies, there is a need for a standardized measure and method of collection that can be utilized across diverse populations living with HIV.

RESUMEN: La evaluación de la carga viral del VIH basada en resultados de laboratorio es el patrón-oro en la atención e investigación del VIH. Sin embargo, el análisis de sangre o el acceso a los registros médicos no siempre es posible debido a los contextos y limitaciones de la investigación o los servicios. El autoinforme de los resultados de las pruebas de carga viral aumenta los recursos de datos, es un método conveniente de recopilación de datos tanto en contextos de investigación como de servicios, y es útil para la vigilancia de VIH. El propósito de esta revisión de alcance fue identificar la literatura existente sobre la validez de los datos de carga viral autoinformados en comparación con análisis de sangre o revisión de registros médicos. Encontramos que la literatura existente es limitada, con variados métodos de recopilación de datos, medidas de autoinforme y diseños de estudio, así como predictores de exactitud. La concordancia entre la carga viral autoinformada y los datos biomédicos varió entre los estudios, pero pareció ser más consistente entre las muestras reclutadas de poblaciones clínicas que indicaron participación en la atención del VIH. Aunque es difícil extraer conclusiones definitivas sobre la validez de la carga viral autoinformada en los estudios existentes, existe la necesidad de una medida y un método de recopilación estandarizados que puedan utilizarse en diversas poblaciones que viven con el VIH.

Detailed analysis of electrogram peak frequency to guide ventricular tachycardia substrate mapping.

AIMS: Differentiating near-field (NF) and far-field (FF) electrograms (EGMs) is crucial in identifying critical arrhythmogenic substrate during ventricular tachycardia (VT) ablation. A novel algorithm annotates NF-fractionated signals enabling EGM peak frequency (PF) determination using wavelet transformation. This study evaluated the algorithms' effectiveness in identifying critical components of the VT circuit during substrate mapping. METHODS AND RESULTS: A multicentre, international cohort undergoing VT ablation was investigated. VT activation maps were used to demarcate the isthmus zone (IZ). Offline analysis was performed to evaluate the diagnostic performance of low-voltage area (LVA) PF substrate mapping. A total of 30 patients encompassing 198 935 EGMs were included. The IZ PF was significantly higher in sinus rhythm (SR) compared to right ventricular paced (RVp) substrate maps (234 Hz (195-294) vs. 197 Hz (166-220); P = 0.010). Compared to LVA PF, the IZ PF was significantly higher in both SR and RVp substrate maps (area under curve, AUC: 0.74 and 0.70, respectively). The LVA PF threshold of ≥200 Hz was optimal in SR maps (sensitivity 69%; specificity 64%) and RVp maps (sensitivity 60%; specificity 64%) in identifying the VT isthmus. In amiodarone-treated patients (n = 20), the SR substrate map IZ PF was significantly lower (222 Hz (186-257) vs. 303 Hz (244-375), P = 0.009) compared to amiodarone-naïve patients (n = 10). The ≥200 Hz LVA PF threshold resulted in an 80% freedom from VT with a trend towards reduced ablation lesions and radiofrequency times. CONCLUSION: LVA PF substrate mapping identifies critical components of the VT circuit with an optimal threshold of ≥200 Hz. Isthmus PF is influenced by chronic amiodarone therapy with lower values observed during RV pacing.

Efficacy and safety of leadless pacemaker: A systematic review, pooled analysis and meta-analysis.

BACKGROUND: Leadless pacemakers have been designed as an alternative to transvenous systems which avoid some of the complications associated with transvenous devices. We aim to perform a systematic review of the literature to report the safety and efficacy findings of leadless pacemakers. METHODS: We searched MEDLINE and EMBASE to identify studies reporting the safety, efficacy and outcomes of patients implanted with a leadless pacemaker. The pooled rate of adverse events was determined and random-effects meta-analysis was performed to compare rates of adverse outcomes for leadless compared to transvenous pacemakers. RESULTS: A total of 18 studies were included with 2496 patients implanted with a leadless pacemaker and success rates range between 95.5 and 100%. The device or procedure related death rate was 0.3% while any complication and pericardial tamponade occurred in 3.1% and 1.4% of patients, respectively. Other complications such as pericardial effusion, device dislodgement, device revision, device malfunction, access site complications and infection occurred in less than 1% of patients. Meta-analysis of four studies suggests that there was no difference in hematoma (RR 0.67 95%CI 0.21-2.18, 3 studies), pericardial effusion (RR 0.59 95%CI 0.15-2.25, 3 studies), device dislocation (RR 0.33 95%CI 0.06-1.74, 3 studies), any complication (RR 0.44 95%CI 0.17-1.09, 4 studies) and death (RR 0.45 95%CI 0.15-1.35, 2 studies) comparing patients who received leadless and transvenous pacemakers. CONCLUSION: Leadless pacemakers are safe and effective for patients who have an indication for single chamber ventricular pacing and the findings appear to be comparable to transvenous pacemakers.

Clinical features and outcomes of adults with coronavirus disease 2019: A systematic review and pooled analysis of the literature.

BACKGROUND: The 2019 coronavirus disease (COVID-19) has become a global pandemic and the published literature describing the virus has grown exponentially. METHODS: We conducted a systematic review of the literature to identify the symptoms, comorbidities present, radiological features and outcomes for adults testing positive for COVID-19 admitted to hospital. The results across multiple studies were numerically pooled to yield total estimated. RESULTS: A total of 45 studies were included in this review with 14 358 adult participants (average age 51 years, male 51%). The pooled findings suggest that the most common symptom among patients was fever (81.2%) followed by cough (62.9%), fatigue (38.0%) and anorexia/loss of appetite (33.7%). The comorbidities that were most prevalent among patients with the virus were hypertension (19.1%), cardiovascular disease (17.9%), endocrine disorder (9.3%) and diabetes (9.2%). Abnormal chest X-ray findings were present in 27.7% of patients and ground-glass opacity was demonstrated on chest computerized tomography in 63.0% of patients. The most frequent adverse outcomes were acute respiratory distress syndrome (27.4%), acute cardiac injury (16.2%) and acute kidney injury (12.6%). Death occurred in 8.2% of patients and 16.3% required intensive care admission and 11.7% had mechanical ventilation. Bacterial or secondary infections affected 8.5% of patients and 6.9% developed shock. CONCLUSIONS: COVID-19 most commonly presents with fever, cough, fatigue and anorexia and among patients with existing hypertension and cardiovascular disease. It is important as serious adverse outcomes can develop such as acute respiratory distress syndrome, acute cardiac injury, acute kidney injury and death.

Do all patients with implantable cardioverter defibrillator need a generator change? A health service evaluation of patients who underwent generator changes from a single tertiary center.

BACKGROUND: The patient characteristics, therapy received and outcomes after one or more implantable cardioverter defibrillator (ICD) generator changes from contemporary practice is not well known. METHODS: We conducted a health service evaluation of patients who underwent ICD implantation and generator change. Patients who had generator changes from February 2016 to October 2019 were identified from our database and electronic records were reviewed for patient characteristics, number of generator changes, receipt of therapy and death. RESULTS: Our database included 88 patients with a generator change. A total of 22 patients (25.0%) received dual chamber ICD, 10 patients (11.4%) received single chamber ICD, 54 patients (61.3%) received cardiac resynchronization therapy defibrillator and 2 patients (2.3%) received subcutaneous ICD. A second generator change occurred in 18 patients and a third generator changes was performed in 6 patients. There were 29 deaths and a follow up period of 9.4 ± 2.9 years. From implant to initial generator change 39 patients had appropriate antitachycardia pacing (ATP), 6 patient had inappropriate ATP, 29 patients had appropriate shocks and 5 patients had an inappropriate shock. Between the 1st and 2nd generator change and the 2nd and 3rd there were no cases of inappropriate ATP or shock. Overall, 42 patients out of the 88 had appropriate therapy (47.7%) and 7 patients had inappropriate therapy (8.0%). CONCLUSIONS: Most patients with ICDs do not receive therapy and a minority have inappropriate therapy which typically occur before the first generator change as we observed no inappropriate therapy beyond the first generator change.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Treatment of Ruptured Wide-Necked Aneurysms using a Microcatheter Injectable Biomaterial.

Ruptured wide-neck aneurysms (WNAs), especially in a setting of coagulopathy, are associated with significant morbidity and mortality. It is shown that by trapping a sub-millimeter clinical catheter inside the aneurysm sac using a flow diverter stent (FDS), instant hemostasis can be achieved by filling the aneurysm sac using a novel biomaterial, rescuing catastrophic bleeding in large-animal models. Multiple formulations of a biomaterial comprising gelatin, nanoclay (NC), and iohexol are developed, optimized, and extensively tested in vitro to select the lead candidate for further testing in vivo in murine, porcine, and canine models of WNAs, including in a subset with aneurysm rupture. The catheter-injectable and X-ray visible versions of the gel embolic agent (GEA) with the optimized mechanical properties outperform control groups, including a subset that receive a clinically used liquid embolic (Onyx, Medtronic), with and without aneurysm rupture. A combinatorial approach to ruptured WNAs with GEA and FDS may change the standard of medical practice and save lives.

The transcriptional response to chronic stress and glucocorticoid receptor blockade in the hippocampal dentate gyrus.

The dentate gyrus (DG) of the hippocampus plays a crucial role in learning and memory. This subregion is unique in its ability to generate new neurons throughout life and integrate these new neurons into the hippocampal circuitry. Neurogenesis has further been implicated in hippocampal plasticity and depression. Exposure to chronic stress affects DG function and morphology and suppresses neurogenesis and long-term potentiation (LTP) with consequences for cognition. Previous studies demonstrated that glucocorticoid receptor (GR) blockade by a brief treatment with the GR antagonist mifepristone (RU486) rapidly reverses the stress and glucocorticoid effects on neurogenesis. The molecular pathways underlying both the stress-induced effects and the RU486 effects on the DG are, however, largely unknown. The aim of this study was therefore (1) to investigate by microarray analysis which genes and pathways in the DG are sensitive to chronic stress and (2) to investigate to what extent blockade of GR can normalize these stress-induced effects on DG gene expression. Chronic stress exposure affected the expression of 90 genes in the DG (P < 0.01), with an overrepresentation of genes involved in brain development and morphogenesis and synaptic transmission. RU486 treatment of stressed animals affected expression of 107 genes; however, mostly different genes than those responding to stress. Interestingly, we found CREBBP to be normalized by RU486 treatment to levels observed in control animals, suggesting that CREB-signaling may play a central role in mediating the chronic stress effects on neurogenesis, LTP and calcium currents. The identified genetic pathways provide insight into the stress-induced adaptive plasticity of the hippocampal DG that is so central in learning and memory and will direct future studies on the functional outcome and modulation of these stress effects.

Treatment of Ruptured and Nonruptured Aneurysms Using a Semisolid Iodinated Embolic Agent.

Saccular aneurysms (SAs) are focal outpouchings from the lateral wall of an artery. Depending on their morphology and location, minimally invasive treatment options include coil embolization, flow diverter stents, stent-assisted coiling, and liquid embolics. Many drawbacks are associated with these treatment options including recanalization, delayed healing, rebleeding, malpositioning of the embolic or stent, stent stenosis, and even rupture of the SA. To overcome these drawbacks, a nanoclay-based shear-thinning hydrogel (STH) is developed for the endovascular treatment of SAs. Extensive in vitro testing is performed to optimize STH performance, visualization, injectability, and endothelialization in cell culture. Femoral artery saccular aneurysm models in rats and in pigs are created to test stability, efficacy, immune response, endothelialization, and biocompatibility of STH in both ruptured and unruptured SA. Fluoroscopy and computed tomography imaging consistently confirmed SA occlusion without recanalization, migration, or nontarget embolization; STH is also shown to outperform coil embolization of porcine aneurysms. In pigs with catastrophic bleeding due to SA rupture, STH is able to achieve instant hemostasis rescuing the pigs in long-term survival experiments. STH is a promising semisolid iodinated embolic agent that can change the standard of medical practice and potentially save lives.

Silk Embolic Material for Catheter-Directed Endovascular Drug Delivery.

Embolization is a catheter-based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. A novel silk-based embolic material (SEM) that is developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics is reported. Natural silk is processed into fibroin proteins of varying lengths and is combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 µm in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs worldwide, demonstrate a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolize porcine arteries without recanalization and lead to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, it is shown that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next-generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors.

Chronic Salmonella Osteomyelitis in a Healthy, Immunocompetent Man: A Case Report.

CASE: A 26-year-old healthcare professional presented with knee pain and was found to have Salmonella osteomyelitis of the distal femur. Two operations, including antibiotic bead placement followed by a 6-week course of oral ciprofloxacin, were successful in eradicating the infection. CONCLUSION: Salmonella osteomyelitis is a well-known complication of hemoglobinopathies but is unusual in healthy individuals. This case required molecular testing and multiple cultures to obtain a diagnosis. Treatment may require debridement and antibiotics.

Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine.

Regenerative medicine is an emerging field that centers on the restoration and regeneration of functional components of damaged tissue. Tissue engineering is an application of regenerative medicine and seeks to create functional tissue components and whole organs. Using 3D printing technologies, native tissue mimics can be created utilizing biomaterials and living cells. Recently, regenerative medicine has begun to employ 3D bioprinting methods to create highly specialized tissue models to improve upon conventional tissue engineering methods. Here, we review the use of 3D bioprinting in the advancement of tissue engineering by describing the process of 3D bioprinting and its advantages over other tissue engineering methods. Materials and techniques in bioprinting are also reviewed, in addition to future clinical applications, challenges, and future directions of the field.

Application of 3D Printing in Preoperative Planning.

Preoperative planning is critical for success in the surgical suite. Current techniques for surgical planning are limited; clinicians often rely on prior experience and medical imaging to guide the decision-making process. Furthermore, two-dimensional (2D) presentations of anatomical structures may not accurately portray their three-dimensional (3D) complexity, often leaving physicians ill-equipped for the procedure. Although 3D postprocessed images are an improvement on traditional 2D image sets, they are often inadequate for surgical simulation. Medical 3D printing is a rapidly expanding field and could provide an innovative solution to current constraints of preoperative planning. As 3D printing becomes more prevalent in medical settings, it is important that clinicians develop an understanding of the technologies, as well as its uses. Here, we review the fundamentals of 3D printing and key aspects of its workflow. The many applications of 3D printing for preoperative planning are discussed, along with their challenges.

Blood-Derived Biomaterial for Catheter-Directed Arterial Embolization.

Vascular embolization is a life-saving minimally invasive catheter-based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood-derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra-arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point-of-care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.

Bioactive-Tissue-Derived Nanocomposite Hydrogel for Permanent Arterial Embolization and Enhanced Vascular Healing.

Transcatheter embolization is a minimally invasive procedure that uses embolic agents to intentionally block diseased or injured blood vessels for therapeutic purposes. Embolic agents in clinical practice are limited by recanalization, risk of non-target embolization, failure in coagulopathic patients, high cost, and toxicity. Here, a decellularized cardiac extracellular matrix (ECM)-based nanocomposite hydrogel is developed to provide superior mechanical stability, catheter injectability, retrievability, antibacterial properties, and biological activity to prevent recanalization. The embolic efficacy of the shear-thinning ECM-based hydrogel is shown in a porcine survival model of embolization in the iliac artery and the renal artery. The ECM-based hydrogel promotes arterial vessel wall remodeling and a fibroinflammatory response while undergoing significant biodegradation such that only 25% of the embolic material remains at 14 days. With its unprecedented proregenerative, antibacterial properties coupled with favorable mechanical properties, and its superior performance in anticoagulated blood, the ECM-based hydrogel has the potential to be a next-generation biofunctional embolic agent that can successfully treat a wide range of vascular diseases.

Development and characterization of an aircraft aerosol time-of-flight mass spectrometer.

Vertical and horizontal profiles of atmospheric aerosols are necessary for understanding the impact of air pollution on regional and global climate. To gain further insight into the size-resolved chemistry of individual atmospheric particles, a smaller aerosol time-of-flight mass spectrometer (ATOFMS) with increased data acquisition capabilities was developed for aircraft-based studies. Compared to previous ATOFMS systems, the new instrument has a faster data acquisition rate with improved ion transmission and mass resolution, as well as reduced physical size and power consumption, all required advances for use in aircraft studies. In addition, real-time source apportionment software allows the immediate identification and classification of individual particles to guide sampling decisions while in the field. The aircraft (A)-ATOFMS was field-tested on the ground during the Study of Organic Aerosols in Riverside, CA (SOAR) and aboard an aircraft during the Ice in Clouds Experiment-Layer Clouds (ICE-L). Initial results from ICE-L represent the first reported aircraft-based single-particle dual-polarity mass spectrometry measurements and provide an increased understanding of particle mixing state as a function of altitude. Improved ion transmission allows for the first single-particle detection of species out to approximately m/z 2000, an important mass range for the detection of biological aerosols and oligomeric species. In addition, high time resolution measurements of single-particle mixing state are demonstrated and shown to be important for airborne studies where particle concentrations and chemistry vary rapidly.

Value for money: putting the patient first.

Canadians spend more on healthcare than people in most other countries. We are fifth in the OECD in terms of health spending per capita, and eighth out of 28 countries in terms of health spending as a percentage of GDP. Given these facts, it is appropriate to discuss the issue of value for money in healthcare. In their paper, McGrail et al. present four challenges to improving value for money in Canadian healthcare: a lack of analysis of the hospital sector; the need to learn from rate variation analysis; the slow uptake of the electronic health record (EHR); and the need to measure health outcomes. Our paper addresses each of these points, but also proposes that a broader outlook is needed to come to grips with this question. It is essential to go beyond supply-side cost control, and also take into account the needs of the patient. Moreover, we need to look beyond our borders to learn how other countries have been able to evolve universal publicly funded health systems without long waiting times.

Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress.

In rodents, stress suppresses adult neurogenesis. This is thought to involve activation of glucocorticoid receptors in the brain. In the present study, we therefore questioned whether glucocorticoid receptor blockade by mifepristone can normalize the effects of chronic stress on adult neurogenesis. Rats received mifepristone on the last 4 days of a 21-day chronic unpredictable and inescapable stress regimen. Neurogenesis was analysed by stereological quantification of adult-generated cell survival (bromodeoxyuridine), young neuronal survival (doublecortin) and cell proliferation (Ki-67). The results show that only 4 days of mifepristone treatment normalized the stress-induced reductions in neurogenesis. Importantly, mifepristone by itself had no effect on neurogenesis. We conclude that, contrary to other compounds interfering with the effects of chronic stress on neurogenesis, like antidepressants, the normalizing effects of mifepristone on neurogenesis are rapid and particularly potent in a high stress environment. This neurogenic action of mifepristone could potentially contribute to its clinical mechanism of action.