Customizable Microfluidic Devices: Progress, Constraints, and Future Advances.

The field of microfluidics encompasses the study of fluid behavior within micro-channels and the development of miniature systems featuring internal compartments or passageways tailored for fluid control and manipulation. Microfluidic devices capitalize on the unique chemical and physical properties exhibited by fluids at the microscopic scale. In contrast to their larger counterparts, microfluidic systems offer a multitude of advantages. Their implementation facilitates the investigation and utilization of reduced sample, solvent, and reagent volumes, thus yielding decreased operational expenses. Owing to their compact dimensions, these devices allow for the concurrent execution of multiple procedures, leading to expedited experimental timelines. Over the past two decades, microfluidics has undergone remarkable advancements, evolving into a multifaceted discipline. Subfields such as organ-on-a-chip and paper-based microfluidics have matured into distinct fields of study. Nonetheless, while scientific progress within the microfluidics realm has been notable, its translation into autonomous end-user applications remains a frontier to be fully explored. This paper sets forth the central objective of scrutinizing the present research paradigm, prevailing limitations, and potential prospects of customizable microfluidic devices. Our inquiry revolves around the latest strides achieved, prevailing constraints, and conceivable trajectories for adaptable microfluidic technologies. We meticulously delineate existing iterations of microfluidic systems, elucidate their operational principles, deliberate upon encountered limitations, and provide a visionary outlook toward the future trajectory of microfluidic advancements. In summation, this work endeavors to shed light on the current state of microfluidic systems, underscore their operative intricacies, address incumbent challenges, and unveil promising pathways that chart the course toward the next frontier of microfluidic innovation.

Contemporary trends of leadless pacemaker implantation in the United States.

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.

Bioactive glasses incorporating less-common ions to improve biological and physical properties.

Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The "classical" elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even "exotic" for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.

Device Therapy in Chronic Heart Failure: JACC State-of-the-Art Review.

The regulatory landscape for device-based heart failure (HF) therapies has seen a major shift in the last 7 years. In 2013, the U.S. Food and Drug Administration released guidance for early feasibility and first-in-human studies, thereby encouraging device innovation, and in 2016 the U.S. Congress authorized the Breakthrough Devices Program to expedite access for Americans to innovative devices indicated for diagnosis and treatment of serious illnesses, such as HF. Since December 2016, there has been an increase in the number of HF devices for which manufacturers are seeking approval through the breakthrough designation pathway. This has led to a rapid uptake in the development and evaluation of device-based HF therapies. This article reviews the current and future landscape of device therapies for chronic HF and associated comorbidities and the regulatory environment that is driving current and future innovation.

Improving Tolerance to Snorkel Mask Use as Alternative Personal Protective Equipment.

Snorkel masks have become an option for personal protective equipment (PPE) due to the shortage of air filtration at least 95% of airborne particle (N95) masks as a result of the coronavirus disease 2019 (COVID-19) pandemic. We developed a 3D design of a triheaded adapter that connects a snorkel mask to 3 different National Institute for Occupational Safety and Health (NIOSH)-approved air filtration at least 99% of airborne particles (N99) filters with the aim of improving wearer comfort. We measured the resistance of the new triheaded adapter to be one-third the resistance of the single adapter. Interdepartmental survey of anesthesiologists showed an improvement in perceived comfort when using the triheaded adapter as compared to the single adapter.

Feasibility of TMS in patients with new generation cochlear implants.

OBJECTIVE: The presence of a cochlear implant is being considered an absolute contraindication for experiments and/or treatments. We aimed to verify TMS (Transcranial Magnetic Stimulation) compatibility of a new generation of cochlear implants. METHODS: In a series of experiments, we test if MED-EL cochlear implants -compatible with stable fields of magnetic resonance imaging scanning- are fully resistant even to rapidly varying magnetic fields as those generated by single pulses and low and high-frequency trains of repetitive TMS (rTMS) applied with a figure of eight coil and different magnetic stimulators. RESULTS: With a TMS intensity equal or below 2.2 Tesla (T) the cochlear implant and all its electronic components remain fully functional, even when the combination of frequency, intensity and number of pulses exceeds the currently available safety guidelines. Induced forces on the implant are negligible. With higher magnetic fields (i.e., 3.2 T), one device was corrupted. CONCLUSIONS: Results exclude the risk of electronic damaging, demagnetizing or displacements of the studied cochlear implants when exposed to magnetic fields of up to 2.2 T delivered through a focal coil. SIGNIFICANCE: They open the way to use focal rTMS protocols with the aim of promoting neural plasticity in auditory networks, possibly helping the post-implant recovery of speech perception performance.

COVID-19 and telehealth: Issues facing healthcare in a pandemic.

ABSTRACT: Providing safe nonemergent care during the coronavirus disease 2019 (COVID-19) pandemic has been challenging for NPs. This article, the first of a three-part series, will overview telehealth and telemedicine and provide a brief history of the two. The benefits, challenges, and temporary changes due to COVID-19 will also be addressed.

Risk Stratification of Percutaneous Edge-to-Edge Repair by MitraClip in Patients with Mitral Regurgitation.

Edge-to-edge repair using the MitraClip system is indicated in patients with severe mitral regurgitation (MR) who are at high risk for open-heart surgery due to comorbidity or reduced cardiac function. However, less is known about pre-procedural risk factors for mortality and morbidity following MitraClip implantation. Consecutive 25 patients with severe MR who underwent MitraClip therapy (mean age, 77 years old, 14 males) were included. Right heart catheterization and echocardiographic data before and after the procedure were collected and their prognostic impacts were investigated. Acute procedural success was 96%. At one week following MitraClip repair, left ventricular ejection fraction (LVEF) remained unchanged and left ventricular end-diastolic volume tended to be smaller. Cardiac index and mean pulmonary artery pressure (mPAP) were markedly improved following the procedure (P < 0.001 for both). In the multivariate analyses using baseline characteristics, both lower LVEF (hazard ratio 0.57, 95% confidence interval 0.30-0.89) and higher mPAP (hazard ratio 1.23, 95% confidence interval 1.06-1.56) were independently associated with post-procedural 1-year death or heart failure readmission (P < 0.05 for both). The lower LVEF and higher mPAP group had lower 1-year survival free from HF readmission compared with those without (16.7% versus 100%; P < 0.001). In conclusion, a combination of baseline mPAP and LVEF might be a useful tool in predicting post-MitraClip procedural clinical outcomes.

Probing expert opinions on the future of kidney replacement therapies.

Patients with kidney failure can only survive with some form of kidney replacement (transplant or dialysis). Unfortunately, innovations in kidney replacement therapy lag behind many other medical fields. This study compiles expert opinions on candidate technologies for future kidney replacement therapies. A worldwide web-based survey was conducted with 1566 responding experts, identified from scientific publications on kidney (renal) replacement therapy, indexed in the Web of Science Core Collection (period 2014-2019). Candidate innovative approaches were categorized in line with the Kidney Health Initiative roadmap for innovative kidney replacement therapies. Most respondents expected a revolution in kidney replacement therapies: 68.59% before 2040 and 24.85% after 2040, while 6.56% expected none. Approaches anticipated as most likely were implantable artificial kidneys (38.6%) and wearable artificial kidneys (32.4%). A majority of experts expect that kidney replacement therapies can be significantly improved by innovative technologies.

Current Practices in Endotracheal Tube Size Selection for Adults.

OBJECTIVES/HYPOTHESIS: Intubation with inappropriately sized endotracheal tubes (ETT) can cause long-term tracheal and laryngeal injuries often requiring surgical intervention. Although tracheal size has been demonstrated to vary based on height and sex, it is unclear whether these guidelines are regularly implemented in patients undergoing endotracheal intubation. The objective of this study is to determine the rate of appropriate ETT size selection in patients undergoing intubation and assess provider decision making in ETT size selection. STUDY DESIGN: Retrospective cohort study. METHODS: The study population was all patients who underwent endotracheal intubation over a two-week period at a tertiary academic medical center. Data were collected on patient age, gender, height, BMI, comorbidities, ETT size, duration of intubation, bronchoscopies, and type of practitioner who performed the intubation. A height-based nomogram for ETT size selection was used to determine the recommended ETT size for each patient. RESULTS: One hundred five patients met the inclusion criteria. 22% of patients were intubated with an inappropriately large tube, defined as 1.0 mm larger than the recommended size. Women were more likely to be intubated with an inappropriately large ETT (OR = 13.58, P = .001), as were patients with height less than 160 cm (OR = 141, P = .001). Other factors related to disease severity, anticipation for bronchoscopy, and BMI were not risk factors for the use of inappropriately large ETT. CONCLUSIONS: Although there is compelling evidence that height is a strong predictor of tracheal morphology and appropriate ETT size, height-based guidelines have yet to be universally adopted for ETT size selection. Laryngoscope, 131:1967-1971, 2021.

A Forensic Disassembly of the BIS Monitor.

BACKGROUND: The bispectral index (BIS) monitor has been available for clinical use for >20 years and has had an immense impact on academic activity in Anesthesiology, with >3000 articles referencing the bispectral index. Despite attempts to infer its algorithms by external observation, its operation has nevertheless remained undescribed, in contrast to the algorithms of other less commercially successful monitors of electroencephalogram (EEG) activity under anesthesia. With the expiration of certain key patents, the time is therefore ripe to examine the operation of the monitor on its own terms through careful dismantling, followed by extraction and examination of its internal software. METHODS: An A-2000 BIS Monitor (gunmetal blue case, amber monochrome display) was purchased on the secondary market. After identifying the major data processing and storage components, a set of free or inexpensive tools was used to retrieve and disassemble the monitor's onboard software. The software executes primarily on an ARMv7 microprocessor (Sharp/NXP LH77790B) and a digital signal processor (Texas Instruments TMS320C32). The device software can be retrieved directly from the monitor's hardware by using debugging interfaces that have remained in place from its original development. RESULTS: Critical numerical parameters such as the spectral edge frequency (SEF), total power, and BIS values were retraced from external delivery at the device's serial port back to the point of their calculation in the extracted software. In doing so, the locations of the critical algorithms were determined. To demonstrate the validity of the technique, the algorithms for SEF and total power were disassembled, comprehensively annotated and compared to their theoretically ideal behaviors. A bug was identified in the device's implementation of the SEF algorithm, which can be provoked by a perfectly isoelectric EEG. CONCLUSIONS: This article demonstrates that the electronic design of the A-2000 BIS Monitor does not pose any insuperable obstacles to retrieving its device software in hexadecimal machine code form directly from the motherboard. This software can be reverse engineered through disassembly and decompilation to reveal the methods by which the BIS monitor implements its algorithms, which ultimately must form the definitive statement of its function. Without further revealing any algorithms that might be considered trade secrets, the manufacturer of the BIS monitor should be encouraged to release the device software in its original format to place BIS-related academic literature on a firm theoretical foundation and to promote further academic development of EEG monitoring algorithms.

A vision for future bioinspired and biohybrid robots.

Bioinspired and biohybrid robots can help respond to diverse, sustainable application needs.

Tethered capsule en face optical coherence tomography for imaging Barrett's oesophagus in unsedated patients.

OBJECTIVE: Barrett's oesophagus (BE) screening outside the endoscopy suite can identify patients for surveillance and reduce mortality. Tethered capsule optical coherence tomography (OCT) can volumetrically image oesophageal mucosa in unsedated patients and detect features of BE. We investigated ultrahigh-speed tethered capsule swept-source OCT (SS-OCT), improved device design, developed procedural techniques and measured capsule contact, longitudinal pullback non-uniformity and patient toleration. DESIGN: OCT was performed in 16 patients prior to endoscopic surveillance/treatment. Unsedated patients swallowed the capsule with sips of water and the tether was pulled back to image the oesophagus. SS-OCT at 1 000 000 A-scans/s enabled imaging 10 cm oesophageal lengths in 10 s with 30 µm transverse and 8 µm axial resolution. Capsule contact, longitudinal image coverage and patient toleration were assessed. RESULTS: Nine patients had non-dysplastic BE, three had ablative treatment-naïve neoplasia and four had prior ablation for dysplasia. Dry swallows facilitated capsule transit through the lower oesophageal sphincter (LES), and waiting 10 s before pullback reduced swallow induced LES relaxation. Slow nasal inhalation facilitated capsule retrieval and minimised gag reflex. The procedure was well tolerated. Ultrahigh-speed SS-OCT generated cross-sectional and subsurface en face images showing BE features, while subsurface en face images were required to assess the gastro-oesophageal junction. Candidate features of dysplasia were also identified which could inform follow-up endoscopy/biopsy. BE features were seen in all patients with histologically confirmed BE. Mean capsule contact over BE was 75%±27% for all patients and better in short segment BE. Mean longitudinal image coverage over BE was 59%±34% and better for long segment BE. CONCLUSIONS: Ultrahigh-speed tethered capsule SS-OCT can image en face and cross-sectional mucosal features over wide areas. Device and procedure optimisation improved performance. BE features could be identified in all patients, but limited capsule contact and longitudinal coverage could cause sampling errors for focal pathologies.

A narrative review on trans-nasal pulmonary aerosol delivery.

The use of trans-nasal pulmonary aerosol delivery via high-flow nasal cannula (HFNC) has expanded in recent years. However, various factors influencing aerosol delivery in this setting have not been precisely defined, and no consensus has emerged regarding the optimal techniques for aerosol delivery with HFNC. Based on a comprehensive literature search, we reviewed studies that assessed trans-nasal pulmonary aerosol delivery with HFNC by in vitro experiments, and in vivo, by radiolabeled, pharmacokinetic and pharmacodynamic studies. In these investigations, the type of nebulizer employed and its placement, carrier gas, the relationship between gas flow and patient's inspiratory flow, aerosol delivery strategies (intermittent unit dose vs continuous administration by infusion pump), and open vs closed mouth breathing influenced aerosol delivery. The objective of this review was to provide rational recommendations for optimizing aerosol delivery with HFNC in various clinical settings.

Successful leadless pacemaker implantation in a patient with profound bradycardia following transcatheter aortic valve replacement and mitral valve-in-valve procedure.

Leadless pacemakers provide a potential alternative to conventional transvenous pacemakers for patients undergoing high-risk transcatheter valve replacement procedures. This is a description of a successful leadless pacemaker implantation in a 51-year-old woman who developed profound bradycardia following a transcatheter aortic valve replacement and mitral valve-in-valve procedure.

Tympanostomy Tube Innovation: Advances in Device Material, Design, and Office-Based Technology.

OBJECTIVES: With tympanostomy tube insertion remaining the most common procedure performed in children to date, growing interests in minimizing both procedural costs and anesthetic exposure in the pediatric population have inspired innovation with respect to tympanostomy tubes. As such, we aim to discuss the current state of tympanostomy tube innovation including insertion devices, tube material, and design. METHODS: Computerized literature review. RESULTS: (1) Numerous single-use devices consisting of a myringotomy knife and preloaded tympanostomy tube offer potential advantages of decreasing or eliminating operating room time and may be performed under moderate instead of a general anesthetic. (2) Innovation with respect to tympanostomy tube material and design may offer enhanced ototopical drug delivery, decreased rates of tube occlusion, and/or the ability to dissolve "on-command" with application of a novel ototopical material. (3) These technologies currently remain in various phases of preclinical and clinical testing. CONCLUSIONS: While clinical testing for a number of new technologies is preliminary and ongoing, tympanostomy tube-related innovations hold exciting promise to supplement or potentially replace the present-day armamentarium of tympanostomy tube design and insertion moving forward.

A Novel Technique for the Management of Massive Hemoptysis: The Customized Endobronchial Silicone Blocker.

OBJECTIVE: Massive hemoptysis (MH) has a high mortality rate. Therapeutic options include bronchoscopy for endobronchial lesions, bronchial artery embolization (BAE), and emergency surgery. Scant options exist for patients who are not candidates for these modalities. Culprit bronchial segment occlusion is an option to prevent "spillover flooding → hypoxia." Applying this concept, we describe a case series of MH control using a novel bronchoscopically inserted customized endobronchial silicone blocker (CESB). We analyzed the safety and efficacy of CESBs in a select subset of patients with MH. METHODS: Inclusion criteria were patients with MH who were unstable for surgery/BAE, failed BAE, or relatively contraindicated/refused BAE. CESBs were manufactured on-site by modifying silicone stents, inserted using rigid bronchoscopy and reinforced with glue. The CESB was removed after 6 weeks when possible. A successful outcome was defined as immediate bleeding control with no recurrence after removal. RESULTS: Over 4.5 years, 13 episodes of MH in 12 patients meeting the criteria specified earlier were treated with CESBs. Seven of 12 patients had tuberculosis, 4 active and 3 inactive. One patient had mucormycosis, 1 post-lobectomy, 1 endobronchial renal cell carcinoma, 1 fibrosing mediastinitis, and 1 patient had metastatic laryngeal Ca. Eight of 12 patients were taken for primary-CESB placement. Four of 12 patients were sent for BAE, which was unsuccessful, and rescue-CESB was done for definitive management. The success rate, as defined earlier, was 92.3%, with no deaths from MH. CONCLUSIONS: Innovative bronchoscopically inserted CESBs are an effective strategy in MH when patients are unstable or fail conventional management.