Lesion Index-guided workflow for the treatment of paroxysmal atrial fibrillation is safe and effective - Final results from the LSI Workflow Study.

Background: Pulmonary vein isolation (PVI) ablation is a standard therapy for paroxysmal atrial fibrillation (PAF). Lesion Index (LSI) is a metric to guide radiofrequency (RF) ablation using the TactiCath Ablation Catheter, Sensor Enabled with the EnSite Cardiac Mapping System (Abbott). Objective: This study (NCT-03906461) was designed to capture best practices using LSI-guided catheter ablation to treat PAF subjects in a real-world setting. Methods: This prospective single-arm observational study enrolled 143 PAF subjects in the United States, Europe, and Japan undergoing de novo PVI with RF ablation. PVI lesions were assigned to 10 anatomically defined segments. Mean LSIs achieved for all lesions were analyzed. Follow-up was conducted between 3-6 months and 12 months after the procedure. Results: Pulmonary veins were isolated in all subjects. The mean achieved LSI was 4.9, with lower values in Europe (4.4) and Japan (4.5) than the United States (5.5). First-pass success, defined as no gaps requiring touch-up ablation after 20 minutes post isolation, was achieved in 76.2% of subjects. Use of high LSI (≥5) resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI (<5). At 12 months, 99.3% of subjects were free from procedure- or device-related serious adverse events and 95.7% (112/117) (35.0% on antiarrhythmic drugs) were free from recurrence and/or a repeat ablation procedure for atrial fibrillation / atrial flutter / atrial tachycardia. Conclusion: LSI-guided ablation strategies proved safe and effective despite differences in LSI workflows. Use of high LSI values resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI.

Human Herpesvirus-6 Detection in Cerebrospinal Fluid on the BioFire FilmArray Meningitis/Encephalitis Panel in a High Human Immunodeficiency Virus-Prevalence African Setting.

The prevalence and clinical relevance of human herpesvirus-6 (HHV-6) detection in cerebrospinal fluid (CSF) using multiplex polymerase chain reaction (PCR) testing in patients with suspected meningoencephalitis in high human immunodeficiency virus-prevalence African settings are not known. We describe the clinical and laboratory characteristics of 13 patients with HHV-6 CSF PCR positivity in Botswana.

Moderated Basicity of Endohedral Amine Groups in an Octa-Cationic Self-Assembled Cage.

A self-assembled FeII4 L6 cage was synthesized with 12 internal amines in the cavity. The cage forms as the dodeca-ammonium salt, despite the cage carrying an overall 8+ charge at the metal centers, extracting protons from displaced water in the reaction. Despite this, the basicity of the internal amines is lower than their counterparts in free solution. The 12 amines have a sliding scale of basicity, with a ≈6 pKa unit difference between the first and last protons to be removed. This moderation of side-chain basicity in an active site is a hallmark of enzymatic catalysis.

Outcomes of Reflex Cryptococcal Antigen (CrAg) Screening in Human Immunodeficiency Virus (HIV)-Positive Patients With CD4 Counts of 100-200 Cells/µL in Botswana.

Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101-200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101-200 cells/µL.

Focal Impulse and Rotor Modulation Ablation vs. Pulmonary Vein isolation for the treatment of paroxysmal Atrial Fibrillation: results from the FIRMAP AF study.

AIMS: Pulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation. Recently, catheter ablation targeting rotors or focal sources has been developed for treatment of AF. This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM)-guided ablation as the sole ablative strategy with PVI in patients with paroxysmal AF. METHODS AND RESULTS: We conducted a multicentre, randomized trial to determine whether FIRM-guided radiofrequency ablation without PVI (FIRM group) was non-inferior to PVI (PVI group) for treatment of paroxysmal AF. The two primary efficacy end points were (i) acute success defined as elimination of AF rotors (FIRM group) or isolation of all pulmonary veins (PVI group) and (ii) long-term success defined as single-procedure freedom from AF/atrial tachycardia (AT) recurrence 12 months after ablation. The study was closed early by the sponsor. At the time of study closure, any pending follow-up visits were waived. A total of 51 patients (mean age 63 ± 10.6 years, 57% male) were enrolled. All PVs were successfully isolated in the PVI group and all rotors were successfully eliminated in the FIRM group. Single-procedure effectiveness was 31.3% (5/16) in the FIRM group and 80% (8/10) in the PVI group at 12 months. Three vascular access complications occurred in the FIRM group. CONCLUSION: These partial study effectiveness results reinforce the importance of PVI in paroxysmal AF patients and indicate that FIRM-guided ablation alone (without PVI) is not an effective strategy for treatment of paroxysmal AF in most patients.

Redox-active ligand controlled selectivity of vanadium oxidation on Au(100).

Metal-organic coordination networks at surfaces, formed by on-surface redox assembly, are of interest for designing specific and selective chemical function at surfaces for heterogeneous catalysts and other applications. The chemical reactivity of single-site transition metals in on-surface coordination networks, which is essential to these applications, has not previously been fully characterized. Here, we demonstrate with a surface-supported, single-site V system that not only are these sites active toward dioxygen activation, but the products of that reaction show much higher selectivity than traditional vanadium nanoparticles, leading to only one V-oxo product. We have studied the chemical reactivity of one-dimensional metal-organic vanadium - 3,6-di(2-pyridyl)-1,2,4,5-tetrazine (DPTZ) chains with O2. The electron-rich chains self-assemble through an on-surface redox process on the Au(100) surface and are characterized by X-ray photoelectron spectroscopy, scanning tunneling microscopy, high-resolution electron energy loss spectroscopy, and density functional theory. Reaction of V-DPTZ chains with O2 causes an increase in V oxidation state from VII to VIV, resulting in a single strongly bonded (DPTZ2-)VIVO product and spillover of O to the Au surface. DFT calculations confirm these products and also suggest new candidate intermediate states, providing mechanistic insight into this on-surface reaction. In contrast, the oxidation of ligand-free V is less complete and results in multiple oxygen-bound products. This demonstrates the high chemical selectivity of single-site metal centers in metal-ligand complexes at surfaces compared to metal nanoislands.

Anatomic site for proximal tibial nerve compression: a cadaver study.

Primary compression of the tibial nerve beneath the fibromuscular sling of the origin of the soleus muscle is rarely discussed in the literature. To evaluate the location and characteristics of the soleal fibromuscular sling and its relationship to the tibial nerve, 36 cadaver limbs were dissected. The leg length, location of soleal fibromuscular sling, presence of a thickened fibrous band at the soleal sling, and narrowing in the tibial nerve were recorded. The average leg length was 47.8 cm (SD +/- 4.16). The fibromuscular soleal sling was 9.3 cm (SD +/- 1.44) distal to the medial tibial plateau. Although 56% (20/36) of specimens had a fibrous band, only 8% (3/36) demonstrated a focal narrowing directly under this fascial sling. This study demonstrates that the fibromuscular sling of the soleus muscle may act as a potential compression site of the tibial nerve. These findings offer insight and potential hope for those patients who have persistent plantar numbness after tarsal tunnel decompression and for those patients with plantar numbness who also have weakness of toe flexion.

Combined peroneal and proximal tibial nerve palsies.

Combined compression of both the common peroneal nerve and the proximal tibial nerve at the level of the popliteal fossa is rare. Recently, an anatomic site of compression of the proximal tibial nerve at the soleal sling (originating arch for the soleus muscle) has been described in cadavers. The present report includes three patients who had a combined compression of the common peroneal nerve at the fibular neck (fibular tunnel syndrome) and compression of the proximal tibial nerve at the soleal sling (soleal sling syndrome). In each case, blunt trauma was the precipitating event. Neurolysis of both nerves resulted in restoration of motor and sensory function in each of these three patients. This is the first clinical report illustrating combined neurolysis of the common peroneal at the knee and the proximal tibial nerve in the soleal sling.

Management of chronic facial pain.

Pain persisting for at least 6 months is defined as chronic. Chronic facial pain conditions often take on lives of their own deleteriously changing the lives of the sufferer. Although much is known about facial pain, it is clear that those physicians who treat these conditions should continue elucidating the mechanisms and defining successful treatment strategies for these life-changing conditions. This article will review many of the classic causes of chronic facial pain due to the trigeminal nerve and its branches that are amenable to surgical therapies. Testing of facial sensibility is described and its utility introduced. We will also introduce some of the current hypotheses of atypical facial pain and headaches secondary to chronic nerve compressions and will suggest possible treatment strategies.

Neurectomy for treatment of intercostal neuralgia.

BACKGROUND: Intercostal neuralgia due to surgical injury of the intercostal nerve is difficult to treat. No treatment modality has given effective pain relief. Experience with other painful neuromas has demonstrated that neuroma resection and muscle implantation has been effective in the upper and lower extremities. This approach was applied to patients with intercostal neuralgia. METHODS: A retrospective review was done of 5 consecutive patients who have had neurectomy of one or more intercostal nerves. Preoperative and postoperative pain levels, patient demographics, length of follow-up, and surgical technique were reviewed. RESULTS: Average patient age was 51.0 years (range, 39.2 to 61.3). Patients presented an average of 42.8 months (range, 10 to 138) after the surgical procedure or trauma that created their painful intercostal neuromas. The mean maximum pain level was 10, and the mean average pain level was 8 (range, 7 to 9). Postoperatively, the mean maximum pain level was 3.4 (range, 0 to 9), and the mean average pain level was 2.2 (range, 0 to 7). The differences were significant: p less than 0.01 for maximum pain level and p less than 0.05 for average pain level. Average follow-up after surgery was 8.8 months (range, 6.5 to 10.9). The most common surgical technique used was intercostal nerve neurectomy proximal to the intercostal nerve neuroma and implantation of the cut nerve into the latissimus dorsi muscle. CONCLUSIONS: Intercostal neurectomy and implantation of the cut nerve into the latissimus dorsi or into the rib for severe intercostal neuralgia was an efficacious treatment in this small consecutive patient series.

3D CT angiography of abdominal wall vascular perforators to plan DIEAP flaps.

PURPOSE: Since the first report of TRAM flap reconstruction, there have been numerous studies to reduce complications of elective breast reconstruction. Current methods of preoperative perforator localization can be time-consuming, inaccurate, and imprecise. Thus, we sought to evaluate ultra-high resolution 3D CT angiography for the preoperative mapping of DIEAP flap perforating vessels. METHODS: We reviewed all perforator-based breast reconstructions performed over a 5-month period. Candidates for DIEAP flap reconstruction were sent for a focused CT scan of the abdominal wall, using the 64 slice multi-detector CT scanner. RESULTS: This article presents our first 23 flaps in 17 patients with preoperative ultra-high resolution 3D CT angiography. The reconstruction plan changed in three patients (18%). There was one take-back for venous congestion, but no partial or total flap loss. CONCLUSIONS: Preoperative perforator flap planning for breast reconstruction utilizing 3D CT angiogram is safe, easy to read, and can change the operative plan.

Designing zonal organization into tissue-engineered cartilage.

Cartilage tissue engineering strategies generally result in homogeneous tissue structures with little resemblance to the native zonal organization of articular cartilage. The objective of this study was to use bilayered photopolymerized hydrogels to organize zone-specific chondrocytes in a stratified framework and study the effects of this three-dimensional coculture system on the properties of the engineered tissue. Superficial and deep zone chondrocytes from bovine articular cartilage were photoencapsulated in separate hydrogels as well as in adjacent layers of a bilayered hydrogel. Histology, mechanical testing, and biochemical analysis was performed after culturing in vitro. To evaluate the influence of coculture on tissue properties, the layers were separated and compared to constructs containing only superficial or deep cells. In the bilayered constructs, deep cells produced more collagen and proteoglycan than superficial cells, resulting in cartilage tissue with stratified, heterogeneous properties. Deep cells cocultured with superficial cells in the bilayered system demonstrated reduced proliferation and increased matrix synthesis compared to deep cells cultured alone. The bilayered constructs demonstrated greater shear and compressive strength than homogenous cell constructs. This study demonstrated that interactions between zone-specific chondrocytes affect the biological and mechanical properties of engineered cartilage. Strategies aimed to structurally organize zone-specific cells and encourage heterotypic cell interactions may contribute to improved functional properties of engineered cartilage.

In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel.

BACKGROUND: Surgical options for cartilage reconstruction can be significantly improved through advances in cartilage tissue engineering, whereby functional tissue replacements are created by growing cells on polymer scaffolds. The objective of this study was to use a photopolymerizable hydrogel to implant bone marrow-derived mesenchymal stem cells subcutaneously in a minimally invasive manner and promote cartilage tissue formation by the cells in vivo. METHODS: Athymic nude mice were injected subcutaneously with polymer solutions of poly(ethylene) oxide diacrylate containing mesenchymal stem cells and placed under a UVA lamp to transdermally photopolymerize (solidify) the injected liquid. Experimental groups included polymer solutions with hyaluronic acid (HA), transforming growth factor (TGF)-beta3, or both. After 3 weeks of implantation, cartilage formation was evaluated by gene expression analysis and histologic techniques. RESULTS: Hyaluronic acid increased the viscosity of the polymer solutions, which helped maintain the injections at the desired site during photopolymerization. Mesenchymal stem cells in hydrogels containing both HA and TGF-beta3 produced the highest quality cartilage, based on expression of the cartilage-specific genes and production of proteoglycan and collagen II. When used independently, TGF-beta3 and HA alone induced cartilage-specific gene expression and collagen type II production; however, TGF-beta3 was essential for proteoglycan production. HA enhanced proteoglycan production when combined with TGF-beta3 and reduced expression and production of collagen I. CONCLUSIONS: This study is the first to demonstrate the minimally invasive implantation and subsequent chondrogenic differentiation of mesenchymal stem cells in the subcutaneous environment. This lays the foundation for further optimization of a novel and practical technology for cartilage reconstruction.

Prognostic significance of microalbuminuria in postdiarrheal hemolytic uremic syndrome.

Patients who survive the acute phase of postdiarrheal hemolytic uremic syndrome (D+ HUS) may develop renal complications after years of apparent recovery. The optimal regimen for monitoring these children is unclear. We therefore determined if screening for microalbuminuria, in the absence of overt proteinuria at follow-up, increased the sensitivity for predicting long-term renal-related sequelae. We found that screening for microalbuminurea, within the first 6-18 months following an episode of HUS, increased the sensitivity for predicting later sequelae from 22 to 66.7%, compared to screening for overt proteinuria alone. These findings, if confirmed by a larger cohort with more years of follow-up, may facilitate early initiation of intervention strategies designed to reduce progressive renal damage.

A palpable, obstructing carcinoma of the colon incarcerated within a large ventral hernia.

Uncovering the etiology of a bowel obstruction in a patient with a hernia represents a diagnostic dilemma. Although the hernia is often initially the presumptive cause of the bowel obstruction, obstructive carcinoma or another pathological process hidden by the hernia are important considerations. Here we describe a case of a man with an obstructing neoplasm of the colon within a large ventral hernia, whose constipation was initially attributed to incarceration of the hernia.

The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells.

Advances in tissue engineering require biofunctional scaffolds that can not only provide cells with structural support, but also interact with cells in a biological manner. To achieve this goal, a frequently used cell adhesion peptide Arg-Gly-Asp (RGD) was covalently incorporated into poly(ethylene glycol) diacrylate (PEODA) hydrogel and its dosage effect (0.025, 1.25 and 2.5 mm) on osteogenesis of marrow stromal cells in a three-dimensional environment was examined. Expression of bone-related markers, osteocalcin (OCN) and Alkaline phosphatase (ALP), increased significantly as the RGD concentration increased. Compared with no RGD, 2.5 mm RGD group showed a 1344% increase in ALP production and a 277% increase in OCN accumulation in the medium. RGD helped MSCs maintain cbfa-1 expression when shifted from a two-dimensional environment to a three-dimensional environment. Soluble RGD was found to completely block the mineralization of marrow stromal cells, as manifested by quantitative calcium assay, phosphorus elemental analysis and Von Kossa staining. In conclusion, we have demonstrated that RGD-conjugated PEODA hydrogel promotes the osteogenesis of MSCs in a dosage-dependent manner, with 2.5 mm being optimal concentration.

Bioresponsive phosphoester hydrogels for bone tissue engineering.

Bioresponsive and intelligent biomaterials are a vehicle for manipulating cell function to promote tissue development and/or tissue engineering. A photopolymerized hydrogel based on a phosphoester- poly(ethylene glycol) polymer (PhosPEG) was synthesized for application to marrow-derived mesenchymal stem cell (MSC) encapsulation and tissue engineering of bone. The phosphor-containing hydrogels were hydrolytically degradable and the rate of degradation increased in the presence of a bone-derived enzyme, alkaline phosphatase. Gene expression and protein analysis of encapsulated MSCs demonstrated that PhosPEG-PEG cogels containing an intermediate concentration of phosphorus promoted the gene expression of bone-specific markers including type I collagen, alkaline phosphatase, and osteonectin, without the addition of growth factors or other biological agents, compared with pure poly(ethylene glycol)-based gels. Secretion of alkaline phosphatase, osteocalcin, and osteonectin protein was also increased in the PhosPEG cogels. Mineralization of gels increased in the presence of phosphorus in both cellular and acellular constructs compared with PEG gels. In summary, phosphate-PEG-derived hydrogels increase gene expression of bone-specific markers, secretion of bone-related matrix, and mineralization and may have a potential impact on bone-engineering therapies.

Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation.

The development of biocompatible photopolymerizing polymers for biomedical and tissue engineering applications has the potential to reduce the invasiveness and cost of biomaterial implants designed to repair or augment tissues. However, more information is needed about the cellular toxicity of the compounds and initiators used in these systems. The current study evaluates the cellular toxicity of three ultraviolet sensitive photoinitiators on six different cell populations that are used for engineering numerous tissues. The photoinitiator 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) caused minimal toxicity (cell death) over a broad range of mammalian cell types and species. It was also demonstrated that different cell types have variable responses to identical concentrations of the same photoinitiator. While inherent differences in the cell lines may contribute to the variable cytotoxicity, a correlation between cellular proliferation rate (population doubling time) and increased cytotoxicity of the photoinitiator was observed. Cell lines that divided more quickly were more sensitive to photoinitiator-induced cell death. In summary, the photoinitiator Irgacure 2959 is well tolerated by many cell types over a range of mammalian species. Cell photoencapsulation strategies may be optimized to improve cell survival by manipulating proliferation rate.