Carbon monoxide poisoning and phototherapy.

Carbon monoxide (CO) poisoning is a leading cause of poison-related morbidity and mortality worldwide. By binding to hemoglobin and other heme-containing proteins, CO reduces oxygen delivery and produces tissue damage. Prompt treatment of CO-poisoned patients is necessary to prevent acute and long-term complications. Oxygen therapy is the only available treatment. Visible light has been shown to selectively dissociate CO from hemoglobin with high efficiency without affecting oxygen affinity. Pulmonary phototherapy has been shown to accelerate the rate of CO elimination in CO poisoned mice and rats when applied directly to the lungs or via intra-esophageal or intra-pleural optical fibers. The extracorporeal removal of CO using a membrane oxygenator with optimal characteristic for blood exposure to light has been shown to accelerate the rate of CO illumination in rats with or without lung injury and in pigs. The development of non-invasive techniques to apply pulmonary phototherapy and the development of a compact, highly efficient membrane oxygenator for the extracorporeal removal of CO in humans may provide a significant advance in the treatment of CO poisoning.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO  device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.

Standard management options for rosacea: The 2019 update by the National Rosacea Society Expert Committee.

In 2017, a National Rosacea Society Expert Committee developed and published an updated classification of rosacea to reflect current insights into rosacea pathogenesis, pathophysiology, and management. These developments suggest that a multivariate disease process underlies the various clinical manifestations of the disorder. The new system is consequently based on phenotypes that link to this process, providing clear parameters for research and diagnosis as well as encouraging clinicians to assess and treat the disorder as it may occur in each individual. Meanwhile, a range of therapies has become available for rosacea, and their roles have been increasingly defined in clinical practice as the disorder has become more widely recognized. This update is intended to provide a comprehensive summary of management options, including expert evaluations, to serve as a guide for tailoring treatment and care on an individual basis to achieve optimal patient outcomes.

Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. Objectives: To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. Design, Setting, and Participants: A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Interventions: Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). Main Outcomes and Measures: The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Results: Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). Conclusions and Relevance: In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. Trial Registration: ClinicalTrials.gov Identifier: NCT02233413.

Fluorescence polarization of tetracycline derivatives as a technique for mapping nonmelanoma skin cancers.

Nonmelanoma skin cancer is the most common form of human cancer, often resulting in high morbidity. Low visual contrast of these tumors makes their delineation a challenging problem. Employing a linearly polarized monochromatic light source and a wide-field CCD camera, we have developed a technique for fluorescence polarization imaging of the nonmelanoma cancers stained using antibiotics from the tetracycline family. To determine the feasibility of the method, fluorescence polarization images of 86 thick, fresh cancer excisions were studied. We found that the level of endogenous fluorescence polarization was much lower than that of exogenous, and that the average values of fluorescence polarization of tetracycline derivatives were significantly higher in cancerous as compared to normal tissue. Out of 86 tumors [54 stained in demeclocycline (DMN) and 32 in tetracycline (TCN)], in 79 cases (51-DMN, 28-TCN) the location, size, and shape of the lesions were identified accurately. The results of this trial indicate that nonmelanoma skin tumors can be distinguished from healthy tissue based on the differences in exogenous fluorescence polarization of TCN and/or DMN. Therefore, the developed technique can provide an important new tool for image-guided cancer surgery.

532 nm pulsed potassium-titanyl-phosphate laser treatment of laryngeal papillomatosis under general anesthesia.

OBJECTIVES: Angiolytic lasers have been shown to be an effective treatment strategy for laryngeal papillomatosis. These lasers precisely target hemoglobin within the microcirculation of papillary lesions. We have previously demonstrated the advantages of the fiber-based pulsed 532-nm potassium-titanyl-phosphate (KTP) laser in an office setting (with local anesthesia). This investigation provides the first report of the pulsed-KTP laser during microlaryngoscopy under general anesthesia. STUDY DESIGN: A prospective pilot study was performed in 55 adult patients with laryngeal papillomatosis to determine disease response. METHODS: During suspension microlaryngoscopy, a solid-state 532 nm pulsed-KTP laser was used (15 ms pulse width, 5.25-7.5 J/pulse maximum output, 2 Hz repetition rate, 0.4 mm fiber, approximately 20-80 J/cm2 fluence) to treat laryngeal papillomatosis. All patients underwent postoperative videolaryngoscopy to assess disease regression based on a previously used rating scale. RESULTS: Thirty-seven patients underwent 55 procedures during the 18-month study period. Near-term follow-up with an early postoperative evaluation was available in 23 patients (35 procedures). Fourteen patients (20 procedures) were geographically distant and only returned after developing symptoms with significant disease recurrence. Of the 35 procedures in which near-term follow-up was available, 90% or greater disease regression was achieved in 28 of 35 (80%), 75% to 89% disease regression was achieved in 4 of 35 (11%), and 50% to 74% disease regression in 3 of 35 (9%). Anterior-commissure disease was present in 51 of 55 (93%) cases, and no new webbing/synechia occurred. All patients reported that their vocal function improved after treatment. CONCLUSIONS: The 532 nm pulsed-KTP laser was effective for treating recurrent respiratory papillomatosis, which was similar to our experience as an office-based procedure.

Horizontal-age prevalence and intensity of trichuris trichiura infection in a rural population in St. Lucia - abstract

The clinical severity of trichuriasis and the rate of production of Trichurius infective stages are dependent upon the size of the worm burden. This study examines the horizontal-age distribution of prevalence and intensity of Trichurius infection in a St. Lucian village, with the twofold aim of identifying the age group which makes the major potential contribution to the transmission of infection and is at its greatest risk of disease. Duplicate faecal specimens from a minimum of 16 individuals in 8 age groups (<0.5->30 years) were examined twice, using the Kato thick-smear technique. A minimum of 16 individuals, infected with Trichuris, from 6 of the age groups (1->30 years) had their worm burdens determined by expulsion with mebendazole (Vermox, Janssen Pharmaceutica). Ovogenic infections occurred in 6 percent of children under 12 months; the youngest case was 5 months. Prevalence increased dramatically after the first year of life, exceeding 90 percent by 3 years of age, and remaining high and constant into adulthood. Intensity rose over a similar time preiod to prevalence but approximately one year later in life. Maximum intensity was attained in the age group 2-10 years old, and thereafter declined with increasing age. These results indicate that the population is exposed and susceptible to trichurius infection before 12 months of age. The decline in worm burden after 10 years of age may reflect age-dependency in the force of infection or the development of an immune response. Children aged 2-10 years have the largest worm burdens and are therefore: (1) the major contributors to the transmission of infection and hence the major focus for targeted chemotherapy; and (2) most likely to develop the clinical manifestations of trichuriasis (AU)

Age-related prevalence and intensity of Trichuris trichiura infection in a St. Lucian community

Age-related changes in the average worm burden and the prevalence of Trichuris trichiura infection, in a village community in St. Lucia, were examined by field studies based on worm expulsion techniques. Horizontal age-intensity profiles were convex in form with peak parasite loads occurring in the 2 to 15-year-old children. Prevalence is shown to be a poor indicator of changes in average worm load with age. Faecal egg counts (epg and epd) provide a qualitative measure of worm burdens since fecundity is shown to be approximately independent of worm load. The parasites were highly aggregated within the study community, with most people harbouring low burdens while a few individuals harboured very heavy burdens. Of the total parasite populations in the study sample, 84 percent were harboured by the 2 to 15-year-old children. Of those individuals harbouring 100 worms or more, 87 percent were in the 2 to 10-year-old age range. Crude estimates of population parameters (basic reproductive rate, 4-5; rate of reinfection, 90 year-1) suggest that the rate of reinfection is higher than for other helminth parasites of man. The control of morbidity and parasite transmission is discussed in the context of targeting drug treatment at the child segment of the study population.(AU)

Seroepidemiological study of the transmission of mumps virus in St. Lucia, West Indies

A seroepidemiological study of the prevalence of mumps virus specific antibodies reveals a pattern of endemic persistence on the island of St. Lucia in the West Indies. In the unvaccinated population the proportion seropositive rose rapidly in the child age classes to attain a stable plateau close to unity in value in the teenage and adult age groups. The average age at infection was estimated to be between 3 and 4 years of age and the average duration of detactable levels of maternally derived antibodies was approximately 3 months. Analyses based on mathematical models of the transmission dynamics of the virus suggest that in excess of 75 percent of each cohort of 1-to 2-year-old children must be effectively immunized to eliminate mumps virus transmission. A mumps radial haemolysis test, developed for quantitive measurements of antibody, is discussed. (AU)

Predisposition to Trichuris trichiura infection in humans

The study examines the distribution of Trichuris trichiura infection in a village community in St. Lucia, West Indies. The infection intensity of the same age-stratified population was assessed (by drug expelled worm burden and faecal egg count) at the intiation of the study, and after 17 months of reinfection following treatment. The frequency distribution of worm numbers per person was similar at both periods of sampling. There was a significant correlation between the initial infection intensity of an individual, and the intensity acquired by the same individual following the 17 month period of reinfection. This relationship was observed in a broad range of host age classes. The study provides firm evidence that individuals are predisposed to heavy (or light) T. trichiura infection. (Summary)

Population distribution of Trichuris trichiura in a community of Jamaican children

The trichuris trichiura worm burdens of 23 children in a Place-of-Safety in Kingston, Jamaica were assessed by stool collection for more than five days after treatment with mebendazole. This procedure was repeated after a seven-month period of natural reinfection. For both collections the maximum rate of worm expulsion was achieved on the fourth day after starting treatment. The worm populations were overdispersed and well described by the negative binomial probability model (k=0.29) in each case. For any one individual, the number of worms passed on the first expulsion was unrelated, absolutely or relatively, to the number passed on the second. These data suggest that: knowledge of the time dependency of helminth expulsion is essential for the accurate determination of worm burdens by this method; populations of Trichuris are more highly aggregated than those of Ascaris and thus may be more susceptible to control by selective rather than random chemotherapy; and the inherent predisposition of hosts to infection may be of minor importance in determining the distribution of worms in the population-heavily infected hosts appear no more or less likely to acquire large worm burdens on subsequent exposures. (AU)

Population dynamics and chemotherapeutic control of Trichuris trichiura infection of children in Jamaica and St. Lucia

Population dynamical parameters of Trichuris trichiura infections in children were estimated from longitudinal intensity and prevalence data from a population (n=23) in a children's home in Jamaica. The theoretical predictions of a deterministic model incorporating these parameters were approximated to observe horizontal-age prevalence data from a naturally infected population (n=203) of children in a St. Lucian village, and a rough estimate of the basic reproductive rate (Ro=8-10) of T. trichiura obtained. The findings suggest that T. trichiura populations are intrinsically more difficult to control by traditional mass-treatment chemotherapy (eradication requires >91 percent of the population to be treated every 6 months for >5 years) than are populations of Ascaris, but may be more susceptible to selective chemotherapy programmes which aim to treat only the most heavily infected individuals (AU)