Patient positioning was corrected for translational and rotational misalignments using a robotic couch in six degrees of freedom if setup errors exceeded 1 mm and 1°. Absolute bilateral kidney motion between inhale and exhale 4D CT imaging phases for left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions was 1.51±1.00mm,8.10±4.33mm, and 3.08±2.11mm, respectively. Residual setup error determined across CBCT type  for x (LR), y (SI), and z (AP) translations was 0.63±0.74mm,1.08±1.38mm, and 0.70±1.00mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24±0.39°,0.19±0.34°, and 0.26±0.43°, respectively. Targets were localized to within 2.1 mm and 0.8° 95% of the time. The frequency of misalignments in the y direction was significant (p<0.05) when compared to the x and z directions with no significant difference in translations between IMRT and VMAT. This technique is robust using BodyFIX for patient immobilization and reproducible localization of kidney and adrenal targets and daily CBCT image guidance for correction of positional errors to maintain treatment accuracy.The purpose of this study was to evaluate bilateral kidney and target translational/rotational intrafraction motion during stereotactic body radiation therapy treatment delivery of primary renal cell carcinoma and oligometastatic adrenal lesions for patients immobilized in the Elekta BodyFIX system. Bilateral kidney motion was assessed at midplane for 30 patients immobilized in a full‐body dual‐vacuum‐cushion system with two patients immobilized via abdominal compression. Intrafraction motion was assessed for 15 patients using kilovoltage cone‐beam computed tomography (kV‐CBCT) datasets (PACS number(s): 87.55.‐x, 87.56.‐v, 87.56.Da Organ motion due to breathing during treatment delivery can result in an organ at risk (OAR) entering the treatment beam and subsequently exceed the tolerance dose while the target may move outside of the treatment beam, restricting the dose it receives to less than the intended prescription dose. Various CT and MR studies report kidney motion due to shallow respiration to occur in a complex pattern with the largest movement in the superior–inferior direction, an average of 6.7–19.0 mm.This study was approved by the institutional ethics committee. Intrafraction motion was retrospectively evaluated by analyzing 4D CT datasets and kV‐CBCT registration records.Bilateral kidney motion was assessed for 30 patients  who were immobilized in the BodyFIX system  with two patients immobilized in the BlueBAG (Elekta) with abdominal compression. Absolute motion was measured at midplane in the left–right, superior–inferior, and anterior–posterior directions using the inhale and exhale phases of the helical 4D CT acquired at simulation.n=10) or IMRT (n=5). The planning CT and CBCT were registered using an automatic gray value match to the PTV and adjacent kidney with manual fine‐tuning adjustments made to ensure that both the target volume and bony anatomy between the image sets were correlated. CBCT registrations were reviewed by a radiation oncologist. For all cases, patient positioning was corrected using a robotic couch in six degrees of freedom if the setup errors exceeded a threshold of 1 mm and 1°. CBCTs were acquired and shifts applied if setup errors exceeded the acceptable threshold following the initial setup registration, pretreatment scan, and intrafraction scan if IMRT was used due to long treatment times. A post‐treatment CBCT scan was acquired to verify the patient's final position. Translational and rotational errors were recorded for each CBCT registration. In total, 151 CBCT records were included in the localization analysis.Intrafraction motion was then determined from the kV‐CBCT setup records of residual error for a subset of 15 patients with renal cell carcinoma or adrenal metastases treated with either VMAT (p<0.05), a post hoc analysis was used to evaluate pairwise comparisons. An unpaired t‐test was used to evaluate differences in patient positioning errors between IMRT and VMAT treatment groups. The 95% confidence interval (CI) was calculated for translations and rotations.Residual patient errors were analyzed using analysis of variance (ANOVA) to evaluate directional differences and, provided the ANOVA was significant , y (superior–inferior), and z (anterior–posterior) translations was 0.63±0.74mm,1.08±1.38mm, and 0.70±1.00mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24±0.39°,0.19±0.34°, and 0.26±0.43°, respectively. The frequency of translational misalignments in the y direction was found to be statistically significant (p<0.001) when compared to the x and z directions while the rotational misalignments were statistically significant when considering intrafraction motion (p=0.027) as well as for IMRT vs. VMAT (p<0.001), as illustrated in The evaluation of absolute bilateral kidney motion across the inhale and exhale 4D CT image acquisitions in the left–right, superior–inferior, and anterior–posterior directions represented as a mean and standard deviation showed breathing induced displacements of  The residual setup error determined from the on‐line CBCT (n=151) alignment corresponds with the absolute motion of the kidneys where the greatest error in localization accuracy occurred in the y direction (superior–inferior) compared to the x (left–right) and z (anterior–posterior) directions, consistent with studies in the literature.The assessment of bilateral kidney motion for patients immobilized in the dual‐vacuum‐cushion system show the largest deviation in the superior–inferior direction with a subset of patients displaying translations larger than 10 mm, while the left–right and anterior–posterior translations were also substantial, albeit consistently lower. These sizeable motions agree with existing data concerning kidney movement due to breathing motion and corroborate the choice to use an ITV for target localization.Breathing‐induced kidney and target intrafraction motion is greatest in the superior–inferior direction in patients positioned in the dual‐vacuum‐cushion immobilization system. In this system, an ITV contoured from the inhale, exhale, and average phases of the 4D CT dataset with a 5 mm isotropic PTV margin is safe to account for target volume intrafraction motion and patient setup accuracy. Evaluation of translational and rotational patient setup errors during highly conformal hypofractionated treatments is necessary to ensure accurate localization of highly mobile targets. Correction of both translational and rotational misalignments is necessary to achieve the improved dose delivery accuracy required of SBRT. Alternate motion management and treatment delivery strategies may further reduce kidney motion, reduce setup errors, and improve target localization.This work is licensed under a Creative Commons Attribution 3.0 Unported License.


Retinal dysfunctions have been integrated in cognitive models of visual hallucinations in several pathologies such as Parkinsonian syndromes or eye diseases. Besides, structural abnormalities of the retinal ganglion cells are documented in schizophrenia and have been associated to visual hallucinations (VH) in neurological disorders. We aim to study functional abnormalities of retinal ganglion cells in schizophrenia patients with VH.We measured the activity of retinal ganglion cells using electroretinogram according to ISCEV criteria. We compared the amplitude and implicit time of the P50 and the N95 waves of the pattern electroretinogram in schizophrenia patients with VH , Auditory Hallucinations or no hallucination  and controls (n = 30).Preliminary findings show a significant increase of the N95 implicit time in the HV group compared with controls (p = .05). No difference was found between the HV and HA/NH groups but a gradient appeared to emerge between the 3 groups.Functional impairment of the retinal ganglion cells appears to be more pronounced in schizophrenia patients with HV. The increase of N95 implicit time may be interpreted as a dysfunction of retinal ganglion celles rather than a cell loss. These preliminary results need to be confirmed with a larger sample.


Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications . It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients. The main nutrition-related goals for people with chronic kidney disease (CKD) involve the slowing of kidney failure progression rate and minimizing uremic toxicity and metabolic disorders of kidney failure, diminishing proteinuria, maintaining good nutritional status, and lowering the risk of secondary complications including cardiovascular disease, bone disease, and disturbed blood pressure control . Howevern-6 fatty acids, folic acid, potassium, magnesium, vitamin E, vitamin C, carotenoids, as well as many phytochemicals [For decades, vegetarianism and kidney disease have been thought to be impossible to combine. Plant-based diets, despite containing low amounts of protein, are also rich in potassium and phosphorus, and therefore they are believed to be unsuitable for CKD patients. However, evidence from clinical studies demonstrate that such a diet can be beneficial for CKD patients when they learn how to use it wisely. Nowadays, there are numerous types of vegetarianism, including lacto-ovo-vegetarianism, lacto-vegetarianism, ovo-vegetarianism, veganism, vitarianism, fruitarianism, liquidarianism, etc. Some of these diets combine plant-based diets with animal products such as eggs, milk, and honey, other are based on fruits or sprouts or juices. Regardless of the type of vegetarianism, such a diet typically contains large amounts of whole-grain cereals, nuts, fruits and vegetables, and is rich in dietary fibers, Bifidobacterium) generate vitamins, such as Folate, Biotin, K, Thiamine, and B12 [Lactobacillus and Bifidobacterium mediate the synthesis of bile acids and produce enzymes that are necessary for carbohydrate breakdown [Bacteroides thetaiotamicron and Faecalibacterium prausnitzii generate anti-inflammatory compounds [The results of small studies suggest that a plant-based diet can delay the progression of CKD, protect endothelium, help to control high blood pressure, and decrease proteinuria ,8. Such  and B12 . Moreovereakdown , and Bacompounds . Howeverompounds .n-3 fatty acids, zinc, iron, and vitamin B12. Some studies indicate that the risk of osteoporosis is higher in vegetarians than in the general population. Low intake of B12 vitamin is a problem in a vegetarian diet. Meat-eaters have much higher plasma vitamin B12 levels than vegetarians, but the cases of true vitamin B12 deficiency accompanied by hematological and neurological damage are very rare and have been reported only in vegans [On the other hand, a vegetarian diet is relatively poor in long-chain n vegans . Bayesian vegans . Also, tn vegans .n-3 fatty acids, which are important for proper functioning of the cardiovascular system, seems to be a drawback of such a diet. However, the inclusion of eggs and dairy products should help to correct such a deficiency [Also, the low content of long-chain ficiency . The conficiency .2) and 1.2 g protein/kg/day for patients with end-stage renal disease (glomerular filtration rate <10 mL/min/1.73 m2). In 2007, the National Kidney Foundation: K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease, recommended the limitation of dietary protein intake to 0.9 g/kg/day in patients with diabetes and CKD stage 2, as it was proved to be beneficial irrespective of established medical therapies [2 (glomerular filtration rate (GFR) categories G4–G5), with appropriate education and recommend the avoidance of high protein intake (41.3 g/kg/day) in adults with CKD at risk of progression (2C) [2 and waist circumference ≤102 cm for men and ≤88 cm for women (2C). The summary of guidelines for patients with mild-moderate CKD is presented in In patients with CKD, an appropriate amount of protein is required to avoid both malnutrition and overnutrition. Protein-energy malnutrition in CKD patients is a strong predictor of adverse outcomes. Its prevalence increases linearly with decreasing renal function in non-dialysis patients and may exceed 50% in those undergoing maintenance dialysis therapy . The Natherapies . The NKFion (2C) . In mildion (2C) . CaloricStudies on animal models suggest that a vegetarian diet is suitable and nutritionally adequate in CKD ,30,31. AHigher glomerular filtration rates have been demonstrated in patients with normal renal function on an animal-protein diet in comparison to persons on a vegetable-based diet ,38. AnotIn CKD patients, disturbances in mineral metabolism are frequent, and they begin usually at stage 3 and 4. As renal function decreases, the ability of kidneys to excrete phosphorus become more and more reduced. As a consequence, compensatory secondary hyperparathyroidism and elevations in fibroblast growth factor-23 (FGF23) occur in order to increase urinary phosphorus excretion and maintain phosphorus balance . AccordiInsulin resistance is a frequent disorder in patients with CKD. According to studies, it is closely associated with atherosclerosis ,47, coroIn chronic kidney disease, dietary acid load may result in acidosis, despite a normal serum bicarbonate concentration . MetabolAdvanced glycation end products (AGEs) and inflammatory cytokine concentrations are frequently elevated in patients with CKD ,64. Thisp = 0.02) for men and 0.66  for women (in case of vegetables) and 0.77  for men and 0.66  for women (in case of fruits) after the adjustment for age, smoking, serum cholesterol, hypertension, body mass index, and energy intake [p < 0.01) after over 10 years of follow-up [The large EPIC-Oxford study demonstrated that age-adjusted mean BMI was highest in individuals on a meat-based diet, while the lowest values were observed in vegans . Severaly intake . A meta-ollow-up . The redollow-up . The abup = 0.012) and serum phosphorus concentrations  [p = 0.011) without affecting TC or Ca levels.Soy consumption has been demonstrated to be beneficial in patients with chronic kidney disease, due to cardiovascular protection, decreased proteinuria, and cancer prevention ,73. A me = 0.00) . Moreovep < 0.05) as well as estimated urea nitrogen intake , respectively.In vegetarian patients undergoing hemodiafiltration (HDF), the levels of indoxyl sulfate (IS) and p cresyl sulfate (PCS) (protein bound toxins that accumulate in CKD) were also demonstrated to be lower . The autp = 0.02) [The effect of a vegetarian diet in CKD patients has been examined in a few clinical trials. Specialized vegetarian diet in patients with 3 and 4 stage CKD was associated with the maintenance or increase in body weight, serum total protein, serum albumin, and transferrin in comparison to patients on a conventional low-protein diet . The com = 0.02) . Moreove = 0.02)  revealedA vegetarian diet was also suggested to be a safe option for pregnant patients with CKD. Due to the fact that pregnancy induces hyperfiltration, diets with restricted amount of protein should be beneficial in this group of patients . In the 2. Therefore, the authors stated that a KD diet was nutritionally safe and could postpone dialysis initiation in some patients with CKD [Vegetarian diet supplemented with a very-low-protein diet was also demonstrated to be safe for pre-dialysis patients, since it exerted no detrimental effect on the short- and long-term outcomes of patients, even those already on renal replacement therapy . A prospwith CKD . In dialwith CKD . The resOn the basis of the presented results, it seems that a vegetarian diet provides adequate nutrition and exerts numerous beneficial effects. The impact of a vegetarian diet is summarized in


Both aging and hypertension are significant risk factors for heart failure in the elderly. The purpose of this study was to determine how aging, with and without hypertension, affects left ventricular function.31P spectroscopy-based measurements of left ventricular structure, global function, strains, pulse wave velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated hypertensive patients (though no other cardiovascular disease or diabetes) stratified into 3 age deciles from 50–79 years.Cross-sectional study of magnetic resonance imaging and Normal aging was associated with significant increases in systolic blood pressure, vascular stiffness, torsion, and impaired diastolic function . Age-matched hypertension exacerbated the effects of aging on systolic pressure, and diastolic function. Hypertension alone, and not aging, was associated with increased left ventricular mass index, reduced energetic reserve, reduced longitudinal shortening and increased endocardial circumferential shortening . Multiple linear regression analysis showed that these unique hypertensive features were significantly related to systolic blood pressure (P<0.05).1) Hypertension adds to the age-related changes in systolic blood pressure and diastolic function; 2) hypertension is uniquely associated with changes in several aspects of left ventricular structure, function, systolic strains, and energetics; and 3) these uniquely hypertensive-associated parameters are related to the level of systolic blood pressure and so are potentially modifiable. In normal aging there are several well described changes in cardiovascular function. Vascular stiffness increases from young adulthood . In the How this accumulation of risk factors leads to HF pEF is not fully understood. A history of hypertension is a particular risk factor for HF pEF . When coWhether hypertension increases the normal aging effects on cardiovascular function, and/or has other effects distinct from the normal aging process are unclear. In the current study we sought to address the hypothesis that hypertension leads to both exaggerated effects of aging on the left ventricle and also effects unique to hypertension, in terms of structure, function, high energy phosphate metabolism, and vascular stiffness. With that in mind, normal controls and hypertensive subjects (without other cardiovascular diseases or diabetes) were recruited in 3 age brackets by decades from the sixth to eighth decades.Forty eight normal subjects were recruited into 3 discrete age bands, with 16 subjects in each decade of 50–59, 60–69 and 70–79 years . Forty A Philips Achieva 3T scanner and a 6 channel receiver array were employed to acquire cardiac magnetic resonance imaging (MRI) data. Details of cardiac cine imaging and our algorithm for contour selection and calculating LV mass and systolic and diastolic parameters have been previously published  S1 Appe. The folAssessment of diastolic function from cine images was performed by calculating the ratio of peak early and late left ventricular filling rates (E/A ratio), and the early filling percentage was calculated as the volume increase from end-systole to the midpoint divided by the stroke volume*100 (EFP) .Longitudinal shortening was determined in the four-chamber view by determining the perpendicular distance from the plane of the mitral valve to the apex in systole and diastole. The myocardial wall thickness at systole and diastole was determined at the same level as the cardiac tagging, and radial thickening was calculated.Pulse wave velocity (PWV) is a marker of vascular stiffness and is an important predictor of cardiovascular events . Phase cCardiac tagging works by applying radiofrequency pulses to cancel MR signal from the myocardium in diastole in a rectangular grid pattern and tracking the deformation of these tags through the rest of the cardiac cycle. Two tagged short axis images were obtained at the same session as previously described ,14 S1 A. The Car31P magnetic resonance spectroscopy. The PCr/ATP ratio is a marker of energetic reserve, as phosphocreatine is the source of phosphorous for ATP. A decrease in this ratio has been associated with an imbalance between oxygen supply and demand in the myocardium [31P surface coil  for transmission/reception of signal, and has been described in detail previously [Cardiac high-energy phosphate metabolism  was assessed using ocardium  and adveocardium . Data weeviously ,19 . Additional analysis also examined the effects of gender. No interaction effects were seen between the factors, so only hypertension and age effects are reported. Post hoc testing was performed with the Scheffé test. Multiple linear regression analysis was used to determine predictors of variables associated with hypertension. Differences in proportions were tested with the Chi Squared test. All statistics were performed using SPSS (version 22). Data are presented as mean ± standard deviation, and There were significant increases in systolic blood pressure and Ees with age with additional effects of hypertension . PWV andDiastolic function, as determined by the E/A ratio and EFP, was impaired with aging . While hypertension did not have an additional (independent) effect on the E/A ratio, it further reduced EFP.Left ventricular mass index, and ejection fraction were increased and PCr/ATP reduced with hypertension only, without effects of aging. End-diastolic volume index and stroke volume index were borderline reduced with age without any additional effect of hypertension. There was a borderline reduction in end-systolic volume index in hypertension.With hypertension there was a significant redistribution of systolic strains. Epicardial circumferential shortening decreased, while endocardial circumferential shortening increased. Midwall circumferential shortening was not significantly changed by age or hypertension . Additio2, P<0.01), and higher ejection fraction . All circumferential strains  were elevated in females .Females had significantly lower left ventricular mass index , systolic blood pressure (positive relationship), Ea/Ees (positive), and stroke volume index (positive). This suggests that higher levels of left ventricular mass in this mixed group of normals and hypertensives are associated with higher systolic blood pressure and adverse ventricular-arterial coupling, but increased left ventricular mass preserves stroke volume. This model accounted for over 50% of the variance associated with left ventricular mass index.For the other 3 models, there were also significant relationships with systolic blood pressure for all the dependent variables. For longitudinal shortening, the opposite effect of systolic blood pressure was seen compared to left ventricular mass index, in that longitudinal shortening decreased as systolic blood pressure increased. With endocardial circumferential shortening, higher levels of systolic blood pressure were associated with higher values of endocardial circumferential shortening. Higher levels of systolic blood pressure were also significantly associated with lower levels of PCr/ATP. In this study we demonstrate in a group of normal subjects and patients with treated hypertension (though no other cardiovascular diagnosis or diabetes) that hypertension has both additive effects to the normal effects of the aging process, and also effects uniquely associated with hypertension . IncreasSystolic blood pressure appears particularly important in the multiple linear regression analysis. Higher levels of systolic blood pressure are related to increased left ventricular mass, reduced longitudinal and endocardial circumferential shortening and reduced PCr/ATP. Also higher levels of stroke volume index are strongly related to higher levels of left ventricular mass index. This suggests that increases in left ventricular mass help preserve stroke volume in the presence of higher systolic pressure. The hypertensive patients were on treatment though these data suggest that despite treatment, there was potential to reduce effects of hypertension on the left ventricle by more intensive reduction of systolic blood pressure. Recently the Systolic Blood Pressure Intervention Trial (SPRINT)  has showIn the hypertensive patients we have documented reduced longitudinal shortening, increased endocardial circumferential shortening, preserved midwall circumferential shortening, and reduced epicardial circumferential shortening. Several conclusions can be drawn from these findings based on the anatomical fiber orientations in the left ventricle. Fibers are oriented at 74±3° at the subepicardium , circumferentially at the midwall, and -70±4° at the subendocardium ,25. Thus2). In contrast to this, Narayanan et al [2). Ahmed and colleagues [2), that circumferential strains were reduced, though no details were provided of variations through the left ventricular wall. Our data showing a more complex pattern in a group with relatively mild hypertension and mild left ventricular hypertrophy suggests that there may be an evolution of changes in circumferential shortening as hypertensive heart disease progresses–from preserved fibre shortening and increased endocardial circumferential shortening in mild hypertension (as seen in this study) to reduced fibre shortening and reduced circumferential shortening in all layers of the left ventricle in advanced hypertensive left ventricular hypertrophy.Preserved left ventricular systolic function and reduced longitudinal shortening are consistent findings in hypertension –30. Theran et al  have sholleagues  have shoEnd-systolic elastance is elevated both by normal aging, and this effect augmented by hypertension. This has been previously recognised ,31. In tth, 7th and 8th decades.Our aging data are from a relatively short time span, limited by the age ranges when we can find community patients with hypertension, and are also cross-sectional. We have previously shown that the PCr/ATP ratio is reduced with aging over a wider range of ages , though PWV was not increased in our hypertensive patients. Using arterial tonometry, hypertension is a significant risk factor for increased PWV . Our finRelaxation of the left ventricle is intrinsically related to afterload , and we Hypertension, when treated and without other cardiovascular diagnosis or diabetes, is associated with significant changes in left ventricular structure, function and energetics in addition to normal aging effects. These are, at least in part, related to the level of systolic blood pressure, and so are potentially modifiable. Recent studies have suggested that intensive blood pressure lowering can improve left ventricular systolic and diastolic function , though S1 Appendix(DOCX)Click here for additional data file.S1 Dataset(XLSX)Click here for additional data file.


Evaluation of perioperative renal function is very important for early diagnosis and treatment of acute kidney injury after coronary artery bypass grafting. Serum creatinine levels, creatinine clearance, and estimated glomerular filtration rates used in determination of postoperative kidney injury can lead to late detection. Therefore, it is necessary to make a diagnosis earlier in clinical practice and to search for a reliable method. The reliability of the use of serum neutrophil gelatinase–associated lipocalin levels in close follow-up of renal function was evaluated in patients with coronary artery bypass grafting under cardiopulmonary bypass in our study. ® NGAL Device; Biosite Inc.) measurements was evaluated in kidney injury developed in the first 5 days after operation that was detected using the Risk-Injury-Failure-Loss-End stage criteria.  A total of 40 patients who underwent coronary artery bypass grafting under cardiopulmonary bypass between September 2009 and February 2010 were included in the study. The reliability of the postoperative 1st day plasma neutrophil gelatinase–associated lipocalin (Triage Ten (25%) women and 30 (75%) male patients were included in the study. The average age is 59 ± 8.6 years. Kidney injury according to Risk-Injury-Failure-Loss-End stage criteria developed in 8 patients (20%). For 150 ng/mL cutoff value of postoperative plasma neutrophil gelatinase–associated lipocalin levels, the area under the receiver-operating characteristic curve was 0.965. Neutrophil gelatinase–associated lipocalin's sensitivity, specificity, and negative and positive predictive values were 100%, 93.8%, 100%, and 80%, respectively.  It has been determined that plasma neutrophil gelatinase–associated lipocalin levels can be reliably used for early diagnosis of kidney dysfunction in patients undergoing coronary artery bypass grafting. One of the leading complications following cardiac surgery is acute kidney injury . CardiopA total of 40 consecutive patients without preexisting renal failure undergoing CABG under CPB between September 2009 and February 2010 were included in the study, who did not have exclusion criteria and were operated by the same surgical team. The kidney injury during the 5-day follow-up period was determined according to the Risk-Injury-Failure-Loss-End stage (RIFLE) criteria, creatinine clearance rate measurements, and estimated glomerular filtration rate measurements according to the Cockcroft–Gault equation, and the reliability of the postoperative first day plasma NGAL values for renal dysfunction was retrospectively investigated .risk (1.5-fold increased serum creatinine levels or GFR decrease higher than 25% or urine output lower than 0.5 mL/kg/h during 6 hours), injury (2-fold increased serum creatinine levels or GFR decrease higher than 50% or urine output lower than 0.5 mL/kg/h during 12 hours), failure , loss , and ESRD  [In the RIFLE criteria, there are 5 subcategories of kidney dysfunction: Concomitant surgical procedures, off-pump surgery, presence of the history of antithrombotic agent usage during 2 weeks preoperatively, presence of accompanying acute infection, presence of chronic infection, presence of preoperative advanced liver or pulmonary insufficiency, and preexisting renal failure were considered among the exclusion criteria.The definition of AKI is used as a general definition for acute kidney dysfunction . Acute DThe NGAL measurements were performed at the time of intensive care follow-up at 24 hours after termination of CPB using the Triage NGAL Test Device . The cutoff value was accepted as 150 ng/mL in the measurements.P value of less than 0.05 was considered significant. IBM SPSS software package version 21.0  was used for statistical analysis. The receiver-operating characteristic (ROC) curve was drawn to calculate the area under the curve (AUC). Values above 0.7 for AUC-ROC were considered to have good test performance. Sensitivity, specificity, and positive and negative predictive values of serum NGAL measurements for detecting AKI were calculated.Categorical variables were expressed as frequency and percentage, and continuous variables were expressed as mean ± standard deviation . The calculation of the confidence of the serum NGAL measurement based on the 150 ng/mL cutoff value of the blood sample taken at 24 hours following termination of the CPB in detecting AKI according to the RIFLE criteria was accepted as the primary end point of the study.2, and the mean body surface area was 1.9 ± 0.2 (1.8–1.9) m2 (Ten (25%) women and 30 (75%) male patients were included in the study. The average age was 58.7 ± 8.6 (56–61.2) years . The mea–1.9) m2 . A total−1·1.73 m2, respectively (The mean ± standard deviation (95% CI) values of creatinine clearance rates on preoperative and postoperative 1st and 5th days were 85.7 ± 30 (76.9–94.5), 109.4 ± 42 (97.8–121.8), and 87.8 ± 32.8 (77.7–97.7) mL·minectively . Kidney ectively . The senThere is an intense relationship between on-pump CABG and the development of the postoperative kidney injury. It is stated that AKI can be developed at high levels up to 30–50% after open-heart surgery under CPB , 15. HowIt has been determined that plasma NGAL levels can be reliably used postoperatively for early diagnosis of kidney dysfunction in patients undergoing on-pump CABG. However, these promising results must be confirmed with further multicenter studies with larger patient populations.


Rabbits are particularly sensitive to develop hypotension during sedation or anaesthesia. Values of systolic or mean non-invasive arterial blood pressure below 80 or 60 mmHg respectively are common under anaesthesia despite an ongoing surgery. A reliable method of monitoring arterial blood pressure is extremely important, although invasive technique is not always possible due to the anatomy and dimension of the artery. The aim of this study was to evaluate the agreement between a new oscillometric device for non-invasive arterial blood pressure measurement and the invasive method. Moreover the trending ability of the device, ability to identify changes in the same direction with the invasive methods, was evaluated as well as the sensibility of the device in identifying hypotension arbitrarily defined as invasive arterial blood pressure below 80 or 60 mmHg.Bland-Altman analysis for repeated measurements showed a poor agreement between the two methods; the oscillometric device overestimated the invasive arterial blood pressure, particularly at high arterial pressure values. The same analysis repeated considering oscillometric measurement that match invasive mean pressure lower or equal to 60 mmHg showed a decrease in biases and limits of agreement between methods. The trending ability of the device, evaluated with both the 4-quadrant plot and the polar plot was poor. Concordance rate of mean arterial blood pressure was higher than systolic and diastolic pressure although inferior to 90%. The sensibility of the device in detecting hypotension defined as systolic or mean invasive arterial blood pressure lower than 80 or 60 mmHg was superior for mean oscillometric pressure rather than systolic. A sensitivity of 92% was achieved with an oscillometric measurement for mean pressure below 65 mmHg instead of 60 mmHg. Non-invasive systolic blood pressure is less sensitive as indicator of hypotension regardless of the cutoff limit considered.Although mean invasive arterial blood pressure is overestimated by the device, the sensitivity of this non-invasive oscillometric monitor in detecting invasive mean pressure below 60 mmHg is acceptable but a cutoff value of 65 mmHg needs to be used. Anaesthesia related mortality at 48 h post-procedure is higher in rabbits than in dogs and cats . RabbitsDirect invasive arterial blood pressure (IBP) measurement is considered the “gold standard” for arterial blood pressure measurement. This technique requires an arterial catheterization that may be technically difficult in small animals and it may lead to blood extravasation with haematoma and risk of ear necrosis . The cenThe Doppler technique showed good agreement with systolic IBP measurements and it can be used to monitor arterial pressure , 4, but Traditional oscillometric techniques that use equipment designed for human use becomes inaccurate at fast pulse rate or with pulse oscillation of small magnitude during hypotension or with alpha-2 agonist sedatives , 7. MoreRecently, a new oscillometric device has become available for arterial blood pressure monitoring in dogs and cats. The device is provided with a ruler to allow selection of the most appropriate cuff size for the particular animal.The aim of this study is to compare the new NIBP oscillometric device with the IBP measured from the auricular artery in anesthetized rabbits undergoing elective neutering. A secondary aim was to study the trending ability of the device and its sensitivity and specificity in detecting systolic and mean IBP lower than 80 and 60 mmHg respectively.Internal institutional ethics committee approved the study and owner’s consent was obtained before each procedure. Nineteen ASA 1–2 cross-breed pet rabbits of both sexes  weighing between 2.5 and 4.6 kg, older than 6 months undergoing elective neutering were enrolled in a prospective clinical study.2 = 0.5) via a circle breathing system with paediatric tubes. The end-tidal concentration of isoflurane was adjusted to maintain an adequate surgical plane of anaesthesia while minimizing the detrimental cardiovascular effects of volatile agent. To maintain a normothermic range between 38° and 39 °C an electric heating pad  was placed under the rabbits. Pulse rate, pulse oximetry, IBP, respiratory rate, end-tidal concentration of isoflurane and carbon dioxide were monitored with a portable pulseoximeter  and a multiparameter monitor ; a mixture of 50:50 lactate Ringer’s solution and 5% dextrose was infused at 5 ml/kg/h IV. After surgery all monitoring devices were removed and the rabbits received subcutaneously 0.5 mg/kg of atipamezole . Heart rate, respiratory rate and signs of pain were evaluated in the recovery period until discharge.The animals were considered healthy based on the medical history and pre-anaesthetic clinical exam. Rabbits had free access to water and food until a combination of dexmedetomidine 50 μg/kg  and midazolam  0.6 mg/kg was administered into the lumbar muscles  to obtain sedation. As the rabbits lost the righting reflex the external pinnae of the left ear and the dorsal aspect of the right foreleg were clipped. A 24-gauge over-the-needle intravenous (IV) catheter was aseptically inserted in the cephalic vein. After IV access was achieved, 0.05 mg/kg of buprenorphine  was administered together with a subcutaneous injection of 1 mg/kg of meloxicam  and 5 mg/kg of enrofloxacin . Anaesthesia was induced with IV propofol  and airways were secured either with an endotracheal tube or a laryngeal mask in 9 and 10 rabbits respectively. The animals were placed in dorsal recumbency and anaesthesia was maintained with isoflurane  in a mixture of oxygen and air  was inserted aseptically in the median portion of central auricular artery and it was secured with tape. If the artery was not catheterized at the first attempt the animal was removed from the study and arterial blood pressure was recorded by a Doppler ultrasound method as previously reported . The arA new oscillometric device  was evaluated. The cuff was placed on the anterior forelimb proximal to the carpus once the animal was in dorsal recumbency; the correct size of the cuff was obtained by the ruler provided by the manufacturer and the inflation cuff line was orientated toward the distal part of the forelimb. The legs were loosely tied with a bandage role. Every 5 min 2 consecutive readings were taken and if the variability was less than 20% the data were averaged otherwise a third reading was done and the values that had the small variance were used .Mean bias, precision defined as standard deviation (SD) of the bias and limits of agreement (mean bias ± 1.96 × SD) for systolic, diastolic and mean arterial blood pressure measured with IBP and NIBP was assessed by the method proposed by Bland and Altman for multiple observations per individual . AnalysiThe “trending ability” of the oscillometric method in tracking dependable changes with the invasive method was evaluated with a four-quadrant plot and a polar plot as reported previously . Both anIntraoperative hypotension was arbitrary defined as invasive SAP or MAP lower than 80 and/or 60 mmHg respectively . SensitiThe number of animals used was estimated on the base of the criteria proposed by ACVIM Hypertension Consensus and Veterinary Blood Pressure Society . To obtaGraphpad , Matlab R2017a , MedCalc v12  and Microsoft Office Excel 2011  were used for the statistical analysis and to plot the data. Data normally distributed are expressed as mean ± SD otherwise as median (min-max).One rabbit was excluded because arterial catheter insertion was unsuccessful; in the remaining 18 rabbits, 172-paired measurements were collected and analysed. None of the rabbits presented postoperative complication due to arterial catheterization. The dose of propofol was 1.2 (0.0–6.0) mg and anaesthesia time was between 30 and 60 min. Natural frequency and damping coefficient were 29 ± 7 Hz and 0.28 ± 0.08 respectively and an adequate dynamic response was obtained for all rabbits. The normothermic range was maintained in all animals, with a mean rectal temperature at recovery of 38.5 ± 0.9 °C.Results of Bland-Altman analysis of matched values for IBP over NIBP are shown in Table The analysis of the trending ability is reported in Table Sensitivity of the device to identify hypotension was higher if the cutoff for the corresponding non-invasive pressure limits were set at 90 and 65 mmHg respectively. Considering those cutoff values the specificity decreased. Positive predictive value for systolic pressure was higher than that of mean blood pressure while the opposite was observed for the negative predictive value Table .Table 3AAccording to the criteria set at priori with mean bias lower than 10 mmHg and precision of 15 mmHg, only non-invasive MAP and DAP showed an acceptable agreement with the IBP technique. If the more restrictive criteria of AAMI standard were assessed, non-invasive MAP met the requirements of the analysis that included only animals with invasive MAP lower than 60 mmHg. The oscillometric device evaluated in this study showed a sensitivity of almost 92% in detecting values of mean IBP below 60 mmHg if the cutoff for the mean NIBP was set at 65 mmHg but specificity was 61%. Non-invasive SAP below 80 or 90 mmHg have a limited ability to identify systolic IBP lower than 80 mmHg. The trending ability of the NIBP device is poor considering the four-quadrant and the polar plot analysis and the concordance rate was below 90% for all the measured pressures.The mean bias was decreased and the limit of agreement was smaller if data points for mean IBP below 60 mmHg were analysed rather than consider the overall values. The evaluation of this subgroup was performed to detect the accuracy of the NIBP monitor in a situation of low arterial blood pressure commonly referred as clinical relevant hypotension requiring a treatment. The bias for MAP in our study is smaller than SAP similarly to the results achieved by Barter and Epstein whom compare an oscillometric device with the carotid artery IBP . Oscillo. The trending ability in this study may also have been affected by a low agreement between measurement methods especially at high blood pressure. Minimal changes in IBP might be associated with opposite changes of high magnitude in NIBP. Those changes, included in the analysis, may have caused a dispersion of data in the four-quadrant and polar plot analysis affecting the concordance rate and the trending ability. Moreover hypotensive episodes in some rabbits responded poorly to a decrease in end-tidal isoflurane and as no other treatments were performed, the assessment of trending ability in our study might be difficult to quantify.Bland-Altman analysis, although widely used to evaluate the agreement between a monitoring device with a reference technique, does not provide any information on the ability of a new technology in detecting changes consistent with those measured by the “gold standard” technique. This characteristic is known as trending ability of a device. Recently an analytical method was introduced to assess the trending ability of new devices for cardiac output measurement and the same analysis was applied to arterial blood pressure monitoring –15. The Rabbits are particularly sensitive to the vasodilatatory effects of volatile anaesthetics despite an ongoing surgical procedure or the application of a supramaximal electrical stimulation , 16. HarOur study presents some limitations: first the agreement between IBP and NIBP was evaluated only in the front limb, while hind limb may have resulted in a different outcome. Ypsilantis et al. demonstrated a good correlation between the oscillometric pressures measured on the front limb with that recorded on the abdominal aorta rather the one recorded on the hind limb . For neuAll the rabbits enrolled in this study were owned patients undergoing elective neutering. While the use of such cases may provide a good evaluation of the oscillometric device in a clinical setting, on the other hand this represents a limitation because these may have introduced confounding factors due to a different haemodynamic status based on the surgical stimulations.Another limitation is that during the surgical procedure, the intensity of the cardiovascular stimulation may have varied rapidly on the base of the manoeuvre performed. The dynamic response test was performed at the beginning of each anaesthesia but it was not repeated during the surgical procedure. The fundamental frequency, represented by the pulse rate (170–200 beats/min), was almost 6 times the natural frequency measured. This contributed to reduce the underdamping of the fluid-filled pressure transducer system due to the low damping coefficient recorded in most of rabbits . UnderdaAgreement is poor between the systolic arterial blood pressure measured with the non-invasive device and that measured invasively at the level of ear artery. Invasive MAP is overestimated at high pressure values although bias decreases if only measurements lower than 60 mmHg obtained invasively were considered and match the requirement of good agreement based on ACVIM and AACI guidelines. Trending ability of the new device is poor although for MAP concordance rate is superior than SAP and DAP. The sensitivity of the device is higher in detecting invasive MAP lower than 60 mmHg if a cutoff value of 65 mmHg is considered and may be used to identify hypotension in anaesthetized rabbits although it has a poor ability to identify false positive.


Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment.A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10.An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients.Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia.p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found.In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012).There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes.Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure  contains supplementary material, which is available to authorized users. Obstructive sleep apnea (OSA) is a disorder characterized by repeated episodes of upper airway collapse during sleep . OSA is The condition of the arterial vessels can be studied by pulse wave velocity (PWV), that can be used as an index of arterial distensibility. Arterial PWV describes how fast a blood pressure (BP) pulse travels from one point to another in an artery. Arterial stiffness is now recognized as a major driver of CV disease, and it depends mainly on age and BP. PWV is a well-established procedure for measuring the arterial stiffness, using arterial tonometry, at the carotid and femoral artery sites: carotid-femoral pulse wave velocity (cf-PWV), the gold standard index. It is a noninvasive biomarker for primary and secondary CV disease prevention, and can be used as an intermediate endpoint for CV events .OSA is associated with increased arterial stiffness, with an improvement after continuous positive airway treatment (CPAP) , 7.However, most of OSA patients remain undiagnosed. Daytime sleepiness, a symptom of OSA easily identifiable, was reported in about 20% of all adults with an Apnea-Hypopnea Index (AHI) ≥ 5/h, in population based studies , 9. DaytAlthough non-sleepy patients have an augmented arterial stiffness when compared to non-OSA controls , the verThe aim of this study is to verify if there are differences in the progression of arterial stiffness in a cohort of patients with OSA, classified as sleepy and non-sleepy, undergoing treatment with CPAP for four months.This is a prospective cohort study conducted between October 2012 to November 2015. Consecutive patients referred for snoring or OSA-related symptoms to the Sleep Outpatient Clinic of a Pneumology Department were recruited if they were male, younger than 65 years old, and with moderate to severe OSA (AHI > 15/h) [The exclusion criteria included other sleep disorders ; alcohol abuse; known CV disease beyond hypertension; and other chronic diseases.Patients with high levels of fasting glucose performed an additional oral glucose tolerance test, and excluded if they were diabetic.Patients were evaluated monthly for assessment of effectiveness and compliance to therapy, presence of nasal complaints, and changes on the equipment. They were excluded from the study if they were not compliant to CPAP (using at least mean of 4 h/night) , if signA laboratorial evaluation, ambulatory blood pressure monitoring (ABPM) and cf-PWV measurements were made before and after 4 months of the beginning of CPAP therapy.ABPM was performed with Ambulatory Blood Pressure - SpaceLabs model 90207®. Patients were considered hypertensive according ABPM values (current guidelines) or when they were under antihypertensive medication.At baseline consultation, the Epworth Sleepiness Scale (ESS) was applied and patients were classified as sleepy (ESS > 10) or non- sleepy (ESS ≤ 10) . The comA detailed operational definition and description of the primary and secondary outcomes assessment can be found in our previous paper . For ethThe diagnosis of OSA was confirmed by home respiratory poligraphy , which includes continuous recording from nasal cannulae (pressure and flow), thoracic-abdominal motion, pulse oximetry, electrocardiogram and body position sensor. Respiratory events were classified using standard criteria .All patients performed CPAP titration using an automatic auto-CPAP device  for 3 nights, and subsequent change to CPAP . After dAssessment of cf-PWV was made using a non-invasive automatic device . Measurements were performed in the morning, without prior consumption of tea or coffee. The assessment was performed in the supine position, and the values took into account the concomitant arterial BP .CF-PWV was measured using the «foot-to-foot» velocity method from the pressure waveforms, obtained using surface tonometry probes at the right common carotid artery and the right femoral artery. The time delay  is measured between the «foot» of these two waveforms. The distance D covered by the waves is incorporated to the skin distance the two tonometry probes, i.e. the common carotid artery and the common femoral artery. PWV is estimated as PWV = D/Dt (m/s) .p-value ≤0.25 were considered for the multivariable analysis. As in this analysis an interaction was identified between ESS group and time (defined by the two assessment instants: before and after CPAP), a stratified analysis by ESS group was also performed in order to investigate potential associations between baseline variables and changes in cf-PWV (∆cf-PWV = cf-PWV before CPAP- cf-PWV after CPAP). In this stratified analysis, linear regression models were only used in the non-sleepy group, attending to the small sample size of sleepy patients’ group.Patients’ characteristics were described using the mean and standard deviation (SD) for continuous variables, and frequencies (percentages) for categorical variables. To compare characteristics of patients before and after CPAP therapy, Wilcoxon signed rank test and McNemar test were used. In this analysis, demographic variables, sleep study parameters, blood tests and vascular parameters were used. Additionally, in order to investigate associations between these variables and cf-PWV, linear mixed effects regression models were applied. All the variables that attained a The level of significance α = 0.05 was considered. All data were analyzed using the Statistical Package for the Social Sciences for Windows 21.0  and Stata .Forty-two patients with moderate to severe OSA were recruited for this study.Three patients refused the treatment and five patients dropped out later due to poor compliance to CPAP treatment.The final cohort included 34 patients, 13 (38.2%) patients with daytime sleepiness, 19 (55.9%) patients with moderate OSA and 15 with severe OSA. Clinical characteristics of patients and home respiratory poligraphy data are shown in Table Most patients  were hypertensive; 6/27 (22.2%) had no treatment and 21/27 (77.8%) were under antihypertensive medication. In 14/27 (51.9%) patients BP was uncontrolled; 10/21 (47.6%) patients were on monotherapy, 7/21 (33.3%) and 4/21 (19.0%) patients were on two or three antihypertensive drugs, respectively. Dyslipidaemia was highly prevalent, as well as metabolic syndrome (MetS) .p ≤ 0.001). Regarding AHI, there was also a significant decrease (p < 0.001)  and LDL-cholesterol (p = 0.031). After treatment with CPAP there was a non-significant decrease in dyslipidaemia prevalence (p = 0.125) , daytime DBP (p = 0.001) and 24 h mean BP (MBP) (p =  0.030), and with an increase in pulse pressure (p = 0.050). Non-dipping prevalence in 24 h BP evaluation decreased from 7 (20.6%) to 5 (14.7%) patients, without significance (p = 0.500).There was also an improvement in BP parameters, with a decrease in 24 h diastolic BP (DBP) (p = 0.086) (Table p = 0.289).Also, a weak evidence of a decrease of cf-PWV values was found (6) Table . AlthougIn univariable analysis there was an association between age, ESS, 24 h SBP, daytime SBP, night-time SBP, pulse pressure, the use of antihypertensive drugs and the presence of MetS with higher values of cf-PWV (Table p = 0.004) and antihipertensive drugs (p < 0.001). Triglycerides (p = 0.002) and glucose (p = 0.003) levels were higher, but presented lower HDL-cholesterol levels (p = 0.004) and lower mean SaO2 (p = 0.002).Relating to the group of patients with MetS and comparing to the patients without MetS, there was a higher prevalence of hypertension (p = 0.04) and follow up (p = 0.04).Moreover, levels of cf-PWV were higher than in patients without MetS, both at baseline . No differences were found in age, BMI, or metabolic parameters between these two groups. There was also no difference in the prevalence rates of BP, antihipertensives or lipid lowering drugs  events/h vs 29.7 (15.7) events/h (p = 0.012) and a non-significant decrease in non-sleepy patients (p = 0.779).After treatment with CPAP, and regarding cf-PWV, there was a significant decrease in sleepy patients (p = 0.034) , and with the presence of lipid lowering drugs .Also, there was a weak association between cf-PWV change with triglycerides , after adjusting for covariates, meaning time, age and pulse pressure.After four months of CPAP treatment there was an improvement in 24 h DBP, daytime DBP, and levels of total cholesterol. Age and SBP were variables associated to cf-PWV, as expected, but daytime sleepiness was also detected. In multivariable analysis, we found that sleepy and non-sleepy groups behaved differently, under CPAP treatment. In the fitted model, sleepiness was an independent determinant of the longitudinal decrease in cf-PWV , and the evaluation of CPAP compliant patients.There are at least two meta-analysis , 7 identThe effect of CPAP reducing cf-PWV was well described in studies with highly selected samples, including very severe and younger OSA patients , 19, or Kohler et al.  studied In contrast with these results, in a meta-regression analysis examining the effect of potential modifiers upon the effect of CPAP on arterial stiffness, the sleepiness score did not have significance .We admit that the role of sleepiness as well as the usefulness of cf-PWV measurements may be best defined in this sample under 60 years old and without a great number of comorbidities, yet very prevalent in the clinical set.Concerning the improvement in lipid profile, our results are in agreement with the meta-analysis results of Nadeem et al. CPAP treatment seems to improve dyslipidaemia, although we did not find an increase in HDL-cholesterol as described .2 levels. In fact, MetS is an additive factor to arterial wall damage and only in very selected populations it has been possible to demonstrate a reduction of some of the syndrome components or its prevalence [MetS was associated to higher levels of cf-PWV, but it was not included in the multivariable regression model. Patients with MetS were found to have significantly higher baseline and follow up levels of cf-PWV than patients without MetS, besides a more severe OSA defined by lower mean SaOevalence .We found, among the variables selected, that pulse pressure was positively related to cf-PWV values, as well as SBP parameters. In the non-sleepy group analysis pulse pressure was predictive of greater cf-PWV changes, and other BP variables were excluded from the model.The predominant association of pulse pressure with cf-PWV variations is interesting as it is probably related to early vascular ageing of OSA patients. Pulse pressure has showed the strongest association with aortic cf-PWV over other haemodynamic BP parameters, namely from age 60 years and over, where it begins to increase precipitously. In OSA patients, Sanner et al. also found that a higher pulse pressure before treatment with CPAP was predictive of a beneficial CPAP effect on BP, over other BP parameters .In the sleepy group of patients and after adjusting for age and pulse pressure, there was a reduction of cf-PWV of 1.31 m/s from baseline. Also, and though there was no difference between groups, we found a difference among them of 0.15 m/s, after CPAP therapy.This is relevant as an increase in aortic PWV by 1 m/s is known to correspond to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15%, and 15% in total CV events, CV mortality, and all-cause mortality, respectively .2 < 90% than the non-sleepy patients. However, sleep study parameters were not correlated to cf-PWV changes, neither predictive of a better outcome in non-sleepy group of patients.Patients with daytime sleepiness tend to experience more severe OSA , and theThe issue of sleepiness as an independent variable was raised in studies on OSA and hypertension . CPAP siIn our study, non-sleepy patients had a mean compliance of 5.9 (0.22) hours, and a significant reduction of 2.4 mmHg occurred in daytime DBP.Regarding the mechanisms involved in the pathophysiology of daytime sleepiness, some studies suggest that it is related to sleep fragmentation , while oOne possible explanation for our findings is based in the knowledge that daytime sleepiness is related to both the systemic inflammation associated with sleep disruption  and to the severity of nocturnal desaturation, which appears to be the primary proatherogenic feature of OSA . It may Limitations of this study were the small sample size, though it was not an obstacle for the general aim, and the lack of a control group, which makes this study mainly hypothesis generating. The results cannot be extended to women, the elderly or patients with comorbidities. The use of polysomnography instead of home respiratory poligraphy would allow a more complete evaluation of associations between sleep variables and cf-PWV changes, although it was time consuming and uncomfortable for patients with active working life.In a cohort of consecutive middle aged men with moderate to severe OSA, mainly with metabolic syndrome and dyslipidaemia, it was found a significant decrease in cf-PWV, in sleepy but not in non-sleepy patients. In non-sleepy patients, pulse pressure and LDL-cholesterol at baseline were predictive of higher cf-PWV changes. Further studies are needed to confirm the use of cf-PWV as a biomarker of response to CPAP therapy in OSA patients with sleepiness and good compliance to the treatment.


Manganese is a trace mineral required for metabolism, growth and tissue formation, and reproduction. It is mainly obtained through food and water, as well as through occupational exposure. This study used data from National Health and Nutrition Examination Survey, combining the 2011–12 and 2013–14 cycles. We conducted linear regression analyses on urinary manganese and blood pressure. Significant negative associations (p<0.01) between urinary manganese and both systolic and diastolic blood pressure existed after adjusting for age, sex, body mass index, race/ethnicity, and status of taking antihypertensive medication. These results indicate that urinary manganese may play some role in blood pressure and protecting against hypertension, a major risk factor for cardiovascular disease. Manganese (Mn) is a trace mineral required at low concentrations for carbohydrate and lipid metabolism, growth and reproduction, and formation of tissues, and various enzymes—including ligases and hydrolases—are Mn-dependent . Normal Despite its label as a toxic heavy metal, manganese could potentially play a role in controlling blood pressure due to its anti-oxidative function . The assIn this study, we focused on urinary manganese and its relationship with blood pressure, using data from the National Health and Nutrition Examination Survey (2011–2014).The United States National Health and Nutrition Examination Survey (NHANES) is an annual cross-sectional survey conducted to assess the health of the population. Health interviews are conducted at the participants’ homes, and examinations and laboratory tests are also administered. The interview collects demographic, socioeconomic, and dietary data, and the exam and lab portions collect medical, dental, and physiological measurements. For this study, survey data from cycles 2011–2012 and 2013–2014 were used because previous years did not include measurements of urinary manganese. The study sample is representative of the national population.Participants age six and over provided urine samples in the mobile examination center (MEC). These were analyzed using mass spectrometry, and the data were recorded into a database. All participants age eight and over had their blood pressure measured; examiners are certified for blood pressure measurement. Three consecutive blood pressure readings were obtained after the participant rested quietly in a seated position for 5 minutes and once the participant’s maximum inflation level was determined; a fourth attempt was made if a blood pressure measurement was interrupted or incomplete. An average value for both systolic and diastolic blood pressure was calculated and used, following the tutorial on NHANES website. Those excluded either did not fit the cuff, or had rashes, casts, edema, paralysis, tubes, open sores/wounds, withered arms, a-v shunts, or radical mastectomy.Race/ethnicity was categorized as Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian, and Other . Missing values for antihypertensive medication were assumed to be “not taking medication”.R2 was calculated for both models based on deviances from the full model and the null model with intercept only [The data were downloaded from the NHANES website and imported into R. The sample weights for the four years were calculated using the formula provided by NHANES. Other design features including stratification and clustering were also accounted for in all analyses. There were significant amounts of missingness in both blood pressure and urinary manganese , with scept only . All anaOut of the original sample size of 19305, 3853 participants were included in the study after excluding participants with missing values for the covariates and the variables of interest. The study population included 1927 females and 1926 males, and the mean age was approximately 37 years. Comparing characteristics of the participants included in the study and those excluded from the study, only BMI and status of taking antihypertensive medication resulted in significant differences , with a pseudo-The 2011–2014 NHANES data from this study showed that higher urinary manganese levels were negatively and significantly associated with both systolic and diastolic blood pressure, even after adjusting for covariates. This potentially suggests that manganese protects against high blood pressure, a relationship that has been explored in previous studies but lacks strong, consistent evidence. Both Jiang and Zheng  and Lee This finding could have important implications since hypertension is a major cause of cardiovascular disease, which according to a 2017 report released by the American Heart Association , is stilThere are several limitations to this study. First, urinary manganese may not be the most accurate measure of Mn exposure. Because of the limited number of studies available, a standard biomarker for measuring Mn exposure has not yet been established. Previous studies suggest that manganese in blood and urine can be used to detect higher-than-normal manganese levels in groups of people, but they are not as successful in reflecting individual Mn exposure ,14. ThisThis study used two cycles of NHANES data from 2011 to 2014. Among the study population, there was a significant negative correlation between urinary manganese and systolic and diastolic blood pressure after adjusting for age, sex, BMI, race/ethnicity, and status of antihypertensive medication. Future research should focus on studying manganese and its relationship with blood pressure and cardiovascular outcomes, as well as establishing a standard biomarker of exposure for manganese.


PurposeTo compare visual outcomes and satisfaction among patients of photorefractive keratectomy  and femtosecond laser-assisted in situ keratomileusis .MethodsWe performed a retrospective study of 409 eyes in 207 patients that underwent either PRK (n=90) or FAL (n=117) at the two centers of Hashmanis Hospital, Karachi, Pakistan. The included refractive outcomes were sphere diopters (D), cylinder D, and spherical equivalent D. Additionally, visual acuities were included. All of these were assessed preoperatively and at the one-month postoperative check-up. Patient satisfaction was gauged at the time of chart review by contacting the patient.ResultsWhen looking at the postoperative outcomes, we found all values to be statistically significant (p<0.001) with superior outcomes in the FAL cohort. Additionally, 90% and 15% of eyes achieved a postoperative uncorrected visual acuity (UCVA) of 20/20 in FAL and PRK, respectively. Furthermore, the efficacy indexes of the FAL and PRK arms were 1.00 and 0.82, respectively. The predictability of the procedures were 92.1% and 64.9%, respectively. Lastly, 93.3% of patients were satisfied with FAL and 95.7% with PRK.ConclusionOur study shows superior visual outcomes in patients undergoing FAL. However, we found a higher satisfaction rate in those that underwent PRK, perhaps due to the higher cost of FAL. The past few decades have witnessed several advancements in the field of refractive surgery. One procedure, photorefractive keratectomy , involves the use of an excimer laser to ablate the corneal stroma after epithelial debridement . The sucThe initial flap in LASIK was traditionally created by a microkeratome. With recent advances, however, it has become possible to create flaps using a femtosecond laser; this variant is known as femto LASIK . FAL creates planar flaps that significantly decrease flap associated complications. Additionally, a smaller deviation in flap thickness is noted when compared to microkeratomes . One stuAlthough studies have evaluated postoperative results of LASIK in Pakistan -11, nonePatientsWe conducted a retrospective analysis of 409 eyes (207 patients) that underwent FAL and PRK at the Hashmanis Hospital, Karachi, Pakistan. Of these, 229 (117 patients) underwent FAL and 180 (90 patients) underwent PRK. The study period lasted from January 2014 to October 2016. All variables were recorded both preoperatively and at the one-month postoperative checkup. Three surgeons performed PRK while one performed FAL. Ethical approval was provided by the Ethics Committee of Hashmanis Hospital and patient consent was sought before carrying out the procedure.Inclusion and exclusion criteriaFor both procedures, our inclusion criteria were: age greater than 18 years with a stable refraction, central corneal thickness (CCT) greater than 480 μm, a presumed residual stromal bed greater than 250 μm, and discontinuing contact lens use for more than a week.The exclusion criteria included any active or residual ocular pathology, like glaucoma or retinal dystrophy, and dry eyes with a Schirmer’s two test value below 2 mm. Furthermore, those who were immunocompromised, pregnant, or nursing were excluded as well.All patients underwent the routine ophthalmological examinations prior to surgery. These included: uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), cycloplegic and subjective refractive error, slit lamp examination, dilated retinal exam, ultrasonic pachymetry, keratometry, and corneal topography.Attempted refractionThe attempted postoperative refraction was emmetropia in all patients that were either greater than -12.00 diopters (D) or less than 6.00 D. For those with a greater refractive error preoperatively, the target was the refractive error subtracted from the above values. However, both targets were dependent on the keratometry reading.The efficacy index was defined as the ratio of the mean postoperative UCVA to the mean preoperative BCVA. Predictability was the percentage of eyes that achieved the target spherical equivalent within ± 1.00 D. Procedure and postoperative careIn the FAL arm, a 120 μm flap was created using a Wavelight FS 200 laser and stromal ablation was performed by the Wavelight EX 500 machine. A tissue separator was used to raise the initial flap and the eye was irrigated using a balanced salt solution after flap replacement at the end of the procedure.During PRK, we used 18% alcohol for 18 seconds to achieve a 9 mm zone of epithelial debridement. Then, we completed a central ablation of 6.5 mm with an excimer laser using a Wavelight EX 500 machine. Subsequent to the procedure, we used a bandage soft contact lens on the cornea.After both surgeries, the patient was advised to follow certain postoperative measures. These included: artificial tears four times a day for three weeks, moxifloxacin eye drops four times a day for 10 days, and combination drops with tobramycin and dexamethasone, four times a day for 10 days. For PRK, we started fluoromethalalone eye drops four times daily for 15 days after stopping the combination drops of dexamethasone and tobramycin.Patient satisfactionPatient satisfaction was tabulated by contacting the patient at the time of chart review. We recorded the response in the following categories: “extremely satisfied”, “very satisfied”, “satisfied”, and “not satisfied”.Statistical analysisThe analysis was performed using the Statistical Package for the Social Sciences (SPSS) , version 23 software. The graphs and tables were constructed using Microsoft Excel  and SPSS. The Shapiro-Wilk test was used to test for normality and the Mann-Whitney U test was used to compare the refractive outcomes. A P-value less than 0.05 was considered to be statistically significant.General characteristicsA total of 409 eyes of 207 patients  were treated. Of these, 229 eyes  underwent FAL and 180  underwent PRK. This is seen in Table Efficacy and predictabilityFor the PRK cohort, the preoperative and postoperative spherical means were -5.0 ± 2.7 D and -0.3 ± 1.5 D, respectively. For the FAL group, they were -4.3 ± 2.3 D and 0.3 ± 0.7 D, respectively. The cylinder preoperative and postoperative means for the PRK arm were -1.0 ± 0.8 D and -0.8 ± 0.6 D, respectively. For FAL, the values were -1.0 ± 1.3 D and, -0.5 ± 0.6 D, respectively.Finally, the PRK cohort’s spherical equivalent preoperative and postoperative means were -5.4 ± 2.7 D and -0.6 ± 1.6 D, respectively. Comparatively, the FAL group’s means were -4.5 ± 2.5 D and 0.0 ± 0.7 D, respectively. All data mentioned above are represented in Tables The preoperative values of the procedures were statistically insignificant in all cases. The postoperative values, on the other hand, were statistically significant.As shown in Figure Patient satisfactionOut of the 75 FAL patients, 93.3% were satisfied (n=70), of which, 13.3% (n=10) were extremely satisfied, as shown in Table PRK has been compared with a variety of LASIK techniques; for example, LASIK performed with a microkeratome  or FAL . HoweverSajjadi, et al. and AlMahmoud, et al. found no statistically significant difference in the refractive outcomes between the two procedures , 14, unlIn this study, 90% of FAL patients achieved a UCVA of 20/20, whereas, only 15% of PRK patients achieved this outcome. Several studies agree with our findings as well . AlMahmoIn our population, the PRK and FAL efficacy indexes were maintained at 0.82 and 1.00, respectively. One meta-analysis conducted in 2006 concluded that the FAL arm had superior efficacy when compared to that of PRK . HoweverIt was interesting to note that a greater percentage of patients were satisfied with PRK despite superior outcomes in the FAL arm. This can be explained by the significantly higher cost of FAL and, therefore, greater expectations from the procedure. We recommend a cost analysis of FAL to determine the efficiency of using this procedure at its current price.There are several limitations to consider in this study. Firstly, this is a retrospective analysis and all associated limitations apply. Secondly, the prevalence of higher order aberrations could not be assessed due to technological deficiencies at our facility. Thirdly, this was a short-term study, and therefore, outcomes in the long-term could not be assessed. Lastly, we did not assess the complications of the two procedures.Our study shows superior visual outcomes in patients undergoing FAL. However, we found a higher satisfaction rate in those that underwent PRK, perhaps due to the higher cost of FAL.