Probiotic-Associated Central Venous Catheter Bloodstream Infections Lead to Increased Mortality in the ICU.

OBJECTIVES: To determine the occurrence rate and impact on patient outcomes of probiotic-associated central venous catheter bloodstream infections in the ICU. DESIGN: Retrospective observational cohort study. SETTING: The cohort was gathered using HCA Healthcare's data warehouse. PATIENTS: Adult patients with central venous catheters in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood culture data were used to determine whether an infection had occurred with an organism contained in an administered probiotic. Eighty-six probiotic-associated central venous catheter bloodstream infections were identified among the 23,015 patient cohort who received probiotics (0.37%). The number needed to harm was 270. Zero infections were found in the cohort that did not receive probiotics. Patients who contracted a probiotic infection had increased mortality (odds ratio, 2.23; 1.30-3.71; p < 0.01). Powder formulations had an increased rate of infection compared with nonpowder formulations (0.76% vs 0.33%; odds ratio, 2.03; 1.05-3.95; p = 0.04). CONCLUSIONS: Probiotic administration is associated with a substantial rate of probiotic-associated bloodstream infection in ICU patients with central venous catheters in place. Probiotic-associated bloodstream infections result in significantly increased mortality. Powder formulations cause bloodstream infections more frequently than nonpowder formulations. In ICU patients with central venous catheters, the risks of probiotic-associated central venous catheter bloodstream infection and death outweigh any potential benefits of probiotic administration.

Monkeypox Virus Infection Resulting from an Occupational Needlestick - Florida, 2022.

In August 2022, the Florida Department of Health notified CDC of a nurse who acquired monkeypox through an occupational exposure while providing care to a patient with monkeypox. To date, occupationally acquired Monkeypox virus (MPXV) infections in health care personnel (HCP) have been rarely reported during the 2022 multinational outbreak (1,2). This report describes the first reported U.S. case and recommends approaches for preventing occupationally acquired MPXV infections in HCP.

Phasor plotting with frequency-domain flow cytometry.

Interest in time resolved flow cytometry is growing. In this paper, we collect time-resolved flow cytometry data and use it to create polar plots showing distributions that are a function of measured fluorescence decay rates from individual fluorescently-labeled cells and fluorescent microspheres. Phasor, or polar, graphics are commonly used in fluorescence lifetime imaging microscopy (FLIM). In FLIM measurements, the plotted points on a phasor graph represent the phase-shift and demodulation of the frequency-domain fluorescence signal collected by the imaging system for each image pixel. Here, we take a flow cytometry cell counting system, introduce into it frequency-domain optoelectronics, and process the data so that each point on a phasor plot represents the phase shift and demodulation of an individual cell or particle. In order to demonstrate the value of this technique, we show that phasor graphs can be used to discriminate among populations of (i) fluorescent microspheres, which are labeled with one fluorophore type; (ii) Chinese hamster ovary (CHO) cells labeled with one and two different fluorophore types; and (iii) Saccharomyces cerevisiae cells that express combinations of fluorescent proteins with different fluorescence lifetimes. The resulting phasor plots reveal differences in the fluorescence lifetimes within each sample and provide a distribution from which we can infer the number of cells expressing unique single or dual fluorescence lifetimes. These methods should facilitate analysis time resolved flow cytometry data to reveal complex fluorescence decay kinetics.

Local Mosquito-Borne Transmission of Zika Virus - Miami-Dade and Broward Counties, Florida, June-August 2016.

During the first 6 months of 2016, large outbreaks of Zika virus disease caused by local mosquito-borne transmission occurred in Puerto Rico and other U.S. territories, but local mosquito-borne transmission was not identified in the continental United States (1,2). As of July 22, 2016, the Florida Department of Health had identified 321 Zika virus disease cases among Florida residents and visitors, all occurring in either travelers from other countries or territories with ongoing Zika virus transmission or sexual contacts of recent travelers.* During standard case investigation of persons with compatible illness and laboratory evidence of recent Zika virus infection (i.e., a specimen positive by real-time reverse transcription-polymerase chain reaction [rRT-PCR], or positive Zika immunoglobulin M [IgM] with supporting dengue serology [negative for dengue IgM antibodies and positive for dengue IgG antibodies], or confirmation of Zika virus neutralizing antibodies by plaque reduction neutralization testing [PRNT]) (3), four persons were identified in Broward and Miami-Dade counties whose infections were attributed to likely local mosquito-borne transmission. Two of these persons worked within 120 meters (131 yards) of each other but had no other epidemiologic connections, suggesting the possibility of a local community-based outbreak. Further epidemiologic and laboratory investigations of the worksites and surrounding neighborhood identified a total of 29 persons with laboratory evidence of recent Zika virus infection and likely exposure during late June to early August, most within an approximate 6-block area. In response to limited impact on the population of Aedes aegypti mosquito vectors from initial ground-based mosquito control efforts, aerial ultralow volume spraying with the organophosphate insecticide naled was applied over a 10 square-mile area beginning in early August and alternated with aerial larviciding with Bacillus thuringiensis subspecies israelensis (Bti), a group biologic control agent, in a central 2 square-mile area. No additional cases were identified after implementation of this mosquito control strategy. No increases in emergency department (ED) patient visits associated with aerial spraying were reported, including visits for asthma, reactive airway disease, wheezing, shortness of breath, nausea, vomiting, or diarrhea. Local and state health departments serving communities where Ae. aegypti, the primary vector of Zika virus, is found should continue to actively monitor for local transmission of the virus.(†).

Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions.

Oxidation is an important method for the synthesis of chemical intermediates in the manufacture of high-tonnage commodities, high-value fine chemicals, agrochemicals and pharmaceuticals: but oxidations are often inefficient. The introduction of catalytic systems using oxygen from air is preferred for 'green' processing. Gold catalysis is now showing potential in selective redox processes, particularly for alcohol oxidation and the direct synthesis of hydrogen peroxide. However, a major challenge that persists is the synthesis of an epoxide by the direct electrophilic addition of oxygen to an alkene. Although ethene is epoxidized efficiently using molecular oxygen with silver catalysts in a large-scale industrial process, this is unique because higher alkenes can only be effectively epoxidized using hydrogen peroxide, hydroperoxides or stoichiometric oxygen donors. Here we show that nanocrystalline gold catalysts can provide tunable active catalysts for the oxidation of alkenes using air, with exceptionally high selectivity to partial oxidation products ( approximately 98%) and significant conversions. Our finding significantly extends the discovery by Haruta that nanocrystalline gold can epoxidize alkenes when hydrogen is used to activate the molecular oxygen; in our case, no sacrificial reductant is needed. We anticipate that our finding will initiate attempts to understand more fully the mechanism of oxygen activation at gold surfaces, which might lead to commercial exploitation of the high redox activity of gold nanocrystals.

A Retrospective Analysis Comparing Post-Operative Bleeding with Various Doses of Aspirin after Lower Extremity Joint Arthroplasty or Revision.

STUDY OBJECTIVE: Previous studies have shown that aspirin is noninferior to other anticoagulation therapies in preventing postoperative venous thromboembolism following lower extremity arthroplasty or revision; however, its optimal dosing for this indication is less clear. This study aims to compare the odds of bleeding between different aspirin dosages following lower extremity joint arthroplasty or revision. DESIGN: This is a 3-year retrospective multi-center cohort study across the United States and its territories. SETTING: This study included patients admitted for total hip or knee arthroplasty or revision and were treated with prophylactic aspirin. PATIENTS, INTERVENTION, MEASUREMENTS: Patients were assigned to groups based on a total daily aspirin dose of 81, 162, 325, or 650 mg. Data were analyzed for postsurgical bleeding and thromboembolism events occurring during the initial admission and up to 40 days following surgery. Other exploratory variables included type of surgery, hip or knee arthroplasty, length of stay, and patient demographic data. MAIN RESULTS: Among 53,848 patients receiving aspirin, 3922 received a total daily dose of 81 mg, 19,341 received a total daily dose of 162 mg, 5256 received a total daily dose of 325 mg, and 25,329 received a total daily dose of 650 mg. Bleeding occurred in 466 (0.87%) patients and venous thromboembolism (VTE) in 209 patients (0.39%). The odds of bleeding were compared using logistic regression, with the 650-mg dose as the reference group. None were statistically significant for bleeding between all studied aspirin doses: 81 mg (OR 1.12, 95% CI 0.83-1.51, p = 0.451), 162 mg (OR 0.83, 95% CI 0.67-1.03, p = 0.097), and 325 mg (OR 0.83, 95% CI 0.59-1.13, p = 0.245). The odds of VTE were also not statistically significant: 81 mg (OR 0.71, 95% CI 0.40-1.17, p = 0.181), 162 mg (OR 0.75 95% CI 0.54-1.03, p = 0.072), and 325 mg (OR 1.00, 95% CI 0.64-1.53, p = 0.989). CONCLUSIONS: There were no significant differences in the odds of bleeding or venous thromboembolism among all studied aspirin dosages in patients receiving aspirin for thromboprophylaxis following lower extremity joint arthroplasty or revision.

Closed-loop stimulation in the control of focal epilepsy of insular origin.

BACKGROUND: Previous studies have shown that closed-loop or responsive neurostimulation can abort induced or spontaneous epileptiform discharges. OBJECTIVE: To assess the effectiveness of a programmable cranially implanted closed-loop neurostimulation system in the control of seizures originating from an area relatively inaccessible by open craniotomy. METHOD: A patient with drug-resistant partial epilepsy had previously undergone open resection of the left frontal opercular cortex and the underlying insular area. Although subdural-depth electrode ictal recordings had been nonlocalizing, depth electrode insular stimulation had produced the patient's habitual aura. Postoperatively, there was a sustained 50% reduction in seizure frequency. The residual seizures were identical to the preoperative seizures. Repeat depth electrode monitoring revealed that the ictal focus was immediately posterior to the previously resected insular area. A closed-loop cranial internal pulse generator system including left anterior insular and posterior orbitofrontal depth electrodes was implanted. RESULT: There was an additional 60% reduction of seizures. CONCLUSION: Preliminary observation indicates that responsive neurostimulation may be an effective alternative to higher-risk resective epilepsy surgery.

Gamma Knife stereotactic radiosurgical treatment of idiopathic trigeminal neuralgia: long-term outcome and complications.

OBJECT: Stereotactic radiosurgery (SRS) with the Gamma Knife (GK) is a rapidly emerging surgical modality in the management of medically refractory idiopathic trigeminal neuralgia (TN). The current study examines the long-term outcome in patients with drug-resistant idiopathic TN who underwent GK surgery at the authors' institution. METHODS: One hundred and six consecutive patients (38 men and 68 women) with proven medically refractory idiopathic TN were included in this retrospective study. Their ages were 41-82 years (mean 72.3 years). All patients underwent SRS with prescribed maximal radiation doses ranging from 70 to 85 Gy. Isocenters 1-3 were used and plugging was used selectively. The follow-up period was 12-72 months (mean 34.3 months). The patients were divided into 2 groups according to their history of previous surgery. RESULTS: The initial response rate in patients with no history of previous surgery was 92.9%; in those who had undergone previous surgery, the initial response rate was 85.7%. At the end of the 1st posttreatment year, an excellent outcome was achieved in 82.5% of patients who had not had previous surgery, and in 69.4% of those who had. The respective outcome rates for the 2nd posttreatment year were 78 and 63.5%, respectively. The most common complication was the development of persistent paresthesia, which occurred in 15.8% of patients with no previous surgery and 16.3% of those with previous surgery. CONCLUSIONS: Stereotactic radiosurgery with the GK is a safe and effective treatment option for patients with medically refractory idiopathic TN.

Transection of Omohyoid Muscle as an Aid During Vagus Nerve Stimulator Implantation.

BACKGROUND: Exposure of the carotid sheath during vagus nerve stimulator (VNS) implantation is usually straightforward but can be difficult for patients with a large body habitus. In addition, the exposure must be done with care if the surgeon wants to keep the vagus nerve in situ without using retractors that might impair access. OBJECTIVE: We describe the use of the omohyoid muscle as a landmark for the jugular vein and report how transection of the omohyoid can facilitate rapid and wide exposure of the carotid sheath. METHODS: We review the records of 59 consecutive patients undergoing VNS implantation from 2009-2015 and describe our technique incorporating omohyoid transection. We also summarize complications such as postoperative hoarseness, cough, dysphagia, or wound issues. RESULTS: Forty-two of the 59 patients (29 adults and 13 children) underwent omohyoid transection during implantation. In all cases, the carotid sheath and jugular vein were immediately visible after transection. One patient developed permanent hoarseness and coughing due to left vocal cord paresis, requiring further surgery. This result was most likely due to manipulation of the vagus nerve rather than division of the omohyoid muscle. CONCLUSION: Omohyoid transection provides excellent exposure of the carotid sheath during VNS implantation.

Spontaneous motor cortex encephalocele presenting with simple partial seizures and progressive hemiparesis. Case report and review of the literature.

Several cases of congenital or acquired temporal encephaloceles have been reported in the literature as the causative mechanism of simple and/or complex partial seizures. In this report the authors describe a rare case of spontaneous parietal encephalocele presenting with simple partial seizures and progressively increasing contralateral upper-extremity motor deficit. The unusual anatomical location of an encephalocele associated with seizures and the delayed seizure onset represent distinctive characteristics in this case. Preoperative imaging included surface electroencephalography, computerized tomography, and brain magnetic resonance imaging. Frameless neuronavigation and intraoperative cortical mapping were used to aid resection of the encephalocele, and the dural and bone defects were reconstructed. The surgical outcome in this case was excellent, and the patient has remained seizure free. The pertinent literature is reviewed in this report.

Toward the measurement of multiple fluorescence lifetimes in flow cytometry: maximizing multi-harmonic content from cells and microspheres.

Flow cytometry is a powerful means for in vitro cellular analyses where multi-fluorescence and multi-angle light scattering can indicate unique biochemical or morphological features of single cells. Yet, to date, flow cytometry systems have lacked the ability to capture complex fluorescence dynamics due to the transient nature of flowing cells. In this contribution we introduce a simple approach for measuring multiple fluorescence lifetimes from a single cytometric event. We leverage square wave modulation, Fourier analysis, and high frequency digitization and show the ability to resolve more than one fluorescence lifetime from fluorescently-labelled cells and microspheres. Illustration of a flow cytometer capable of capturing multiple fluorescence lifetime measurements; creating potential for multi-parametric, time-resolved signals to be captured for every color channel.

Improvements in access to care for HIV and AIDS in a statewide Medicaid managed care system.

BACKGROUND: Some experimental Medicaid managed care systems have expanded eligibility criteria for chronically ill persons, but these systems' impact on access to care remains unknown. OBJECTIVE: To determine whether initiating a statewide Medicaid managed care system (TennCare) guaranteeing universal access for persons living with HIV or AIDS (PLWHs) increased their enrollment in public sector insurance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal descriptive analysis of trends in population characteristics during the study period was performed. The study population included all PLWHs in Tennessee (1992-1997) identified by the State Health Department. These data linked with Medicaid/TennCare enrollment files identified percentages of Tennessee's HIV/AIDS population enrolled in Medicaid (1993) or TennCare (1994-1997) and eligi-bility/demographics changes during program initiation. MAIN OUTCOME MEASURE: Annual percentage of PLWHs enrolled in Medicaid/TennCare. RESULTS: Absolute numbers of PLWHs served by Medicaid/TennCare increased 475% from 1992 (n = 593) to 1997 (n = 2818). Similar increases in Tennessee's overall HIV-positive population occurred. Percentages of PLWHs enrolled in Medicaid/TennCare increased (1993 to 1997): HIV (28% to 34%) and AIDS (32% to 44%). The largest percentage of PLWHs added to the program were uninsured/uninsurable. CONCLUSIONS: Absolute numbers of PLWHs covered by Medicaid/TennCare substantially increased. Percentages of PLWHs covered increased more modestly, partly owing to large increases in overall numbers of HIV-positive Tennesseans during the study period. Increases in coverage were greatest for the AIDS population. Tennessee's broad expansion of eligibility for PLWHs resulted in improved access, but did not result in enrollment of most PLWHs. States contemplating similar Medicaid expansions should not expect all PLWHs to crowd into public sector insurance programs.

Measuring and sorting cell populations expressing isospectral fluorescent proteins with different fluorescence lifetimes.

Study of signal transduction in live cells benefits from the ability to visualize and quantify light emitted by fluorescent proteins (XFPs) fused to different signaling proteins. However, because cell signaling proteins are often present in small numbers, and because the XFPs themselves are poor fluorophores, the amount of emitted light, and the observable signal in these studies, is often small. An XFP's fluorescence lifetime contains additional information about the immediate environment of the fluorophore that can augment the information from its weak light signal. Here, we constructed and expressed in Saccharomyces cerevisiae variants of Teal Fluorescent Protein (TFP) and Citrine that were isospectral but had shorter fluorescence lifetimes, ∼ 1.5 ns vs ∼ 3 ns. We modified microscopic and flow cytometric instruments to measure fluorescence lifetimes in live cells. We developed digital hardware and a measure of lifetime called a "pseudophasor" that we could compute quickly enough to permit sorting by lifetime in flow. We used these abilities to sort mixtures of cells expressing TFP and the short-lifetime TFP variant into subpopulations that were respectively 97% and 94% pure. This work demonstrates the feasibility of using information about fluorescence lifetime to help quantify cell signaling in living cells at the high throughput provided by flow cytometry. Moreover, it demonstrates the feasibility of isolating and recovering subpopulations of cells with different XFP lifetimes for subsequent experimentation.

Subcellular localization-dependent changes in EGFP fluorescence lifetime measured by time-resolved flow cytometry.

Intracellular protein transport and localization to subcellular regions are processes necessary for normal protein function. Fluorescent proteins can be fused to proteins of interest to track movement and determine localization within a cell. Currently, fluorescence microscopy combined with image processing is most often used to study protein movement and subcellular localization. In this contribution we evaluate a high-throughput time-resolved flow cytometry approach to correlate intracellular localization of human LC3 protein with the fluorescence lifetime of enhanced green fluorescent protein (EGFP). Subcellular LC3 localization to autophagosomes is a marker of the cellular process called autophagy. In breast cancer cells expressing native EGFP and EGFP-LC3 fusion proteins, we measured the fluorescence intensity and lifetime of (i) diffuse EGFP (ii) punctate EGFP-LC3 and (iii) diffuse EGFP-ΔLC3 after amino acid starvation to induce autophagy-dependent LC3 localization. We verify EGFP-LC3 localization with low-throughput confocal microscopy and compare to fluorescence intensity measured by standard flow cytometry. Our results demonstrate that time-resolved flow cytometry can be correlated to subcellular localization of EGFP fusion proteins by measuring changes in fluorescence lifetime.

Avoidance of electrode related MRI artifact during staged deep brain stimulator implantation.

BACKGROUND: Centers implanting deep brain stimulator (DBS) electrodes on different days often protect the first electrode tip with a protective cap, tunnel it under the scalp, and connect it to the generator at a later procedure. If magnetic resonance imaging (MRI) is used for planning during the second implantation, MRI artifacts from the protective cap could potentially corrupt the stereotactic coordinates. The importance of this problem may increase if emerging MRI safety data lead to more frequent use of MRI for these purposes. OBJECTIVE: To describe an MRI artifact arising from the use of the standard protective DBS cap that corrupts stereotactic planning and to describe a way to avoid the artifact. METHODS: After noting the artifact during a staged DBS procedure, a nonmetallic silastic sleeve contained in the existing DBS implantation kit was used in nine subsequent patients. Two caps with standard metallic screws were also tested with MRI phantoms. RESULTS: The silastic sleeve protected the DBS electrode but did not produce MRI artifact. The phantom studies demonstrated significant artifact from caps containing screws. CONCLUSION: A silastic sleeve provides adequate protection of the DBS electrode during staged implantation and avoids the MRI artifact associated with protective caps with screws.

Capture of Fluorescence Decay Times by Flow Cytometry.

In flow cytometry, the fluorescence decay time of an excitable species has been largely underutilized and is not likely found as a standard parameter on any imaging cytometer, sorting, or analyzing system. Most cytometers lack fluorescence lifetime hardware mainly owing to two central issues. Foremost, research and development with lifetime techniques has lacked proper exploitation of modern laser systems, data acquisition boards, and signal processing techniques. Secondly, a lack of enthusiasm for fluorescence lifetime applications in cells and with bead-based assays has persisted among the greater cytometry community. In this unit, we describe new approaches that address these issues and demonstrate the simplicity of digitally acquiring fluorescence relaxation rates in flow. The unit is divided into protocol and commentary sections in order to provide a most comprehensive discourse on acquiring the fluorescence lifetime with frequency-domain methods. The unit covers (i) standard fluorescence lifetime acquisition (protocol-based) with frequency-modulated laser excitation, (ii) digital frequency-domain cytometry analyses, and (iii) interfacing fluorescence lifetime measurements onto sorting systems. Within the unit is also a discussion on how digital methods are used for aliasing in order to harness higher frequency ranges. Also, a final discussion is provided on heterodyning and processing of waveforms for multi-exponential decay extraction.

Intracranial stimulation study of lateralization of affect.

As part of their evaluation for epilepsy surgery, 53 patients underwent stimulation of depth or subdural electrodes. Responses obtained from depth stimulation included motor responses at 34 sites, sensory responses at 114 sites, language alterations at 6 sites, and affective responses at 22 sites. Responses obtained from subdural stimulation included motor responses at 19 sites, sensory responses at 31 sites, speech alterations at 10 sites, and affective responses at 1 site. Of 23 affective responses, 21 were dysphoric responses of fear, a sense of dying, or unpleasantness with or without some type of experiential phenomenon. Dysphoric responses were statistically associated (P=0.01) with right-sided stimulation (N=18) as compared with left-sided stimulation (N=3) of mesial frontal, orbitofrontal, mesial temporal, and insular stimulation sites. Two euphoric responses occurred, one with left-sided and one with right-sided stimulation. No affective responses were obtained with convexity or neocortical stimulation.

Implantation of a closed-loop stimulation in the management of medically refractory focal epilepsy: a technical note.

Open-loop stimulation studies have shown varying control of seizures with stimulation of different anatomical targets. A recent multi-institutional clinical study utilizing an external closed-loop stimulation system had promising results. A novel implantable closed-loop Responsive Neurostimulation System (RNS) (Neuropace, Inc., Mountainview, Calif., USA) consisting of a cranially implanted pulse generator, one or two quadripolar subdural strip or depth leads and a programmer is under testing in a prospective clinical trial. The RNS pulse generator continuously analyzes the patient's electrocortigrams (ECoGs) and automatically triggers electrical stimulation when specific ECoG characteristics programmed by the clinician, as indicative of electrographic seizures or precursor of epileptiform activities, are detected. The pulse generator then stores diagnostic information detailing detections and stimulations, including multichannel stored ECoGs. The RNS programmer communicates transcutaneously with the implanted pulse generator when initiated by a clinician. The RNS programmer can download diagnostics and store ECoGs for review. The RNS programmer can then be used to program detection and stimulation parameters. In our current communication, we describe the selection criteria for implanting this system, the preparation of the surgical candidates as well as the surgical technique. We also present our preliminary results with 8 patients who had an RNS implanted. Seven patients (87.5%) had more than 45% decrease in their seizure frequency. The mean follow-up time in our series was 9.2 months. The implantation of a closed-loop stimulation system, in our experience, represents a safe and relatively simple surgical procedure. However, the efficacy of this new treatment modality remains to be determined in further multi-institutional, prospective clinical studies.

Nonhabitual seizures in patients with implanted subdural electrodes.

The implantation of subdural electrodes has been widely employed in the invasive monitoring of patients with medically refractory epilepsy. The use of subdural electrodes, though, has been associated with rare but occasionally troublesome complications. We report the occurrence of nonhabitual seizures after implanting subdural grid electrodes. Among 57 patients diagnosed with medically refractory epilepsy who were evaluated in our department over a 12-month period, 21 patients underwent craniotomy for subdural grid/strip electrode implantation. Subdural grids and strips (AdTech, Racine, Wisc., USA) were used for continuous video EEG monitoring. In 3 patients, during subdural monitoring, consistent nonhabitual seizure activity was recorded. This was both clinically and electrographically different than the patients' habitual seizures. The patients' nonhabitual seizures disappeared postoperatively after removing the implanted electrodes. The occurrence of nonhabitual seizures, though quite rare, could lead to mislocalization of an epileptogenic focus. This complication might be the result of direct mechanical cortical irritation or chemical irritation caused by blood breakdown products. The occurrence of nonhabitual seizures comes to add itself to the existing list of complications associated with employment of subdural electrodes for invasive monitoring.