Total Cumulative Dose Research Articles

Cardiovascular variability and β-ARs gene expression at two stages of doxorubicin – Induced cardiomyopathy

Using comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac β-1 (β-1AR) and β-2 (β-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal. A 15 mg/kg total cumulative dose of doxorubicin was injected i.p. to rats to induce DCM or saline for control (n=18). Rats were assessed for general toxicity, cardiovascular hemodynamic and echocardiography before treatment (n=6), 35 days (DOX35; n=6) and 70 days (DOX70; n=6) post-treatment. HRV was evaluated by spectral analysis, Poincaré plots, sample and approximate entropy. Expression of β-1AR and β-2AR mRNA was evaluated by RT-qPCR. Doxorubicin-treated rats exhibited poor general condition and lower survival than saline-treated rats. In DOX35 rats, there were no echocardiography signs of decompensation, no increase in serum cardiac troponins, but there was an increase of HRV and decrease of HR complexity. In these rats typical microscopic signs of cardiotoxicity were seen along with over-expression of β-1AR mRNA. 70 days post-treatment echocardiography revealed signs of decompensation and serum cardiac troponin T was increased. At this stage BPV decreased. In conclusion, HRV increase matches transient over-expression of cardiac β-1AR mRNA in compensate stage of DCM while decompensate stage of DCM is characterized by a decrease of BPV and no changes in β-1AR and β-2AR gene expression.

Symptom-triggered therapy for assessment and management of alcohol withdrawal syndrome in the emergency department short-stay clinical decision unit

IntroductionWe previously reported that benzodiazepine detoxification for alcohol withdrawal using symptom-triggered therapy (STT) with oral diazepam reduced length of stay (LOS) and cumulative benzodiazepine dose by comparison with standard fixed-dose...

The consequences of overcoming the human skin barrier by siloxanes (silicones) Part 1. Penetration and permeation depth study of cyclic methyl siloxanes

Dynamic production of cyclic siloxanes: octamethylcyclotetrasiloxane D4, decamethylcyclopentasiloxane D5 and dodecamethylcyclohexasiloxane D6 increases their concentrations in environment. It is considered that both environmental pollution and the usage of personal care products and cosmetics containing cyclic siloxanes can be the main source of the human exposure by transdermal route.The aim of the study was to verify the possibility to overcome the skin barrier by cyclic siloxanes (ATR-FTIR and GC-FID), evaluation of diffusion pathway to stratum corneum SC (Fluorescence microscopy), and determination of depth of permeation to deeper skin layers: epidermis and dermis (ATR-FTIR) and also of potential interaction with SC lipids and proteins (Fluorescence microscopy, ATR-FTIR) and the cytotoxicity studies against HaCaT cells (MTT test).The results show that D4, D5 and D5 can penetrate to SC and permeate into the deeper layers of the skin: epidermis and dermis. The quantitative analysis (GC-FID) showed that total cumulative doses for D4, D5 and D6 were: 42.50; 95.37 and 77.19 μg/cm2/24 h, respectively. The microscopic analysis proved, transepidermal route through the lipid matrix as well as through the canyons (intercluster spaces) were a diffusion pathway to the SC as well as disruption of human SC lipid structure by: D4 (the most), D5 and D6 (the least). The cytotoxicity studies demonstrated that the tested range of concentrations of D5 and D6 (up to 300 mM, 111 300 mg and 133 500 mg respectively) did not impaired the HaCaT growth, while D4 had IC50 value of 40 098 mM ± 7.94 (10 906 ± 872,5 mg).

Effects of Gamma Radiation on Resonant and Antiresonant Characteristics of Piezoelectric Wafer Active Sensors

This paper presents gamma radiation effects on resonant and antiresonant characteristics of piezoelectric wafer active sensors (PWAS) for structural health monitoring (SHM) applications to nuclear-spent fuel storage facilities. The irradiation test was done in a Co-60 gamma irradiator. Lead zirconate titanate (PZT) and Gallium Orthophosphate (GaPO4) PWAS transducers were exposed to 225 kGy gamma radiation dose. First, 2 kGy of total radiation dose was achieved with slower radiation rate at 0.1 kGy/h for 20; h then the remaining radiation dose was achieved with accelerated radiation rate at 1.233 kGy/h for 192 h. The total cumulative radiation dose of 225 kGy is equivalent to 256 years of operation in nuclear-spent fuel storage facilities. Electro-mechanical impedance and admittance (EMIA) signatures were measured after each gamma radiation exposure. Radiation-dependent logarithmic sensitivity of PZT-PWAS in-plane and thickness modes resonance frequency (∂(fR)/∂( logeRd)) was estimated as 0.244 kHz and 7.44 kHz, respectively; the logarithmic sensitivity of GaPO4-PWAS in-plane and thickness modes resonance frequency was estimated as 0.0629 kHz and 2.454 kHz, respectively. Therefore, GaPO4-PWAS EMIA spectra show more gamma radiation endurance than PZT-PWAS. Scanning electron microscope (SEM) and X-ray diffraction method (XRD) was used to investigate the microstructure and crystal structure of PWAS transducers. From SEM and XRD results, it can be inferred that there is no significant variation in the morphology, the crystal structure, and grain size before and after the irradiation exposure.

Timing of post-resistance exercise nutrient ingestion: effects on gastric emptying and glucose and amino acid responses in humans.

This study examined the effects of post-resistance exercise protein ingestion timing on the rate of gastric emptying (GE) and blood glucose (BG) and plasma branched-chain amino acid (BCAA) responses. In all, eleven healthy participants randomly ingested 400 ml of a nutrient-rich drink containing 12 g carbohydrates and 20 g protein at rest (Con), at 5 min (post-exercise (PE)-5) or at 30 min (PE-30) after a single bout of strenuous resistance exercises. The first and second sets comprised ten repetitions at 50 % of each participant's one-repetition maximum (1RM). The third, fourth and fifth sets comprised ten repetitions at 75 % of 1RM, and the sixth set involved repeated repetitions until exhaustion. Following ingestion of the nutrient-rich drink, we assessed the GE rate using 13C-sodium acetate breath test and evaluated two parameters according to the T max-calc (time when the recovery per hour is maximised), which is a standard analytical method, and T 1/2 (time when the total cumulative dose of [13CO2] reaches one-half). T max-calc and T 1/2 were slower for the PE-5 condition than for either the PE-30 or Con condition (T max-calc; Con: 53 (sd 7) min, PE-5: 83 (sd 16) min, PE-30: 62 (sd 9) min, T 1/2; Con: 91 (sd 7) min, PE-5: 113 (sd 21) min, PE-30: 91 (sd 11) min, P<0·05). BG and BCAA responses were also slower for the PE-5 condition than for either the PE-30 or Con condition. Ingesting nutrients immediately after strenuous resistance exercise acutely delayed GE, which affected BG and plasma BCAA levels in blood circulation.

Radiation-tolerance analysis of I-gate n-MOSFET according to isolation oxide module in the CMOS bulk process

The n-type metal-oxide-semiconductor field-effect transistor (n-MOSFET) produced in the widely used CMOS bulk process takes radiation damage by the total ionizing dose (TID) effects in radiation environments, so the radiation-tolerant properties of semiconductor integrated-circuits (ICs) used in high-radiation environments is a critical issue. The formation method of the isolation oxide module (IOM), which induces the radiation-induced leakage currents, differs depending on the chip density of the CMOS bulk process. In this paper, we designed and fabricated I-gate n-MOSFETs for bulk process and analyzed the radiation-tolerant characteristics according to IOM. The I-gate n-MOSFET chips are fabricated using the shallow trench isolation (STI) 0.18um and local oxidation of silicon (LOCOS) 0.35um processes of the CMOS bulk process. Tests and evaluation of the TID effects on the chips are carried out by irradiating a total cumulative dose up to 2 Mrad(Si). As the results, in the standard n-MOSFET, the leakage currents of the LOCOS and STI processes are 27.7uA and 16.4uA, and in I-gate n-MOSEFT, are 1.1uA and 0.7uA. The leakage currents of standard n-MOSFET increased by about 25 times before and after irradiation, but the electric characteristics of I-gate n-MOSFET is maintained regardless of the process. Therefore, the process versatility of the I-gate n-MOSFET with the radiation-tolerant performance has been verified.

Treatment-Related Radiation Toxicity Among Cervical Cancer Patients.

The purpose of this study is to identify incidence of and factors associated with severe late toxicity in women treated with radiation for cervical cancer. All patients with cervical cancer treated with radiation as primary or adjuvant therapy from 2005 to 2017 in a single academic institution were included. Records were reviewed for demographic information, Charlson Comorbidity Index, treatment details, toxicities, and outcomes. Patients with and those without severe late gastrointestinal toxicity (SLGIT), severe late genitourinary toxicity (SLGUT), or any SLGIT or SLGUT, defined as any toxicity (AT), were compared. Overall survival and progression-free survival were also compared. Of 179 patients identified, 21.2% had AT, 17.3% had SLGIT, and 10% had SLGUT. Estimated AT rate at 3 years was 24.2%. The mean duration of follow-up was 37 months (range, 3-146 months). Most patients (84.1%) received 3-dimensional conformal therapy, and 15.9% received intensity-modulated radiation therapy. Factors associated with AT were lower body mass index (24.9 vs 28.3, P = 0.043), white race (63.2% vs 44%, P = 0.035), and active tobacco smoking during treatment (59.5% vs 40.2%, P = 0.036). Any toxicity was not associated with 3-dimensional versus intensity-modulated radiation therapy planning, low-dose versus high-dose-rate brachytherapy or time to complete radiation treatment. Higher total cumulative radiation dose to clinical target volume was associated with SLGIT. Progression-free survival and overall survival were similar among patients with AT compared to those without toxicity. In patients with cervical cancer, radiation toxicity is correlated with lower body mass index, white race, and smoking. Despite technologic advances in radiotherapy planning and delivery, toxicity remains high and interventions to reduce the burden of treatment are needed.

Optical coherence tomography angiography for screening of hydroxychloroquine-induced retinal alterations.

The purpose of the study was to evaluate the retinal and choroidal changes via optical coherence tomography angiography (OCTA) in patients who received hydroxychloroquine (HCQ). Sixty eyes of 60 female patients who received HCQ were included in the study. Patients were categorized into two groups as high-risk (≥ 5years) and low-risk (< 5years) in terms of HCQ-induced retinal toxicity. Spectral domain-OCT, OCTA, and visual field tests were performed. Retinal thickness, vascular density, flow rates, choroidal thickness (CT), and visual field parameters were compared between the groups, and the correlation between total HCQ cumulative dose, duration of use, and these parameters was assessed. Compared to low-risk group, patients in the high-risk group had vascular density loss (p < 0.05). In this group, foveal avascular zone (FAZ) was found to be wider (p < 0.05). Retinal and choroidal flow rates were found to be decreased markedly in the high-risk group (p < 0.05). CT was found to be thinner in the high-risk group (p < 0.05). HCQ cumulative dose and duration of use had a negative significant correlation with all vascular density, flow rate, CT parameters, and positive significant correlation with FAZ parameters (p < 0.05). In visual field tests, mean defect (MD) was found to be increased in the high-risk group (p < 0.05). Moreover, MD had a positive correlation with HCQ cumulative dose and duration of use (p < 0.05). Evaluation of microvascular changes via OCTA may contribute to the early detection of HCQ-induced retinal toxicity, which cannot be detected through other imaging devices, at the stage when it is reversible.

Prise en charge des patients porteurs de stimulateurs cardiaques ou défibrillateurs automatiques implantables traités par irradiation

An increasing number of patients with cardiac implantable electronic devices benefit from radiotherapy, warranting specific collaborative management between both radiation oncologists and cardiologists. Interactions between electromagnetic fields, secondary particles and cardiac implantable electronic devices may result in transient and reversible malfunctions with significant consequences depending on the underlying cardiac pathology and the level of patient's cardiac implantable electronic devices dependency. Numerous international guidelines on patients’ management have been proposed and all agree on a total cumulated dose limit at the battery of 5Gy and on the need for an initial as well as repeated evaluation over time, up to 6months after the last radiation. The analysis of the published data revealed relatively rare incidence of significant adverse events. The most recent international guidelines underline the feasibility and safety of radiotherapy for cardiac implantable electronic devices holders, with the need for systematic local protocol in all radiotherapy centers.

Symptomatic osteonecrosis as a treatment complication in Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG).

The majority of patients with Hodgkin Lymphoma (HL) can be cured with stage and risk adapted treatment today. Therefore, current research focuses on reducing long-term sequelae of treatment. Osteonecrosis (ON) is a severe long-term complication of HL treatment which has so far not been systematically evaluated. Hence, we investigated incidence, risk factors and timing of symptomatic ON in HL patients. Further endpoints included localization, intervention and outcome of ON. We included all qualified HL patients of the randomized German Hodgkin Study Group trials HD10-15 and HD18, recruited between 05/1998 and 07/2014 and aged from 16 to 60 years. Among 11 330 patients, 66 developed symptomatic ON after first-line treatment, 83.3% within three years. The incidence of symptomatic ON was 0.2% in early-stage HL and 1.0% in advanced-stage HL. Logistic regression revealed the total cumulative corticosteroid dose to be a strong risk factor interacting with younger age. Male sex additionally increased the risk of symptomatic ON. The prognostic value of the corresponding logistic regression model was rather high (AUC = 0.78). Other tested potential risk factors including obesity, IPS and radiotherapy did not further increase the risk of ON. Further development of current treatment protocols should aim to reduce the cumulative corticosteroid dose.

A facility for the study of Single Event Effects in the TANDAR accelerator

Abstract Semiconductor devices used in space applications suffer degradation due to the space radiation environment, which affects their electric parameters, eventually reducing the in-orbit lifetime. This relatively slow behavior is due to cumulative total dose effects. On the other hand, radiation can destroy information or even damage electronic parts of the device in a sudden way. These processes are known as Single Event Effects (SEE). Heavy ion beams from electrostatic tandem or other accelerators can be used to test and characterize the response of the electronics to SEE. Two conditions are necessary for this purpose: to use very low fluxes of only a few hundred to hundreds of thousand particles/(cm2·s), and to browse over a wide Linear Energy Transfer (LET) interval by changing the energy and/or the type of the impinging particles. In this work we describe the facility developed at the Argentine tandem accelerator (Tandar) to study SEE, and especially the fabrication and use of a perforated Ta foil to reduce the beam current to the required values. The determination of the resulting beam uniformity over the area of irradiation is also reported. The system has been tested by a SEE experiment on a webcam sensor.

Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants.

We determined the influence of cumulative dosing of caffeine citrate on the neurodevelopmental outcomes of low birth weight (VLBW) infants at 18-22 months of postmenstrual age. This retrospective chart analysis was conducted at Detroit Medical Center, Michigan, USA. The 181 infants we included were born between January 2006 and December 2016, were less than 32 weeks of gestational age and weighed less than 1500 grams. Data on their perinatal and postnatal characteristics were retrieved from their medical records and they were assessed using the Bayley Scales of Infant Development - Third Edition. The 64 infants with no neurodevelopmental disability or a mild disability received a significantly higher average daily dose (mg/kg/day) of caffeine citrate with a median of 7.58 (range 2.7-12.2) mg/kg/day, than the 79 infants with a moderate to severe disability, who received a median of 6.47 (range 3.1-12.5, p = 0.01). The total cumulative dose had no effect on bronchopulmonary dysplasia or neurodevelopmental outcomes. A higher average daily dose of caffeine citrate was associated with better neurodevelopmental outcomes of VLBW infants. However, the cumulative dose did not have an impact on their short-term or long-term outcomes. Further research is needed to confirm our findings.

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity.

Purpose To determine whether treatment affects MRI signal intensity in pediatric patients with primary brain tumors independent of the administration of macrocyclic gadolinium-based contrast agents (GBCAs). Materials and Methods This retrospective, single-center study included 78 patients (mean age, 7.7 years ± 5.4) with primary brain tumors who underwent macrocyclic GBCA-enhanced MRI from 2015 to 2018. Three groups were compared: (a) patients who had undergone radiation therapy (37 patients, 26 of whom had undergone concurrent chemotherapy), (b) patients who had undergone chemotherapy only (17 patients), and (c) patients who had received no treatment ("no-treatment group," 24 patients). The signal intensity in the globus pallidus (GP), thalamus, dentate nucleus (DN), and pons was measured on unenhanced T1-weighted images. GP-to-thalamus and DN-to-pons signal intensity ratios were compared among groups with analysis of variance by using the Kruskal-Wallis test, followed by post hoc pairwise tests with Tukey adjustment, and were analyzed relative to group, total cumulative doses of GBCA, age, and sex with multivariable linear models. Results The mean number of GBCA-enhanced MRI examinations in the radiation therapy, chemotherapy-only, and no-treatment groups was 7.11, 7.29, and 4.96, respectively (P < .01 for the radiation therapy and chemotherapy groups compared with the no-treatment group). The DN-to-pons ratio in the radiation therapy group was higher than that in both the no-treatment group and the chemotherapy-only group (P < .01 for both). There was no significant difference in the DN-to-pons ratios between the chemotherapy-only group and the no-treatment group (P = .99). The GP-to-thalamus ratios did not differ among all three groups (P = .09). There was no dose-dependent effect of GBCA on the DN-to-pons and GP-to-thalamus ratios when adjusting for the effects of treatment (P = .21 and P = .38, respectively). Conclusion Brain irradiation contributes to a higher dentate nucleus signal intensity in pediatric patients with brain tumor independent of the administration of macrocyclic gadolinium-based contrast agents. © RSNA, 2018.

Radiation-induced changes in the optical properties of NaMgF3(Sm): Observation of resettable Sm radio-photoluminescence

Stable radio-photoluminescence (RPL) is observed in NaMgF3(Sm) after X-ray irradiation due to valence conversion of Sm3+ to Sm2+. This valence conversion can be reversed by deep UV (254 nm) illumination. It is likely that this reversible process occurs via defects near some of the Sm3+ sites that act as hole traps. The ratio of the Sm2+/Sm3+ RPL emissions follows an exponential-type curve dependence on X-ray dose where the ratio saturates above ∼500 Gy. Optically stimulated luminescence (OSL) is also observed but only from Sm3+ and primarily from electrons trapped at F-centers. The OSL response is demonstrated to be linear up to 100 Gy. Thus, NaMgF3(Sm) has potential as a dosimeter where individual irradiations can be monitored via OSL and the total cumulative dose via non-destructive RPL readout. The RPL can be optically reset when required.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Biochemical bone markers in children with steroid sensitive nephrotic syndrome in remission

Background: Glucocorticoids, the recommended first line treatment of steroid sensitive nephrotic syndrome (SSNS), are notorious for causing osteoporosis. There are very few studies from tropical countries looking at the lasting effects of a short course of glucocorticoids in SSNS. The objective is to study the effect of glucocorticoids and its dose on Vitamin D levels and biochemical markers of calcium metabolism in children with SSNS and to formulate a criterion to administer prophylactic calcium and vitamin D supplementation to such patients.Methods: A cross-sectional case-control study was conducted on 30 children with SSNS in remission and 30 healthy controls. Serum levels of 25 hydroxycholecalciferol [25(OH)D], calcium, phosphorous, albumin, alkaline phosphatase (ALP) and intact parathyroid (PTH) were measured. Total glucocorticoid exposure during the illness was summarized.Results: Children with SSNS had significantly lower height [median-100.00 (interquartile range {IQR}- 14.5) vs. controls [115.50 (17.5)] cm; P= 0.0003. Serum ALP levels was significantly higher in the cases [median 264 (IQR-80.7)] IU/L vs. controls [median 234 (IQR- 132)] IU/L; P= 0.028. Though hypovitaminosis D was universal in the study cohort; children with SSNS had worse Vitamin D status (76.7%) than healthy controls (50%). Levels of serum calcium, phosphorous, vitamin D and PTH were not significantly different between the two groups, nor were they related to total cumulative dose of steroid. Vitamin D levels showed no significant co-relation with number of relapses, age, calcium, phosphate, ALP, or PTH levels.Conclusions: Children with SSNS may benefit from routine measurement of 25 (OH) D and prophylactic supplementation with calcium and Vitamin D.

Abstract P-478: DEXMEDETOMIDINE AND IATROGENIC WITHDRAWAL SYNDROME IN CRITICALLY ILL CHILDREN

Aims & Objectives: Many children whom require invasive mechanical ventilation need sedation in order to tolerate the associated discomfort. Classically opioids and benzodiazepines are used, however, these drugs may lead to Iatrogenic Withdrawal Syndrome (IWS), when stopped. Up to a third of all children admitted to the Pediatric Intensive Care Unit are at risk for IWS. When a proper level of sedation cannot be reached, dexmedetomidine is added to the drug therapy. We performed a review of the literature to study whether additional dexmedetomidine influences the risk of IWS in critically ill children. Methods Search of PubMed, Cochrane and CINAHL. No limits were applied. The articles were selected on title, abstract and full text according predefined inclusions and exclusion criteria. We assessed study quality and extracted data using tools of the Cochrane Collaboration. Results Twelve studies were included in our review. A systematic review found no eligible studies in critically ill children. Other relevant articles we found had a high risk of bias and did not show a clear effect on the risk of IWS. Another review showed a potential beneficial effect of dexmedetomidine in the treatment of IWS, but included studies were very small. One study showed a significant correlation between the increase of IWS in critically ill children and (a)total cumulative dosage dexmedetomidine (p=0.039) and (b)total duration of dexmedetomidine (p=0.037). Conclusions There is a lack of high quality evidence on the influence of dexmedetomidine on the risk of IWS in critically ill children.

Epinephrine administration in non-shockable out-of-hospital cardiac arrest

BackgroundEpinephrine is recommended for the treatment of non-shockable out of hospital cardiac arrest (OHCA) to obtain return of spontaneous circulation (ROSC). Epinephrine efficiency and safety remain under debate. ObjectiveWe propose to describe the association between the cumulative dose of epinephrine and the failure of ROSC during the first 30 min of advanced life support (ALS). MethodologyA retrospective observational cohort study using the Paris SAMU 75 registry including all non-traumatic OHCA. All OHCA receiving epinephrine during the first 30 min of ALS were enrolled. Cumulative epinephrine dose given during ALS to ROSC was retrieved from medical reports. ResultsAmong 1532 patients with OHCA, 776 (51%) had initial non-shockable rhythm. Fifty-four patients were excluded for missing data.The mean value of cumulative dose of epinephrine was 10 ± 4 mg in patients who failed to achieve ROSC (ROSC−) and 4 ± 3 mg (p = 0.04) for those who achieved ROSC.ROC curve analysis indicated a cut-off point of 7 mg total cumulative epinephrine associated with ROSC− (AUC = 0.89 [0.86–0.92]).Using propensity score analysis including age, sex and no-flow duration, association with ROSC− only remained significant for epinephrine > 7 mg (p ≤10–3, OR [CI95] = 1.53 [1.42–1.65]). ConclusionAn association between total cumulative epinephrine dose administered during OHCA resuscitation and ROSC− was reported with a threshold of 7 mg, best identifying patients with refractory OHCA. We suggest using this threshold in this context to guide the termination of ALS and early decide on the implementation of extracorporeal life support or organ harvesting in the first 30 min of ALS.

UVA-1 phototherapy for the management of atopic dermatitis: a large retrospective study conducted in a low-middle income country.

Medium-dose ultraviolet light A - 1 (UVA-1) phototherapy, given in short courses, has shown efficacy in atopic dermatitis flares; little is known about its use, efficacy, and side effects in prolonged exposure used in the chronic disease despite its extensive use. A descriptive retrospective study was conducted; convenience sampling of patients with atopic dermatitis treated with UVA-1 phototherapy was made; evaluation of clinical response by SCORAD, adverse effects, and protocols used in each patient were evaluated. Patients exposed to UVA-1 phototherapy showed a decrease in the SCORAD (30.1 points) - total cumulative dose-dependent (P<0.0001) - regardless of multiple variables studied. There were low rates of relapse and adverse effects. The most frequent doses were 30 and 60J/cm2 , three times per week; patients had similar clinical responses and adverse effects in these groups independent of the other variables studied (P=0.057). UVA-1 phototherapy can be an alternative for patients with severe atopic dermatitis even at lower doses than those described in other series (30J/cm2 ) and not only for acute flares. Cumulative total dose is a variable that affects the clinical response directly. Large prospective studies are needed.

Genesis of Antibiotic Resistance (AR) XXXIX: Universal Implementation of Simplified Acute Physiology Score (SAPS‐II) score inclusive of AR as an effective prognostic indicator of mortality in Traumatic Brain Injury (TBI) induced Coma

Based on an appraisal of the criteria required for deriving the SAPS‐II scores reinforced by statistical significance, a rationale is presented to include factors determining AR, thus enable the clinical decision making to withdraw life support in TBI subsequent to coma (Glasgow Coma Scale (GCS) ranging from a Severe: GCS 3–8; Moderate: GCS 9–12; Mild: GCS 13–15). The SAPS‐II is a severity score and mortality estimation tool developed from a large sample of medical and surgical patients in North America and Europe. The SAPS II includes 17 variables of which 12 physiological variables, age, types of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Within the first 24 hours of admission to Intensive Care Unit (ICU), following factors which determine AR, are suggested to be included: a. performing a culture and sensitivity lab test on the patient's Cerebrospinal fluid (CSF), b. generating an Antibiograms (Antimicrobial Susceptibilities of Selected Pathogens), c. implementation of antibiotics timeout (ATO), and also d. performing antibiotic prophylaxis in case of surgical intervention in TBI is essential for an acceptable neurological outcome. In the event of using the External ventricular device (EVD) for monitoring intracranial pressure (ICP), it is pivotal to monitor the infection of central nervous system (CNS). Acinetobacter baumannii is a known risk factor as a nosocomial infectious agent and associated with high mortality ranging from 15% to 71%. (J Neurosci Rural Pract 2016;7:450–2). Data shows that continuation of antibiotic therapy in TBI with scheduled surgical, or unscheduled surgical cases, are determined based on the detection of AR pathogens causing sepsis. If the patient had antibiotic resistance pathogen including (Colistin resistance) septicemia (Sepsis (Blood Infection) and Septic Shock (J. Neurotrauma 2007;24 Suppl 1: S45–54; Lancet Infect Dis 2009;9:245–55; Infection 2014;42:801–9) a poor neurological outcome is likely. Colistimethate sodium (CMS) as primary or salvage therapy for multi‐drug resistant (MDR) Gram‐negative organisms are known to cause nephrotoxicity, and neurotoxicity in critically ill patients (Ann Intensive Care. 2011; 1:14). Detection of Colistin resistant pathogens in a TBI patient is a reflection of impending septicemia, nephrotoxicity and/or renal failure (associated with poor neurological outcome. Though renal failure depends on the total cumulative dose and duration of Colistin therapy, the severity of TBI, factors such as AR, age, are at a higher risk for nephrotoxicity, possibly a higher rate of mortality. In essence, it is suggested that inclusion of factors causing AR, and SAPS‐II scores ranging from 77 to &gt;80 points would be a determining factor in the clinical decision to withdraw life support in TBI patients in ICU by forestalling an irreversible coma. In the event of the patient (TBI) with Moderate: GCS 9–12; to Mild: GCS 13–15, measures to mitigate AR would plausibly increase acceptable neurological outcome with a possibility of recovery (Lancet.1974 Jul 13; 2(7872):81–4); J Trauma Acute Care Surg. 2015 Oct; 79(4 Suppl 2): S197–203Support or Funding InformationSupported by the Professional Development Funds by SWTJC to Subburaj Kannan.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.