Human Reproductive Sciences

From the Editor's Desk Madhuri Patil Journal of Human Reproductive Sciences 2019 12(2):75-77

Body composition, metabolic characteristics, and insulin resistance in obese and nonobese women with polycystic ovary syndrome Anil Satyaraddi, Kripa Elizabeth Cherian, Nitin Kapoor, Aleyamma Thaiparambil Kunjummen, Mohan S Kamath, Nihal Thomas, Thomas V Paul Journal of Human Reproductive Sciences 2019 12(2):78-84 Objectives: The objective was to compare body composition, metabolic characteristics, and insulin resistance between obese (body mass index [BMI] ≥25 kg/m2) polycystic ovary syndrome (PCOS) and nonobese PCOS (BMI <25 kg/m2) women and their age- and BMI-matched controls. Materials and Methods: A total of 81 PCOS women (Rotterdam criteria) (obese – 42; nonobese – 39) and 86 controls (obese – 42; nonobese –44) were recruited in this cross-sectional study. All women underwent a detailed assessment of clinical, anthropometric, and metabolic parameters, insulin resistance indices, and body composition measurements with visceral adipose tissue assessment (VAT) (dual-energy X-ray absorptiometry scan). Results: Of PCOS women, 27% (80% – obese PCOS; 20% – nonobese PCOS) were diagnosed with metabolic syndrome (International Diabetes Federation criteria), 35% of PCOS women (46% – obese PCOS; 54% – nonobese PCOS) had impaired glucose tolerance, and 7% of PCOS women (2/3rd – obese PCOS; 1/3rd – nonobese PCOS) had diabetes mellitus. Insulin resistance was seen in about 80% in obese PCOS women and 20% in nonobese PCOS women based on various insulin resistance indices such as fasting insulin (≥12.2 μU/ml), Homeostasis Model Assessment-Insulin Resistance (≥2.5), and Quantitative Insulin Sensitivity Check Index (<0.33). Total body fat, estimated (Est.) VAT, and corrected Est. VAT (corrected for body weight) were significantly increased (P = 0.0001) in both obese and nonobese PCOS women when compared to those of their age- and BMI-matched controls. However, corrected Est. VAT (corrected for body weight) was not significantly different between obese and nonobese PCOS women. Conclusion: Both obese and nonobese PCOS women when compared with their age- and BMI-matched controls were metabolically worse and had more visceral adiposity. Nonobese PCOS poses similar risk as that of obese PCOS in having similar amount of VAT (corrected for body weight).

Genetics of female infertility: Molecular study of newborn ovary homeobox gene in poor ovarian responders Osamah Batiha, Nour Alhoda Alahmad, Amer Sindiani, Khaldon Bodoor, Sherin Shaaban, Mohammad Al-Smadi Journal of Human Reproductive Sciences 2019 12(2):85-91 Background: Newborn ovary homeobox (NOBOX) gene plays a critical role in the transcriptional regulation of oocyte-specific genes. Previous studies have demonstrated a pathogenic effect of NOBOX variants on premature ovarian insufficiency (POI) patients. Poor ovarian response (POR) is a risk factor for POI. Therefore, genetic variants in the NOBOX gene may also be studied as risk factors for POR development. Aims: The aim of the study is to investigate the association between seven known NOBOX single-nucleotide polymorphisms (SNPs) and POR in Jordanian females. Settings and Design: This was a case–control study of 60 females with POR for controlled ovarian hyperstimulation and 59 healthy females with no history of reproductive problems. Blood samples were collected from the participants and seven SNPs of NOBOX gene were screened. Subjects and Methods: DNA was extracted from blood samples. Polymerase chain reaction with primers specific for seven known SNPs in NOBOX gene was used to amplify the specified region within the gene followed by Sanger sequencing. Results: The seven SNPs investigated in this study, namely, rs77587352 (c.271G>T, p. Gly91Trp), rs7800847 (c.349C>T, p. Arg117Trp), rs193303102 (c.907C>T, p. Arg303X), rs193303103 (c.1025G>C, p. Ser342Thr), rs193303104 (c.1048G>T, p. Val350Leu), rs201947677 (c.1064G>A, p. Arg355His), and rs146227301 (c.1856C>T, p. Pro619Leu), only represent the wild-type allele in both females with POR and healthy participants. Conclusions: The results show that only monomorphic genotype of the NOBOX variants was found in Jordanian females studied.

Chromosomal aberrations in primary amenorrhea: A retrospective study Seema Korgaonkar, Somprakash Dhangar, Vinayak Kulkarni, Lily Kerketta, Babu Rao Vundinti Journal of Human Reproductive Sciences 2019 12(2):92-97 Objectives: The aim of this study was to estimate the frequency of chromosomal abnormalities and establish the association with clinical of factors such as secondary sexual characters and gonad development in primary amenorrhea (PA). Study Design: The study was carried out in a large cohort of PA. The chromosomal aberrations were correlated with secondary sexual characters and anatomical abnormalities. Materials and Methods: The data of 490 cases of PA were collected retrospectively. The chromosomal preparations were done from the peripheral blood and subjected to giemsa-trypsin-giemsa banding and karyotyped according to the International System of Human Cytogenetic Nomenclature 2013. The fluorescence in situ hybridization was carried out using centromeric and whole painting probes for X and Y chromosome. Statistical Analysis: Statistical analysis of the data was performed using online version of social science statistics software. Results: A high frequency of abnormal uterus (81.9%) and ovaries (86.7%) were detected in our study. A total of 121 (24.7%) cases were identified with abnormal karyotype. The numerical chromosomal abnormalities were identified in 53 (43.8%) cases while structural abnormalities were identified in 32 (26.4%) cases. The XY karyotype was detected in 29.8% females with PA. The PA individuals with anatomical abnormalities (84.3%) had a high frequency (24.6%) of chromosomal aberrations. Conclusions: The present study concluded that cytogenetics plays an important role in precise diagnosis which helps in the management of PA. The cytogenetic analysis should be carried out to know the genetic basis of PA.

Clinical outcome analysis and correlation of reproductive outcome with endometriosis fertility index in laparoscopically managed endometriosis patients: A retrospective cohort study Neha Negi, Kallol Kumar Roy, Sunesh Kumar, Vinod G Nair, P Vanamail Journal of Human Reproductive Sciences 2019 12(2):98-103 Background: Laparoscopy is important for management of endometriosis patients with estimation of endometriosis fertility index (EFI) which can predict reproductive outcome. Aims: This study aims to evaluate clinical outcome in laparoscopically managed pelvic endometriosis and correlation of reproductive outcome with EFI. Setting and Design: Retrospective cohort study carried out in the Department of Obstetrics and Gynecology. Materials and Methods: Our study included 123 patients who had undergone laparoscopic management of endometriosis from January 2017 to March 2018. Case files were retrieved and meticulously analyzed. All patients were contacted and interviewed. Symptomatic relief and pregnancy in infertility patients were recorded. EFI was calculated. Statistical Analysis: Data analyses were carried out using statistical software STATA version 12.0. P < 0.05 was considered statistically significant. Results and Conclusions: A total of 123 cases were enrolled; the most common complaint was infertility 107 (86.99%); the mean age was 32.4 years. EFI was found to be (6 to 10) in 28(26.2%) patients, EFI of (4 to 5) in 49 (45.8%) and EFI of (0 to 3) in 30 (28.0%). Post surgery, dysmenorrhoea was relieved in 56 (65.88%) patients, menstrual irregularities were relieved in 45 (76.27 %) patients, dyspareunia in 32 (54.24%) and chronic pelvic pain in 24 (40.5%) patients. 8 (40%) patients with low EFI conceived, 20 (58.82%) with moderate, and 26 (96.29%) with high EFI conceived. EFI score showed statistically significant positive correlation with pregnancy outcome P = 0.001, higher the EFI score, better the reproductive outcome. Laparoscopic surgeries are important for managing patients of endometriosis. It provides significant symptomatic relief, and EFI estimation can be done, which is a good tool to predict reproductive outcome of infertility patients with endometriosis.

Establishing an Anti-Müllerian hormone cutoff for diagnosis of polycystic ovarian syndrome in women of reproductive age-bearing Indian ethnicity using the automated Anti-Müllerian hormone assay Nalini Mahajan, Jasneet Kaur Journal of Human Reproductive Sciences 2019 12(2):104-113 Context: Polycystic ovary syndrome diagnosed by Rotterdam criteria, is the most common cause of anovulatory infertility. The criteria of polycystic ovarian morphology (PCOM) are subject to operator variability and technological advances. Serum anti-Müllerian hormone (AMH) level has been proposed as a more reliable alternative to antral follicle count. There is a paucity of data on use of AMH for diagnosis of PCOS in Indian women. Aim and Objectives: The aim of this study is to determine a cutoff level for AMH that could facilitate diagnosis of PCOS and its phenotypes in women of Indian origin using the automated (Roche) assay and to compare the competence of oocytes in PCOS and non-PCOS women undergoing in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI). Materials and Methodology: A total of 367 women undergoing treatment at our fertility center between February 2017 and August 2017 were prospectively enrolled in this study. Of these, 133 were diagnosed with PCOS, 69 had isolated PCOM, and 165 (controls) had normal ovaries on ultrasound examination. Serum AMH levels were assessed using the fully automated Roche Elecsys® immunoassay. Gonadotropin-releasing hormone antagonist protocol was used for IVF-ICSI in all patients. Statistical Analysis Used: Quantitative variables were compared using the Mann–Whitney test. Qualitative variables were correlated using the Chi-square test. P < 0.05 was considered to be statistically significant. Results: Mean AMH concentrations in women with PCOS was higher (7.56 ± 4.36 ng/mL) in comparison to PCOM and controls. Serum AMH concentration >5.03 ng/mL could facilitate diagnosis of PCOS (area under the curve = 0.826); sensitivity –70.68%, specificity of 79.91%. There was no difference in the ratio of mature to total oocytes retrieved in the three groups (P > 0.05). Mean number of mature oocytes was lower in controls than PCOS and PCOM (P < 0.001). Conclusions: Serum AMH concentration >5.03 ng/mL could be used as cutoff value for the diagnosis of PCOS in women of Indian origin.

p53 protein evaluation on spermatozoa DNA in fertile and infertile males Salvatore Raimondo, Tommaso Gentile, Mariacira Gentile, Alessia Morelli, Francesca Donnarumma, Felice Cuomo, Stefania De Filippo, Luigi Montano Journal of Human Reproductive Sciences 2019 12(2):114-121 Introduction and Objectives: Protein p53 role in the spermatogenesis is demonstrated, it guarantees both the appropriate quality and quantity of mature spermatozoa. In this observational study we evaluate the eventual correlation between “corrected” p53 concentration on human spermatozoa DNA and male fertility potential. Materials and Methods: Our work is based on an observational study made of 169 male in a period between March 2012 and February 2017. The entire study group is composed by 208 male partners aged between 26-38 years with ejaculate volume from 0.6 to 5.8 mL and heterogeneous seminal valuation: 86/208 (41,3%) normospermic; 19/208 (9,1%) mild oligospermic; 51/208 (24,5%) moderate oligospermic to; 52/208 (25,1%) with severe oligospermic. The “control” group A includes 39 male partners considered “fertile”, because we did the p53 “corrected” test on their spermatozoa after 28 ± 3,5 days from the positives of their partners pregnancy test (betaHCG> 400 m U/m L). The group B, subdivided in B1, B2 and B3, includes 169 male partners for a observational period of 60 months. This partners don't report previous conceptions, they aren't smokers, don't make use neither of alcohol nor drugs and don't present pathologic varicocele studied with ecoColorDoppler. They are all married or stable cohabitants from a period of 27-39 months and report to have frequent sex without protection with their partners. Determination of p53 procedure: To separate the spermatozoa from seminal fluid we utilized the Differex™ kit System and the DNA IQ™ kit (Promega). For the p53 test we used the direct DuoSet IC kit and quantitative (R&D System). The p53 values were corrected in respect to the spermatozoa concentration expressed in ng/millions of spermatozoa. Results: Group A (39 male) presents “correct” p53 values that vary from 0.35 to 3.20 ng/millions of spermatozoa and group B presents values that vary from 0.68 to 14.53. From group B (48 male) in the observational period we have recorded 21 pregnancies with initial “correct” p53 values that vary from a minimum of 0.84 to a maximum of 3.29. In the subgroup B1 we obtained 8 pregnancies from male partners with a “correct” p53 concentration included between 0.84 to 1.34. In the subgroup B2 we obtained 13 pregnancies from male partners with a “correct” p53 concentration included between 1.66 and 3.29. In the subgroup B3 (121 male) there weren't neither pregnancies nor miscarriages and “correct” p53 values were included between 3.58 and 14.53. Conclusion: The results show that the member of the group A with values of 'corrected' p53 between 0.35 and 3.20 were considered “Fertile”, although in the observational period 3 miscarriages happened for 3 partners. 36 partners on 39 (92,3%) had a p53 concentration inferior to 1.65, this value were considered as the extreme to identify this group. The member of the group B1 had “corrected” p53 concentration that were included in the group. In the group B2 were observe 13 pregnancies, so its member were considered “potentially fertile” In the group B3 (121 male) weren't observe neither pregnancies nor miscarriages, so its member were considered “potentially infertile”. If further studies confirm these data, we will consider the p53 test ELISA inspected in “correct” p53 as a new and accurate marker of the potential of male fertility.

Effect of spermatic nuclear quality on live birth rates in intracytoplasmic sperm injection Maroua Hachemi, Mustapha Bensaada, Abdelkader Rouabah, Abdelali Zoghmar, Sebti Benbouhedja, Leila Rouabah, Mehdi Benchaib Journal of Human Reproductive Sciences 2019 12(2):122-129 Background: Our study defines the clinical role of sperm DNA damage in the assisted reproductive technology procedure. Aim: To investigate if the compaction of chromatin explored added to the analysis of the sperm DNA fragmentation allows obtaining a new indicator for sperm genome quality linked to live birth rate (LBR). Design: This was a prospective study, undergoing 101 cycles in the intracytoplasmic sperm injection (ICSI) program. Materials and Methods: The sperm DNA fragmentation index (DFI) has been measured with sperm chromatin dispersion examination. The sperm decondensation index (SDI) of chromatin has been measured with aniline blue procedure; with these indexes, a new parameter has been created: DFI × SDI. Statistical Analysis: Pearson's correlation coefficient, Student's t-test, and Chi-square test were used. The quantitative variables were described as mean ± standard deviation. Multivariate logistic regressions were performed with live birth as outcome. Results: The sperm concentration, motility, and normal morphology were lower when the DFI was high (P = 0.001). The fertilization rates and the number of obtained embryos were not statistically significant different according to the DFI groups. The SDI does not appear to be linked either with the spermatic parameters or with the ICSI parameters. A low DFI seems to be a beneficial factor to obtain a live birth in ICSI procedure (P = 0.064). In case of high DFI, a high SDI allows to obtain a higher LBR than a low SDI. Conclusion: The DFI is a good prognostic for a delivery rate in ICSI procedure, and the SDI could be added to DFI to create a new parameter of sperm nuclear quality. This new parameter seems to be linked to LBR.

Evaluation of periodontal status among men undergoing infertility treatment Chethana Kunthur Chidambar, Shrinidhi Maji Shankar, Raj Kishen Agarwal, Kala S Bhushan, Soumya Badravalli Gururaj Journal of Human Reproductive Sciences 2019 12(2):130-135 Aims: It has been estimated that >30% of male infertility cases are of idiopathic etiology. Recent studies revealed a positive connection between periodontal pockets and sperm submotility, which proposes that periodontitis may have a role in male infertility and inadequate semen quality. The aim of the present investigation was to inspect the relationship between male fertility parameters and the periodontal status of male patients attending in vitro treatment (IVF) clinic. Materials and Methods: The study participants comprised 85 men going to the facility for sperm investigation before semen insemination. The nature of sperm was surveyed by the WHO 2010 criteria. On the same day, male patients were examined for periodontal parameters. Results: The patients were determined to have either gingivitis (24.7%) or periodontitis (75.3%). Normospermia was credited to 23.5% and oligozoospermia to 43.5%. Sperm submotility was seen in 76.4% of patients. A higher number of sites with clinical attachment loss showed a positive correlation with sperm submotility and sperm count. Conclusions: The findings of the present study showed a conceivable relationship between male infertility, decreased semen quality, and periodontal diseases in men visiting IVF centers. Periodontitis may subsequently play a role in male infertility.

Correlation between serum progesterone level on the day of ovulation trigger during In vitro fertilization and its effect on treatment outcome N Nagaraja, Pankaj Talwar, Bhaskar Mukherjee, Barun Kumar Chakrabarty Journal of Human Reproductive Sciences 2019 12(2):136-140 Background: Premature luteinization (PL) is defined as a premature rise in serum progesterone concentration on or before the day of ovulation trigger with human chorionic gonadotropin. The incidence of PL varies between 5% and 30% during in vitro fertilization and embryo transfer (IVF-ET). Materials and Methods: The prospective observational study comprising 380 patients undergoing IVF-ET. Blood samples were collected for serum progesterone level estimation on the day of ovulation trigger. Ovum pickup was done 36 h later and serum progesterone levels were correlated with IVF-ET outcome. Study Outcome: To correlate serum progesterone level on the day of ovulation trigger during IVF and its effect on treatment outcome. Results: Mean serum progesterone level in the positive pregnancy group and negative pregnancy group was 0.892 ± 0.752 ng/ml and 0.91 ± 0.688 ng/ml, respectively (P = 0.961). The overall incidence of PL was 12.8% with 12.7% and 13.6% in the agonist and antagonist protocol respectively (P = 0.9001). PL incidence was 13.5% and 13.4% in positive pregnancy and negative pregnancy group (P = 0.223). Conclusion: PL has been associated with 12.8% of the IVF cycles. There was no statistically significant difference observed in the incidence of PL between different IVF stimulation protocols. PL does not seem to affect IVF outcome.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Disease

Use of World Health Organization susceptibility test for malaria vector control in South-Eastern Nigeria: A discourse Joel D Akilah, Ibanga Eyo Ekong Environmental Disease 2019 4(2):29-32 Background: With growing evidence of mosquito vector resistance to pyrethroids and other classes of insecticides globally, we employed one of the two important tools for the monitoring of insecticide resistance in selected states in southeastern part of Nigeria via the World Health Organization (WHO) susceptibility test. Aim: This study tested the effectiveness of WHO susceptibility test for the use in identifying and monitoring the resistance of Anopheles and Aedes mosquitoes which transmit malaria and arbovirus-related diseases in Nigeria. Methods: Larval sampling of mosquitoes was embarked upon with ovitraps set in various study sites; eggs were hatched and reared and subsequently subjected to susceptibility tests according to the WHO test procedures. Summary and Conclusion: Resistance to dichloro diphenyl trichloroethane and the pyrethroids has been established to a large extent. The loss of efficacy of pyrethroids may result in operational failure of disease control programs.

Primary prevention of snakebite envenoming in resource-limited settings Joel Noutakdie Tochie, Frank-Leonel Tianyi, Diego Nitcheu Tchouakam, Armand Seraphin Nkwescheu Environmental Disease 2019 4(2):33-34

Loss of productivity interfering with the attainment of universal health coverage in African nations Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava Environmental Disease 2019 4(2):35-36

Primary prevention of snakebite envenoming in resource-limited settings: A narrative review Godpower Chinedu Michael, Ibrahim Aliyu, Bukar Alhaji Grema Environmental Disease 2019 4(2):37-44 Background: Snakebite envenoming is a neglected tropical disease that accounts for preventable morbidity and mortality, especially in resource-limited settings. This review aimed at examining the snake and human behaviors that facilitate snake-human encounters and highlighting the primary preventive measures for snakebite and the resultant envenoming. Materials and Methods: Google Scholar, Medline (via PubMed), and African Journal Online were searched from January 1959 to April 2019 for peer-reviewed studies addressing primary prevention of snakebite. We extended our search to grey literature from conference proceedings, documents from organizations, book chapters, and thesis. Results: We found few studies in medical literature on community knowledge of the intrinsic characteristics of snakes (e.g., its unique venom apparatus for nutrition, defense and competition, and its habitat and activities); however, there is appreciable amount of studies on human activities associated with snakebite envenoming. Deservedly, more studies appear to focus on snakebite management (secondary and tertiary prevention) with inadequate emphasis on primary prevention of snakebite (which may be the only intervention in some resource-limited settings). Conclusion: Synergy of efforts toward improving community knowledge of human behaviors associated with snakebite and snake behaviors may generate appropriate environmental and behavioral responses to curtail human-snake encounters. Hence, intensive promotion of primary prevention may be a useful approach toward reducing snakebite burden in resource-limited settings.

Effects of low-molecular-weight heparin and unfractionated heparin on patients with exertional heat stroke with thrombocytopenia: A prospective study Li Cheng, Eric Allen Klomparens, De Lin Liu, Min Na Wang, Xiao Xue Yin, Wei Liu, Yuan Liu, Qi Feng Zhang, Gang Ye Environmental Disease 2019 4(2):45-49 Background: Thrombocytopenia often occurs in patients with exertional heat stroke (EHS). We aimed to investigate the effect of low-molecular-weight heparin sodium (LMWH) and unfractionated heparin (UFH) on coagulation and prognosis in the treatment of EHS with thrombocytopenia. Methods: In a prospective cohort study, 64 patients admitted to the emergent intensive care unit (ICU) were studied between July 2015 and October 2018. Patients were randomized to receive LMWH or UFH. Thirty-three patients were given LMWH 4000 IU twice a day for 5 days, by subcutaneous injection. Thirty-one patients were given UFH 5&#8211;10 U/kg &#215; h for 5 days, by 24-h continuous intravenous infusion. Demographic and clinical data (platelets [PLTs] counts, activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen [FIB], D-dimer, presence of diffuse intravascular coagulation [DIC]), and mortality in the ICU were recorded along with the 28-day survival rate. The acute physiology and chronic health evaluation (APACHE) II score was calculated within 24 h of admission and used to indicate the severity of disease. Results: There were no significant differences in sex, age, APACHE II score, and core temperature between the two groups (P > 0.05). PLT and FIB were significantly increased after treatment in both groups (P < 0.05), while aPTT, PT, and D-dimer were significantly decreased after treatment in both groups (P < 0.05). No significant differences between the two groups were found in the incidence of DIC or ICU mortality (P > 0.05), but the incidence of bleeding in the LMWH group was significantly lower than in the UFH group (P < 0.05). There was not a significant difference in the 28-day survival rate between the two groups (P > 0.05). Conclusions: The results of this study support that the efficacy of LMWH and UFH in the prevention of thrombosis is equivalent. However, the incidence of bleeding was lower in LMWH group. LMWH and UFH had statistically similar rates of ICU mortality, 28-day mortality, and incidence of DIC. Our results suggest that LMWH may be safer than UFH for use in patients with EHS with thrombocytopenia.

Effect of conbercept or ranibizumab in the treatment of wet age-related macular degeneration Dawei Zhang, Zahrah Khan, Tao Chai Environmental Disease 2019 4(2):50-54 Objective: The aim of this study was to investigate the effects of conbercept or ranibizumab in the treatment of wet age-related macular degeneration (AMD) and to explore the influence on central retinal thickness (CRT), visual acuity, and choroidal neovascularization (CNV) permeation. Patients and Methods: A total of 85 patients (85 eyes) with wet AMD were enrolled in this study. All patients were treated by intravitreal injection of anti-vascular endothelial growth factor and were randomly divided into two groups. Patients in Group A were treated by intravitreal injection of conbercept, whereas those in Group B were treated by intravitreal injection of ranibizumab once a month for 3 consecutive months. The best-corrected visual acuity (BCVA) was measured. Subfoveal choroidal thickness (SFCT) and CRT of affected eyes and healthy eyes were examined with optical coherence tomography. Fundus fluorescein angiography was performed, and the area of CNV permeation was calculated. Results: BCVA (logarithm of the minimum angle of resolution) of affected eyes in the two groups was significantly better at 1 month, 2 months, and 3 months after treatment as well as at the end of follow-up than that of before treatment. Meanwhile, CRT was obviously decreased. SFCT of affected eyes was significantly smaller than that of before treatment, which was also remarkably smaller when compared with that of healthy eyes. At 3 months after treatment and at the end of follow-up, the areas of CNV permeation in the two groups were significantly decreased. In addition, the average times of injection in Group A were significantly less than that of Group B. Conclusions: Intravitreal injection of conbercept and ranibizumab significantly decreased SFCT of affected eyes. However, the length of conbercept medication injection time was lower than that of ranibizumab.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Orthopaedics

Rising to the challenge: Spinal ailments in India Harvinder Singh Chhabra Indian Journal of Orthopaedics 2019 53(4):489-492

A comparison of clinical and functional outcomes following anterior, posterior, and combined approaches for the management of cervical spondylotic myelopathy Gautam R Zaveri, Nitin Parmeshwarlal Jaiswal Indian Journal of Orthopaedics 2019 53(4):493-501 Background: The key determinants when planning surgery in patients with CSM are the direction of compression, number of levels, sagittal alignment and instability. However there is no literature that compares the clinical and functional outcomes following different approaches in patients selected for surgery. Aims: Prospective non-randomized study that aims to compare the clinical and functional outcomes following surgical approaches with the goal of planning the optimal surgical strategy. Material and Methods: 75 patients- 61 males and 14 females (mean age: 64.2 years) with CSM underwent spinal decompression using an anterior (30), posterior (35) or combined approach (10).The surgical approach was selected based on the above mentioned key determinants. Functional disability was measured using the modified Japanese Orthopaedic Association score for myelopathy. Based on this the recovery rate was calculated. The mean followup duration was 21 months (range 6-72 months). Results: The preoperative mJOA score was 11.01 and the functional disability was graded as mild in 15, moderate in 50 and severe in 10. Postoperatively, the mJOA score improved to 16.41.The overall recovery rate was 77.25%.Patients with mild deficits/disability preoperatively had a significantly better recovery (<0.01) than those with more severe disability. There was comparable improvement in the functional status within the groups with the recovery rates were 83.37%, 76.6% and 64.13%.The blood loss, operative time and peri-operative complication rate were significantly higher with a combined surgery (33%) as compared to anterior (13.3%) or posterior approaches 14.8%. Conclusions: Outcomes are excellent following surgery for CSM. The best recovery is seen in patients with mild to moderate functional disability at the time of surgery.

The radiologic and clinical outcomes of oblique lateral interbody fusion for correction of adult degenerative lumbar deformity Ravish Shammi Patel, Seung Woo Suh, Seong Hyun Kang, Ki-Youl Nam, Shiblee Sabir Siddiqui, Dong-Gune Chang, Jae Hyuk Yang Indian Journal of Orthopaedics 2019 53(4):502-509 Background: Osteotomies aimed at correcting adult spinal deformity are associated with higher complications and perioperative morbidity. Recently, oblique lumbar interbody fusion (OLIF) was introduced for degenerative lumbar diseases. The aim of our study is to demonstrate the effectiveness of OLIF on the management of adult degenerative lumbar deformity (ADLD). Materials and Methods: Patients with ADLD who underwent deformity correction and decompression using OLIF and posterior instrumentation were enrolled. For radiologic evaluation, Cobb's angle (CA), sagittal vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), and pelvic incidence (PI) were evaluated. Visual analog scale (VAS), Oswestry disability index (ODI), and perioperative parameters were recorded for clinical evaluation. Results: Fifteen patients with a mean age of 67 years (63–74 years) were enrolled prospectively and an average of 3 OLIFs (range 1–4) was performed. Posterior instrumentations were done at average of six levels (range 4–8). The mean operative blood loss was 863 ml (range 500–1400 ml) with a mean surgical duration of 7 h (range 3–11 h). SVA, TK, LL, CA, PT, and SS showed significant correction (P < 0.05) in immediate postoperative period and all parameters except TK were maintained at final followup. At the end of 24 months of average followup, 86% (13/15) showed fusion. VAS (leg pain), VAS (back pain), and ODI improved by 74% (range 40–100), 58% (range 20%–80%), and 69.5% (range 4%–90%), respectively. There were two major complications requiring revision (1 infection and 1 adjacent vertebral body fracture). Transient hip weakness present in two patients (13%) recovered within 6 weeks. Conclusions: OLIF gives favorable short term clinical and radiological outcomes in patients of ADLD. It could potentially reduce the need for morbid pelvic fixation and posterior osteotomies in patients with degenerative lumbar deformity.

Outcome evaluation of modified uninstrumented open-door cervical laminoplasty for ossified posterior longitudinal ligament with cervical myelopathy Charanjit Singh Dhillon, Shrikant Rajeshwari Ega, Raviraj Tantry, Narendra Reddy Medagam, Nilay Chhasatia, Chetan Pophale, Anand Khatavi Indian Journal of Orthopaedics 2019 53(4):510-517 Study Design: This was a retrospective study. Purpose: To evaluate the short term outcomes of a novel self-developed technique of performing uninstrumented open-door cervical laminoplasty (ODCL) in patients with cervical myelopathy secondary to ossified posterior longitudinal ligament (OPLL). Review of Literature: Published literature on cervical laminoplasties largely focuses on the outcomes of instrumented variants. Materials and Methods: Retrospective data were collected from 54 patients who underwent uninstrumented ODCL for cervical OPLL at a single institution from January 2010 to February 2017. The preoperative and postoperative modified Japanese Orthopaedic Association score (mJOA) and Nurick grading were documented. Cervical lordotic angle at C2–C7 and range of motion (ROM) were obtained from the preoperative and postoperative lateral cervical radiographs in neutral and flexion extension views, respectively. Descriptive and analytical statistics were generated by SAS 9.4 University Edition (SAS Institute, Cary. North Carolina, USA). Results: The average age was 58.6 ± 7.8 years. The average time of presentation from the onset of symptoms was 7.6 ± 3 months. Of the 54 patients who were included in the study, majority (48.14%) had segmental type of OPLL while C3–C6 was the most commonly operated level (66.67%). The mean operating time was 115 ± 31 min with a mean blood loss of 165.9 ± 75 ml. There was a significant improvement in the mJOA scores (9.2 ± 1.1–13.7 ± 0.9, P < 0.0001) and Nurick grading (3.4 ± 0.8–1.6 ± 0.5, P < 0.0001) at 24-month followup. Preoperative C2–C7 angle had an average decrease of 4.5° at 24-month followup (19.3 ± 7.2–14.8 ± 8.8, P < 0.0001). There was a mean reduction of 4.3° ± 3.78° noted in the C2–C7 ROM between the preoperative and final followup. Conclusion: Uninstrumented ODCL is an easily reproducible and economical alternative to the standard instrumented laminoplasty with equivalent short term outcomes. This technique is a valuable option in the treatment of cervical OPLL, especially in regions with scarce resources.

Management of combined atlas fracture with type II odontoid fracture: A review of 21 cases Zhong-Sheng Zhao, Guang-Wen Wu, Jie Lin, Ying-Sheng Zhang, Yan-Feng Huang, Zhi-Da Chen, Bin Lin, Chun-Song Zheng Indian Journal of Orthopaedics 2019 53(4):518-524 Purpose: To evaluate the therapeutic effects of combined atlas fracture with type II (C1-type II) odontoid fractures and to outline a management strategy for it. Patients and Methods: Twenty three patients with C1-type II odontoid fractures were treated according to our management strategy. Nonoperative external immobilization in the form of cervical collar and halo vest was used in 13 patients with stable atlantoaxial joint. Surgical treatment was early performed in 10 patients whose fractures with traumatic transverse atlantal ligament disruption or atlantoaxial instability. The visual analog scale (VAS), neck disability index (NDI) scale, and American Spinal Injury Association (ASIA) scale at each stage of followup were then collected and compared. Results: Compared to pretreatment, the VAS score, NDI score, and ASIA scale were improved among both groups at followup evaluation after treatment. However, in the nonsurgical group, one patient (1/11) developed nonunion which required surgical treatment in later stage and one patient (1/13) with halo vest immobilization had happened pin site infection. Two patients of the surgical group (2/11) had appeared minor complications: occipital cervical pain in one case and cerebrospinal fluid leakage in one case. Two patients (2/23) were excluded from nonsurgical treatment group because their followup period was less than 12 months. Twenty one patients were followed up regularly with an average of 23.9 months (range 15–45 months). Conclusions: We outlined our concluding management principle for the treatment of C1-type II odontoid fractures based on the nature of C1 fracture and atlantoaxial stability. The treatment principle can obtain satisfactory results for the management of C1-type II odontoid fractures.

A prospective study of clinicoradiologic-urodynamic correlation in patients with tuberculosis of the spine Roop Singh, Milind Tanwar, Santosh Singh, Rajesh Kumar Rohilla Indian Journal of Orthopaedics 2019 53(4):525-532 Introduction: Involvement of spinal cord in spinal tuberculosis (TB) has been associated with bladder disturbances on which literature is scarce. The present study aimed at evaluating the urodynamic profile, its correlation with clinical and radiological features, and the prognosis with treatment in these patients. Materials and Methods: Thirty patients of spinal TB were prospectively evaluated clinically, radiologically, and urodynamically in this single center prospective study. All patients underwent urodynamic assessment at presentation; and those with bladder dysfunction on initial urodynamics were followed with sequential testing at 3, 6, and 12 months. Results: Patients were divided into two groups on the basis of the absence (Group 1, n = 14) or presence (Group 2, n = 16) of bladder dysfunction. The magnitude of deformity (P = 0.011), sensory deficit (P = 0.025), and tenderness (P = 0.030) at presentation was found to be significantly more in Group 2 and involvement of posterior elements, reduction in disc height, endplate erosion, and nerve root were significantly higher. The initial urodynamic assessment showed delayed sensations in 23.3% and early sensations in 13.3%, respectively; decreased bladder compliance in 3.33%; underactive detrusor in 16.6%, and overactive in 13.3% of cases. The sphincter was dyssynergic in 13.3% of cases. Statistically significant (P < 0.001) improvement in sensory parameters of bladder, detrusor contractility, and compliance with treatment was observed. Thirteen (81.3%) patients of Group 2 showed overall improvement on serial urodynamics after chemotherapy. Patients with bladder disturbances had poorer functional recovery at 6 and 12 months. Conclusion: Significant bladder comorbidity is associated with spinal TB and its presence can be recognized as a poor prognostic factor. Urological morbidity is strongly linked to the nerve root and posterior element involvement; reduction in disc height; and end plate erosion. Clinical/neurological improvement correlates with marked radiological and urological improvement.

Therapeutic impact of percutaneous pedicle screw fixation on palliative surgery for metastatic spine tumors Hiroshi Uei, Yasuaki Tokuhashi Indian Journal of Orthopaedics 2019 53(4):533-541 Background: Percutaneous pedicle screw (PPS) fixation has been introduced into palliative surgery for metastatic spine tumors; however, the therapeutic effects of PPS on the outcomes of multidisciplinary treatment for such tumors are unclear. Therefore, the therapeutic impact of PPS was investigated among patients with metastatic spine tumors and with revised Tokuhashi scores of ≤8. Materials and Methods: A total of 47 patients who underwent conventional palliative surgery (posterior decompression and stabilization, 33; posterior stabilization alone, 14) before the introduction of PPS and 38 patients who underwent PPS (posterior decompression and stabilization, 19; posterior stabilization alone, 19) were included. Surgical stress (operative time, blood loss, complications, etc.) and treatment outcomes (postoperative survival time, visual analog scale scores, Frankel classification, and the Barthel index at the final followup) were compared between the conventional and PPS groups. Results: The age of the indicated patients significantly increased after the introduction of PPS (P < 0.05). Regarding posterior decompression and stabilization, there were no significant intergroup differences in surgical stress or treatment outcomes. As for posterior stabilization alone, there were significant preoperative differences in various parameters between the conventional and PPS groups (P < 0.01) and also significant postoperative intergroup differences between surgical stress and treatment outcomes (P < 0.01). Conclusions: For patients with early-stage metastatic spine tumors, the use of PPS-based posterior stabilization combined with multidisciplinary adjuvant therapy has changed the age range of the patients indicated for surgery and caused significant improvements in surgical stress, postoperative survival time, and Barthel index.

A comparison study of three posterior fixation strategies in transforaminal lumbar interbody fusion lumbar for the treatment of degenerative diseases Yong Hu, Bing-Ke Zhu, Christopher K Kepler, Zhen-Shan Yuan, Wei-Xin Dong, Xiao-Yang Sun Indian Journal of Orthopaedics 2019 53(4):542-547 Background: There are various posterior fixations utilized with transforaminal lumbar interbody fusion (TLIF). Previous studies have focused on the comparison of two fixation techniques. Materials and Methods: Sixty five patients with single-level lumbar disease were included in this retrospective study. Group A was treated by TLIF with bilateral pedicle screw (BPS), Group B treated by TLIF with unilateral pedicle screw (UPS), and Group C treated by TLIF with UPS plus contralateral translaminar facet screw (UPSFS). The operative time, blood loss, Oswestry disability index (ODI), Japanese Orthopaedic Association Scores (JOA), and visual analog scores (VAS) were recorded. Radiographic examination was used to assess fusion rates and incidence of screw failure. Results: The blood loss and operative times were 188.69 ± 37.69 ml and 132.96.5 ± 8.69 min in BPS group, 117.27 ± 27.11 ml and 99.32 ± 12.94 min in UPS group, and 121.50 ± 22.54 ml and 112.55 ± 9.42 min in UPSFS group; UPS and UPSFS were better than BPS (P < 0.05). The mean followup time was 38.2 months. Fusion rates were – BPS group: 95.6%, UPS group: 90%, UPSFS: 95% (P > 0.05). Screw and/or rod failures were found in three groups (BPS group: 1, UPS group: 2 and UPSFS: 1, P > 0.05). The average postoperative VAS, ODI, and JOA scores of BPS, UPS, and UPSFS were improved significantly in each group compared to preoperative scores (P < 0.05); there were no significant differences between any two groups at each followup time point (P > 0.05). Conclusion: UPSFS with TLIF is a viable treatment option that provides satisfactory clinical results; the clinical outcome and the complication rate were comparable to BPS. In addition, the invasive of UPSFS cases was comparable to UPS and better than BPS cases. For UPS, it could be used in suitable patients.

Greater trochanter apophysiodesis in Legg–Calve–Perthes disease: Which implant to choose? Evren Akpinar, Osman Nuri Ozyalvac, Ilhan Avni Bayhan, Kubilay Beng, Ahmet Kocabiyik, Mehmet Firat Yagmurlu Indian Journal of Orthopaedics 2019 53(4):548-553 Background: Greater trochanter apophysiodesis (GTA) is relatively minimal invasive technique for the treatment of trochanteric overgrowth. Various types of implants can be used in each procedure. The purpose of this study was to compare outcomes of three different types of implants that were used in treatment of trochanteric overgrowth in Legg–Calve–Perthes disease. Materials and Methods: We retrospectively studied radiological results of three implants (screw, screw washer, and EP) on inhibiting trochanteric growth in 32 patients. Articulo-trochanteric and trochanter-trochanter distances (TTDs) were measured on radiographs. Embedding of implant evaluated on final radiographs. Results: The mean of age at the surgery was 10 ± 2.3 years, and the mean of follow up period was 50.0 ± 16.7 months. In all groups, articulo-trochanteric distance was decreased on final radiographs. In screw and screw washer group, increase of TTD was not statistically significant (P < 0.05). Twelve, one, and two implants were embedded, respectively, in screw, screw washer, and EP groups. Two patients in EP group had revision surgery due to loosening. Conclusions: In this study group, GTA using screw and screw washer methods could slow down but did not restore trochanteric overgrowth. We suggest using washer to reduce embedding of the screw.

Results of rodding and impact on ambulation and refracture in osteogenesis imperfecta: Study of 21 children Atul R Bhaskar, Deepak Khurana Indian Journal of Orthopaedics 2019 53(4):554-559 Introduction: Delay in presentation and surgical intervention is quite usual in osteogenesis imperfecta (OI) because of various local and cultural beliefs. The purpose of this study is to review the results of 21 children who had intramedullary rodding and its effect on ambulation and refracture. Methods: We reviewed 21 children with a clinical diagnosis of OI. The mean age of children at presentation was 8.74 years (3–21 years). All children had recurrent fractures of long bones. Twenty eight femurs and 21 tibiae were stabilized with intramedullary rodding. Ambulatory status was assessed by the Hoffers and Bullock's (H and B) grading, and muscle power was recorded using the Medical Research Council, U. K., grade. Ten children had received intravenous bisphosphonates preoperatively. Postoperatively, the children were assessed for ambulatory status, pain, and ability for independent self-care. Results: The mean followup period was 34 months (24–48 months). Rush rods were used in 20 femurs, the Fassier–Duval (FD) rods in 6 femurs, and in two cases, with narrow intramedullary canals, Kirshner (K) wires were used. For the tibiae, 15 children received rush rods and in 6 cases, an FD rod was used. The mean time to fracture union was 8 weeks (6–12 weeks). Before surgery, 13 children were in H and B Grade 4 (wheel-chair independent or carried by parents usually in a developing country), four were able to ambulate with a walking aid (H and B Grade 3b), and four children were able to walk about in the house without aids (H & B Grade 2). After the rodding procedure, the ambulatoty status improved in 11 (50%) children. Seven children (33%) became household physiologic walkers (H & B Grade 3b), three achieved independent ambulation with orthosis (H & B Grade 1b), and one child with mild OI could walk unaided (H & B Grade 1a). No child had deterioration in ambulatory status. Only two children had refractures at the distal end of the rod due to continual growth of bones. Conclusions: Intramedullary rodding treatment for recurrent fractures in children with OI improves their mobility potential. It also and prevents repeated cast application, disuse wasting, and osteopenia which can lead to deterioration in the quality of the long bones.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Investigative Radiology

Assessment of Hepatic Perfusion Using GRASP MRI: Bringing Liver MRI on a New Level Purpose The aim of this study was to demonstrate the feasibility of hepatic perfusion imaging using dynamic contrast-enhanced (DCE) golden-angle radial sparse parallel (GRASP) magnetic resonance imaging (MRI) for characterizing liver parenchyma and hepatocellular carcinoma (HCC) before and after transarterial chemoembolization (TACE) as a potential alternative to volume perfusion computed tomography (VPCT). Methods and Materials Between November 2017 and September 2018, 10 patients (male = 8; mean age, 66.5 ± 8.6 years) with HCC were included in this prospective, institutional review board–approved study. All patients underwent DCE GRASP MRI with high spatiotemporal resolution after injection of liver-specific MR contrast agent before and after TACE. In addition, VPCT was acquired before TACE serving as standard of reference. From the dynamic imaging data of DCE MRI and VPCT, perfusion maps (arterial liver perfusion [mL/100 mL/min], portal liver perfusion [mL/100 mL/min], hepatic perfusion index [%]) were calculated using a dual-input maximum slope model and compared with assess perfusion measures, lesion characteristics, and treatment response using Wilcoxon signed-rank test. To evaluate interreader agreement for measurement repeatability, the interclass correlation coefficient (ICC) was calculated. Results Perfusion maps could be successfully generated from all DCE MRI and VPCT data. The ICC was excellent for all perfusion maps (ICC ≥ 0.88; P ≤ 0.001). Image analyses revealed perfusion parameters for DCE MRI and VPCT within the same absolute range for tumor and liver tissue. Dynamic contrast-enhanced MRI further enabled quantitative assessment of treatment response showing a significant decrease (P ≤ 0.01) of arterial liver perfusion and hepatic perfusion index in the target lesion after TACE. Conclusions Dynamic contrast-enhanced GRASP MRI allows for a reliable and robust assessment of hepatic perfusion parameters providing quantitative results comparable to VPCT and enables characterization of HCC before and after TACE, thus posing the potential to serve as an alternative to VPCT. Received for publication March 19, 2019; and accepted for publication, after revision, April 18, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Jakob Weiss, MD, Department of Diagnostic and Interventional Radiology, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. E-mail: Jakob.Weiss@uni-tuebingen.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Quantitative Assessment of Bone Metastasis in Prostate Cancer Using Synthetic Magnetic Resonance Imaging Objectives The aims of this study were to evaluate the feasibility of quantitative synthetic magnetic resonance imaging (SyMRI) for characterizing bone lesions in prostate cancer and to discriminate viable progressive osteoblastic bone metastasis from nonviable bone metastases with treatment-induced sclerosis during the treatment course. Materials and Methods This institutional review board–approved prospective study included 96 consecutive prostate cancer patients who underwent whole-body MRI including diffusion-weighted imaging at the time of staging at diagnosis or starting a new line of anticancer treatment. Additional synthetic MRI of the lumbosacral spine, pelvis, and proximal femurs was performed. A region of interest of 1.0 cm in diameter was set in each bone lesion by 2 independent readers who were blinded to bone lesions' diagnosis. Differences in SyMRI variables between the different bone lesions were compared with the Wilcoxon rank sum test, and associations of SyMRI variables with active disease were analyzed with logistic regression analysis. Performance of T1, T2, and proton density (PD) for diagnosing active disease was assessed using the area under the receiver operating characteristic curve. Results Ninety-three bone lesions were eligible for analysis. The PD values of active (viable) bone metastatic lesions were significantly higher than those of inactive (nonviable) bone metastatic lesions without sclerosis and those of red bone marrow (P < 0.001 for both readers). The PD values of inactive bone metastatic lesions with sclerosis were significantly lower than those of inactive bone metastatic lesions without sclerosis and red bone marrow (P < 0.001 for both readers). The PD value proved to be an independent significant indicator (P < 0.001) for differentiating bone lesions. The areas under the curve of T1/T2/PD for identifying active disease were 0.81/0.69/0.93 for reader 1 and 0.78/0.70/0.92 for reader 2, respectively. Conclusions Signal quantification on SyMRI provides objective assessment of bone lesions in the lower trunk. The PD value can be useful to determine the viability of bone metastases in prostate cancer. Received for publication February 23, 2019; and accepted for publication, after revision, April 6, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Yuki Arita, MD, Department of Diagnostic Radiology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: yarita@rad.med.keio.ac.jp. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T Purpose The relaxivities of 3 macrocyclic gadolinium-based contrast agents (GBCAs) were determined in human plasma and blood under standardized and clinically relevant laboratory conditions. Methods The T1 relaxivity, r1, was determined in human plasma at 1.5, 3, and 7 T, and in human blood at 3 T at 37°C in phantoms containing 4 different concentrations of the macrocyclic GBCAs gadobutrol, gadoteridol, and gadoterate. An inversion recovery turbo spin echo sequence was used to generate images with several inversion times. The T1-times were obtained by fitting the signal intensities to the signal equation. r1 was obtained by a 1/y-weighted regression of the T1-rates over the concentration of the GBCAs. Results For gadobutrol, the obtained r1 [L/(mmol·s)] in human plasma at 1.5 T, 3 T, and 7 T, and in human blood at 3 T was 4.78 ± 0.12, 4.97 ± 0.59, 3.83 ± 0.24, and 3.47 ± 0.16. For gadoteridol, r1 was 3.80 ± 0.10, 3.28 ± 0.09, 3.21 ± 0.07, and 2.61 ± 0.16, and for gadoterate, 3.32 ± 0.13, 3.00 ± 0.13, 2.84 ± 0.09, and 2.72 ± 0.17. Conclusions The relaxivity of gadobutrol is significantly higher than that of gadoteridol and gadoterate at all magnetic field strengths and in plasma as well as in blood, whereas that of gadoteridol was higher than gadoterate only in plasma at 1.5 and 7 T. This is in accordance with results from 3 previous studies obtained in different media. Received for publication January 31, 2019; and accepted for publication, after revision, April 6, 2019. Conflicts of interest and sources of funding: The authors P.S., I.M.N.-H., and S.T. declare no conflicts of interest. The authors M.R., T.F., G.J., J.E. and H.P. are employees of Bayer AG. This study was funded by the Vienna Science and Technology Fund (WWTF-LS11-018), Austrian Science Fund (FWF KLI541-B30), and Slovak Grant Agency (APVV-15-0029). Financial support to the Medical University of Vienna was also provided by Bayer AG. Correspondence to: Siegfried Trattnig, MD, MR Centre-Highfield MR, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waerhringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: siegfried.trattnig@meduniwien.ac.at. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

AcidoCEST-UTE MRI for the Assessment of Extracellular pH of Joint Tissues at 3 T Objectives The goal of this study was to demonstrate feasibility of measuring extracellular pH in cartilage and meniscus using acidoCEST technique with a 3-dimensional ultrashort echo time readout (acidoCEST-UTE) magnetic resonance imaging (MRI). Materials and Methods Magnetization transfer ratio asymmetry, radiofrequency (RF) power mismatch, and relative saturation transfer were evaluated in liquid phantoms for iopromide, iopamidol, and iohexol over a pH range of 6.2 to 7.8, at various agent concentrations, temperatures, and buffer concentrations. Tissue phantoms containing cartilage and meniscus were evaluated with the same considerations for iopamidol and iohexol. Phantoms were imaged with the acidoCEST-UTE MRI sequence at 3 T. Correlation coefficients and coefficients of variations were calculated. Paired Wilcoxon rank-sum tests were used to evaluate for statistically significant differences. Results The RF power mismatch and relative saturation transfer analyses of liquid phantoms showed iopamidol and iohexol to be the most promising agents for this study. Both these agents appeared to be concentration independent and feasible for use with or without buffer and at physiologic temperature over a pH range of 6.2 to 7.8. Ultimately, RF power mismatch fitting of iohexol showed the strongest correlation coefficients between cartilage, meniscus, and fluid. In addition, ratiometric values for iohexol are similar among liquid as well as different tissue types. Conclusions Measuring extracellular pH in cartilage and meniscus using acidoCEST-UTE MRI is feasible. Received for publication January 31, 2019; and accepted for publication, after revision, April 3, 2019. Drs Ya-Jun Ma and Rachel High contributed equally to this work. Conflicts of interest and sources of funding: The authors gratefully acknowledge grant support from the VA Rehabilitation Research and Development Service (Merit Award I01RX002604), VA Clinical Science Research and Development Service (Merit Award I01CX001388), and National Institutes of Health (2R01AR062581, 1R01AR068987, and 1R21AR073496). The authors declare no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.investigativeradiology.com). Correspondence to: Eric Y. Chang, MD, Radiology Service, VA San Diego Healthcare System, 3350 La Jolla Village Drive, MC 114, San Diego, CA 92161. E-mail: ericchangmd@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Imaging Features of Hepatocellular Carcinoma: Quantitative and Qualitative Comparison Between MRI-Enhanced With Gd-EOB-DTPA and Gd-DTPA Objectives The aim of this study was to compare the major imaging features of hepatocellular carcinoma (HCC) on magnetic resonance imaging (MRI) scans with Gd-EOB-DTPA (EOB) and extracellular agent (ECA; Gd-DTPA) contrast media. Materials and Methods Among 184 surgically proven HCCs in 169 patients who underwent a liver MRI with either EOB (n = 120) or ECA (n = 49), 55 HCCs were matched according to tumor size, Edmonson grade (major and worst), and gross type for each of the 2 contrast media. For the qualitative analysis, 2 board-certified radiologists independently reviewed arterial phase hyperenhancement, hypointensity on portal venous phase, hypointensity on delayed or transitional phase (DP/TP, 120–150 seconds), and capsule appearance. For the quantitative analysis, a third radiologist measured the signal intensity at each phase by placing the region of interest for tumor and normal liver parenchyma. The lesion-to-liver contrast (LLC) and lesion-to-liver contrast enhancement ratio (LLCER) were calculated. Results On qualitative analysis, hypointensity on DP/TP was seen more frequently with EOB (91% in reader 1, 89% in reader 2) than with ECA (73% in reader 1, 75% in reader 2; P = 0.026). Capsule appearance was seen less frequently with EOB (31% in reader 1, 44% in reader 2) than with ECA (73% in reader 1, 78% in reader 2; P < 0.001). On quantitative analysis, the LLC on arterial phase (AP) was better with ECA (P = 0.003), whereas LLC on DP was better with EOB (P < 0.001). The LLCER from precontrast to AP was higher with ECA (P = 0.022), whereas the LLCER from portal venous phase to DP was higher with EOB (P < 0.001). Conclusions ECA-MRI revealed better LLC on AP and detection rate of capsule appearance than EOB-MRI. EOB-MRI showed superior LLC on TP. Received for publication December 27, 2018; and accepted for publication, after revision, February 18, 2019. Jinwoo Son and Shin Hye Hwang contributed equally to this study. Conflicts of interest and sources of funding: none declared. Correspondence to: Mi-Suk Park, MD, PhD, Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonse-ro, Seodaemun-gu, Seoul 03722, South Korea. E-mail: radpms@yuhs.ac. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases With Reduced Kinetic Stability of the Agent Objectives This preclinical study was devised to investigate potential cellular toxicity in human neurons induced by gadolinium-based contrast agents (GBCAs) used for contrast-enhanced magnetic resonance imaging (MRI). Neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is 1 of 2 brain regions that displays the greatest T1-dependent signal hyperintensity changes. Methods Eight GBCAs were tested. Dopaminergic neurons modeling a subset of those in the basal ganglia were differentiated from an established human neuroblastoma cell line and exposed to increasing concentrations of each agent for 7 days. The tested dosages ranged from clinically relevant concentrations measured in some autopsy patients who had received repeated injections of contrast for MRI, to higher concentrations to reveal dose-dependent toxicity trends. Cell death, mitochondrial membrane potential, mitochondrial oxidative capacity, and mitochondrial function measured by oxygen consumption were quantified in cells treated with each GBCA or the osmolality control mannitol and compared to untreated cells which served as a negative control. Results Mannitol caused no change from negative controls in any of the tests, at any concentration tested. For all GBCAs, cell death increased with exposure dose, with toxicity at clinically relevant doses for agents with lower kinetic stability. Reduction of mitochondrial membrane potential and oxidative respiratory function also generally mirrored the agents' structural kinetic stabilities, with greater impairment at lower concentration for the less stable agents. Conclusions In human neurons modeling a subset of those in the basal ganglia, these results demonstrate a toxic effect of gadolinium-containing MRI contrast agents on mitochondrial respiratory function and cell viability. Toxicity increases as agent concentration increases and as the kinetic stability of the agent decreases. Received for publication January 8, 2019; and accepted for publication, after revision, March 1, 2019. Johannes T. Heverhagen and Val M. Runge share the senior authorship. Author contributions: D.V.B. and V.M.R. conceived of the overall project. D.V.B. conceived the experimental plans, designed the protocols, conducted the experiments, analyzed the data, and produced the final figures. J.K.R. validated reproducibility of quantifications as a second reader. D.V.B. wrote and revised the manuscript. H.v.T.K. and J.T.H. financed and oversaw the project. All authors discussed the results and approved the final manuscript. This work was performed in the laboratory for Experimental Radiology, Inselspital, University Hospital of Bern, located in the Department for BioMedical Research (DBMR), University of Bern. Imaging was conducted at the Live Cell Imaging Core Facility of the Microscopy Imaging Center at the University of Bern. The experiments measuring oxygen consumption and acidification were performed in the laboratory of Stefan Freigang in the Institute of Pathology at the University of Bern. This study was funded by the Department of Diagnostic, Interventional, and Pediatric Radiology, Inselspital, University Hospital of Bern, University of Bern, Bern, Switzerland. The authors declare no conflicts of interest. Correspondence to: Danielle V. Bower, MD, PhD, Department of Diagnostic, Interventional, and Pediatric Radiology, Inselspital, University Hospital of Bern, University of Bern, Freiburgstrasse 10, 3010 Bern, Switzerland. E-mail: danielle.bower@insel.ch. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Computer-Aided Diagnosis of Pulmonary Fibrosis Using Deep Learning and CT Images Objectives The objective of this study is to assess the performance of a computer-aided diagnosis (CAD) system (INTACT system) for the automatic classification of high-resolution computed tomography images into 4 radiological diagnostic categories and to compare this with the performance of radiologists on the same task. Materials and Methods For the comparison, a total of 105 cases of pulmonary fibrosis were studied (54 cases of nonspecific interstitial pneumonia and 51 cases of usual interstitial pneumonia). All diagnoses were interstitial lung disease board consensus diagnoses (radiologically or histologically proven cases) and were retrospectively selected from our database. Two subspecialized chest radiologists made a consensual ground truth radiological diagnosis, according to the Fleischner Society recommendations. A comparison analysis was performed between the INTACT system and 2 other radiologists with different years of experience (readers 1 and 2). The INTACT system consists of a sequential pipeline in which first the anatomical structures of the lung are segmented, then the various types of pathological lung tissue are identified and characterized, and this information is then fed to a random forest classifier able to recommend a radiological diagnosis. Results Reader 1, reader 2, and INTACT achieved similar accuracy for classifying pulmonary fibrosis into the original 4 categories: 0.6, 0.54, and 0.56, respectively, with P > 0.45. The INTACT system achieved an F-score (harmonic mean for precision and recall) of 0.56, whereas the 2 readers, on average, achieved 0.57 (P = 0.991). For the pooled classification (2 groups, with and without the need for biopsy), reader 1, reader 2, and CAD had similar accuracies of 0.81, 0.70, and 0.81, respectively. The F-score was again similar for the CAD system and the radiologists. The CAD system and the average reader reached F-scores of 0.80 and 0.79 (P = 0.898). Conclusions We found that a computer-aided detection algorithm based on machine learning was able to classify idiopathic pulmonary fibrosis with similar accuracy to a human reader. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Received for publication February 15, 2019; and accepted for publication, after revision, March 19, 2019. Conflicts of interest and sources of funding: This study was funded by the Swiss National Science Foundation, Roche Pharma Ltd, and the Lindenhof Foundation. The authors declare no conflicts of interest. Correspondence to: Andreas Christe, MD, Department of Diagnostic, Interventional, and Pediatric Radiology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010 Bern, Switzerland. E-mail: andreas.christe@insel.ch. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Super-Resolution Contrast-Enhanced Ultrasound Methodology for the Identification of In Vivo Vascular Dynamics in 2D Objectives The aim of this study was to provide an ultrasound-based super-resolution methodology that can be implemented using clinical 2-dimensional ultrasound equipment and standard contrast-enhanced ultrasound modes. In addition, the aim is to achieve this for true-to-life patient imaging conditions, including realistic examination times of a few minutes and adequate image penetration depths that can be used to scan entire organs without sacrificing current super-resolution ultrasound imaging performance. Methods Standard contrast-enhanced ultrasound was used along with bolus or infusion injections of SonoVue (Bracco, Geneva, Switzerland) microbubble (MB) suspensions. An image analysis methodology, translated from light microscopy algorithms, was developed for use with ultrasound contrast imaging video data. New features that are tailored for ultrasound contrast image data were developed for MB detection and segmentation, so that the algorithm can deal with single and overlapping MBs. The method was tested initially on synthetic data, then with a simple microvessel phantom, and then with in vivo ultrasound contrast video loops from sheep ovaries. Tracks detailing the vascular structure and corresponding velocity map of the sheep ovary were reconstructed. Images acquired from light microscopy, optical projection tomography, and optical coherence tomography were compared with the vasculature network that was revealed in the ultrasound contrast data. The final method was applied to clinical prostate data as a proof of principle. Results Features of the ovary identified in optical modalities mentioned previously were also identified in the ultrasound super-resolution density maps. Follicular areas, follicle wall, vessel diameter, and tissue dimensions were very similar. An approximately 8.5-fold resolution gain was demonstrated in vessel width, as vessels of width down to 60 μm were detected and verified (λ = 514 μm). Best agreement was found between ultrasound measurements and optical coherence tomography with 10% difference in the measured vessel widths, whereas ex vivo microscopy measurements were significantly lower by 43% on average. The results were mostly achieved using video loops of under 2-minute duration that included respiratory motion. A feasibility study on a human prostate showed good agreement between density and velocity ultrasound maps with the histological evaluation of the location of a tumor. Conclusions The feasibility of a 2-dimensional contrast-enhanced ultrasound-based super-resolution method was demonstrated using in vitro, synthetic and in vivo animal data. The method reduces the examination times to a few minutes using state-of-the-art ultrasound equipment and can provide super-resolution maps for an entire prostate with similar resolution to that achieved in other studies. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received for publication December 18, 2018; and accepted for publication, after revision, February 20, 2019. Conflicts of interest and sources of funding: The authors would like to thank the following funding agencies: Science and Technology Facilities Council (ST/M007804/1), Medical Research Council UK (MRC/CIC3/027 and G0800896), British Heart Foundation (PG/10/021/28254), Engineering and Physical Sciences Research Council (EP/N015320/1), and BK Medical Ltd (Herlev, Denmark) for their support. Correspondence to: Vassilis Sboros, PhD, Institute of Biochemistry, Biological Physics, and Bio Engineering, Engineering and Physical Sciences, Heriot-Watt University, Riccarton, EH14 4AS United Kingdom. E-mail: V.Sboros@hw.ac.uk. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Prophylaxis in High-Risk Patients With eGFR < 30 mL/min/1.73 m2: Get the Balance Right Objectives Clinical guidelines recommend prophylactic intravenous fluids for patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 to prevent adverse postcontrast outcomes. These patients represent a small minority of the population receiving intravascular iodinated contrast material, and data are not readily available. The current study aim is to gain insight into positive and negative effects of prophylaxis by comparing postcontrast outcomes in high-risk patients who did and did not receive prophylaxis. Materials and Methods Observational data were gathered over 4 years. Inclusion criteria were age 18 years or older, eGFR less than 30 mL/min/1.73 m2, and elective intravascular iodinated contrast administration. Exclusion criteria were dialysis and nonstandard periprocedural prophylaxis. Primary outcome was postcontrast acute kidney injury (>25% or >44 μmol/L serum creatinine increase within 2–5 days). Secondary outcomes were change in eGFR, 5 mL/min/1.73 m2 or greater eGFR decline, dialysis, and mortality at 1 month postcontrast including primary cause, as well as complications of prophylaxis. Results were stratified by contrast procedure type and corrected for potential confounders. Results Of all 55,474 elective procedures with intravascular contrast administration, 362 patients met the inclusion criteria: 281 (78%) received standard 0.9% NaCl prophylaxis and 81 (22%) received no prophylaxis. Prophylaxis versus no prophylaxis adjusted odds ratios were nonsignificant and less than 1 for postcontrast renal outcomes (postcontrast acute kidney injury, eGFR decline, dialysis), indicating a trend toward a protective effect of prophylaxis. For mortality, adjusted odds ratios were nonsignificant and greater than 1, indicating a trend toward higher mortality risk after prophylaxis. Of the primary causes of death analyzed in prophylaxis patients, 24% (5/21) were related to prophylaxis. Among 281 prophylaxis patients, 18 (6.4%) complications of prophylaxis occurred: 15 heart failures and 3 arrhythmias. Conclusions Based on this study, no standard recommendation with regard to giving or withholding prophylaxis can be given. Prophylactic fluids may confer some protection against postcontrast renal adverse events but may also contribute toward increased risk of short-term death. In this setting, benefits and risks of prophylaxis must be carefully weighed and cardiac parameters assessed for each individual patient. Received for publication February 8, 2019; and accepted for publication, after revision, March 14, 2019. Conflicts of interest and sources of funding: The authors declare no conflicts of interest. The study was funded by Stichting de Weijerhorst. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.investigativeradiology.com). Correspondence to: Estelle C. Nijssen, MSc, Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands. E-mail: estelle.nijssen@mumc.nl. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Increased Retention of Gadolinium in the Inflamed Brain After Repeated Administration of Gadopentetate Dimeglumine: A Proof-of-Concept Study in Mice Combining ICP-MS and Micro– and Nano–SR-XRF Objectives The aim of this study was to determine in vivo if brain inflammation leads to increased gadolinium (Gd) retention in brain tissue after repeated applications of Gd-based contrast agents (GBCAs). Materials and Methods Experimental autoimmune encephalomyelitis (EAE) was induced in female SJL/J mice (n = 6). Experimental autoimmune encephalomyelitis and healthy control mice (n = 4) received 2.5 mmol/kg Gd-DTPA over 10 days (8 injections, cumulated dose of 20 mmol/kg), starting at day 14 post immunization when EAE mice reached the maximal clinical disability. In a group of mice, T1-weighted 2-dimensional RARE images were acquired before the first GBCA injection and 1 day after the last injection. Mice were killed either 1 day or 10 days after the last Gd application. From each single animal, a brain hemisphere was used for Gd detection using inductively coupled plasma mass spectrometry, whereas the other hemisphere was processed for histology and synchrotron x-ray fluorescence spectroscopy (SR-XRF) analysis. Results Gadolinium deposition in inflamed brains was mapped by SR-XRF 1 day after the last Gd-DTPA injections, although only mild signal hyperintensity was found on unenhanced T1-weighted images. In addition, using inductively coupled plasma mass spectrometry, we detected and quantified Gd in both healthy and EAE brains up to 10 days after the last injections. However, EAE mouse brains showed higher levels of Gd (mean ± SD, 5.3 ± 1.8 μg/g; range, 4.45–8.03 μg/g) with respect to healthy controls (mean ± SD, 2.4 ± 0.6 μg/g; range, 1.8–3.2 μg/g). By means of micro–SR-XRF, we identified submicrometric Gd hotspots in all investigated samples containing up to 5893 μg Gd/g tissue. Nano–SR-XRF further indicated that Gd small hotspots had an average size of ~160 nm diameter and were located in areas of high inflammatory activity. Conclusions After repeated administrations of Gd-DTPA, ongoing inflammation may facilitate the retention of Gd in the brain tissue. Thus, neuroinflammation should be considered as a risk factor in the recommendation on use of linear GBCA-enhanced MRI. Received for publication December 14, 2018; and accepted for publication, after revision, March 11, 2019. Shuangqing Wang and Bernhard Hesse contributed equally to this article. Conflicts of interest and sources of funding: There are no conflicts of interest to declare. This work was supported by the European Synchrotron Radiation Facility and the German Research Foundation (Deutsche Forschungsgemeinschaft; SFB1340-1/B05, IN156/4-1, and GRK2260 [BIOQIC]). Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.investigativeradiology.com). Correspondence to: Carmen Infante-Duarte, PhD, Experimental Neuroimmunology, Institute for Medical Immunology, Charité–Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: carmen.infante@charite.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Neurosurgical Anesthesiology

Effective Cerebral Perfusion Pressure: Does the Estimation Method Make a Difference? Introduction: The effective cerebral perfusion pressure (CPPe), zero-flow pressure (ZFP), and resistance area product (RAP) are important determinants of cerebral blood flow. ZFP and RAP are usually estimated by linear regression analysis of pressure-velocity relationships of the middle cerebral artery. The aim of this study was to validate 4 other estimation methods against the standard linear regression method. Methods: In a previous study, electroencephalography, arterial blood pressure, and middle cerebral artery flow velocity were measured in patients during internal cardioverter defibrillator implantation procedures to determine the electroencephalography frequency ranges that represent ischemic changes during periods of circulatory arrest. In this secondary analysis, arterial blood pressure and middle cerebral artery flow velocity were used to estimate CPPe, ZFP, and RAP by 4 different methods—the 3-point intercept calculation (LR3, systolic/mean/diastolic) and methods described by Czosnyka (systolic/diastolic), Belford (mean/diastolic), and Schmidt (systolic/diastolic)—and compare them with the reference linear regression method. CPPe was calculated as the difference between mean arterial pressure and ZFP. The primary endpoint was the difference, correlation, and agreement of these differently estimated CPPe measurements. Results: In total, 174 measurements in 35 patients were collected under steady-state conditions before the first circulatory arrest phase during internal cardioverter defibrillator testing. CPPe, ZFP, and RAP measurements based on the 3-point intercept and Czosnyka calculation methods showed small mean differences, good agreement, low percentage errors, and excellent correlation when compared with the reference method. Agreement and correlation were moderate for the Belford method and unsatisfactory for the Schmidt method. Conclusions: CPPe, ZFP, and RAP measurements based on 2 alternative calculation methods are comparable to the linear regression reference method. The primary analysis was supported by The Netherlands Heart Foundation (grant no. 93.149) (Visser et al, 2001). In the secondary analysis, support was provided solely from institutional and/or departmental sources. Work is attributed to: Erasmus MC, Rotterdam, NL. The authors acknowledge that the enclosed manuscript is part of a larger series of prospective studies about cerebral circulation and cerebral metabolism in the perioperative setting. In 56 patients during internal cardioverter defibrillator (ICD) device testing under general anesthesia, we determined 4 main EEG frequency ranges that represent ischemic changes during short periods of circulatory arrest. These former results have been published (Visser et al, 2001). Medical Ethical Research Committee Utrecht. Trial: Cerebral effects of repeated periods of circulatory arrest by induced ventricular fibrillation during ICD implantation (Cerebrale effecten van herhaalde perioden van circulatiestilstand door geïnduceerd kamerfibrilleren tijdens ICD implantatie), Nr.:92/59. The trial was planned and done before CONSORT 2010. Dutch laws did not require international registration of this type of clinical trial at that time. The Netherlands Trial register does not accept closed studies (www.trialregister.nl). A registration at "clinical trials" was not possible, too (www.clinicaltrials.gov). Here, the completion date of our study was before December 26, 2007, which is an exclusion criterion following the FDAAA 801 note (https://clinicaltrials.gov/ct2/manage-recs/fdaaa). The authors have no conflicts of interest to disclose. Address correspondence to: Frank Grüne, MD, E-mail: f.grune@erasmusmc.nl. Received March 31, 2018 Accepted April 18, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Optimizing Design for the Way Clinicians Use Critical Event Cognitive Aids No abstract available

The Effect of Depth of Anesthesia on Hemodynamic Changes Induced by Therapeutic Compression of the Trigeminal Ganglion Background: Percutaneous compression of the trigeminal ganglion (PCTG) has been used to treat trigeminal neuralgia since 1983. A PCTG-related trigeminocardiac reflex (TCR) can induce dramatic hemodynamic disturbances. This study investigates the effects of depth of propofol anesthesia on hemodynamic changes during PCTG. Materials and Methods: A total of 120 patients who underwent PTCG for trigeminal neuralgia were randomly assigned to control group-intravenous saline pretreatment before PCTG puncture and anesthesia targeted to bispectral index (BIS) 40 to 60 throughout, and study group-intravenous propofol 1 to 2 mg/kg pretreatment to deepen anesthesia to BIS<40 before PCTG. Mean arterial pressure, heart rate (HR), cardiac output, system vascular resistance, and BIS were measured at 9 time points during the procedure, and the incidence of the TCR was observed at T5 and T6. Results: BIS was lower in the study group compared with the control after pretreatment with propofol or saline, respectively. Compared with the control group, mean arterial pressure was lower in the study group at several points during the procedure, but there was no difference in HR between the 2 groups at any point. Cardiac output was higher and system vascular resistance lower in the study compared with the control group. In the control group, 42 (70.0%) and 52 (86.7%) of patients developed a TCR at the 2 points, and 37 (67.1%) and 45 (75.0%) in the study group. There was no difference in the incidence of TCR between the 2 groups. Conclusion: Increasing the depth of propofol anesthesia partially attenuated PTCG-related elevation of blood pressure but did not modify the abrupt reduction in HR. This work was funded by the Liaoning Natural Science Foundation of China (no. 20170540524) and the National Nature Science Foundation of China (no. 81671311 and no. 81870838), the Key Research and Development Program of Liaoning Province (no. 2018225004), and the Outstanding Scientific Fund of Shengjing Hospital (no. 201708). Supported by the Department of Anaesthesiology, Second Department of Neurosurgery, People's Hospital of China Medical University (Liaoning Provincial People's Hospital), and the Department of Anaesthesiology, Shengjing Hospital of China Medical University, P.R. China. C.-M.W.: wrote the manuscript. Z.-Y.G. and Q.-C.W.: were responsible for data statistics. All operations were performed by Y.M. J.Z., and P.Z. intensively supervised the work and substantially helped in the writing process. All authors read and approved the final manuscript. The authors have no conflicts of interest to disclose. Address correspondence to: Ping Zhao, MD, E-mail: zhaopingdoctor@yeah.net. Received January 9, 2019 Accepted April 10, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Defining a Taxonomy of Intracranial Hypertension: Is ICP More Than Just a Number? Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension. Supported by Department of Health and Human Services, National Institutes of Health, and National Institute of Neurological Disorders and Stroke, 1R01NS082309-01A1. W.A.K.: funded by 1R01NS082309-01A1. Legal consultant; multiple legal and health care entities. Royalty payments Oxford University Press and Elsevier. Honoraria NIH study sections. Editorial Board Neurocritical Care. Editorial Board J Neurosurg Anesth. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. R.B.: funded by 1R01NS082309-01A1. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. The remaining authors have no conflicts of interest to disclose. Address correspondence to: W. Andrew Kofke, MD, MBA. E-mail: kofkea@uphs.upenn.edu. Received November 26, 2018 Accepted April 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Subanesthetic Dose of Ketamine Improved CFA-induced Inflammatory Pain and Depression-like Behaviors Via Caveolin-1 in Mice Background: Ketamine, a commonly used nonbarbiturate anesthetic drug, possesses antidepressant properties at subanesthetic doses; however, the underlying mechanisms remain unclear. Materials and Methods: The analgesic and antidepressant effects of ketamine were explored using a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model in vivo. Mice were first divided into sham or CFA injection group randomly, and were observed for mechanical hyperalgesia, depression-like behavior, and mRNA expression of caveolin-1. Then ketamine was administered in CFA-treated mice at day 7. Results: The behavioral testing results revealed mechanical hyperalgesia and depression in mice from days 7 to 21 after CFA injection. Ketamine reversed depression-like behaviors induced by CFA injection. It also restored the brain-regional expression levels of caveolin-1 in CFA-treated mice. In addition, caveolin-1 mRNA and protein expression were increased in the prefrontal cortex and nucleus accumbens of CFA-treated mice. However, ketamine reversed the increase in caveolin-1 expression in the ipsilateral and contralateral prefrontal cortex and nucleus accumbens, supporting the distinct roles of specific brain regions in the regulation of pain and depression-like behaviors. Conclusions: In CFA-treated mice that exhibited pain behavior and depression-like behavior, ketamine reversed depression-like behavior. The prefrontal cortex and nucleus accumbens are the important brain regions in this regulation network. Despite these findings, other molecules and their mechanisms in the signal pathway, as well as other regions of the brain in the pain matrix, require further exploration. J.L. and R.H. contributed equally to this work. J.W. and Q.Z. are co-first authors. This work was funded by the Beijing Municipal Administration of Hospitals' Ascent Plan (code number DFL20180502) and Clinical Medicine Development of Special Funding Support (code number ZYLX201708). R.H. is a member of the Editorial Board of the Journal of Neurosurgical Anethesiology. The authors have no conflicts of interest to disclose. Address correspondence to: Ruquan Han, MD, PhD. E-mail: ruquan.han@ccmu.edu.cn. Received November 21, 2018 Accepted April 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Remifentanil Patient-controlled Analgesia in Awake Craniotomy: An Introduction of an Innovative Technique No abstract available

Effect of Daytime Versus Night-Time on Outcome in Patients Undergoing Emergent Neurosurgical Procedures Background: Timing of neurosurgical procedures is controversial. Challenges identified with night-time surgeries include physician fatigue and sleep deprivation, and fewer staff and resources compared with daytime surgery. These might contribute to medical errors and complications, and, hence, worse patient outcomes. Methods: This single center retrospective study of 304 patients who underwent emergent neurosurgical procedures between January 1, 2010 and December 31, 2016 included 2 groups based on the timing of surgery: daytime (7:00 AM to 6:59 PM) and night-time (7:00 PM to 6:59 AM) surgery groups. Patient demographics, diagnosis, surgical characteristics, complications, and neurological outcome were obtained from the medical records. Results: There was no difference in patient demographics, intraoperative complications, and length of surgery between the 2 groups. Although there was no statistically significant difference in neurological outcome between the 2 groups at hospital discharge and 1 month postdischarge, there was a higher proportion of patients in the night-time surgical group with unfavorable neurological outcome (Glasgow Outcome Score 1 to 3) at both these times. There were differences in hospital length of stay, location of postoperative management (postanesthesia care unit or intensive care unit), midline shift, baseline Glasgow Coma Scale score, and acuity of surgery between the 2 groups. Logistic regression analysis showed that age, baseline Glasgow Coma Scale score, surgery acuity status, procedure type, and intraoperative complications influenced neurological outcome. Conclusions: This study found no difference in the rate of unfavorable neurological outcome in patients undergoing emergent neurosurgical procedures during the daytime and night-time. However, our findings cannot exclude the possibility of an association between timing of surgery and outcome given its limitations, including small sample size and omission of potentially confounding variables. Further well-designed prospective trials are warranted to confirm our findings. This study is a part of Bachelor of Science (Medicine) project thesis of A.H.Q., and he received a stipend from the University of Manitoba to conduct this research project. This project is funded by Anesthesia Oversight Committee, Department of Anesthesiology, Perioperative and Pain Medicine, University of Manitoba, Winnipeg, Canada. T.C. (primary supervisor) received the above-mentioned grant. Support was provided solely from institutional and/or departmental sources. Presented at: Neuroanesthesia Rounds, August 15, 2018, University of Manitoba; Bachelor of Science (Medicine) Research Symposium, August 23, 2018, University of Manitoba. The authors have no conflicts of interest to disclose. Address correspondence to: Tumul Chowdhury, MD, DM, FRCPC. E-mail: tumul.chowdhury@umanitoba.ca. Received September 9, 2018 Accepted March 12, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Language Monitoring in Brain Surgery Under General Anesthesia Background: Awake surgeries for cerebral lesion resection have several limitations including patient fear, discomfort, or pain. This study aimed to determine whether components of language function could be measured under general anesthesia. In this study, the occurrence of mismatch negativity (MMN) was searched in evoked potentials for phonological sounds. Materials and Methods: Five normal hearing, French native speaker, awake volunteers participated in evaluating the phonological task (4 females and 1 male). Eleven normal-hearing, French native speaker patients (6 left and 5 right hemisphere lesions) participated at the time of their tumor neurosurgery (3 females and 8 males). Repetitions of the standard syllable /pa/ with the insertion of 1 deviant /po/ were presented through earphones. The difference between averaged epochs of standards and deviants syllables determined the MMN. During surgery, total intravenous anesthesia was performed with propofol and synthetic opioid sufentanil. The bispectral index was targeted (40 to 60). Results: The MMN was found in all awake volunteers and validated by an N250 component. In the patient group, the electroencephalogram analysis was not possible in 4 of 11 patients because of anesthesia being too deep, burst suppression, or a high level of noise (>40 μV). Significant N250 response was obtained in 5 of 7 (71.4%) patients under general anesthesia. The 2 other patients also showed MMN which did not reach significance. Conclusions: To our knowledge, this is the first demonstration that phonological processing can be measured during brain surgery under general anesthesia, suggesting that some language processing persists under the condition of unconsciousness. These results encourage further study of language processing under general anesthesia with the goal of making intraoperative neuromonitoring. Supported by the University Hospital of Geneva (in particular with the fund PRD no. 10-2015-I "Advanced electrophysiological monitoring in neurosurgery"). The authors have no conflicts of interest to disclose. Address correspondence to: Colette Boëx, PhD. E-mail: colette.boex@hcuge.ch. Received December 7, 2018 Accepted March 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Comparison of 2 Automated Pupillometry Devices in Critically Ill Patients Background: Automated pupillometry may help detect early cerebral disturbances in critically ill patients. It remains unclear whether different automated pupillometry devices can detect pupillary abnormalities with similar accuracy. The aim of this study was to compare the performance of 2 commercially available automated pupillometry devices—Neurolight Algiscan (NL) and NPi-200 (NP) versus standard pupillary light reflex (PLR) examination in an unselected cohort of critically ill patients. Materials and Methods: This prospective study included all adult (>18 y) patients admitted to the intensive care unit of a university hospital over a 20-day period. Measurements were made consecutively with each method once during the intensive care unit stay in each patient. To assess sensitivity and specificity, we calculated areas under the curve of the receiver operating characteristic curve. Results: A total of 112 patients were included in the study. There was a significant correlation between the 2 automated pupillometry devices for pupil size, constriction to light stimulation, and constriction velocity but not for pupillary latency. The mean bias for pupil size measured by the NL and the NP devices was −0.12 (limit of agreement [LoA], −1.29 to 1.06) mm, for pupil constriction −1.0% (LoA, −9.3% to 7.2%), and for latency 0.02 (LoA, −0.22 to 0.25) ms. There was a significant correlation between pupil size evaluated by clinical examination and that using the NL or NP. The areas under the curves for pupil constriction measured by NL and NP were 0.93 and 0.91, respectively, to detect clinically reactive pupils. Conclusions: Although there was a significant correlation between NL and NP values as well as with clinical examination of the PLR, the 2 devices were not always interchangeable, especially for the evaluation of pupillary latency. F.S.T., B.M.S., and S.P.: conceived and designed the study. F.S.T., B.M.S., S.P., and J.C.: selected the population. B.M.S., F.S.T., S.P., J.C., and J.L.V.: screened and collected data from the population. F.S.T., M.O., and C.R.: conduced the statistical analysis. F.S.T., M.O., and C.R.: wrote the first draft of the manuscript. J.L.V., J.C., B.M.S., and S.P.: revised the text for intellectual content. All the coauthors read and approved the final text. M.O. has received lectures fees from Neuroptics. The remaining authors have no funding or conflicts of interest to disclose. Address correspondence to: Fabio S. Taccone, MD, PhD. E-mail: ftaccone@ulb.ac.be. Received November 17, 2018 Accepted March 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Bilateral Ultrasound-guided Erector Spinae Plane Block for Postoperative Analgesia in Lumbar Spine Surgery: A Randomized Control Trial Background: Major lumbar spine surgery causes severe postoperative pain. The primary objective of this randomized controlled study was to compare the effect of ultrasound (US)-guided erector spinae plane (ESP) block on 24-hour postoperative cumulative opioid requirements with standard (opioid-based) analgesia. Postoperative pain control and patient satisfaction were also assessed. Materials and Methods: Adults scheduled for elective lumbar spine surgery under general anesthesia were randomly assigned to the following (and they are): Control group-no preoperative ESP block, or ESP block group-preoperative bilateral US-guided ESP block. Both groups received standard general anesthesia during surgery. Postoperative pain score, number of patients requiring rescue analgesia, and total morphine consumption during the first 24 postoperative hours were recorded. Patient satisfaction was assessed 24 hours after surgery. Results: Postoperative morphine consumption was significantly lower in patients in the ESP group compared with those in the control group (1.4±1.5 vs. 7.2±2.0 mg, respectively; P<0.001). All patients in the control group required supplemental morphine compared with only 9 (45%) in the ESP block group (P=0.002). Pain scores immediately after surgery (P=0.002) and at 6 hours after surgery (P=0.040) were lower in the ESP block group compared with the control group. Patient satisfaction scores were more favorable in the block group (P<0.0001). Conclusions: US-guided ESP block reduces postoperative opioid requirement and improves patient satisfaction compared with standard analgesia in lumbar spine surgery patients. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Swati Singh, MD. E-mail: deepakswat@yahoo.com. Received November 24, 2018 Accepted March 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Alexandros Sfakianakis
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