To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory ...flows in endotoxic shock.
Animal experimental study.
University translational research laboratory.
Fifteen Landrace pigs.
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
Hypotension was significantly shorter in i-NE group (7.5 min 5.5-22.0 min vs 49.3 min 29.5-60.0 min; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
Introducción: El objetivo de este estudio fue comparar la tasa de hernia incisional (HI) tras la extracción de piezas operatorias por mini-laparatomia media periumbilical (MM) versus mini-laparotomía ...transversa suprapúbica (MTS) en cirugía laparoscópica por cáncer colorrectal (CLCC), y evaluar factores asociados. Material y método: Estudio de cohorte no concurrente de pacientes consecutivos sometidos a CLCC en nuestro centro entre septiembre 2006 y diciembre 2017, cuya pieza operatoria fuese extraída por MM o MTS y contaran con un control tomográfico en el seguimiento. El diagnóstico de HI se realizó mediante tomografía computada. Se evaluaron tasas de HI según sitio de extracción y se realizó regresión logística para identificar factores asociados. Resultados: Se identificaron 1090. 254 cumplieron los criterios de inclusión. La edad media fue 63 años (53,5% son hombres) e IMC de 26,4 kg/m2. El sitio de extracción fue MTS en 53,1% y MM en 46,9%. Se identificó un total de 41 (34,5%) HI en el grupo de MM versus 17 (12,6%) en MTS (p=0,001) en TAC de seguimiento realizado en una mediana de 18 meses (RIC 12-32) postoperatorios. En la regresión logística, la MM (OR = 3,33, IC 95% 1,72-7,14, p<0,001) y la presencia de patología bronquial obstructiva se asociaron de manera independiente con HI (OR = 3,45, IC 95% 1,11-11,11, p= 0,03). Conclusión: La MTS se asocia a menor tasa de HI que la MM en pacientes sometidos a CLCC. Esto se debe tener en consideración al momento de elegir el sitio de extracción de pieza operatoria en CLCC.
Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk ...factor for osteoporosis and fracture. We determined serum levels of 25‐hydroxyvitamin D 25(OH)D, intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X‐ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency 25(OH)D ≤ 15 ng/ml was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 ± 5.3 ng/ml vs. 21.8 ± 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio OR, 4.17, 1.83‐9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.
Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific ...therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD.
We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7–16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (<9 years vs ≥9 years), duration of previous corticosteroid use (6 months to <12 months vs ≥12 months), and baseline 6MWD (<350 m vs ≥350 m). Patients, parents and caregivers, investigational site personnel, PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487.
Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was −47·7 m (SE 9·3) for ataluren-treated patients and −60·7 m (9·3) for placebo-treated patients (difference 13·0 m SE 10·4, 95% CI −7·4 to 33·4; p=0·213). The least-squares mean change for ataluren versus placebo in the prespecified subgroups was −7·7 m (SE 24·1, 95% CI −54·9 to 39·5; p=0·749) in the group with a 6MWD of less than 300 m, 42·9 m (15·9, 11·8–74·0; p=0·007) in the group with a 6MWD of 300 m or more to less than 400 m, and −9·5 m (17·2, −43·2 to 24·2; p=0·580) in the group with a 6MWD of 400 m or more. Ataluren was generally well tolerated and most treatment-emergent adverse events were mild to moderate in severity. Eight (3%) patients (n=4 per group) reported serious adverse events; all except one event in the placebo group (abnormal hepatic function deemed possibly related to treatment) were deemed unrelated to treatment.
Change in 6MWD did not differ significantly between patients in the ataluren group and those in the placebo group, neither in the intention-to-treat population nor in the prespecified subgroups with a baseline 6MWD of less than 300 m or 400 m or more. However, we recorded a significant effect of ataluren in the prespecified subgroup of patients with a baseline 6MWD of 300 m or more to less than 400 m. Baseline 6MWD values within this range were associated with a more predictable rate of decline over 1 year; this finding has implications for the design of future DMD trials with the 6-minute walk test as the endpoint.
PTC Therapeutics.
Third Universal Definition of Myocardial Infarction Thygesen, Kristian; Alpert, Joseph S; Jaffe, Allan S ...
Journal of the American College of Cardiology,
10/2012, Letnik:
60, Številka:
16
Journal Article, Conference Proceeding, Web Resource
Recenzirano
Odprti dostop
.1595 Abbreviations and acronyms ACCF = American College of Cardiology Foundation ACS = acute coronary syndrome AHA = American Heart Association CAD = coronary artery disease CABG = coronary artery ...bypass grafting CKMB = creatine kinase MB isoform cTn = cardiac troponin CT = computed tomography CV = coefficient of variation ECG = electrocardiogram ESC = European Society of Cardiology FDG = fluorodeoxyglucose h = hour(s) HF = heart failure LBBB = left bundle branch block LV = left ventricle LVH = left ventricular hypertrophy MI = myocardial infarction mlBG = meta-iodo-benzylguanidine min = minute(s) MONICA = Multinational MONItoring of trends and determinants in CArdiovascular disease MPS = myocardial perfusion scintigraphy MRI = magnetic resonance imaging mV = millivolt(s) ng/L = nanogram(s) per liter Non-Q Ml = non-Q wave myocardial infarction NSTEMI = non-ST-elevation myocardial infarction PCI = percutaneous coronary intervention PET = positron emission tomography pg/mL = pictogram(s) per milliliter Q wave Ml = Q wave myocardial infarction RBBB = right bundle branch block sec = second(s) SPECT = single photon emission computed tomography STEMI = ST elevation myocardial infarction ST-T = ST-segment -T wave URL = upper reference limit WHF = World Heart Federation WHO = World Health Organization Introduction Myocardial infarction (MI) can be recognized by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. Additionally, the management of patients with MI has significantly improved, resulting in less myocardial injury and necrosis, in spite of a similar clinical presentation. ...it appears necessary to distinguish the various conditions which may cause MI, such as 'spontaneous' and 'procedure-related' MI. ...physicians, other healthcare providers and patients require an up-to-date definition of MI.
Changes in the Health Status of Women During and After Pregnancy Haas, Jennifer S.; Jackson, Rebecca A.; Fuentes‐Afflick, Elena ...
Journal of general internal medicine : JGIM,
January 2005, 2005, 2005-Jan, 2005-1-00, 20050101, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Objective: To characterize the changes in health status experienced by a multi‐ethnic cohort of women during and after pregnancy.
Design: Observational cohort.
Setting/Participants: Pregnant women ...from 1 of 6 sites in the San Francisco area (N=1,809).
Measurements and Main Results: Women who agreed to participate were asked to complete a series of telephone surveys that ascertained health status as well as demographic and medical factors. Substantial changes in health status occurred over the course of pregnancy. For example, physical function declined, from a mean score of 95.2 prior to pregnancy to 58.1 during the third trimester (0–100 scale, where 100 represents better health), and improved during the postpartum period (mean score, 90.7). The prevalence of depressive symptoms rose from 11.7% prior to pregnancy to 25.2% during the third trimester, and then declined to 14.2% during the postpartum period. Insufficient money for food or housing and lack of exercise were associated with poor health status before, during, and after pregnancy.
Conclusions: Women experience substantial changes in health status during and after pregnancy. These data should guide the expectations of women, their health care providers, and public policy.
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to ...enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units BU) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
To study the relationships among prepregnancy body mass index (BMI), women's target gestational weight gain, and provider weight gain advice.
Project WISH, the acronym for Women and Infants Starting ...Healthy, is a longitudinal cohort study of pregnant women in the San Francisco Bay area. We excluded subjects with preterm birth, multiple gestation, or maternal diabetes.
Among overweight women (prepregnancy BMI 26.1-29.0), 24.1% reported a target weight gain above the Institute of Medicine (IOM) guidelines, compared with 4.3% of normal weight women (P < .001). Among women with a low prepregnancy BMI (< 19.8), 51.2% reported a target weight gain below the guidelines, compared with 10.4% of normal weight women (P < .001). These patterns persisted in a multivariate analysis. Latina ethnicity, lower maternal education, low prepregnancy BMI (< 19.8), lack of provider advice about weight gain, and provider advice to gain below guidelines were all independently associated with a target weight gain below IOM guidelines. Prepregnancy BMI more than 26, multiparity, lower age, and provider advice to gain above guidelines were all associated with a target gain above IOM guidelines.
Women's beliefs about the proper amount of weight gain and provider recommendations for weight gain vary significantly by maternal prepregnancy BMI. Many women report incorrect advice about gestational weight gain, and women with high or low prepregnancy BMI are more likely to have an incorrect target weight gain. New approaches to provider education are needed to implement the IOM guidelines for gestational weight gain.
Obesity is defined as abnormal or excessive body fat accumulation that may have negative effects on health. Healthy diet induces a balance of gut microbiota, helping in turn to combat this metabolic ...disorder. Amaranth is well known because of its beneficial properties on health, but its effects on microbiota profile are still unknown. The aim of this study was to analyse the changes of gut microbiota in diet-induced obese mice due to amaranth protein consumption and to compare them with the changes due to soybean protein intake. Male C57BL/6 mice were fed for 8 weeks with regular (RD) or high-fat (HF) diet, without or with complementation with amaranth or soybean protein isolates. Morphological changes in caecum ultrathin sections were measured after hematoxylin/eosin staining. Microbiota was isolated from the caecum and 16S rRNA gene was sequenced. Caecal Short Chain Fatty Acids (SCFAs) were quantified by gas chromatography. The consumption of soybean protein induced the ectopic deposition of fat in the whole intestine while amaranth proteins increased caecal crypt depth and calceiform cells number sustaining its beneficial effect on health. The count of Ruminococcacea family bacteria was increased in mice fed with HF diet, but amaranth proteins intake reduced its abundance. In turn, Lachnospiraceae bacteria abundance decreased in mice fed the Control-HF and amaranth HF diets, but increased in mice fed the soybean diets. In mice fed the RD diets, amaranth induced the abundance of Prevotellaceae, an acetate-producing bacteria. Study results indicate that the modulation of caecal microbiota could be one of the mechanisms by which amaranth exerts its beneficial effects on health.
PDF
