Effect of site of lactate infusion on regional lactate exchange in pigs

Background The rate of extra-hepatic lactate production and the route of influx of lactate to the liver may influence both hepatic and extra-hepatic lactate exchange. We assessed the dose-response of hepatic and extra-hepatic lactate exchange during portal and central venous lactate infusion. Methods Eighteen pigs randomly received either portal (n=5) or central venous (n=7) lactate infusion or saline (n=6). Sodium lactate was infused at 33, 66, 99, and 133 µmol kg−1 min−1 for 20 min each. Systemic and regional abdominal blood flows and plasma lactate were measured at 20 min intervals until 1 h post-infusion, and regional lactate exchange was calculated (area under lactate uptake-time curve). Results Total hepatic lactate uptake [median (95% confidence interval)] during the experimental protocol (140 min) was higher during portal [8198 (5487-12 798) µmol kg−1] than during central venous lactate infusion [4530 (3903-5514) µmol kg−1, P<0.05]. At a similar hepatic lactate delivery (∼400 µmol kg−1 min−1), hepatic lactate uptake [mean and standard deviation (sd)] was higher during portal [118 (sd 55) µmol kg−1 min−1] than during central venous lactate infusion [44 (12) µmol kg−1 min−1, P<0.05]. Time courses of arterial lactate concentrations and lactate uptake at other measured regions were similar in both groups. Conclusions Higher hepatic lactate uptake during portal compared with central venous lactate infusion at a similar total hepatic lactate influx underlines the role of portal vein lactate concentration in total hepatic lactate uptake capacity. Arterial lactate concentration does not depend on the site of lactate infusion. At higher arterial lactate concentrations, all regions participated in lactate uptak

Photodynamische Therapie bei altersbedingter Makuladegeneration am schlechteren und besseren Auge

Zusammenfassung: Hintergrund: Die PDT ist die Standardbehandlung vieler Formen der exsudativen bzw. neovaskulären Makuladegeneration (AMD). Trotz Therapie fällt die Sehschärfe häufig in den Low-vision-Bereich ab. Die Kosteneffizienz der Therapie am schlechteren Auge wird daher kontrovers diskutiert. Patienten und Methoden: Retrospektive Fallkontrollstudie aller Patienten, welche zwischen September 1999 und November 2004 am Universitätsspital Zürich eine PDT erhalten haben. Die Situation bei Präsentation und der Verlauf unter Therapie wurden bei ersten (schlechteren) und zweiten (besseren) Augen verglichen. Ergebnisse: In 117/228Fällen (51,3%) war der Visus am behandelten Auge bei Präsentation besser (oder gleich) als der Visus am Partnerauge. Der Visus vor Behandlung betrug bei den besseren Augen im Mittel 0,58±0,27logMAR [Snellen: 0,26 (0,14-0,49)] und 0,69±0,4logMAR [Snellen 0,20 (0,08-0,51)] bei den schlechteren Augen (p=0,015). Nach Behandlung bestand zwischen den Gruppen weder bezüglich Visus bzw. Visusveränderung noch bezüglich Membrangröße bzw. Größenveränderung der Membran ein signifikanter Unterschied. Schlussfolgerung: Die Resultate nach PDT sind beim zweiten (bzw. besseren) Auge nicht signifikant besser als beim ersten (bzw. schlechteren) Aug

Response to ranibizumab therapy in neovascular AMD - an evaluation of good and bad responders

Background: Treatment of neovascular age-related macular degeneration (AMD) with Lucentis® shows a broad spectrum regarding the course of visual acuity (VA). While some patients show a good response (increase in VA), others disclose much less promising results. Patients and Methods: A retrospective data analysis of all eyes treated for neovascular AMD at the University Hospital of Zurich, Switzerland for at least 12 months was carried out. The courses of VA between the 90th (good responders, GR) and the 10th (bad responders, BR) percentiles were compared at 3, 12 and 24 months from baseline. An analysis regarding demographic data, lesion type and size as well as injection frequency and visits was done and predictive factors for GR and BR were evaluated. Results: Marked differences in the course of VA between GR (n = 30) and BR (n = 30) are already observed 3 months from baseline. In GR the gains in VA after 3, 12 and 24 were 15.7 ± 9 letters ETDRS, 25.3 ± 7 and 14.0 ± 14. BR showed a deterioration of 8.3 ± 11 letters ETDRS after 3, 22.1 ± 8 after 12 and 23.6 ± 13 after 24 months. The gender distribution was equal with a higher percentage of female patients (64 % in BR and 66 % in GR). The baseline VA was statistically significantly lower in GR (45.7 ± 10 vs. 55.4 ± 11, p < 0.05) than in BR. No other significant differences in baseline data were found, and no predictor for group membership could be identified. Conclusions: Only the course of VA in the first three months seems to be of value for an estimation of the response to treatment. In the future the response to treatment in the early phase may influence the treatment algorithm and the injection frequency

Constraints from orbital motions around the Earth of the environmental fifth-force hypothesis for the OPERA superluminal neutrino phenomenology

It has been recently suggested by Dvali and Vikman that the superluminal neutrino phenomenology of the OPERA experiment may be due to an environmental feature of the Earth, naturally yielding a long-range fifth force of gravitational origin whose coupling with the neutrino is set by the scale M_*, in units of reduced Planck mass. Its characteristic length lambda should not be smaller than one Earth's radius R_e, while its upper bound is expected to be slightly smaller than the Earth-Moon distance (60 R_e). We analytically work out some orbital effects of a Yukawa-type fifth force for a test particle moving in the modified field of a central body. Our results are quite general since they are not restricted to any particular size of lambda; moreover, they are valid for an arbitrary orbital configuration of the particle, i.e. for any value of its eccentricity $e$. We find that the dimensionless strength coupling parameter alpha is constrained to |alpha| <= 1 10^-10-4 10^-9 for 1 R_e <= lambda <= 10 R_e by the laser data of the Earth's artificial satellite LAGEOS II, corresponding to M_* >= 4 10^9 -1.6 10^10. The Moon perigee allows to obtain |alpha| <= 3 10^-11 for the Earth-Moon pair in the range 15 R_e <= lambda = 3 10^10 - 4.5 10^10. Our results are neither necessarily limited to the superluminal OPERA scenario nor to the Dvali-Vikman model, in which it is M_* = 10^-6 at lambda = 1 R_e, in contrast with our bounds: they generally extend to any theoretical scenario implying a fifth-force of Yukawa-type.Comment: LaTex2e, 18 pages, 4 figures, 1 table, 81 reference

The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.

PURPOSE: To characterize in detail the phenotype of five unrelated families with autosomal dominant bull's eye maculopathy (BEM) due to the R373C mutation in the PROM1 gene. METHODS: Forty-one individuals of five families of Caribbean (family A), British (families B, D, E), and Italian (family C) origin, segregating the R373C mutation in PROM1, were ascertained. Electrophysiological assessment, fundus autofluorescence (FAF) imaging, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT) were performed in available subjects. Mutation screening of PROM1 was performed. RESULTS: The R373C mutant was present heterozygously in all affected patients. The age at onset was variable and ranged between 9 and 58 years, with most of the individuals presenting with reading difficulties. Subjects commonly had a mild to moderate reduction in visual acuity except for members of family C who experienced markedly reduced central vision. The retinal phenotype was characterized by macular dystrophy, with retinal pigment epithelial mottling in younger subjects, progressing to typical BEM over time, with the development of macular atrophy in older patients. In addition, all members of family C had typical features of RP. The electrophysiological findings were variable both within and between families. CONCLUSIONS: Mutations in PROM1 have been described to cause a severe form of autosomal recessive RP in two families of Indian and Pakistani descent. The results of this study have demonstrated that a distinct redundant PROM1 mutation (R373C) can also produce an autosomal dominant, fully penetrant retinopathy, characterized by BEM with little inter- and intrafamilial variability, and retinal dystrophy with variable rod or rod-cone dysfunction and marked intra- and interfamilial variability, ranging from isolated maculopathy without generalized photoreceptor dysfunction to maculopathy associated with very severe rod-cone dysfunction

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30–120 min in duration, high values of mean power (MPVE) and slope (MSlopeVE) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89 %, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MPVE) and cardiac (MPLF HR) oscillations and cardiorespiratory coherence (MPLFCoher), but reduced ventilation entropy (SampEnVE), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.Peer ReviewedPostprint (author’s final draft

Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration

Purpose To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. Design Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). Methods Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. Results Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. Conclusions The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses

Energy, SBS symptoms, and productivity in Swiss open-space offices: Economic evaluation of standard, actual, and optimum scenarios

The fundamental aspiration of new-generation high-performing buildings is to reduce energy use while securing indoor environmental quality conducive to human health and productivity. However, existing frameworks for identifying Key Performance Indicators (KPIs) of buildings are sporadic and limited to a few parameters. Based on two Swiss open-space buildings, this paper demonstrates an economic comparison combining three KPIs: health (represented by sick building syndrome (SBS) symptoms), occupants' productivity (based on the thermal environment and ventilation), and operational energy for heating (based on building simulations using measured inputs). Monetization translated various criteria into the same unit currency and compared them on equal terms. Three scenarios for human- and energy-related performance analysis were actual (considering measured data), standard (using parameters from the national standard), and optimal (maximized productivity). The actual environment in case studies measured in the Fall and Winter seasons was relatively warm, with poor ventilation in one of the two buildings as no mechanical ventilation was on. Therefore, there was some loss of productivity (0.11-0.4%) and SBS symptoms (e.g., dry eyes, fatigue) present in both buildings resulting in up to 2 times the difference between the energy and human costs. The minimum energy costs for the standard scenario indicated that standard settings prioritize energy objectives. Oppositely, energy costs were the highest (47.6-69.6%) in the optimal scenario minimizing the human-related costs but not the weekly SBS symptoms. The analysis presented highlights the conflicting goals when one parameter is prioritized over another one, thus demonstrating the importance of a multi-criteria approach

Assessing Choroidal Nevi, Melanomas and Indeterminate Melanocytic Lesions Using Multimodal Imaging-A Retrospective Chart Review

Using multimodal imaging, the literature proposed the following risk factors for choroidal nevus growth into melanoma: increased tumor thickness, subretinal fluid, decreased visual acuity, presence of orange pigment, ultrasound acoustic hollowness, and increased tumor diameter. This study investigated the presence of the mentioned risk factors in choroidal nevi, choroidal melanomas, and indeterminate choroidal melanocytic lesions. This retrospective, single-center chart review assessed choroidal melanocytic tumors with multimodal imaging. We defined our primary outcome as the cumulative presence of mentioned risk factors. Further, we evaluated various optical coherence tomography (OCT), ultrasound, and autofluorescence findings. We analyzed 51 tumors from 49 patients during the period from April 2008 to June 2021. The median (IQR) age was 64.0 (56.0 to 70.5) years, with 23 of 49 (46.9%) patients being female. The follow-up time for all tumors was median (IQR) 25.0 (12.0 to 39.0) months. The choroidal nevi had a median (range) risk score of 0.0 (0.0 to 3.0), and the choroidal melanoma of 5.0 (3.0 to 6.0), with statistically significant different ratings (p &lt; 0.001). Multimodal imaging creates a score that may help to distinguish choroidal nevi from choroidal melanomas objectively

Real-World 5-Year Outcomes of Age-Related Macular Degeneration with Bevacizumab as First-Line Anti-VEGF

Introduction: To evaluate long-term outcomes of anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) in the Netherlands (NL), where bevacizumab is the mandated first-line drug, compared to high-income countries using ranibizumab or aflibercept as initial treatments. Methods: Five-year data from the Fight Retinal Blindness! (FRB) registry, a real-world prospective registry, were analyzed. Outcomes from 1473 Dutch eyes (1229 patients) treated with bevacizumab were compared with 7144 eyes (5884 patients) in a reference group (RG) from 13 socioeconomically similar countries. The primary outcome was mean visual acuity (VA) at yearly intervals; secondary outcomes included injection frequency and switching rates to alternative anti-VEGF agents. Results: Throughout the 60 months, mean VA was consistently higher in Dutch eyes (baseline: NL 60.2 vs. RG 59.2; 60 months: NL 64.9 vs. RG 62.6). The Dutch group cumulatively received 14.5 more injections over 5 years and had a higher rate of switching (70.9% vs. 50.9%) with a shorter median time to switching (11.9 months vs. 17.7 months). Conclusions: Patients treated in Dutch FRB! clinics have good long-term outcomes with a 2.3-letter higher mean VA at the 60-month timepoint compared to FRB! clinics in the RG. The Dutch patients, who began treatment with bevacizumab, received 14.5 more injections over 5 years and had a 40% higher rate of switching to an alternative drug, with switching occurring 5.8 months earlier. This study highlights the benefits of early and more intensive management to optimize visual outcomes, which appear more important than the choice and price of the first-line drug.</p