Determination of skeletal maturity and bone age from cervical vertebrae has been well documented. Most methods described use subjective evaluation of morphological characteristics of cervical vertebrae and may be prone to variability and error. A few objective methods have also been developed, specific for certain populations and genders. The aim of this study was to establish and validate an objective method to determine cervical vertebral bone age from lateral cephalometric radiographs, for Asian South Indian patients of both genders.Ninety boys and 90 girls between 9 and 15 years of age were recruited, and their lateral cephalograms were taken. Using measurements made from the third and fourth cervical vertebrae, a formula to determine cervical vertebral bone age was derived using stepwise regression analysis. To validate the formula, a separate sample of 30 boys and 30 girls was chosen, and hand-wrist radiographs and lateral cephalograms were obtained. Cervical vertebral bone age (CVBA) was determined by applying the formula derived. Bone age was also calculated using the Tanner-Whitehouse 3 method. The bone ages determined by both methods were compared to each other and chronological age, using one-way ANOVA, Tukey’s post hoc analysis, and Pearson’s correlation coefficient.p value = 0.425) and girls . A moderate to strong positive correlation was found between CVBA, bone age, and chronological age.The formulae derived in the current study to determine CVBA differed for both genders. No statistically significant difference was found between CVBA, bone age derived by the Tanner-Whitehouse 3 method, and chronological age for both boys (The formulae derived in this study were validated and are reliable for objectively determining cervical vertebral bone age and skeletal maturation from lateral cephalograms for Asian South Indian patients of both genders. Craniofacial growth is an integral part of orthodontic diagnosis and treatment planning. Growth is characterized by variation in the amount, rate, time, pattern, and progress towards maturity . EvaluatThe developmental status of a growing child can be assessed by various indicators, including chronological age, dental development, secondary sexual characteristics, peak height velocity, and skeletal maturation –5. ChronTo reduce both radiation exposure and diagnostic cost to the patient, assessment of cervical vertebral maturation, as seen in routine lateral cephalograms, has been explored. Lamparski  was the Since then, cervical vertebral maturation method has been increasingly used to determine skeletal maturation in dentofacial orthopedics, without the need for hand-wrist radiographs , 3, 18. Till date, there is inadequate literature on objective evaluation of CVBA in the Asian South Indian population. The aim of the present study, therefore, was to establish and validate a formula in this population group that would determine the skeletal age from cervical vertebral maturation indicators.The present prospective cohort study was designed to derive a formula to determine cervical vertebral bone age for boys and girls of South Indian origin and validate the same. Ethical committee clearance was granted by the Institutional Review Board of Saveetha University. The sample for the study was chosen from patients visiting the Department of Orthodontics, Saveetha Dental College, for orthodontic treatment. Patients in the age group of 9 to 15 years, in good general health and of South Indian origin, were included for the study. Patients who had a history of trauma, surgical intervention, or severe systemic illness or those who showed malformation of the cervical vertebrae or hand bones were excluded. Eligible patients were recruited serially until the desired sample size was achieved. The nature of the study was explained to the patients and their parents, and informed consent was obtained. As this study was restricted to Asian South Indians, patients who had one or both parents belonging to other ethnicities were also excluded.The study consisted of two phases. In the first phase, we attempted to derive a formula for determining the cervical vertebral bone age for both boys and girls. For this part, a total of 180 patients (90 boys and 90 girls), in the age group of 9–15 years were recruited. Patients were divided into six age groups  with 30 patients in each group (15 boys and 15 girls). For all patients, digital lateral cephalograms were taken .Cephalometric analysis was done according to the method described by Mito et al. . The outUsing the above measurements, seven ratios were calculated Table . PearsonThe second phase of the study attempted to validate the formula that was derived in the first phase of the study. A different sample of sixty patients of both genders, in the age group of 9–15 years, was chosen from patients visiting the Department of Orthodontics, Saveetha Dental College. The inclusion criteria were the same as that of part 1 of the study. The sample was subdivided into two groups, 30 each for boys and girls. Digital lateral cephalograms and hand-wrist radiographs (Wipro GE CARES DX525 radiographic machine) were taken for all 60 patients.All the 60 lateral cephalograms were analyzed. Cervical vertebral bone age (CVBA) was determined by applying the formulae derived during the first part of the study for both boys and girls. Hand-wrist radiographs were evaluated to determine bone age by Tanner and Whitehouse method (TW3). Specific ossification centers of the radius, ulna, selected metacarpals, and phalanges were assessed, leading to their classifications into one of several stages. The scores were derived from each bone stage and calculated to compute the skeletal age or bone age.The one-way ANOVA test was applied to identify differences between both the methods  and the chronological age. To identify specific differences, the Tukey’s post hoc test was used. The relationship between the cervical vertebral bone age and the other two groups was also determined using Pearson’s correlation coefficient.p value of less than 0.05 was considered as significant (α error—95%).All the above statistical analysis was done using SPSS version 15. The study power was set at 80% and a Analysis of the various parameters measured on third and fourth cervical vertebrae Figs. , and 5 rDahlberg’s analysis for intra-operator reliability gave values between 0.092 and 0.599. These values indicated adequate accuracy of measurement and reliability (DV < 1).Among the seven ratios established between the parameters measured for boys and girls separately, only five ratios in both genders showed a higher level of correlation with chronological age and were included in the formulae for determination of cervical vertebral bone age (CVBA). A gender variation was evident in the ratios selected for multiple regression analysis. Therefore, two separate formulae were derived to determine cervical vertebral bone age for boys and girls, through stepwise multiple regression analysis.3/AP3) − (0.087 × H3/AP3) + (2.26 × AH3/AP3) − (2.126 × AH4/AP4) + (8.513 × AH4/H4)Cervical vertebral bone age for girls: 0.774 + (4.033 × PH3/AP3) − (1.582 × H3/AP3) + (8.716 × CONC3/H3) + (1.753 × AH4/AP4) + (1.604 × H4/AP4)Cervical vertebral bone age for boys: 7.137 +  in the Asian South Indian population. Similar objective methods of determining CVBA have been utilized by previous researchers, in other ethnic groups. Mito et al.  was the The slight differences in formulae for the above studies could be explained by the fact that growth patterns tend to vary with race and gender. Zhang et al.  showed tAlthough skeletal maturation usually occurs in all seven vertebrae, only the vertebral bodies of C3 and C4 were selected for measurements. The first cervical vertebra is not clearly visible, and the second cervical vertebra shows minimal morphological changes. Cervical vertebrae below C4 cannot be visualized when a thyroid protection collar is worn during radiation exposure , 19, 20.In the current study, for both genders, growth acceleration occurred between 13 and 14 years of age. This was reflected through changes in the anterior, middle, and posterior heights, as well as antero-posterior lengths. A distinct and pronounced growth was also noted in the posterior height of C3 in girls and anterior and middle height of C3 in males between 13 and 14 years of age. These findings contrast with those of Caldas et al., who noted that in their study, accelerated growth occurred in anterior, middle, and posterior height of C3 and C4 from 10 to 13 years in females . In maleThe formula derived by stepwise regression analysis was found to be substantially different from other studies. For Japanese girls, the formula included ratio of anterior height to anteroposterior length and anterior height to posterior height . The stuFor validating the formula, the Tanner-Whitehouse 3 method was used for evaluation of bone age from hand-wrist radiographs . The TanEstablishing skeletal bone age from cervical vertebrae can in turn predict other variables that may be useful for treatment planning. For instance, Sato et al. found that mandibular growth potential could be accurately assessed based on CVBA, which was useful in planning the timing of treatment, and treatment options in patients with class 3 malocclusions . StudiesThe main limitation of this study is that it was cross-sectional, and measurements for all patients were only taken at one point in time. A longitudinal study would have allowed further validation of the formula at different stages of maturation. However, this would have led to further radiation exposure and may have been prone to attrition bias.Most formulae generated for calculating cervical vertebral bone age in different ethnic groups are cumbersome and prone to error if worked out manually. The next logical step, as suggested by Caldas et al. , would bIn conclusion, the present study highlights that skeletal maturation indicators have slight variations across diverse ethnic groups, and may require different methods of objective evaluation. The formula derived in the current study has been validated for the Asian South Indian population and may be effectively used to determine cervical vertebral bone age from lateral cephalograms in this population.


Interventional bronchoscopy for hypoxemic patients with central airway obstruction (CAO) is typically performed under general anesthesia. This approach poses remarkable challenge for both bronchoscopist and anesthesiologist. Noninvasive ventilation (NIV) during flexible bronchoscopy (FB) has been successfully used in hypoxemic patients, but rarely in the treatment of hypoxemic patients with CAO.To evaluate the feasibility of therapeutic FB assisted with NIV for therapy of hypoxemic patients with CAO.Twenty-nine hypoxemic CAO patients treated with FB from December 2010 to May 2016 in our hospital were retrospectively reviewed, either aided with NIV under sedation (NIV group ) or through artificial airway under general anesthesia (control group). Interventional procedures included balloon dilation, electrocautery and argon plasma coagulationp = 1.0), procedure time  and oxygenation improvement between the two groups have no significant difference. Less reduction of systolic blood pressure and heart rate during procedure was observed in the NIV group. The NIV group showed shorter admission time before procedure than the control group . In addition, procedure fee in the NIV group was significantly less than that in the control group .Fifteen patients were enrolled in the NIV group and 14 in the control group. The success rate (93.3% VS 92.9%, FB assisted with NIV is a safe, efficient and economic method for therapy of selected hypoxemic patients with CAO. The syndrome of central airway obstruction(CAO), a common problem in medical and surgical settings , is gene2 by 10–20 mmHg  under general anesthesia performed in our hospital. The results of this medical research are reported as follows.This is a retrospective review approved by the Institutional Ethics Committee of the Eighth Affiliated Hospital of Sun Yat-sen University (Ref # 2016091001). Hypoxemic CAO patients who were treated with interventional flexible bronchoscopy in our hospital during the period between December 2010 and May 2016 were included. Verbal informed consent was provided by every participant or their legal representatives. The authors did not have access to information that could identify individual participants during or after data collection.Inclusion criteria are (1) patients conform to the diagnostic criteria of hypoxemic CAO; (2) Blood gas analysis on admission shows that PaO2 < 60 mmHg and CO2 PaCO2 ≥50 mmHg; (3) >50 years old; (4) on admission, with severe dyspnea symptoms, such as cough, purulent sputum, shortness of breath, jugular vein distention, etc.; with increased respiratory function, such as chest abdominal contradictory movement or intercostal muscle contraction.Exclusion criteria are (1) stent placement; (2) significantly enhanced computed tomography (CT) of the lesion ; (3) obvious respiratory depression, apnea, or obstruction of upper respiratory tract; (4) unstable cardiovascular system function, including hypotension, arrhythmia, myocardial infarction, or serious hemodynamic instability, no response to liquid therapy and vasoactive drugs; (5) the secretion is thick and large, which may cause aspiration; (6) serious liver and kidney dysfunction; (7) obesity, craniofacial trauma, nasopharyngeal abnormalities, etc., which can not be treated by FB; (8) other contraindication of FB as previously described . The intStandard preoperative assessment was made for each patient, consisting of laboratory investigations , diagnostic FB and chest CT. Data of location, percentage and length of the lesion and condition of distal airway were all obtained for making a decision of interventional procedure. Patients’ oral intake, except for water, was refrained for 4 h in the NIV group and 8 h in the control group prior to the intervention. All patients had venous access before the procedures.Additional exclusion criteria were ETI patients and patients with contraindications for NIV, including reduced level of consciousness, recent facial or esophageal surgery, and inability to tolerate the face mask .Patients were sent to the bronchoscopy center and initiated on NIV to allow acclimatization. Dezocine (2.5–5 mg) was given intravenously 10min before the examination while midazolam (1–3 mg IV) was given immediately prior to FB, according to age and body weight. 2% lidocaine was used as topical anesthesia. A swab with 1% ephedrine and 2% lidocaine was retained in one nostril, 5 min before the insertion of FB.2O, pressure support at 10 cmH2O and FiO2 at 0.30. These parameters were adjusted during the procedures to make sure SpO2>90% and tidal volume>8 ml/kg. FiO2 was confirmed at 0.4 or below before thermal ablation to avoid airway fire.NIV mode of the ventilator (MAQUET SERVO) was delivered with positive endexpiratory pressure (PEEP) via a resuscitation full-face mask secured with headstraps . PEEP waFB (OlympusBF-1T40) was performed after the patients had received topical anesthesia. A T-adapter was attached to the face mask for insertion of FB via nasal route. If this initial insertion failed, a mouthpiece was placed for oral insertion to replace. Additional lidocaine (2%) was administered through the bronchoscope as needed for topical aneasthesia of the airway. Subsequent boluses of 1–2 mg midazolam were administered if the subject was not sufficiently sedated during the procedure.Balloon Dilation, electrocautery needle /loop and APC via bronchoscope were selected solely or combined in accordance at the bronchoscopists discresion.2 at 0.4 or below just before thermal ablation to avoid airway fires.Patients were sent to the operating room,and subsequently Anesthetized intravenously. The intravenous anesthesia included target controlled infusion (TCI) of propofol (2 ug/ml) and remifentanil (4–6 ng/ml) with Dexmedetomidine (0.5 ug/kg/h). The patients were ventilated by volume-controlled mode of anesthesia machine (Dräger GS) through ETI or LMA via a T-adapter . Tidal volume, was set at 6∼10 ml/kg, respiratory rate at 12∼16/min and oxygen flow at 5 litters. Oxygen and air flow were adjusted to ensure FiODuring the procedures, pulse-oximetry and heart rhythm (5-lead ECG) were continuously monitored. For NIV group, automated noninvasive blood pressure was monitored, while for control group, an arterial catheter was inserted into radial artery for blood withdrawal and hemodynamic monitoring.p-value < 0.05 was considered statistically significant.All statistical analysis was done with GraphPad Prism4 software . Numeric and categorical parameters were analyzed by Fisher exact test. Differences of measurement data were presented as mean ±  standard deviation (SD) and were analyzed by t test for two groups or one-way analysis of variance for multiple groups. Mann–Whitney U test was used for analysis of admission hours before procedure and procedure fee. A A total of 29 patients were enrolled in this study: 15 in the NIV group and 14 in the control group. Subject characteristics of both groups were comparable based on age, gender, and concomitant diseases, including hypertension, coronary heart disease and COPD. There was no significant difference between the two groups in lesion characteristics, including malignant rate, elevated CT value and site of obstruction .2 during procedure and improvement of PaO2 in the NIV group were similar to those in the control group , p < 0.0001), Less reduction of systolic blood pressure and heart rate during procedure was observed in the NIV group . CompareThe present study shows that the use of NIV is both safe and cost-effective in the treatment of hypoxemic patients with CAO.2 between the two groups during procedures. All the procedures were successfully performed. However, the suppression of blood pressure and heart rate is less in the NIV group than that in the control group. FiO2 and PEEP can be adjusted with NIV to ensure oxygenation, and inspiratory pressure can also be adjusted to ensure adequate ventilation. In case of longer procedure duration, Midazolam and dezocine, which were effective in our previous diagnostic bronchoscopy research (Safety is the top concern of interventional therapy for hypoxemic CAO. There is no significant difference in SpOresearch , are useAs bronchoscopy for the control group is performed through an artificial airway under general anesthesia in the operation room, the patients and the interventional equipment in the control group have to be moved to operation room for the procedures. Sometimes the procedures are delayed due to the unavailability of operation room or skillful anesthesiologist. In contrast, procedures to the patients in the NIV group are performed without anesthesiologist in the bronchoscopy room. The procedures are carried out during NIV with normal adapter via resuscitation mask under moderate sedation. All the instruments, including NIV machine, adaptor and mask, are easy-to-get and equipped in the bronchoscopy room. As we Chinese pulmonologists are familiar with NIV and sedation techniques, the procedures are convenient and smooth.The procedure duration of the control group is similar to what was described in the previous reports, from 67 min to 87 min . AlthougAs it may be hard to handle massive hemoptysive under NIV, significant CT enhanced lesions are excluded in the study. It has been shown that both the incidence and mortality of massive bleeding induced by therapeutic bronchoscopies are significantly higher than those by diagnostic bronchoscopies . In the As mentioned above, the procedures in the control group sometimes are delayed. Therefore, the admission hour before procedure in the NIV group is significantly shorter than that in the control group. The cost for the procedures in the NIV group, without general anesthesia and the involvement of anesthesiologist, is also significantly lower than that in the control group.This study has some limitations. First, it is a retrospective study. Second, due to the limitation of case number in our hospital and the lack of medical records of some patients, the number of patients included in this study is small, and the reliability of the conclusions is weak. The number of samples needs to be further expanded to increase the credibility of this study. Third, procedures on most patients in the control group were performed prior to those in the NIV group, introducing the possibility of increased operation experience in the NIV group. Fourth, stent placements were excluded as it is hard to place airway stent with FB under NIV. Fifth, significant CT enhanced lesions are excluded in the study to avoid massive hemoptysis which is hard to manage in study group.In conclusion, the use of NIV with moderate anesthesia may be a safe and cost-effective procedure for non-stent therapeutic brochoscopy in treatment of hypoxemic CAO patients with: mild to moderate CT enchanced lesions. More perspective studies with larger sample sizes are required to make a more thorough assessment of the technique.10.7717/peerj.8687/supp-1Data S1Click here for additional data file.


Knowledge regarding pain relief during labor remains insufficient. We aimed to determine and compare the effectiveness and safety of epidural analgesia, combined spinal–epidural analgesia, and parenteral meperidine on both mothers and fetuses. This study was designed as an observational case-control study. We collected prospective data from patients whose labor pain management was conducted with meperidine in addition to retrospective cohort data of neuraxial methods; 138 patients were enrolled. Epidural analgesia group consisted of 68 patients, whereas combined spinal-epidural (CSE) analgesia group and meperidine group consisted of 50 and 20 patients, respectively. We compared the delivery patterns, labor durations, pain levels, side effects, maternal satisfaction levels, and neonatal outcomes of the various pain management methods.  Patient demographics, duration of first, second, and third labor stages, and instrumental delivery rates were comparable among groups (P > 0.05). Cesarean section tended to be less frequent in the CSE group. In the meperidine group, visual analog scale (VAS) values and sedation were significantly higher (P < 0.001) and maternal satisfaction lower (P < 0.001). Hypotension tended to be more frequent in the meperidine group. APGAR scores at the 1st and 5th min were similar among the groups and between meperidine subgroups defined by three different administration times . Neuraxial methods had no effect on instrumental delivery rates. CSE represented a near significant risk reduction in cesarean section. Our results demonstrated that regional analgesia methods were reasonably safe for both mother and fetus, and regional analgesia methods resulted in greater maternal satisfaction and pain control compared to meperidine.  Labor pain is one of the most painful experiences for most women. It alters respiratory, cardiovascular, neuroendocrine, and limbic systems and may lead to adverse outcomes as a result. In addition, it triggers psychodynamic behaviors resulting in stress and anxiety [1], which might cause metabolic acidosis and decreased uteroplacental blood flow [2]. Achieving sufficient pain relief is a significant factor for successful labor and maternal satisfaction. Numerous pharmacological and nonpharmacological methods are currently being used to reduce labor pain [3]. The choice of analgesic method depends on the expectations of the mother, the joint decision of anesthesiology and reanimation and the obstetrics clinics, and the progress of labor [4]. Neuraxial methods provide almost perfect pain control when the mother is fully awake and cooperative [5]. The side effects of these methods on the maternal cardiovascular-pulmonary system and fetal physiology are considered minimal [6]. However, there is conflicting information regarding the issue. There are studies reporting that neuroaxial analgesia significantly increases the cesarean rate , whereas some studies reported the contrary . Furthermore, controversies remain regarding the risk of instrumental delivery. Instrumental deliveries are associated with various long-term disadvantages, including an increased likelihood of fecal incontinence, sexual dysfunction, and hospital stay extensions [11–13]. Recent trials have reported the lowered risk of instrumental delivery with modern low-dose epidural regimens; however, these regimens do not completely mitigate these adverse outcomes. Systemic analgesics may be used for pain relief in labor. The commonest opioid used for labor is meperidine [14], administered by intramuscular (im) injection. Meperidine remains the standard of care for labor pain in some clinics; it can also be used at the request of the patient or in cases when neuraxial analgesia is not feasible. However, current knowledge remains uncertain. Some studies have reported an increase in the frequency of the neonatal depression when delivery occurred after 2‒3 h after meperidine administration [15] while some studies have not . Furthermore, there is a gap of knowledge in terms of maternal satisfaction with meperidine treatment [18]. In 2018, a Cochrane review assessed the effectiveness and safety of all types of epidural analgesia on mothers and infants compared to nonepidural methods. They reported the superior efficacy of epidural analgesia in reducing pain and improving maternal satisfaction. In addition, they reported that studies regarding this topic provided low-quality evidence, limited by inconsistency and imprecision and underlined the need for more robust research to evaluate possible maternal and fetal effects, in particular, side effects and maternal satisfaction[18].In view of the controversies and knowledge gap existing in the literature, we aimed to determine the effectiveness and safety of epidural analgesia, combined spinal–epidural analgesia, and parenteral meperidine on both the mother and fetus.n = 35), gestation week lower than 37 weeks or higher than 41 weeks , catheter problems , and spinal anesthesia (n = 5). Eventually, the retrospective arm comprised 118 patients, including 68 patients who were administered with epidurals and 50 patients with CSE analgesia. In addition to the retrospective cohort data, we collected the prospective data of patients whose labor pain management was done with meperidine. Twenty patients who were unwilling to have neuraxial analgesia and given instead meperidine according to the standard protocol were included in the study. Patients who were in gestational periods less than 37 or higher than 41 gestational weeks were excluded in addition to those with fetal presentation and multiple pregnancies.This study was designed as a case-control study. Informed consent was obtained from patients. This study was approved by the ethical committee of Hacettepe University (Date: 24/06/2015- Number: 16969557-721 NO: GO 15/376-15). After the approval of the local ethic committee, the files of patients who had regional analgesia for labor pain were analyzed retrospectively. Among 167 cases, 49 cases were excluded due to missing data ;· intervention information ; · complications, presence, and duration of motor-sensorial block; · cervical dilatation and contraction rate at the moment of catheter insertion, durations of the Stages 1, 2, and 3;· amount of drug used during infusion, bolus amount, other drug use, the number of bolus need; · hemodynamic data ;· delivery patterns , usage of vacuum or forceps, indication for cesarean section, if there is any;· general pain evaluations ;· maternal satisfaction levels ;· newborn outcomes .For the CSE technique, 15‒25 µg of fentanyl with 2.5 mg bupivacaine was used for spinal analgesia. Continuous infusion was started half an hour after the spinal application. In the pure epidural technique, bolus 0.125%‒0.25% bupivacaine (10 mL) was given after the test. In both methods, after the block placement, patient-controlled analgesia (PCA) with baseline infusion followed. The baseline rate was set to 8‒12 mL/h, the bolus to 5 mL, the lock duration to 10 min, the hourly limit to 30 min with a solution of 1%‒2% µg/fentanyl and 0.0625% bupivacaine. We considered birth a natural process. If patients demanded pain control, we offered neuraxial analgesia as the standard treatment for labor pain. Patients who did not want neuraxial analgesia and those administered meperidine for labor pain were enrolled as the prospective observational group; 25 mg intravenous (IV) and 50 mg intramuscular (IM) meperidine were administered to these patients, respectively. Aforementioned variables, with the exception of the intervention and regional block information, were also recorded for those patients administered meperidine.The data were analyzed with SPSS 21.0 for Windows. We examined the suitability of the numerical variables to normal distribution using visual (histogram and probability graphs) and analytical methods (the Kolmogorov–Smirnov/Shapiro–Wilk tests). We made comparisons of numerical data between groups using analysis of variance (ANOVA) or Kruskal–Wallis (where appropriate). A 5% type I error level was used to infer statistical significance. Further pairwise comparisons were analyzed with post hoc Tukey test or Mann–Whitney U-tests using Bonferroni correction and setting the statistical significance at 1.67% type I error level (where appropriate). p1 represents hypothesis between the epidural and CSE groups; p2, between CSE and meperidine group; and p3, between the epidural and meperidine groups. We compared nominal data with Chi-square or Fisher’s test. We presented descriptive analyses as mean ± standard deviation (s.d.) or median (minimum and maximum) values according to distribution. Exceptional cases were specified on the tables. The minimum number of participants required was determined using power analysis. In order to detect a minimum clinically significant difference of one-unit change on the satisfaction scale with a statistical power at the 80% level and 5% type-1 error, we selected a minimum of 20 patients for meperidine treatment and at least 50 participants for each of the other two groups.Table 1 details the demographic and clinical characteristics of the patients. Epidural treatment included 68 patients, CSE treatment included 50 patients, and the meperidine group included 20 patients. The mean age of the patients was 27.3 ± 4.9 years, and the mean gestational age was 39 ± 1.0. Age, body mass index (BMI), gestational age, nulliparity, ASA classification, and cervical dilatation at the time of catheter insertion were comparable between the groups. No significant difference between drugs’ doses (infusion/bolus/infusion+bolus) in epidural and CSE groups (P > 0.05) were detected.Table 2 outlines labor and delivery characteristics. One hundred patients (72.5%) delivered their infant via normal vaginal delivery, and 38 (27.5%) ended up with cesarean sections. The duration of the vaginal delivery stages was similar between groups (P > 0.05). Instrumental delivery was used only for one patient in the epidural group (P = 0.55). There was a trend towards to decrease of risk in the cesarean delivery rate in the CSE group .n = 45) and ≥4 cm (n = 42). There was no statistically significant difference among the groups regarding the proportion of the nulliparity (P = 0.76). The duration of the first stage was 12 h  in patients with cervical dilatation measuring <4 cm at the time of catheter insertion, 7.25 h  in patients with cervical dilatation measuring ≥4 cm. The duration of the first stage was significantly longer in the group with cervical dilatation measuring <4cm (P = 0.012). The duration of the second stage was similar .Among patients who were applied neuraxial methods, those who gave birth through vaginal delivery were divided into two groups according to the width of cervical dilatation at the time of catheter insertion: <4 cm (n = 21), arrest of labor (n = 13), patients own will (n = 1), an unknown indication (n = 2), and uterine tetany (n = 1). The cesarean section rates due to deceleration or arrest of labor were comparable between groups (P > 0.05). Maternal satisfaction and VAS values at the 15th min, first stage, second stage, time of episiotomy, and time of pushing were differed between groups (P < 0.001). Pairwise comparisons demonstrated that VAS values in the meperidine group were significantly higher, whereas maternal satisfaction was lower (P < 0.001) . Cesarean section was performed due to deceleration in the nonstress test (NST) (n = 2), small gestational age (n = 2), and unknown indication (n = 2).Table 3 details the motor block and side effects of the various methods. Motor block and pruritus was comparable between groups . Sedation was more frequent in the meperidine group, whereas hypotension was more common in the CSE and epidural groups. Frequency of nausea, vomiting, shivering, need for ephedrine use, and back pain were similar among groups. The 1st- and 5th-min Apgar scores were similar between the epidural, CSE, and meperidine groups . Apgar scores in the 1st and 5th min were not affected by the elapsed time between meperidine administration and birth . Six infants all of whom were delivered with epidural analgesia (P = 0.047) were admitted to the neonatal intensive care unit due to respiratory distress  that we used. Besides the techniques used, the variable rates of instrumental and cesarean delivery could also be explained by the experience of the center and the history of the patient population.Second, we found that regional analgesic methods did not affect the duration of the various labor stages in the whole study population. However, subgroup analysis revealed that the first stage of delivery was lengthened for patients whose cervical dilatation was less than 4 cm at the time of catheter insertion. In accordance with our findings, studies have indicated that regional anesthesia that were initiated when cervical dilatation was less than 4 cm prolonged labor . On the contrary, a randomized controlled study showed that regional anesthesia had no effect on labor durations, instrumental delivery, or cesarean section rates, even when neuraxial intervention was applied for under 2 cm of cervical dilatation [22]. Third, we found the decrease in the VAS values were significantly higher in patients whose pain management was done with epidural or CSE analgesia compared to the meperidine group. These results are in agreement with previous studies [23–25]. Indeed, our results are noteworthy. We selected patients who expressed an explicit desire not to have an epidural analgesia; in that case, the prospect of access and knowledge to better care could not bias results. Although patient satisfaction was significantly lower in the meperidine group, it was better than our expectations. This may be due to the sedation and drowsiness caused by meperidine. In a metaanalysis from 2010 [15], it was shown that sedation and somnolence were more frequent in patients who were on meperidine. There was no difference among the groups in terms of the 1st- and 5th-min Apgar scores of the newborns of patients, which is also consistent with the literature .Fourth, we demonstrated that the administration time of meperidine did not affect the fetal outcomes. It has been shown that the peak plateau level of the fetal concentration of meperidine appeared 1‒5 h after administration. Although reports on the issue have been conducted, the clinical significance of different administration times have not been proven yet [15]. In our study, considering meperidine pharmacokinetics [29], patients who completed vaginal delivery were divided according to elapsed time between the birth and the meperidine administration . First- and fifth-minute Apgar scores were similar in these groups.The neonatal ICU admission rates were higher in the epidural group. This result was somewhat unexpected since the neonatal intensive care admission rates are known to be similar among the different analgesia groups [27]. Selection bias might explain this since three of the newborns were already scheduled for neonatal intensive care follow-up before the initiation of labor. However, as per the reported limitations of the recent Cochrane review [18], it is important to report any kind of side effects that may be associated with neuraxial analgesia. Ours is one of the very few studies that have analyzed the effects of all three techniques on the entire range of outcomes related to the mother and fetus. However, the retrospective nature of the neuraxial groups remained a major limitation. Our study sought to respond to the contradictions in the literature and reported the efficacy and side effects of each method meticulously. We demonstrated that regional analgesia methods were reasonably safe for both mother and fetus and that regional analgesia methods resulted in greater maternal satisfaction and pain control compared to meperidine. Extensive patient monitoring and accurately chosen methods with appropriate dosing of local anesthetics could minimize the side effects of neuraxial methods. The authors have no related conflict of interest to disclose.


Free-range facilities may present a biosecurity risk in some situations, but range use has also been associated with better hen welfare. We investigated the association between early-life range use (when hens were 18–21 weeks of age) and hen survival during the entire housing period as well as various health and welfare parameters at 74 weeks of age. Hens that preferred to use the range at early life were three times more likely to survive. Early range users were also 1.6 times more likely to become infected with gastrointestinal nematodes and showed significantly more frequent signs indicating spotty liver disease. Hens that preferred to stay in the shed during early life had a higher prevalence of Fatty Liver Syndrome and significantly less feather cover. In conclusion, hens that do not range during early life may benefit from additional management strategies to increase their likelihood of survival. Further investigations under controlled environmental conditions are warranted to quantify further the observed effects.p = 0.001). Overall, rangers had significantly better feather cover and more lesions associated with spotty liver diseases compared to roamers and stayers (p = 0.001). Similarly, rangers and roamers had a higher prevalence of A. galli infection and less frequent signs of fatty liver syndrome compared to stayers. Rangers had a higher proportion of hens with full ovary follicle production compared to stayers and roamers (p = 0.035). This information is highly relevant to consider the targeted support of different flock subpopulations to improve hen health and welfare, directly affecting farm profitability. Further research on other farms is warranted to investigate the transferability of the observed results.While free-range laying hens frequently experience health and welfare challenges, the contribution of range use towards these risks are largely unknown. The aim of this pilot study was to investigate the survival, health and welfare of commercial free-range laying hens and explore the association with early range use. Range use of 9375 Lohmann Brown hens housed within five flocks was assessed during 18–21 weeks of age and individual hens were classified as “rangers” (frequent range users), “roamers” (intermittent range users), and “stayers” (rare/no range users) were then subject to necropsy at 74 weeks of age. Rangers and roamers were three times and 2.4 times more likely to survive than stayers, respectively ( One of the main goals of free-range egg production is to optimise laying performance and egg quality while supporting hen health and welfare. However, opportunities provided in the free-range system allow for the expression of a variety of behaviours, interactions and physical experiences  which may impact hen health, welfare, and survival ,2,3. ForMany investigators described a non-uniform range usage where up to 21% of hens within a flock never accessed the outdoors within a given time period ,26. The All procedures carried out in this study were approved by the University of New England’s Animal Ethics Committee (AEC 16-087).A total of 5 flocks (Flocks A–E) each housing 40,000 Lohmann Brown hens were kept on the same commercial farm. In each flock, 3125 randomly chosen hens were leg-banded at the day of placement (at 16 weeks of age) for individual identification and then placed in partitioned cross-sections of the shed, allowing for the monitoring of individual range access using a Radio-Frequency Identification (RFID) system with technical details described and validated in Sibanda et al., (2020c) . All henBased on the early range usage of the 3125 hens/flock during 18–21 weeks of age, individual hens were selected and arranged into 3 groups  with 625 hens/group, leading to the study population of n = 1875 hens/flock for further investigation. “Stayers” referred to the flock population that spent the least days on the range (4.72% ± 0.31% of their available days), “roamers” included those hens that occasionally visited the range (40.6% ± 0.74% of their available days), and “rangers” spent the most days on the range (77.8% ± 0.56% of their available days). These percentages equated to 2.09 ± 0.15 min/hen/day (stayers), 18.3 ± 0.51 min/hen/day (roamers), and 55.6 ± 0.76 min/hen/day (rangers) on the range. While initially 9375 hens were tracked (1875 hens in each of the 5 flocks), 4085 hens were excluded from the health and welfare statistical analysis at 74 weeks of age due to lost or malfunctioning RFID tags as well as hen mortalities. Details obtained from the surviving hens where range use could be recorded until 74 weeks of age are shown in Ascaridia galli  noted. Evaluation of the follicle ovulation stage of the ovaries was performed by visual scoring where 1 indicated no active follicles, 2 indicated the presence of follicles in late regression, 3 indicated the presence of follicles in early regression, and 4 indicated full follicle production. All observations of all hens were performed by the same investigator.At 74 weeks of age, flocks were subject to depopulation which allowed for individual evaluation of all surviving hens for gastro-intestinal helminths, keel bone damage, liver health, plumage condition and ovary egg follicle production. After the hens were captured, the identification number was recorded and the plumage damage for each body region  of individual hens was visually assessed using a 4-point system modified from Tauson et al. (2005) , where 1p < 0.05 unless stated otherwise. Four sets of data analysis are presented: firstly, mortality data were investigated using Kaplan-Meyer survival analysis including the Log-rank (Mantel-Cox) test and the Gehan–Beslow–Wilcoxon test with censored data based on day of death. This was followed by the calculation of the odds ratios for survival. Furthermore, odds ratios were calculated for each health parameter obtained at 74 weeks of age using a nominal regression model. The keel bone and fatty liver scores were modified and reported as the presence and absence of findings regardless of the severity to calculate the odds ratio. Secondly, descriptives of flock and subpopulation regarding keel bone damage, cestodes and A. galli infestations, spots on the liver, Fatty Liver Syndrome, egg follicle, and feather  are presented where the individual hen (n = 5290) was used to describe the flock and group proportions. In all parameters, the percentage proportion of hens with different scores in each treatment group was calculated using the total number of hens in each treatment group while the total proportion was calculated using the total number of hens in the flock. Thirdly, to investigate the impact of early range use on health parameters at the end of lay, the average score of all flocks was analysed using a restricted maximum likelihood (REML) model with the sub-group as a fixed factor, flock as random factor and the individual hen as statistical unit. The REML was used to reduce the effect of the non-independency of data points and the unbalanced design. Random effects in the REML allow for the control of non-independence by constraining non-independent ‘experimental units’ to have the same intercept and slope [Data were analysed using JMP Statistics software  and statistical significance set at nd slope ,32. Furtp < 0.001; p = 0.001), while the roamers were 2.39 times more likely to survive compared to the stayers , respectively compared to stayers (p = 0.001), furthermore roamers were 1.31 more likely to be affected by cestodes compared to stayers. There was a significant flock*group interaction for cestodes infestation . Stayers had up to 3% less A. galli worms (p = 0.001) compared to rangers while rangers had a 10.8% and 19.3% higher prevalence of cestodes compared to roamers and stayers, respectively (p = 0.001). Furthermore, stayers had a significantly lower A. galli score compared to the roamers, rangers, and the pooled flock average . Rangers of Flock A had a higher spot on the liver score compared to the roamers and rangers in the same flock (p = 0.001). When comparing hens affected by spots on the liver, a total of 4.99% of stayers  had spots on their livers, while 6.12% and 8.62% of the roamers and rangers were affected . When all the five flocks were pooled together, up to 10.6% and 6.01% of the hens had mild and severe Fatty Liver Syndrome, respectively. Overall, a total of 15.2% of the 5290 necropsied hens from the five flocks were affected by Fatty Liver Syndrome.The stayers were 1.26 and 1.36 times more likely to be affected by the Fatty Liver Syndrome compared to roamers and rangers , and comparable good cover compared to rangers . The stayers and rangers had similar wing plumage condition scores of 3.17 ± 0.02 and 3.22 ± 0.02, which was statistically significantly lower compared to the roamers . There was a significant flock*group interaction (p = 0.001) when considering the cumulative feather score. Flock A and Flock B had the highest overall feather score while in Flocks C, D, and E, the stayers had significantly lower plumage condition compared to rangers.The prevalence of plumage condition of different body parts is shown in A significant interaction was observed between flock and group regarding egg follicle scores, where in Flock B & D rangers had significantly more egg follicles in full production compared to stayers, but in Flock E rangers had significantly less egg follicles in full production . When thp = 0.001; Stayers were three times more likely to experience overall mortality   where 66There was an overall high variation in keel bone damage which was similar to results obtained by others investigating non-caged housing systems ,56,57,58As mentioned before, it is a major limitation of this study that the lack of data obtained at hen placement does not allow us to investigate causation. Investigation of health parameters of individual hens at placement and at several time points during their laying cycle before depopulation would allow for more applied recommendations for egg producers to improve and maintain hen health and welfare. Resource occupancy combined with time series data might be indicators of health, welfare, and productive performance of free-range laying hens. Furthermore, these time series could then be used to predict the effect of resource usage on the health and welfare of the free-range laying hens. However, it is remarkable that early range use was still associated with significantly different outcomes 50 weeks later, despite a variety of factors that could have intervened during this time and despite the fact that many stayers become rangers later in life . To our In this pilot study, hen health and welfare at 74 weeks of age differed significantly depending on early range use, which suggests that early range usage could potentially be used as a predictor of these outcomes, which might further be modified if targeted management decisions would apply. Despite the fact that stayers, ranges and roamers have the same resources available and were exposed to the same microclimate , the prevalence of infectious diseases, such as Spotty Liver Diseases or intestinal parasites, differed significantly amongst these groups. This suggest that intervention can successfully reduce the transmission of these diseases within the flock. Despite the higher biosecurity risk associated with range use, rangers had a significantly higher chance of survival, according to several better health and welfare indicators. Further investigation of the causation could result in robust methods to predict overall health and welfare and allow for effective intervention methods.


In the present study we aimed to investigate whether the earlobe crease (ELC) might provide predictive information about white matter intensities (WMIs) in the brain that reflect brain aging. A total of 350 individuals examined from January 2016 to July 2016 were screened. Patients with known demyelinating white matter disease, neurodegenerative disorders, cerebrovascular event history, or brain tumors were excluded from the study. Finally, 285 cases were included in the study. The four-point cerebral intensity classification system of Fazekas was used in the evaluation of the brain. The ELC was evaluated by inspection.A total of 285 patients were enrolled consecutively. The incidence of WMI was significantly higher in patients with ELC than the others. Age  and ELC  were found as an independent determinants of abnormal WMI. ELC predicted abnormal WMIs with 89% specificity and 62% sensitivity.The presence of an ELC may provide predictive information in terms of detecting abnormal WMIs with prognostic impact in apparently healthy subjects. White matter intensities (WMIs) are generally discovered incidentally but are more prevalent with age, hypertension, and other cerebrovascular risk factors (1–3). WMIs are thought to be heterogeneous, such as in ischaemic small vessel disease (4). White matter injury lesions are associated with an increased risk of stroke (5), gait disturbance (6), cognitive impairment and decline (7), and dementia (8). In addition, white matter lesions from small vessel disease are associated with a regional pattern of gray matter atrophy that is reduced by blood pressure control, increased by aging, and linked with cognitive performance. In this regard, early detection of subtle WMIs might be important in terms of diagnosis and treatment, as some pharmacological and behavioral changes may delay the progression of WMI. WMIs are associated with cerebral ischemic white matter disease. WMIs are related to ischemic white matter disorders affecting the same region of the brain. The progression of small vessel disease is common and more extensive in patients with cardiovascular or cerebrovascular diseases and atherosclerotic risk factors. Cardiovascular risk factors are related to cerebrovascular morphology and WMIs (9). The skin fold from the tragus to the auricle is called the earlobe crease (ELC) . Several studies have demonstrated an association between ELCs and systemic atherosclerosis. As there is a close association between the ELC and atherosclerosis, we hypothesized that we could obtain information related to brain aging simply by observing the presence of the ELC.All patients referred to our department of neurology with headache or cognitive deterioration were consecutively included in the study.Patients with known demyelinating white matter disease, neurodegenerative disorders, cerebrovascular event history, or cerebral malignancies were excluded. This study was approved by the local ethics committee (2015/47) with written informed consent as acquired. This prospective study was designed according to the Helsinki Declaration and good clinical study guidelines. The individuals were examined with a 1.5 T magnetic resonance scanner (Siemens MAGNETOM Aera) in the department of radiology of a university hospital with routine clinical indications.A radiologist with more than 15 years of experience in neuroradiology performed all investigations. The radiologist was blinded to the clinical inspection findings, laboratory results, early clinically suspected differential diagnoses, and final diagnoses of the patients.A total of 350 subjects were evaluated in our MRI department from January 2016 to July 2016. Images from 17 patients were not obtained in sufficient quality because of patient movement. These 17 patients and 48 patients who did not want to participate in the study were excluded. Finally, 285 cases were included and 58 of these were evaluated as ELC-positive.A survey questionnaire was filled out by all participants after approval of the information form. First questions were asked about age, sex, hypertension, diabetes mellitus, and smoking; then the presence of neurological complaints, such as headache, dizziness, walking imbalance, sudden neurological complaints, and double vision, was addressed; and finally the presence of the ELC was evaluated by inspection.The standard MRI protocol for neuroimaging was as follows: T2-weighted axial plane, voxel size (VS) 0.9 mm × 1.12 mm, slice thickness (ST) 3 mm, interslice distance (ISD) 0.3 mm, TE 110 ms, TR 4250 ms, flip angle 90°, fluid attenuated inversion recovery (FLAIR); axial plane, sagittal plane, VS 0.9 mm × 1.12 mm, ST 4 mm, ISD 0.4 mm, TE 100 ms, TR 4000 ms, T1-weighted VS 0.94 mm × 1.13 mm × 2 mm, TE 4.6 ms, TR 9.1 ms, axial plane, VS 2.05 mm × 2.56 mm, ST 5 mm, ISD 1 mm, TE 25 ms, TR 700 ms, flip angle 90°. All images were stored in our hospital’s PACS DATA system.The MRI studies were evaluated by a radiologist with more than 15 years of neuroradiology experience. The Fazekas scale (10) was used to evaluate WMIs, especially on T2W FLAIR sequences, as an indicator of ischemic small vessel disease and brain aging.The T1WI and T2WI sequences were evaluated. T1WI is commonly used to evaluate anatomy and T2WI is used for additional pathological findings.The level of WMI was scored on the special cerebral hyperintensity classification system of Fazekas with four-point scale. The classification was evaluated on MRI images with the T1W, T2W, and FLAIR sequences. Images from Fazekas 0–3 scale examples are demonstrated in Figure 2.WMIs on MRI were described as indistinct hyperintense foci of 5 mm on both transverse T2 and FLAIR images. Ischemic lacunae were well-defined regions of hyperintense focuses of 2 mm on T2 as well as similar intensity of cerebrospinal fluid. Foci with similar size and appearance were considered as perivascular spaces. Nevertheless, perivascular spaces neighboring the anterior commissure may be larger. Basal ganglia lesions were evaluated similarly to white matter lesions, even those located in the gray matter.WMIs and lacuna observed on MRI in the elderly population are often regarded as a sign of ischemic small vessel disease. The overall degree of WMI in the brain can be assessed with the Fazekas scale. We used a four-point Fazekas scale scoring system to classify the WMIs. Fazekas score of 0 indicated normal white matter intensity without WMI, Fazekas 1 (F1) indicated multiple WMIs, Fazekas 2 (F2) indicated WMIs tending towards bridging, and Fazekas 3 (F3) indicated large, intermingled, and fused WMIs.F1 is accepted as normal in older adults. F2 and F3 are considered pathological, but may be seen in cases with normal intellect and function. On the other hand, this was a high-risk population for intellectual and functional loss, as subjects in the Fazekas 3 group have a 25% loss of function within 1 year (11).Three-year follow-up showed rapid functional loss in these patients with severe white matter lesions (12).Continuous variables are presented as mean ± standard deviation, and categorical variables are presented as percentages. The differences between the categorical variables between the groups were evaluated by chi-square test. P < 0.05 was considered significant. Sensitivity and specificity values were calculated when a significant threshold was found. Statistical analysis was performed with SPSS 22.0 (13).Analysis of the study population is presented in Table 1. Mean age was 58 ± 16 years. The ELC was found in 58 (20%) patients. A total of 233 (81%) patients had normal WMI compared to 52 (19%) patients who had abnormal WMI. Two groups were created from among the patients: group A had normal WMIs (Fazekas 0), and group B had abnormal WMIs (Fazekas score of ≥1). Age, presence of the ELC, and hypertension differed significantly between the two groups (Table 2). The frequency of WMI according to the incidence of the ELC is demonstrated in Figure 3.Binary logistic regression analysis was performed to identify the independent determinants of abnormal WMI (Table 3). It demonstrated that age  and the ELC  were independent determinants of the existence of abnormal WMI.We also calculated the specificity and sensitivity of the ELC in terms of diagnosing abnormal WMI. The ELC predicted abnormal WMI with 89% specificity and 62% sensitivity.In the present study, we have found a significant relationship between ELC and asymptomatic WMI. The ELC may be useful to predict WMI abnormalities with high sensitivity and specificity in an apparently healthy population.The incidence of cognitive impairment is increasing with aging, and its social, economic, and emotional burden is immense (14). Understanding the etiopathogenesis of impaired consciousness associated with aging can prevent this condition and protect cognitive abilities. Brain lesions due to ischemic small vessel disease and especially WMI have independently been related with cognitive impairment. Evidence suggests that white matter changes have a significant impact on daily activities, including gait and executive functioning. Silent brain infarction, i.e. WMI and lacunae viewed as cerebral small vessel disease, is being reported more frequently in older people with the development of medical technology (15). The Rotterdam MRI Scan Study showed that newly developed silent brain infarcts are associated with the presence of cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, carotid plaques, smoking, and age (15). Several reports revealed that the increasing severity of WMI and lacunae is related to a decline in cognitive function scores in these patients (15). Risks for cardiovascular disease and the development of cognitive impairment are the same. Cerebrovascular disease is considered an important contributing factor to vascular cognitive impairment. Furthermore, silent brain infarction provoked by small vessel disease, rather than large cortical cerebral infarction, is more considerable in the occurrence of vascular cognitive decline, although various cardiovascular risk factors are related with the development of both types of cerebral infarction.The relationship between cerebrovascular events and CAD suggests that brain and cardiovascular diseases may have similar etiopathogenesis, although both are strongly associated with advanced age.There is little known in terms of the possible etiopathogenesis producing ischemic small vascular disease in the brain and injury of CAD. However, the etiopathogenesis of both disease groups is closely related to atherosclerosis due to hypertension, endothelial damage, and local inflammatory events.The possible relationship between the ELC and CAD was first reported by Frank in 1973 (16). A recent review of the skin manifestations of atherosclerosis suggests that ELC may be an early marker of atherosclerosis (17). A metaanalysis suggested that ELC may be an early sign of CAD with 67% specificity and 62% sensitivity (18). In spite of these results, no certain statement of etiopathogenesis was determined between ELC and CAD.The myocardium and ELC have a common genetic microvascular origin (19) and therefore the ELC and CAD are thought to be formed by a common pathophysiological process due to atherosclerosis. In addition, the ELC is significantly associated with increased arterial stiffness and carotid intima media thickness, which are considered surrogate markers of atherosclerosis.Several limitations to our study should be mentioned. The size of the study was relatively small and it may not reflect the general population, as we did not include patients with overt cerebrovascular disease. The clinical significance of the WMIs found in our study was not established because of the absence of long-term follow-up. We also did not grade WMI abnormalities because only a few patients had a Fazekas score of ≥3. We attribute this to the study protocol, whereby we included only asymptomatic patients. Finally, our study design was cross-sectional; therefore, it did not provide any details related to the causative mechanisms of the association between the ELC and WMI.In conclusion, although the etiopathogenesis of the relation between the ELC and WMI remains to be clarified, this is the first study to report a highly positive association between the ELC and WMI in a large group of participants. Physicians could obtain valuable information related to the white matter of the brain by observing the ELC during clinical examinations.


Our aim was to investigate the effects of obesity and weight loss on aortic Pulse Wave Velocity as assessed by vascular magnetic resonance imaging.Obesity is an escalating global health problem associated with both an increased risk of death and an increased risk of cardiovascular events. The various mechanisms by which obesity mediates cardiovascular risk are not well understood but may be related to aortic stiffness, both present in obesity and linked to increased mortality. Our goal was to determine the effect of obesity, in the absence of the traditional cardiovascular risk factors on aortic pulse wave velocity (PWV) as assessed by vascular magnetic resonance imaging, a reliable, reproducible and accurate clinical measure of aortic stiffness.2) and eighteen normal weight controls (BMI 22.0 ± 1.7 kg/m2) with no identifiable cardiovascular risk factors underwent vascular magnetic resonance imaging at 1.5 T to assess of PWV at three points, the ascending (Ao) and proximal descending aorta (PDA) at the level of the pulmonary artery and the abdominal aorta (AA) 12 cm below the pulmonary artery. Aortic flow/time curves, at these three points, were used to calculate the arrival times of aortic pulse waveform. The time of arrival of the pulse wave (Δt (ms)) was determined to be the intercept of the tangent to the curve at the half maximal point of flow. The distance over which the pulse wave had travelled (Δx) was measured from oblique sagittal aortic images. PWV was then calculated as Δx/Δt. 28 subjects underwent repeat imaging after weight loss, 16 obese subjects underwent a supervised low glycaemic index diet, while twelve underwent bariatric surgery.Fifty obese . Obesity was associated with a 14% increase in PWV when compared to the normal weight controls (p = 0.021) and furthermore was associated with significantly higher leptin (p < 0.001) and C-reactive protein levels (p < 0.01), factors known to affect aortic mechanical function. After a one year period of weight loss  there was a significant 14% decrease in aortic pulse wave velocity when measured between the ascending and abdominal aorta (p = 0.03). In contrast, while showing a trend, aortic pulse wave velocity improvements in proximal sections did not reach statistical significance. Both leptin and C-reactive protein levels were also reduced with weight loss. See Table Obesity, in the absence of the traditional risk factors of hypertension, diabetes and hypercholesterolaemia, is associated with significant increases in aortic PWV, a non invasive clinical measure of aortic stiffness known to be independently predictive of cardiovascular mortality. Furthermore, a period of one year of weight loss is associated with a reduction in pulse wave velocity. This may provide a potential explanation for both the link between obesity and increased mortality, and the link between weight loss and increased survival.


PAX6 gene expression. WAGR syndrome is comprised of Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. Numerous genitourinary pathologies may be associated with WAGR syndrome, necessitating an evaluation of the genitourinary anatomy. The WT1 is vital for the development of kidneys, ovaries in females, and testes in males. WT1 gene mutations result in a WT1 protein with a decreased ability to bind to DNA, leading to uncontrolled growth, and cell division in the kidney which permits the development of Wilms tumor. A congenital ureteral valve is an exceedingly rare cause of obstructive uropathy.Congenital aniridia involves total or partial hypoplasia of the iris and is due to a deficiency in PAX6  and no abnormalities of WT1, excluding WAGR syndrome.A renal and bladder ultrasound demonstrated a renal cyst. A voiding cystourethrogram revealed grade 3 vesicoureteral reflux, and a MAG3 renal scan showed ureteropelvic junction obstruction and hydronephrosis. A ureteral stent was inserted at 3 months of age after which the renal cyst resolved. The patient was urinary tract infection‐free at 27 months of age. Genetic testing confirmed a heterozygous alteration in The genitourinary risks potentially associated with aniridia necessitate prompt genetic analysis to evaluate for WAGR syndrome. Congenital aniridia involves total or partial hypoplasia of the iris and is due to a deficiency in PAX6 gene expression. WAGR syndrome is comprised of Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. A congenital ureteral valve is an exceedingly rare cause of obstructive uropathy. The genitourinary risks potentially associated with aniridia necessitate prompt genetic analysis to evaluate for WAGR syndrome. There was no history of urinary tract infections, hematuria, or constipation. She was born full‐term to a mother who was positive for Group B streptococcus. The amniotic fluid volume was normal. The infant's mother, as well as maternal grandmother, uncle, and great‐grandfather all had congenital and isolated aniridia. Additionally, the infant's mother had photophobia and glaucoma, and the infant's father had incomplete achromatopsia (x‐linked blue cone monochromatism) and was red green color deficient with limited vision. The pediatric urologist discussed the association between aniridia and WAGR syndrome with the infant's mother and grandmother, as well as the importance of performing genetic testing on the infant to rule out WAGR syndrome due to the risk of malignancy.A 4‐week‐old girl (height: 20.5 inches (52 cm), 8 lbs [3.6 kg]; Body Mass Index [BMI]: 13.4 kg/mThe infant had bilateral aniridia Figure , roving 2.2A renal and bladder US at 3 days of age demonstrated a cyst on the superior aspect of the left kidney measuring 2.4 cm . This sequence change created a premature translational stop signal (p.Thr166Leufs*41) in PAX6. This was expected to result in an absence of disrupted protein product. This variant was not present in the population (ExAC) and has been reported to segregate with aniridia in two previous families . Therefore, this project did not require IRB review. The infant's mother provided written consent to use her daughter's medical records, photograph, and ultrasounds in our work.3An infant presenting with genitourinary and ocular abnormalities warrants a thorough investigation involving family history, imaging studies, and genetic evaluations. Wilms tumor is the most common renal cancer in childhood  and a negative WT1 which excluded WAGR syndrome.We report the first case in the literature of a patient with bilateral aniridia and a congenital ureteral valve. Renal scans were performed to evaluate her renal cyst diagnosed prenatally which revealed the ureteral valve in the left ureter. Following the opening of the ureteral valve by the stent at 3 months of age, the renal cyst resolved. The infant's genetic testing confirmed a heterozygous alteration in Exon 7 of 4The genitourinary risks and mental disabilities potentially associated with aniridia warrant prompt genetic testing to evaluate for WAGR syndrome. Recognizing Wilms tumor early and in its most treatable stage offers the best prognosis. A high level of suspicion of ureteral valves is warranted when encountering a patient with similar but more common conditions such as ureteral stricture, primary megaureter, and PUJ obstruction. Timely diagnosis and surgical intervention of ureteral valves increase the likelihood of preserving renal function. A multidisciplinary approach involving geneticists, pediatricians, pediatric urologists, radiologists, and pediatric surgeons is essential to promptly identify and successfully treat multiple renal pathologies that may afflict a single patient.The authors have no conflict of interest to declare.


Supraglottic superimposed high‐frequency jet ventilation (SSHFJV) maximises surgical field during endoscopic upper airway surgery.In our retrospective series of 224 cases, there was a low incidence (12%) of failure with the use of SSHFJV in upper airway surgery.Positive history of pulmonary pathology (OR = 4.91) and high BMI (OR = 1.15) were found to be significant independent factors for failure of SSHFJV in adult patients undergoing upper airway surgery.Converting ventilation techniques could be safely performed when SSHFJV failed.2 laser.SSHFJV is a safe ventilation technique during upper airway surgery, even in combination with the application of CO12 saturation and accumulation of CO2.During endoscopic upper airway surgery, anaesthetists and surgeons have to share the airway. Therefore, alternative ventilation techniques have been developed in the past decades. To optimise the surgical field high‐frequency jet ventilation (HFJV) was developed. A “tubeless” HFJV method has been introduced in the late 90s: supraglottic superimposed HFJV (SSHFJV).The aim of the present study was to identify factors which can predict failure of SSHFJV in upper airway surgery.22.1Data were retrospectively collected and the anonymity of the patients has been guaranteed; therefore, no approval of the Institutional Review Board is needed in accordance with Dutch Medical Research Law legislation.2.2This retrospective study included 163 adult patients who underwent 224 upper airway procedures with SSHFJV between November 2007 and November 2017 at our tertiary referral centre.2.3Under general anaesthesia, after pre‐oxygenation through a mask, a modified laryngoscope  was inserted and the SSHFJV was connected . Figure  During S2.4Relevant data from the electronic patients’ files were extracted and retrospectively analysed. Clinical imaging data were available in all cases and were reassessed to estimate the severity of the airway stenosis.The following variables were extracted from the electronic patients’ files: age, sex, weight, smoking status, comorbidity status (according to the Adult Comorbidity Index‐27 (ACE‐27) and the American Society of Anaesthesiologist Physical Status (ASA), and the presence of cardiovascular or pulmonary pathology), body mass index (BMI), airway anatomy , level of the actual airway pathology , severity of airway stenosis , diagnosis and type of surgery (including the application of laser).2.5When the saturation drops during ventilation with SSHFJV the anaesthesiologist may choose to intubate with endotracheal tube for a short period of time to reoxygenate. When the saturation of the patient is normalised, the operation with SSHFJV can be continued (temporary conversion); however, sometimes it is not possible (definitive conversion). Failure of SSHFJV was defined as temporary and/or definitive conversion.2.6t test was used in case of continuous variables.Patient characteristics and other variables were compared between the converted and non‐converted patients using chi‐square test (or Fisher's exact test). The P‐values were calculated.The potentially predictive variables for conversion of ventilation were analysed using univariable logistic regression. Odds ratios with corresponding 95% confidence intervals and ibm spss statistics 23.0 .Statistically significantly variables were included in the multivariable logistic regression model and analysed using the backward stepwise method. All statistical analyses were performed using 33.1In 198 (88%) cases, satisfactory ventilation by SSHFJV was achieved; however, during 26 interventions (12%) ventilation had to be definitively or temporarily converted to endotracheal tube ventilation. The main reason for conversion was desaturation of the patient (25/26 cases).P = <.001). In the converted group, the percentage of obstruction was estimated at 51% compared with 33% in the non‐converted group (P = .011). There was no difference in CO2 laser use between conversion and non‐conversion groups . No complications due to use of SSHFJV were observed in any of patients.A detailed rendering of the patient characteristics, including age, sex, weight, smoking status, laryngological history, anatomical level of the pathology, diagnosis, treatment and comorbidities, are described in Table 3.2In univariable analyses Table , we foun3.3Multivariable model, containing BMI, pulmonary pathology, ASA class and percentage of obstruction after backward stepwise elimination, included BMI and pulmonary pathology only Table . In the 44.12‐elimination and gas‐exchange during SSHFJV and not on factors that may influence the success of SSHFJV.This is the first study investigating the predictors of unsuccessful SSHFJV. In this retrospective analysis of 224 adult cases, we confirmed that SSHFJV is applicable in the vast majority of the cases. The risk of conversion to endotracheal intubation is higher in patients with a history of pulmonary disease or elevated BMI. The identification of these predictors may help the surgical team, including surgeons and anaesthesiologists, to prepare for an eventual temporary or definitive conversion to an alternative ventilation technique. An eventual conversion to endotracheal intubation does not jeopardise patient safety if the team is properly prepared. Previous studies focused on the safety, feasibility, limitations, complications of this technique, and analysis of CO4.2We found no severe complications, like barotrauma, subcutaneous emphysema, endotracheal fire or death in our series. This is in line with other, larger studies including 500 and 1515 cases.4.3We found a significantly increased chance of conversion SSHFJV to endotracheal intubation in patients with a positive history of pulmonary pathology; however, a notable percentage 41/55; 74.5%) of patients with pulmonary pathology could undergo surgery with SSHFJV. In another study, high‐risk patients including patients with COPD, emphysema, bronchial asthma or pulmonary metastases were reported to be adequately ventilated; however, in that series two of three converted cases had pulmonary comorbidities.5; 74.5% 4.4Obese patients have impaired oxygen reserve, respiratory mechanics and often diverse comorbidities4.5In line with other studies, we experienced no correlation in the multivariable analysis between the severity of the stenosis and the chance of conversion. An Austrian group described safe application of SSHFJV in patients with severe stenosis.4.62 laser requires low oxygen concentration of the ventilating gas in order to avoid airway fire2 concentration of the ventilating gas to lower than 40%. Despite this, the application of CO2 laser did not increase the chance of conversion from SSHFJV to an alternative ventilation technique. Furthermore, we did not experience any incidents related to CO2 laser application during SSHFJV, just like other studies.The application of CO4.7The study included a consecutive series of patients without any selection; therefore, our database includes high‐risk patients, too. We used validated scoring systems in our analysis which makes our results comparable with other studies. Furthermore, beyond reviewing clinical charts, we have reassessed the clinical photographs in order to minimise missing data and to avoid incorrect data that may come from inaccurate registration.Of course, the study suffers from its retrospective nature with some missing data and also some bias in the inclusion, as anaesthetists might have contraindicated SSHFJV ahead of the procedure, for instance based on comorbidities. Furthermore, the point of conversion is also strongly depending on the anaesthesiologist: some anaesthesiologists convert earlier, some later.5Upper airway surgery ventilated with SSHFJV is possible in the vast majority of the patients. However, clinicians have to be alert in patients with positive history of pulmonary pathology and with higher BMI, as these patients have higher risk for failure.The authors have no conflict of interest to declare.


Mechanical properties and microstructure are investigated for a martensitic stainless steel (AISI 420) fabricated by selective laser melting (SLM) in three build directions. The tensile specimens built by SLM are classified into three groups. Group A is horizontally built in the thickness direction, Group B is horizontally built in the width direction, and Group C is vertically built in the length direction. The loading direction in tensile test is parallel to the build direction of Group C, but perpendicular to that of Groups A and B. Experimental results indicate build direction has significant effects on the residual stress, hardness, and tensile properties of SLM builds. Microstructural analyses indicate the as-fabricated SLM AISI 420 builds exhibit elongated cells and acicular structures which are composed of martensite and retained austenite phases growing along the build direction. Such anisotropy in the microstructure leads to anisotropic mechanical properties as Group C specimens (length direction) exhibit greater yield stress, ultimate tensile stress, and elongation than the specimens of Groups A (thickness direction) and B (width direction). The residual compressive stress in the gauge section also contributes to the superior tensile properties of Group C (length direction), as compared to Groups A (thickness direction) and B (width direction), which exhibit residual tensile stress in the gauge section. Additive manufacturing (AM) has recently been applied for direct fabrication of near net shape components. It is different from the conventional manufacturing processes which cut or remove material to make the final shape, while it adds material during the fabrication process . MetalliEffects of build direction on the microstructure and mechanical properties have been studied for several metallic alloys produced through SLM processes, such as Ni-based superalloys ,6,7,8, tFor a 316L stainless steel produced through SLM, horizontally built specimens exhibit the highest fatigue resistance followed by vertically built ones, while diagonally built specimens possess the lowest fatigue strength, as presented by Shrestha et al. . Such anAISI 420 is a martensitic stainless steel which has excellent mechanical properties and moderate corrosion resistance. It is used in a wide range of applications from low to high temperatures, including injection molds, pressure vessels, steam generators, surgical instruments, blades, and others . Recentlt), width direction (w), and length direction (l), respectively. In other words, Group C is vertically built, and Groups A and B are horizontally built in the short transverse and wide transverse directions, respectively. Three specimens are fabricated for each group. After the SLM process, the built specimens are cut out of the baseplate by wire electrical discharge machining. To investigate the inherent effects of build direction on the microstructure, residual stress state, and mechanical properties, the specimens are kept in the as-built condition. Therefore, heat treatment is not applied to the specimens.Commercial AISI 420 stainless steel powder  is used to fabricate the tensile test specimens. According to the data sheet provided by the vendor, the powder size is in the range of 10–53 μm and the major elements in chemical composition include 12.0–14.0 wt% Cr, 0.3–0.4 wt% C, ≤ 1.0 wt% Si, ≤ 1.0 wt% Mn, ≤ 0.6 wt% Ni, and balance of Fe. Specimens are fabricated by a commercial powder-bed SLM machine . The SLM machine is equipped with an ytterbium-doped fiber laser, a nitrogen gas generator, a powder supply mechanism, and a working table. The given SLM process parameters and scanning strategy are listed in ρr = ρsample/ρreference. ρsample is the density of the specimen and ρreference = 7800 kg/m3 is the reference density of AISI 420 steel [α radiation . An X-ray beam of 2-mm diameter is employed to determine the residual stress, using a cos α method and two-dimensional detectors (imaging plates). Note that the error range of each measurement is about ± 25 MPa. Details of such residual stress measurement method are given in Reference [lσ and wσ in the length (l) and width (w) directions, respectively, are measured at each selected position.Densification of the SLM specimens is measured by Archimedes’ principle. The accuracy of the electronic balance for measuring the mass of density sample is 0.01 g. The relative density of the SLM specimen is defined as 20 steel . A hardneference . Four poTo determine the tensile properties, such as yield stress, ultimate tensile stress, and elongation, uniaxial tensile test is conducted using a commercial servo-hydraulic material test machine . The accuracy of the load cell for measuring the applied load is 1 N. A uniaxial extensometer  is attached on the gauge section to measure the strain during testing. The mechanical test is performed under displacement control with an initial stroke rate of 0.5 mm/min followed by 2 mm/min when the strain reaches 1%. An engineering stress–strain curve is then obtained for each specimen tested.2O3 paste. After polishing, the samples are chemically etched for 20–30 s in an acidic solution of 2% HF and 8% HNO3. For better imaging results, the SEM specimens are sputter coated with a thin conductive Pt film. In addition, X-ray diffraction analysis (XRD) is applied to determine the crystalline phases in the given SLM specimens. The XRD samples are taken out of the gauge section. The X-ray energy applied is 15 KeV with a wavelength of 0.82656 Å. The beam size is 500 μm and the diffraction signals during measurement are recorded using an image plate detector . The X-ray diffraction data are refined using the General Structure Analysis System  to obtain the θ-2θ X-ray diffraction profiles.After tensile testing, fracture surface is observed using a scanning electron microscope  to find the fracture origin and fracture pattern. An attached energy dispersive spectrometer (EDS) is used to determine the elemental composition at specific regions. Optical microscopy  and SEM in backscattered electron (BSE) mode are employed to investigate the microstructure. To explore the grain growth direction, some cross sections and surface areas are selected for microstructural observation. These metallographic samples are ground using sandpapers up to #2000 and polished using 1-μm and 0.3-μm AlThe relative density measured for each sample is listed in l- and w-directions on the top length-width plane. This is expected because the measured points of Group A are on the final layer in the SLM build. The process of cooling and contraction of the melt material after being heated by the laser generates the tension seen in the deposited layer [Residual stresses are unavoidably generated in SLM builds due to high temperature gradient and high cooling rate caused by the local heat input of high-energy laser beam during the SLM process . The resed layer . Accordied layer . Group BRepresentative stress–strain curves of specimens tested are shown in Typical SEM micrographs of fracture surface of Group A specimens are shown in A representative fracture surface of Group B specimens is shown in lσ) along the loading direction is compressive in the gauge section for the Group C specimen. Comparison of EDS analysis between the fracture origin and other regions indicates the fracture origin is also an inclusion containing a large amount of carbon (73 wt%) and a small amount of iron (10 wt%) and chromium (1 wt%). Crack tends to initiate at such irregular inclusion due to a greater stress concentration effect. Typical micro-pores observed on the fracture surfaces of the given SLM specimens are shown in sM) to martensite-finish temperature (fM) [XRD results  indicateure (Mf) . Some auure (Mf)  using thure (Mf) . Group ATypical microstructure observed in low-magnification OM micrograph for each group is shown in sM temperature, the prior austenite phase transforms to martensite during the rapid cooling stage. As a result, the cellular structures are outlined by the prior austenite grain boundaries, and the martensite laths are embedded in the sub-grain structures, as shown in As shown in As shown in the OM micrographs of AM/CM and BM/CM for the SLM builds of Groups A and B, respectively. AM, BM, and CM represent the average value of each mechanical property  of Groups A, B, and C, respectively. In other words, the mechanical properties of Groups A and B are normalized by that of Group C to define the anisotropy ratio. The calculated anisotropy ratios of various mechanical properties are summarized in As described above, build direction has noticeable effects on mechanical properties, residual stress distribution, and fracture origin site. To quantitatively describe the build direction effect on mechanical properties, an anisotropy ratio is defined as As described in The anisotropy in mechanical properties of the given SLM builds is mainly attributed to an anisotropic microstructure, particularly the prior austenite grain boundary, as a result of directional grain growth. As evidenced by the microstructural analysis presented in (1)The dependence of microstructure and mechanical properties on build direction is confirmed for the martensitic mold steel, AISI 420 stainless steel, fabricated by SLM in a vertical direction and two horizontal directions.(2)Build direction effect causes anisotropic mechanical properties as the vertically built SLM specimens possess superior mechanical properties  to those of horizontally built ones. This is mainly attributed to the anisotropic microstructure in which the orientation of elongated cells and acicular structures in the vertical and horizontal builds is respectively parallel and perpendicular to the tensile loading direction. The residual compressive stress existing in the gauge section also contributes to the superior tensile properties of the vertical builds, as compared to the horizontal builds which exhibit residual tensile stress in the gauge section.(3)The SLM AISI 420 builds in as-built state exhibit elongated cells and acicular structures which are composed of martensite and retained austenite phases. The elongated cellular structures are generally oriented with the build direction due to a directional grain growth mechanism. However, build direction has a limited effect on the phase content as the SLM builds contain a comparable amount of martensite, namely 78.82%, 71.69%, and 76.71% for Groups A–C, respectively.(4)Fractography analysis reveals residual tensile stress and irregular inclusions both play an important role in determining the fracture origin site of the given SLM builds when subjected to uniaxial tensile loading.