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Concept: 3rd millennium


Background Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Methods Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. Results The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Conclusions Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE number, NCT01467466 .).

Concepts: Renal failure, Kidney, Nephrology, Renal physiology, Sodium chloride, Placebo, 3rd millennium, 25th century


Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61-0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24-1.05], P = 0.079).

Concepts: Blood, Intensive care medicine, Renal physiology, Starch, Septic shock, Hypovolemia, Blood transfusion, 3rd millennium


BACKGROUND: Energy intake is a key determinant of weight. OBJECTIVE: Our objective was to examine trends in energy intake in adults in the United States from 1971-1975 to 2009-2010. DESIGN: The study was a trend analysis of 9 national surveys in the United States that included data from 63,761 adults aged 20-74 y. RESULTS: Adjusted mean energy intake increased from 1955 kcal/d during 1971-1975 to 2269 kcal/d during 2003-2004 and then declined to 2195 kcal/d during 2009-2010 (P-linear trend < 0.001, P-nonlinear trend < 0.001). During the period from 1999-2000 to 2009-2010, no significant linear trend in energy intake was observed (P = 0.058), but a significant nonlinear trend was noted (P = 0.042), indicating a downward trend in energy intake. Significant decreases in energy intake from 1999-2000 to 2009-2010 were noted for participants aged 20-39 y, men, women, and participants with a BMI (in kg/m(2)) of 18.5 to <25 and ≥30. CONCLUSION: After decades of increases, mean energy intake has decreased significantly since 2003-2004.

Concepts: United States, United Kingdom, Poverty in the United States, U.S. state, Trend, 3rd millennium, Humid subtropical climate, Albert Einstein


Skeletal muscle possesses the ability to regenerate after injury, but this ability is impaired or delayed with aging. Regardless of age, muscle retains the ability to positively respond to stimuli, such as exercise. We examined whether exercise is able to improve regenerative response in skeletal muscle of aged mice. Twenty-two-mo-old male C57Bl/6J mice (n = 20) underwent an 8-wk progressive exercise training protocol (O-Ex). An old sedentary (O-Sed) and a young sedentary (Y-Ctl) group were included. Animals were subjected to injections of cardiotoxin into the tibialis anterior muscle. The tibialis anterior were harvested before [O-Ex/O-Sed/Y-Ctl control (CTL); n = 6], 10 d (O-Ex/O-Sed/Y-Ctl d 10; n = 8), and 28 d (O-Ex/O-Sed/Y-Ctl d 28; n = 6) postinjection. Average fiber cross-sectional area was reduced in all groups at d 10 (CTL: O-Ex: 2499 ± 140; O-Sed: 2320 ± 165; Y-Ctl: 2474 ± 269; d 10: O-Ex: 1191 ± 100; O-Sed: 1125 ± 99; Y-Ctl: 1481 ± 167 µm(2); P < 0.05), but was restored to control values in O-Ex and Y-Ctl groups at d 28 (O-Ex: 2257 ± 181; Y-Ctl: 2398 ± 171 µm(2); P > 0.05). Satellite cell content was greater at CTL in O-Ex (2.6 ± 0.4 satellite cells/100 fibers) compared with O-Sed (1.0 ± 0.1% satellite cells/100 fibers; P < 0.05). Exercise conditioning appears to improve ability of skeletal muscle to regenerate after injury in aged mice.-Joanisse, S., Nederveen, J. P., Baker, J. M., Snijders, T., Iacono, C., Parise, G. Exercise conditioning in old mice improves skeletal muscle regeneration.

Concepts: Regeneration, Ageing, Tibialis anterior muscle, Tibialis posterior muscle, 3rd millennium


Background/Objectives:The main objective was to test the hypothesis that dietary energy density (DED) decreases after Roux-en-Y gastric bypass (gastric bypass).Subjects/Methods:A total of 43 patients (31 women and 12 men) aged 43 (s.d. 10) years, with body mass index (BMI) 44.3 kg/m(2) (4.9), were assessed preoperatively at 6 weeks and 1 and 2 years after gastric bypass. Self-reported energy intake (EI), food weight (FW) and food choice were assessed using a dietary questionnaire. DED was calculated by dividing EI by FW (kcal/g). Number of dropouts was 4 of 203 visits.Results:Percent weight loss (%WL) was 13.5% at 6 weeks, 30.7% at 1 year and 31.8% at 2 years post surgery (P<0.001 for all). EI decreased from 2990 to 1774, 2131 and 2425 kcal after 6 weeks and 1 and 2 years postoperatively, respectively (P<0.001 at all time points). FW changed from 2844 to 1870 g/day at 6 weeks (P<0.001) and 2416 g/day after 1 year (P<0.05), but was not significantly different from baseline 2 years postoperatively (2602 g/day, P=0.105). DED decreased from 1.07 to 0.78 kcal/g at 6 weeks (P<0.001) and 0.90 kcal/g (P<0.001) and 0.96 kcal/g (P=0.001) after 1 and 2 years, respectively. All statistical comparisons were made from baseline. There was no correlation between changes in DED and %WL, neither after 1 year (r=-0.215; P=0.183) nor after 2 years (r=-0.046; P=0.775) post surgery.Conclusions:Besides substantial reduction in EI and large variation in FW, patients reported decreased DED over 2 years following gastric bypass. Despite lack of association between the reduction in DED and percentage weight loss, changes in food choice were overall nutritionally beneficial.European Journal of Clinical Nutrition advance online publication, 9 January 2013; doi:10.1038/ejcn.2012.208.

Concepts: Nutrition, Obesity, Mass, Body mass index, Bariatric surgery, Gastric bypass surgery, Duodenum, 3rd millennium


Oral carbohydrate (CHO) rinsing has been demonstrated to provide beneficial effects on exercise performance of durations of up to one hour. The aim of the present study was to investigate the effects of CHO mouth rinsing on morning high-intensity exercise performance. Following institutional ethical approval and familiarisation, 12 healthy males (mean ± SD age: 23 ± 3 years, height: 175.5 ± 7.4 cm, body mass: 75.4 ± 7.5 kg) participated in this study. Countermovement jump (CMJ) height, isometric mid-thigh pull peak force, 10 m sprint time and bench press and back squat repetitions to failure were assessed following CHO and placebo (PLA) rinsing or a control condition (CON). All testing took place at 07:30 following an 11 hour overnight fast. Performance of CMJ height (CHO: 39 ± 7 cm; PLA: 38 ± 7 cm; CON: 36 ± 6 cm; P = .003, [Formula: see text] = 0.40), 10 m sprint time (CHO: 1.78 ± 0.07 s; PLA: 1.81 ± 0.07 s; CON: 1.85 ± 0.05 s; P = .001, [Formula: see text] = 0.47), the number of bench press (CHO: 25 ± 3; PLA: 24 ± 4; CON: 22 ± 4; P < .001, [Formula: see text] = 0.55) and squat (CHO: 31 ± 4; PLA: 29 ± 5; CON: 26 ± 6; P < .001, [Formula: see text] = 0.70) repetitions and mean felt arousal (CHO: 5 ± 1; PLA: 4 ± 0; CON: 4 ± 0; P = .009, [Formula: see text] = 0.25) improved following CHO rinsing. However, isometric mid-thigh pull peak force was unchanged (CHO: 2262 ± 288 N; PLA: 2236 ± 354 N; CON: 2212 ± 321 N; P = .368, [Formula: see text] = 0.08). These results suggest that oral CHO rinsing solution significantly improved the morning performance of CMJ height, 10 m sprint times, bench press and squat repetitions to failure and felt arousal, although peak force during an isometric mid-thigh pull, rating of perceived exertion and heart rate were unaffected.

Concepts: Exercise, Mass, Bench press, 3rd millennium, 23rd century, Powerlifting, Weight training exercises, Spotting


The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.0% accuracy. The model distinguishing CRA-H from healthy individuals was established with 90.0% specificity and 86.7% sensitivity. Additionally, five peaks (2202, 5821, 3260, 2480, and 2218) showing differential expression in advanced colorectal adenoma patients with a family history of colorectal cancer were selected. The protein Kininogen 1 (KNG1) was identified in colorectal adenoma patients and validated using Western Blotting. KNG1 may be a biomarker for colorectal adenoma patients with a family history of colorectal cancer.

Concepts: Family, Oncology, Molecular biology, Mass spectrometry, Colorectal cancer, 3rd millennium, Kininogen, High-molecular-weight kininogen


Skin lesions are often submitted to oral and maxillofacial pathology practices. The purpose of this study is to evaluate the frequency, distribution, variability, and composition of dermatologic lesions within a large oral and maxillofacial pathology biopsy service. An IRB-approved retrospective search of skin lesions diagnosed at University of Florida oral and maxillofacial pathology biopsy service between 1994 and 2015 was performed. 2487 cases were included in the study. Gender was reported in 2466 cases, of which 59% were male and 41% female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with an average of 55 years. Location was indicated in 2473 cases. Lips were the most common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487 cases (2.8%) resulted in dermatopathologic consultation prior to final reporting. Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and maxillofacial pathology biopsy service. This study found a large variation in the dermatologic lesions submitted to an oral pathology biopsy service. Although most were routine in complexity, dermatopathology consultation was an important tool in the diagnosis of the more challenging cases. This study may help pathologists gain a better understanding of the frequency and variability of dermatologic lesions submitted to an oral and maxillofacial pathology biopsy service and promote more interdisciplinary consultation within the field. This study evaluated the incidence and scope of dermatologic lesions submitted to a large oral and maxillofacial pathology biopsy service over a long time period. A wide scope of lesions was found, and dermatopathology consultation was important to quality assurance.

Concepts: Cancer, Pathology, Anatomical pathology, Squamous cell carcinoma, Basal cell carcinoma, 3rd millennium, Nevus, 25th century


Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and improve advanced breast cancer (ABC) outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to the standard of care (SOC) treatment in ABC. The electronic databases Ovid, PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs), disease control rates (DCRs) and toxicity were meta-analysed using the Mantel-Haenszel method and generic inverse variance. Five studies were included. In unselected patients, the addition of a PI3K inhibitor decreased the risk of progression by 21% (2329 participants, HR = 0.79; 95% confidence interval [CI], 0.71-0.88). A marginal improvement in ORR (2329 participants, RR = 1.26; 95% CI, 1.01-1.57) and no improvement in DCR (2146 participants, RR = 1.05; 95% CI, 0.94-1.18) were achieved with a significant increase in toxicity of any grade (2386 participants, RR = 1.05; 95% CI, 1.03-1.06) and of grade III and higher (2386 participants, RR = 1.91; 95% CI, 1.76-2.08). A PFS benefit was seen in patients with and without PI3K pathway activation assessed on tumour and only in patients with an activated PI3K pathway when it was assessed from the plasma using circulating tumour DNA (ct-DNA) analysis. The addition of a PI3K inhibitor decreases the risk of progression in unselected ABC patients and particularly in patients with an activated PI3K pathway detected on ct-DNA analysis. However, their significant dose-limiting toxicity is a limiting factor. Selective PI3K inhibitors are being tested to assess whether these better-tolerated agents have a role in ABC treatment.

Concepts: Cancer, Breast cancer, Oncology, Evidence-based medicine, Randomized controlled trial, Phosphoinositide 3-kinase, 3rd millennium, Phosphoinositide 3-kinase inhibitor


Changing definition of TIA from time to a tissue basis questions the validity of the well-established ABCD3-I risk score for recurrent ischemic cerebrovascular events. We analyzed patients with ischemic stroke with mild neurological symptoms arriving < 24 h after symptom onset in a phase where it is unclear, if the event turns out to be a TIA or minor stroke, in the prospective multi-center Austrian Stroke Unit Registry. Patients were retrospectively categorized according to a time-based (symptom duration below/above 24 h) and tissue-based (without/with corresponding brain lesion on CT or MRI) definition of TIA or minor stroke. Outcome parameters were early stroke during stroke unit stay and 3-month ischemic stroke. Of the 5237 TIA and minor stroke patients with prospectively documented ABCD3-I score, 2755 (52.6%) had a TIA by the time-based and 2183 (41.7%) by the tissue-based definition. Of the 2457 (46.9%) patients with complete 3-month followup, corresponding numbers were 1195 (48.3%) for the time- and 971 (39.5%) for the tissue-based definition of TIA. Early and 3-month ischemic stroke occurred in 1.1 and 2.5% of time-based TIA, 3.8 and 5.9% of time-based minor stroke, 1.2 and 2.3% of tissue-based TIA as well as in 3.1 and 5.5% of tissue-based minor stroke patients. Irrespective of the definition of TIA and minor stroke, the risk of early and 3-month ischemic stroke steadily increased with increasing ABCD3-I score points. The ABCD3-I score performs equally in TIA patients in tissue- as well as time-based definition and the same is true for minor stroke patients.

Concepts: Stroke, Transient ischemic attack, Traumatic brain injury, Neurology, UCI race classifications, Recurrence relation, Tour de Georgia, 3rd millennium