Medium‐chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE).To evaluate the short‐term efficacy of MCTs administered as an add‐on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles.Twenty‐eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used.A 6‐month multicenter, prospective, randomized, double‐blinded, placebo‐controlled crossover trial was completed, comparing an MCT‐DS with a control‐DS. A 9% metabolic energy‐based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study.P = .02) and seizure‐day frequency were significantly  lower when dogs were fed MCT‐DS in comparison with the control‐DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency.Seizure frequency (median 2.51/month [0‐6.67] versus 2.67/month [0‐10.45]; These data show antiseizure properties of an MCT‐DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug‐resistant dogs with epilepsy. ASDantiseizure drugBHBbeta hydroxybutyric acidC10decanoic acid = capric acidC8octanoic acid = caprylic acidDSdietary supplementIEidiopathic epilepsyITTAintention to treat analysisIVETF IIInternational Veterinary Epilepsy Task Force Tier IIKBrpotassium bromideLEVlevetiracetamMBWmetabolic body weightMCTmedium‐chain triacylglycerideMEmetabolic energyPBphenobarbitalQoLquality of lifeRERresting energy requirementRVCRoyal Veterinary CollegeVASvisual analog score1Seizures and epilepsy are the most common neurological signs in dogs affecting an estimated 0.6%‐0.8%Manipulation of nutrition has attracted increasing considerations as an alternative approach to impacting seizure activity and behavior.A 6‐month prospective, randomized, double‐blinded, placebo‐controlled crossover dietary trial comparing a medium‐chain triacylglyceride (MCT) kibble diet  to a standardized placebo diet was completed in 21 chronically ASD‐treated dogs with IE  in dogs with IE compared with a standardized control‐DS.2This study was conducted in accordance with the guidelines of the International Cooperation of Harmonization of Technical Requirements for Registration of Veterinary Products GL9 Good Clinical Practices and the European Agency for the evaluation of Medical Products. This study was approved by the Royal Veterinary College (RVC) Clinical Research Ethical Review Board and ethical approval was granted (URN 2016 1558).2.1The study design has been published separately.Based on the former research conducted 22 dogs completing the trial appeared sufficient to reach significance between groups.The study involved a 6‐month prospective, randomized, double‐blinded, placebo‐controlled, multicenter dietary crossover trial comparing the MCT‐DS to a standardized control oil DS for canine epilepsy. As a multicenter study, dogs were recruited over 6 study sites . Dogs enrolled onto this study were fed for 3 months (day 1 to day 90 ± 2) initially with either control‐DS or MCT‐DS alongside their normal diet, followed by a respective switch for another 3 months (day 90 to day 187 ± 2) to the other supplement alongside their normal diet. The first 7 days of dietary crossover, DS period 2 (day 90 to day 97 ± 2), were excluded from data collection and considered as the wash‐out period. Dogs were fed twice per day when each feed was supplemented with the respective DS‐oil representing 4.5% daily metabolic energy requirement for each dog . The DS allocations were block‐randomized and only available to the study nurse who was also the DS dispenser based at clinical investigation center at the RVC. Dog owners, investigators, other nurses, and statisticians involved were blinded throughout the study.ASD treatment was not altered by any person involved at any point in this study. Per visit all dogs were evaluated on‐site. On each study visit relevant data were collected at the enrolment visit and start of the study (V1 = day 0), and at the end of each dietary intervention period  including general physical and neurological examination, seizure frequency ; body weight; measurements of serum phenobarbital (PB), potassium bromide (KBr), or both concentrations as appropriate; dynamic bile acids; CBC; standard clinical serum chemistry; canine pancreatic lipase activity; adverse events; and visual analog scores (VAS) for ataxia, sedation, and QoL. Behavioral comorbidities and cognition have been measured but will be reported separately.2.2n = 19) on palatability, preference, side effects, and eating behavior confirming comparability.The experimental control and test products were commercially available DSs suitable for human consumption. The test oil was a MCT‐DS purified from palm and rapeseed oil containing 50%‐65% octanoic acid (C8) and 30%‐50% decanoic acid (C10) with 8.37 kcal/mL from 93% saturated fatty acids . The control oil was colorless, extra‐virgin olive oil with 8 kcal per ml containing 11% saturated, 11% polyunsaturated, and 78% monounsaturated fat . Both oils were dispensed in brown bottles ensuring blinding of all involved. Prior to study setup, both oil supplements have been tested in a small cohort of healthy nonepileptic dogs  was allowed taking into consideration differences in activity level, physical condition, and to prevent gain or loss of body weight.2.3Dogs were recruited by a 2‐step screening system through different media in the United Kingdom and Europe. An online prestudy questionnaire (SurveyMonkey) was completed for each dog, capturing all relevant data of epilepsy phenotype. Dogs were enrolled only when level of IE diagnosis3Information from a standardized seizure diary per dietary intervention period was used to assess the short‐term effects of MCT‐DS on seizure control.3.1Visual analog score for ataxia, sedation and overall QoL was completed by the owner at each study visit. The owner was asked to mark a measurement line ranging from 0 to 100 mm (0%‐100%) perpendicularly with a secondary intersecting line that presented best the subjective severity . A perpendicular line at 0 mm, baseline (B), represented “asymptomatic/normal” and at 100 mm represented either “ataxia so severe dog is unable to walk” or “sedation to the extent dog only sleeps” or “QoL is so poor euthanasia is requested,” respectively. The length from 0 to the perpendicular line in mm was compared between periods and expressed as a percentage value .3.2In addition to the QoL VAS, the impact from dietary supplementation on epilepsy and its treatment on the QoL of the dogs and their owners was assessed at the end of each dietary intervention period. A questionnaire based on the carer's perception of their dogs and their own QoL  was used to study QoL aspects and adverse effect profiles associated with MCT‐DS use.3.3Preprandial and postprandial BHB concentrations were analyzed on each visit day (V1‐V3). Preprandial blood samples were collected at initial presentation in the morning after fasting for at least 12 hours. Postprandial samples were taken 2 hours after consumption of their usual diet including the prescribed amount of DS per period. Both samples were stored using clotting activator dipotassium ethylenediaminetetraacetic acid‐containing (with serum‐separation gel) polypropylene blood‐collection tubes and plain polypropylene blood‐collection tubes . Blood samples were allowed to clot and shipped for subsequent analysis for BHB concentrations at 1 of the local laboratories .3.4Any adverse, abnormal, or both events occurring after enrolment were reported to the investigator and documented Table . Seizure3.5t tests for parametric data and Wilcoxon matched‐pairs signed rank test for nonparametric data . The presence of cluster seizures was compared between DS periods using the McNemar test. The relationship between 2 continuous variables, such as seizure frequency and body weight, were analyzed using Pearson's correlation coefficient analysis. All comparisons were 2‐sided, and P < .05 was considered significant. Nonparametric data are presented as median (25th to 75th percentile), and parametric data are represented as mean values and SD values. Considering potential‐fixed (type of DS) and random effects  of the study design on seizure occurrence a multivariate analysis was performed using a linear mixed model.Seizure frequency, defined as the number of seizures per month, and seizure day frequency, defined as the number of days in which seizures occurred within a month, were compared between DS periods. Monovariate comparisons between the MCT‐DS and control DS groups were conducted using match‐paired Student's 44.1The study protocol was completed by 28 of the 36 recruited dogs, which included 18 different breeds at 5 different study sides in 3 different countries . One dog of each of the following breeds were included unless otherwise specified: Australian shepherd, Basset Griffon Vendeen (Petit), Bernese Mountain dog, Border Collie (N = 3), Border Terrier, Cairn Terrier, Chihuahua, Cross breeds (N = 8), Dogue de Bordeaux, German shepherd, golden retriever, Hungarian Vizsla, Keeshond, Labrador retriever, Samoyed (N = 2), Slovakian Rough Haired Pointer, Staffordshire Bull Terrier, Whippet Table . The stu4.2All 28 dogs were drug resistant to at least 1 of the ASD given and defined as partial ASD‐nonresponders with less than 50% reduction in seizure frequency. Two dogs received imepitoin only, the rest were under chronic ASD combination treatment  were fed dry food as a single diet (46%) or in combination with wet food (11%), raw feed (14%), or home‐cooked feed (11%). The remaining 18% were fed self‐cooked food or raw feed. Independent of the predominant feeding type, chicken was in 50% of all dogs (N = 14), the main source of meat, followed by beef (29%), salmon (20%), and lamb (14%). Cereals , potatoes , other vegetables , or fruits  were other main components in their feed. In 68% (N = 19) of participating dogs, it was possible to calculate an average dry matter (DM)‐based composition of the baseline diet from company provided analytical data mirroring a low fat and low protein diet  Table . While 54.4P = .02, Figure Seizure frequency was significantly lower when dogs were fed MCT‐DS  in comparison with the control‐DS , but this was not significantly different. No other associations were identified  or the effect of the study center were considered in monovariate comparison and multivariate statistical mixed model.r = .1793, X2 = 0.03216, P = .36) or study center  has been identified.On monovariate comparison, the average reduction rate in seizure frequency appeared not significantly different for treatment order or study center; and no association of the supplementation group with treatment order (P = .02) and seizure day frequency (P = .01) appeared significantly reduced during MCT treatment period compared to control.Using the type of DS as fixed and treatment order and study location as random effects in a multivariate analysis as linear mixed model, seizure frequency (4.5P = .01). Alkaline phosphatase activity was also lowered during the MCT‐DS study period . However, KBr serum concentrations , pancreas lipase activity (90 μg/mL [30‐146.3] versus 83.5 μg/mL [30‐150.8]), and weight  were not significantly different between control‐DS and MCT‐DS periods, respectively.There was a significant reduction in serum concentrations of PB during MCT‐DS consumption when compared to the control‐DS period , respectively. However, the differences between preprandial and postprandial BHB blood concentrations within DS periods were not significantly different . All other CBC, biochemistry, glucose, and bile acids stimulation results were not significantly different between the DS groups.There were significantly higher concentrations of BHB in both pre and postprandial blood samples during the MCT‐DS period when compared to the control‐DS period , less ataxic  than baseline and had an overall better owner reported QoL . Apart of sedation , there were no other significant differences in VAS comparisons between MCT and control‐DS or both with baseline  and that their dog had a less severely ataxic gait . In addition, the owners reported that they better tolerated the ASD adverse effects seen in their dogs  than before or in comparison to the control oil.Similarly, in the EpiQoL questionnaire, the owner's perceptions between both dietary periods  and the baseline (B) have been compared. Owners reported that during the MCT‐DS study period they were less “bothered” by their dog's mental status  and ethical approval has been granted (URN 2016 1558). The data collected in this trial are collated and stored at the Royal Veterinary College in London (RVC). Data were anonymized as appropriate, and only used for analysis. All dog's personal information was held and used in accordance with the GDPR 2018 and will not be disclosed to any unauthorized person or body.Authors declare human ethics approval was not needed for this study.Table S1. Adverse events recorded for dogs during the dietary supplementation with the control and MCT‐DSTable S2. Concomitant treatmentTable S3. Age, weight, sex, neuter status, breed and base diet composition of the all dogsTable S4. Antiepileptic drug medication regimes of each individual dog included in this studyTable S5. Trial diet composition—the average macronutrient profile of the base dietTable S6. Overview of seizure frequency per month and seizure day frequency per month in each dog during the control DS and MCT‐DSTable S7. Correlation coefficient analysis between seizure frequency reduction and seizure day frequency reduction with age, weight and BHB concentrationsClick here for additional data file.


The Journal of Bone and Joint Surgery (JBJS) and The Bone and Joint Journal (BJJ) with a particular emphasis on trends regarding author gender. Data was collected and analyzed for manuscripts published in JBJS and BJJ over the past 30 years. For manuscripts published in 1986, 1996, 2006, and 2016, we recorded the numbers of authors, manuscript pages, references, collaborating institutions, the position in the byline of the corresponding author, the country of the corresponding author, and the names of the first and corresponding author. We also calculated the normalized number of citations and corresponding author position. The number of authors, institutions, and countries collaborating on manuscripts published in both JBJS and BJJ increased over time. JBJS published more manuscripts from North America and BJJ published more manuscripts from Europe. In both journals, the percentage of women as first and/or corresponding author increased over time. Trends over the past 30 years have shown increased collaborations with greater citations in manuscripts published in JBJS and BJJ. In the same time period, both journals demonstrated a rise in the percentage of manuscripts with women first and/or corresponding authors, suggesting a decrease in the gender gap.Publishing original peer-reviewed research is essential for advancement through all career stages. Fewer women than men hold senior-level positions in academic medicine and, therefore, examining publication trends relative to gender is important. The goal of this study was to examine and compare publication trends in  Original research in peer-reviewed journals allows the review and dissemination of new information. The increasing complexity of research has resulted in increased collaboration among researchers  to obtain appropriate expertise –3. CollaThe Journal of Bone and Joint Surgery (JBJS) and The Bone and Joint Journal (BJJ) in bibliometric variables over time and (2) specifically to study author gender trends. These two journals were chosen as they are well-known orthopedic surgery journals covering material from all orthopedic subspecialties and highly regarded in both the English and non-English speaking world. As JBJS is a US-based journal and BJJ a UK-based journal, it also allows for studying author gender trends between the USA and UK. Such data will be helpful for trainees, junior faculty, and senior faculty in mentorship positions.Medicine has traditionally been a field dominated by men, although women have made significant gains; in 2018-2019, women represented 49.5% of US medical school matriculates . Due to JBJS and BJJ over the past 30 years were analyzed using a well-established method [Manuscripts published in d method . Data wahttp://www.gpeters.com/names/baby-names.php). The “Baby Name Guesser” website produces a gender and gender ratio for first names. This method was previously used in several bibliometric studies from our group [The first and corresponding author gender was determined using the “Baby Name Guesser” software of Geoff Peters' . Nonparametric tests were used to analyze differences in continuous data due to nonnormal distributions . Observed trends over the 10-year intervals were analyzed using the Cochran linear trend test. Statistical analyses were performed with Systat 10 software™  with a significance level of 0.05.Discrete data are reported as frequencies and percentages and continuous data as the mean ± 1 standard deviation. Differences in categorical data were analyzed using Fisher's exact test (2 × 2 tables) or Pearson's JBJS and 893 BJJ manuscripts; JBJS manuscripts had more authors , references , printed pages , and normalized citations  than BJJ manuscripts. There were no differences between journals for standardized CAP , the number of collaborating institutions , countries , or single author manuscripts .There were 989 JBJS and 882 BJJ manuscripts. For JBJS, the manuscripts came from North America (n = 758), Europe (n = 158), Asia (n = 61), and Australia/New Zealand (n = 10). For BJJ, the manuscripts came from Europe (n = 587), North America (n = 128), Asia (n = 118), and Australia/New Zealand (n = 49).The regions were known for 987 JBJS  and the least from Australia/New Zealand (4.2 ± 1.9). Manuscripts with the greatest standardized CAP, for both JBJS and BJJ, came from Australia/New Zealand (0.56 ± 0.43 and 0.54 ± 0.35) followed by North America (0.45 ± 0.33 and 0.50 ± 0.32). For JBJS, the lowest standardized CAP was for manuscripts from Europe (0.37 ± 0.30) whereas for BJJ it was the lowest for those from Asia (0.41 ± 0.30). There was a difference for JBJS in the number of collaborating countries between North America (1.1 ± 0.5), Europe (1.4 ± 1.0), Asia (1.1 ± 0.2), and Australia/New Zealand (1.7 ± 0.7), but there was no difference for BJJ. There were no statistically significant differences in the number of institutions or printed pages. There were no differences in the number of normalized citations for JBJS; there was a difference for BJJ with the highest from North America (3.48 ± 3.67) and Asia the lowest (1.90 ± 1.92). There were no regional differences in the number of references for JBJS; in BJJ, the most came from North America (30.5 ± 17.1), and the least from Europe (24.8 ± 18.6).For JBJS , manuscrJBJS, there were 154 in 1986, 159 in 1996, 400 in 2006, and 276 in 2016. For BJJ, there were 159 in 1986, 178 in 1996, 298 in 2006, and 258 in 2016. The number of single-authored manuscripts in JBJS did not show a significant change (p = 0.17) but declined in BJJ (p < 10−6) (JBJS (p < 10−6) and BJJ (p < 10−6) (JBJS (p = 0.02) and BJJ (p < 10−6) (JBJS (p < 10−6) and BJJ (p < 10−6) (JBJS (p = 0.0004) and BJJ (p = 0.02) (p < 10−6) (JBJS (p = 0.30), there was a 41% increase in the number of printed pages from 1986 to 2016 in BJJ (p < 10−6) (JBJS from 3.6 ± 4.0 in 1986 to 5.9 ± 6.4 in 2006 and then decreased to 3.0 ± 3.8 in 2016 (p < 10−6)  (The number of manuscripts published increased from 1986 to 2006 before declining in 2016. For  < 10−6) . The num < 10−6) . The sta < 10−6) . The num < 10−6)  as did t = 0.02) . For bot < 10−6) . While t < 10−6) . The num < 10−6) ; for BJJ < 10−6) .JBJS and 90.6% of BJJ manuscripts. For JBJS, 11.5% of first authors were women and 10.6% for BJJ (p = 0.60). Corresponding author gender was available for 84.7% of JBJS and 93.2% of BJJ manuscripts. In JBJS, 10.9% of the corresponding authors were women and 9.1% for BJJ (p = 0.25).First author gender was available for 97.0% of JBJS for the numbers of authors, institutions, collaborating countries, normalized citations, references, printed pages, or standardized CAP. The findings were the same in BJJ except for the number of printed pages; manuscripts with women first authors were longer (6.4 ± 2.2) than those with men first authors (5.4 ± 1.9).There were no differences by first author gender  in JBJS JBJS. Findings were the same for BJJ, except for the number of references and printed pages. BJJ manuscripts with women corresponding authors were longer (6.3 ± 2.2) than those with men corresponding authors (5.4 ± 1.9) with more references .There were no differences by corresponding author gender  for the JBJS manuscripts for all four decades varied by region with Australia/New Zealand having the most (30%), then Europe (13%), North America (11.6%), and Asia (2%) (p = 0.046). The percentage of manuscripts with women first authors in BJJ did not vary by region , Europe (11.4%), Asia (8.4%), and North America (8.1%) (p = 0.60)).The percentage of women first authors in JBJS (p = 0.00001) and from 6.3% to 15.3% in BJJ (p = 0.01) (JBJS (p = 0.0003) and from 6.2% to 15.2% in BJJ (p = 0.003) (The percentage of manuscripts with women first authors increased from 2.0% to 16.1% in  = 0.01) . The perJBJS. For JBJS, the percentage of manuscripts with women first authors (p = 0.0025) for those from North America, from 0.0% to 19.2% (p = 0.034) for those from Europe, and with no significant change in those from Asia. For BJJ, the percentage of manuscripts with women first authors (p = 0.013) for those from Europe, with no significant changes in those from North America, Australia/New Zealand, or Asia. For JBJS, the percentage of manuscripts with women corresponding authors (p = 0.0052) for those from North America and 0.0% to 20.8% (p = 0.044) for those from Europe, with no significant changes for those from Asia. For BJJ, the percentage of manuscripts with women corresponding authors (p = 0.015) for those from Asia and from 0.0% to 25.0% (p = 0.041) for those from Australia/New Zealand, with no significant changes for those from North America or Europe.We also analyzed differences in author gender over time by region . Due to  authors  rose fro authors  rose fro authors  rose fro authors  rose froJBJS and one from BJJ). Reporting percentages of women first authors relative to the total manuscripts within each subspecialty (JBJS was in pediatrics (22%) and the lowest in the spine (9%). In BJJ, the largest percentage of women first authors was in hand (29%) and the lowest in pediatrics (5%). These differences between journals were significant (p = 0.002). Reporting percentages of women first authors in a subspecialty relative to the total manuscripts across all subspecialties (JBJS and 37% for BJJ). The second highest was in pediatrics for JBJS (16%) and general for BJJ (25%); the lowest percentage of women first authors was in hand for JBJS (4%) and in pediatrics for BJJ (2%) (p = 0.0014).Manuscripts were categorized by subspecialty into foot and ankle, general, hand, joint arthroplasty, oncology, pediatrics, spine, sports medicine, and trauma . The spopecialty , the larcialties , the larp = 0.80). There were significant differences over time for two gender combinations for JBJS (p = 0.023) and MM (p = 0.013), but not WM (p = 0.10) or MW (p = 0.51). There were significant differences over time for two gender combinations for BJJ (p = 0.032) and MM (p = 0.01), but not WW (p = 0.15) or WM (p = 0.30).Manuscripts were categorized into one of four gender combinations between the first author and corresponding author: WW (women as first and corresponding authors), WM (women as first and men as corresponding authors), MW (men as first and women as corresponding authors), and MM (men as first and corresponding authors). Single author manuscripts and those where the first author was also the corresponding author were excluded from these analyses. There were no significant differences in any of the four gender combinations between journals   and no more than 6 authors for JBJS [JBJS and BJJ and manuscript length for BJJ.The number of authors, institutions, and countries collaborating on manuscripts published in both journals increased from 1986 to 2016. The increase in author number may be due to the need for individuals with different skill sets/expertise due to increasing research complexity . Similaritations . The numfor JBJS  and 4000for JBJS . HoweverJBJS and BJJ increased from 1986 to 2006 before decreasing in 2016. The largest number of manuscripts for JBJS came from North America and for BJJ from Europe. This is expected as authors from North America would likely favor JBJS and European investigators BJJ. It is not clear why the number of manuscripts in both journals increased up to 2006 and then dropped in 2016. Possible explanations are the increasing number of subspecialty journals as well as the introduction of several other journals under the umbrella of JBJS and BJJ.The number of manuscripts published in both One goal of this study was to examine the author's gender over time. In both journals, there was an increase in the percentage of women first and corresponding authors, but it was lower than the percentages of women US medical school graduates (50%)  and womeJBJS and BJJ. This suggests an increase in the overall percentage of women, early in their careers, serving as the first author and being mentored by more senior women. This likely reflects the fact that over the last ten years women have now become President of the British Orthopaedic Association (2008), Royal College of Surgeons (2014), and American Academy of Orthopaedic Surgeons (2019). As women take on more leadership positions and mentor more junior women, the percentages of women first and corresponding authors will likely continue to increase. Another interesting observation was that while the overall gender combinations were the same between JBJS and BJJ, when looking at trends over time, there were significant differences. In both journals, MM combinations were reduced with time, but which categories were responsible for the reduction varied. For JBJS, there was a significant increase in the percentage of WW authors, whereas, for BJJ, there was a significant increase in the percentage of MW authors. While not conclusively tested here, these findings may indicate that for JBJS, and the North American region by proxy, the increase in WW authors is likely a reflection of the increase in women orthopedic surgeons in the field, both at the more senior levels and at the trainee/junior levels. Perhaps, more interesting is the increase in MW combinations observed in BJJ. There are a number of ways this data can be interpreted, but it may reflect a larger change in approach/attitude toward mentee/mentorship. This may suggest that for BJJ (and Europe by proxy), more junior men are seeking women as mentors or that women are seeking to serve as mentors to more men. This may be a positive sign that change is on the horizon when considering the gender gap in authorship.We next began to explore possible mentorship trends and gender in authorship. To accomplish this, we used first and corresponding author gender composition ratios as a surrogate for mentorship, making the assumption that when first and corresponding authors were different individuals, the first author is the mentee of the corresponding author. With this in mind, WW gender combinations for first and corresponding authors increased in JBJS with time, and 2016 was also the first time that WW gender combinations were present in both JBJS and BJJ during the years examined in the current study. Outside of joint arthroplasty, the greatest percentage of manuscripts with women as first authors was in pediatric orthopedics for JBJS and general for BJJ when considering women first authors across all subspecialties and in pediatric orthopedics and hand for JBJS and BJJ, respectively, when considering the total number of manuscripts in a particular subspecialty. This corroborates a 2016 survey of Ruth Jackson Orthopaedic Society women members which reported larger percentages of women surgeons listing hand (22%) and pediatrics (16%) as their subspecialty. In our study, the lowest percentage of manuscripts with women first authors for JBJS was the hand (3.9%) and for BJJ was pediatrics (2.4%) when considering women first authors across all subspecialties and the lowest were in the spine and pediatric orthopedics in JBJS and BJJ, respectively, when considering the total number of manuscripts in a particular subspecialty. While the finding in JBJS correlates with the 2016 survey reporting that women comprised the highest percentage of fellowship applicants for pediatrics (25%), the BJJ finding that pediatric subspecialty manuscripts had few women first authors was surprising; this may reflect continental differences in subspecialty selection.Although there are fewer women orthopedic surgeons compared to men, studies have shown that women choose particular orthopedic subspecialties more than others , 44. In JBJS and BJJ over the past 30 years have shown increases in the number of collaborating institutions, collaborating countries, references, and citations. The gender gap has decreased with the percentage of manuscripts with women first and/or corresponding authors increasing over the past 30 years.Manuscripts in


There may be significant histopathologic overlap between EBV‐positive DLBCL, NOS, and other diagnoses including angioimmunoblastic T‐cell lymphoma (AITL). Resolution of this differential diagnosis may be particularly challenging and require extensive investigation of clinicopathologic features. There may be an significant histopathologic overlap between EBV‐positive DLBCL, NOS, and other diagnoses including angioimmunoblastic T‐cell lymphoma (AITL). Resolution of this differential diagnosis may be particularly challenging and require extensive investigation of clinicopathologic features. Resolution of this differential diagnosis may be particularly challenging and require extensive investigation of clinicopathologic features. We report an unusual case of cervical lymphadenopathy and retroperitoneal mass in a 34‐year‐old male patient. This case demonstrates significant histopathologic overlap between EBV‐positive diffuse large B‐cell lymphoma, NOS, and AITL, which can be a diagnostic pitfall.22.13/µL, hemoglobin 7.6 g/dL, platelet count 32 × 103/µL). Epstein‐Barr virus PCR detected 608 515 copies per mL in whole blood. Serum immunoglobulin levels were in normal range except for decreased IgM (15.75 mg/dL). Direct antiglobulin test was positive for both IgG and complement, and warm autoantibody was detected. Computed tomography scan showed bilateral cervical lymphadenopathy extending to the anterior mediastinum and a retroperitoneal mass, as well as splenomegaly  and lactate dehydrogenase (700 U/L), mildly increased aminotransferases levels (79 U/L), and pancytopenia , CD30 (variable intensity), CD79a (variable intensity), PAX5 (strong), MUM1, BOB1, OCT2, and BCL6  while negative for CD10, CD15, and T‐cell antigens. A subset of large cells were positive for PDL1, ~30%. The background small‐ to intermediate‐sized lymphoid cells were T cells positive for CD3, CD5, and TCR‐beta, with a subset showing diminished expression of CD7. T cells were cytologically atypical and showed increased expression of PD1 and coexpression of CD10 and BCL6 in a subset  was performed on the cervical lymph node tissue and showed a prominent and specific‐sized product peak indicating a B‐cell gene rearrangement. There was no evidence of T‐cell gene rearrangement.3+DLBCL, NOS, and the Ann Arbor stage III, with secondary HLH syndrome, was therefore made. International Prognostic Score (IPI) score for risk stratification was 3. EPOCH‐R chemotherapy regimen was started, and six cycles were completed resulting in partial remission. Follow‐up PET‐CT demonstrated significant decrease in size of cervical lymphadenopathy, anterior and superior mediastinum mass, upper retroperitoneal mass, and spleen , was formerly designated as EBV‐positive DLBCL of the elderly, but the restriction to elderly patients has been removed given that the neoplasm is now recognized to occur over a wide age range. While most studies have shown similar poor survival in all patients regardless of age, more recent reports have described a significantly better overall survival in young patients.+ DLBCL, NOS, are composed of only scattered or loosely clustered large lymphoma cells, frequently with Hodgkin‐like features, amidst a prominent polymorphic reactive hematolymphoid background, and in these cases, the diagnosis may be more challenging due to overlapping features with other lymphomas. In cases in which scattered large B cells are present on a background rich in T cells and histiocytes, the morphologic and immunophenotypic features may raise the differential possibility of T‐cell/histiocyte‐rich large B‐cell lymphoma (TCHRLBCL).Epstein‐Barr virus–positive diffuse large B‐cell lymphoma, not otherwise specified , EBV‐related polymorphic hematolymphoid proliferations arising in the context of immunosuppression, or AITL. In these circumstances, differentiating these lesions from classic Hodgkin lymphoma can be done by immunophenotyping in almost all cases. History of immunosuppression is required to exclude EBV‐related polymorphic‐type proliferations. As in the case presented here, separating EBV+DLBCL, NOS.Angioimmunoblastic T‐cell lymphoma is a relatively common subtype of peripheral T‐cell lymphoma of T‐helper cell origin characterized histologically by the frequent presence of a polymorphic hematolymphoid infiltrate within which the neoplastic T cells may be the minority of cells. The nearly constant association of AITL with EBV has led to the suggestion of a possible etiologic role for the virus, possibly through antigen stimulation or immune dysregulation.+ DLBCL (AITL progressing to EBV+ DLBCL).+ DLBCL and AITL in the same anatomical site (composite AITL/B‐cell lymphoma) is also described.In patients with established AITL, high‐grade histologic progression, when occurring on infrequent occasions, is almost always to EBV+ DLBCL and its microenvironment. In the meantime, this case highlights the importance of awareness of this potential diagnostic pitfall, careful morphologic review, comprehensive immunohistochemical studies, and integration of ancillary testing results including clonality assays in classification of these lymphomas.In the case we describe, T cells were abundant, heterogeneous, and cytologically atypical in appearance, showed diminished expression of CD7, and were enriched for T cells expressing PD1, creating overlapping features with those of T‐cell lymphomas of T‐helper immunophenotype and specifically with AITL. While the presence of atypical T cells occurring in the background of nodular lymphocyte‐predominant Hodgkin lymphoma has been reported, the presence of such atypical T cells is unusual in EBV‐positive DLBCL, NOS, and to our knowledge has not been reported in the context of this lymphoma.None declared.CHK: wrote and edited the manuscript. TG: contributed to the editing of the figures. YZ: reviewed the slides and flow cytometry. JRC: supervised and revised the manuscript.All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study does not require any ethical committee approval.


A 70‐year‐old male was diagnosed with tiny capillary hemangioma of the ileum using double‐balloon endoscopy. Capillary hemangiomas should be included in the differential diagnoses of OGIB. For two consecutive years, a 70‐year‐old male patient presented with persistent iron deficiency anemia. Laboratory investigations showed a hemoglobin level of 9.9 g/dL, hematocrit of 35.8%, and mean corpuscular volume of 73.2 fL. Physical examination showed no signs of vascular changes in the skin. Investigations such as contrast‐enhanced computed tomography, esophagogastroduodenoscopy, and colonoscopy could not determine the source of the patient's bleeding. Transoral double‐balloon endoscopy revealed no lesions; however, transanal double‐balloon endoscopy revealed a submucosal‐like lesion with ulceration in the ileum Fig. . As the Hemangioma of the small intestine is a rare benign vascular tumor, which causes obscure gastrointestinal bleeding (OGIB).


The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non‐malignant diseases and may predict outcomes after autologous HCT.2 [body mass index (BMI) < 25 kg/m2] or < 53 cm/m2 [BMI ≥ 25 kg/m2] and female: <41 cm/m2 [regardless of BMI]) and obesity  were assessed from single‐slice abdominal pre‐HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30‐day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan–Meier analysis and Gray's test.This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non‐Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/mMedian age at HCT was 53.3 years ; 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre‐HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization , intensive care unit admission , and unplanned readmission after HCT . Patients who were sarcopenic obese also had the highest mortality risk at 1 year  and 5 years , compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese.Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT. Autologous haematopoietic cell transplantation (HCT) is an established treatment approach in patients with lymphoma, either as a frontline therapy or as more commonly, in the relapsed/refractory setting.Conventional methods for predicting adverse outcomes from HCT include the Karnofsky Performance Score (KPS) and the HCT‐comorbidity index (HCT‐CI).Sarcopenia is the progressive loss of muscle mass and muscle function caused by aging, inactivity, and disease, and it is associated with physical disability, frailty, and premature mortality; outcomes are especially poor for patients with both sarcopenia and obesity.prior to HCT, and follow‐up is performed by a dedicated research team throughout the life of the survivor. A data collection form is completed by research staff, capturing demographics, cancer diagnosis, pre‐HCT treatment information (e.g. radiation and chemotherapy), and HCT‐related exposures (e.g. conditioning intensity). Importantly, this protocol uses a number of strategies  to collect information on health‐related outcomes after HCT. Complications are coded using a standardized set of definitions for each outcome, with appropriate source documentation (e.g. pathology reports and imaging studies) available for confirmation of outcomes. This information is entered into an electronic database that can be queried for research studies, allowing us to accurately describe the epidemiology and risk factors {demographics, pre‐HCT, HCT‐related treatment exposures , and comorbidities at the time of HCT} for de novo health‐related complications after HCT. The COH long‐term follow‐up after HCT research programme has been approved by the COH Institutional Review Board (IRB# 00029), and data abstraction and associated procedures are performed in accordance with the Declaration of Helsinki. For the current study, medical records were abstracted for patient demographics , diagnosis, remission status at HCT [complete radiographic remission (CR) or not in CR], variables necessary to calculate the HCT‐CI using an established web‐based calculator (www.hctci.org),This was a retrospective cohort study of patients who underwent autologous HCT for non‐Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) as adults (≥18 years old) at City of Hope (COH) between 1 January 2009 and 31 December 2014. Patients were identified from the long‐term follow‐up after HCT research programme at COH, which ensures the active and comprehensive follow‐up of all patients who have undergone HCT at COH since 1976. Patients are consented N = 5) or because the images were of poor quality (N = 6). With the exception of race/ethnicity, there were no statistically significant differences in patient and treatment‐related characteristics between those included in the study vs. those who were not  at the third lumbar vertebra (L3); an inter‐observer coefficient of <2% was required for 32 patients (10% of the cohort) selected at random, a threshold that is consistent with similar reports in the literature.FigureP < 0.001),The quantity of muscle and adipose tissue was measured on CT images, which were collected either alone or as part of positron emission tomography imaging 2 (BMI < 25 kg/m2) or <53 cm/m2 (BMI ≥ 25 kg/m2) and female: <41 cm/m2 (regardless of BMI)]. Measures of adiposity included the following: visceral  adipose tissue , subcutaneous adipose tissue , intramuscular adipose tissue . Total adiposity (TAT) was the sum of VAT, SAT, and IMAT. Because of a lack of well‐established definitions for these adiposity measures, we used sex‐specific upper tertiles as the cutoff for abnormal VAT , SAT , IMAT , TAT . Obesity was defined as abnormal TAT, and sarcopenic obesity was defined as having both an abnormal SMI and an abnormal TAT. Separate exploratory analyses were performed using the established BMI‐derived definition (≥30 kg/m2) of obesity (The following muscles were included in the muscle area measurements (HU range −29 to 150): psoas, paraspinal (quadratus lumborum and erector spinae), transversus abdominis, external and internal obliques, and rectus abdominis. The skeletal muscle index (SMI) was defined as the muscle area at L3 divided by height. obesity Table S2.2 test for categorical, t‐test or analysis of variance for parametric continuous variables, Kruskal–Wallis for non‐parametric) were performed to compare baseline demographic, clinical, treatment‐related factors, and body composition measures between male and female patients. Additionally, we compared LOS, ICU admission, 30‐day unplanned readmission rate by body composition phenotype, categorized as (i) normal body composition (not sarcopenic and not obese), (ii) obese (obese and not sarcopenic), (iii) sarcopenic (not obese and sarcopenic), (iv) sarcopenic obese (obese and sarcopenic). We used paired t‐tests to compare changes in muscle and adiposity measures between pre‐HCT and post‐HCT scans. The Kaplan–Meier method was used to examine the effect of body composition measures on overall survival; log‐rank tests were used to compare survival rates for the overall cohort and by sex  on select health outcomes {logistic regression [adjusted odds ratio (OR)]: prolonged LOS , ICU admission , 30‐day unplanned readmission ; Cox‐proportional hazard models [hazard ratio (HR)]: 1‐ and 5‐year survival}, adjusting for a priori‐determined variables. These variable included: age at HCT (continuous), sex, HCT‐CI , KPS (continuous), lymphoma diagnosis , and remission status at HCT (CR or not in CR); as a result of high collinearity between conditioning therapy and diagnosis, conditioning therapy was not included in the final models. A two‐sided TableThe median age at HCT was 50.8 years (range 18.5 to 78.1 years), and the majority of patients were male (61.9%), non‐Hispanic white (55.6%), had a diagnosis of diffuse large b‐cell lymphoma (56.4%), received BEAM conditioning (57.1%), were in complete remission at HCT (56.3%), had a good KPS , and had a low HCT‐CI score [(0–2) 83.8%] at HCT TableTable S3P = 0.003; TableTableCompared with patients with normal body composition, patients who were sarcopenic obese had the longest LOS (mean 28.6 days vs. 23.4 days), followed by those who were only sarcopenic (mean 24.6 days); P = 0.002; TableTableForty‐three (13.4%) patients required ICU admission during their HCT. Compared with patients with normal body composition, patients who were sarcopenic obese had the highest rate of ICU admission (32.0% vs. 8.5%), followed by those who were only sarcopenic (20.2%); TableP = 0.037; TableTableTwenty 6.25%) patients had an unplanned readmission within 30 days of hospital discharge. Compared with patients with normal body composition, patients who were sarcopenic obese had the highest rate of readmission .The overall survival probability of the cohort was 90.3% at 1 year and 73.9% at 5 years after HCT. The 1 and 5 year survival probabilities were significantly worse for patients who were sarcopenic compared with those who were not . Of note, there were no statistically significant demographics, clinical, and treatment‐related predictors of de novo sarcopenia . De novo sarcopenia was associated with a significantly higher risk of 1 year  and 5 year mortality  compared with patients with no sarcopenia.There were 275 patients (85.9% of the cohort) who had both a pre‐HCT and post‐HCT scan available for review; there were no statistically significant clinical or treatment‐related differences between patients with and without post‐HCT scans Table S4.rcopenia Table S6.de novo sarcopenia after HCT had a significantly higher risk of mortality compared with patients who maintained normal muscle mass throughout. Of note, BMI, the most commonly utilized measure of body habitus, was not significantly associated with any of the adverse outcomes examined in our study. The overall findings of this study speak to the importance of careful evaluation of body composition prior to and after HCT and the need to consider innovative interventions to minimize the short‐term and long‐term adverse consequences in high‐risk patients.In this contemporary cohort of patients undergoing autologous HCT for lymphoma, we found a significant association between pre‐HCT sarcopenia and clinically important outcomes such as LOS, ICU admission, and 30‐day hospital readmission risk after HCT. Patients who were sarcopenic obese fared especially worse across all outcomes. There were also clear differences in 1 and 5 year survival rates by pre‐HCT body composition measures, with sarcopenic obese patients having a 51% 5 year survival rate compared with 80% for patients who had normal body composition. After adjusting for well‐established modifiers of overall survival such as disease status at HCT, age, comorbidity burden, and diagnosis, there was a >2‐fold risk of all‐cause mortality in patients who were sarcopenic obese compared with those who were not. Muscle mass was the only body composition measure that significantly changed from pre‐HCT to post‐HCT. Patients who developed Body composition measures for the current study were acquired from archived CT images obtained as part of standard of care, a strategy that has been successfully used in other oncology and non‐oncology populations.FigureUnderstanding the impact of change in body composition can allow for implementation of appropriate interventions for primary or secondary prevention. For some high‐risk patients, such as those who are sarcopenic obese, clinicians may consider alternatives to autologous HCT, such as long‐term targeted therapy or immunotherapy, taking into account the relative survival benefit offered by autologous HCT.There are some limitations to our study. First, the analysed images were from scans obtained at a range of pre‐HCT time points for purposes other than measurement of body composition, which may have resulted in inter‐patient variability. However, we used a well‐established protocol to perform blinded ascertainment of the body composition measures, minimized inter‐observer variability (coefficient <2%) through strict quality control, relied on standardized and validated cutoffs for abnormal SMI, and implemented sex‐based cutoffs for abnormal adiposity, an important consideration given the sex‐based differences in body composition at baseline; of note, the use of BMI‐based definitions of sarcopenic obesity resulted in similar magnitudes of risk with many of the outcomes examined, albeit with wider confidence intervals because of the smaller number of patients who were categorized as such Table S2.In conclusion, this is the largest study to comprehensively examine the association between pre‐HCT and post‐HCT measures of body composition and outcomes after autologous HCT. We found a one‐time pre‐HCT measure of sarcopenia, and adiposity was a significant and independent predictor of mortality at 1 and 5 years after HCT, and the association with sarcopenia persisted after HCT as well. Sarcopenic obesity not only limited the duration of survival but also decreased the quality of survival, as patients with sarcopenic obesity were more likely to experience prolonged hospital LOS, ICU admission, and unplanned re‐hospitalization. The information obtained from this study may help clinicians develop risk reduction strategies, such as evaluating alternatives to HCT in patients at highest risk, or better management of comorbid health conditions, such as dietary optimization, increasing physical activity, and strength training, during and after autologous HCT. The growing number of patients undergoing HCT worldwide makes the development of personalized approaches to transplantation imperative, to safeguard the well‐being of patients well‐beyond the immediate post‐HCT period.S.H.A designed the research, collected and assembled the data, analysed and interpreted the data, and wrote the paper. C.L.S. and F.L.W. analysed and interpreted the data and contributed to the writing of the paper. A.I., J.B.T, K.M., A.H., J.M.Z., and T.J.S. collected and assembled the data and contributed to the writing of the paper. J.M.S., S.M.M., S.M., L.W.J., S.J.F., and R.N., analysed and interpreted the data and contributed to the writing of the paper.S.H.A. declares he has no disclosures, A.I. declares he has no disclosures, J.B.T. declares she has no disclosures, K.M. declares she has no disclosures, A.H. declares he has no disclosures, J.S.M. declares she has no disclosures, J.M.Z declares she has no disclosures, S.M.‐M. declares she has no disclosures, S.M. declares she has no disclosures, T.J.S. declares he has no disclosures, J.M.S. declares she has no disclosures, L.W.J. owns stock in Pacylex Inc., C.‐L.S. declares she has no disclosures, S.J.F. declares he has no disclosures, F.L. W. declares she has no disclosures, R.N. declares he has no disclosures.Table S1. Patients who underwent a first autologous HCT for lymphoma as adults between 2009 and 2014, including those who were ineligible for the current study.Table S2. Exploratory analyses using BMI‐derived definition (≥30 Kg/m2) of obesity.Figure S1 Kaplan‐Meier plots of overall survival in males according to (A) pre‐HCT sarcopenia, and (B) the combination of sarcopenia and abdominal obesity.Figure S2 Kaplan‐Meier plots of overall survival in females according to (A) pre‐HCT sarcopenia, and (B) the combination of sarcopenia and abdominal obesity.Figure S3. Cumulative incidence of non‐relapse mortality and relapse‐related mortality according to pre‐HCT sarcopenia status for the overall cohort (A), males (B), females (C)Table S3. Correlation between imaging parameters and conventional measures such as body weight and body mass index for the overall cohort and by sexTable S4. Patient characteristics: individuals with and without post‐HCT scansTable S5. Pairwise t‐test comparison of pre‐ and post‐HCT measuresTable S6. Multivariable regression analysis, predictors of de novo sarcopenia after HCTClick here for additional data file.


Materials and methods. A total of 327 consecutive patients referred for CCTA were randomized into one of the three CM injection protocols, where CM injection was based on either BW (112 patients), LBW (108 patients), or CO (107 patients). LBW and CO were calculated via formulas. All scans were ECG-gated and performed on a third-generation dual-source CT with 70–120 kV (automated tube voltage selection) and 100 kVqual.ref/330 mAsqual.ref. CM injection protocols were also adapted to scan time and tube voltage. The primary outcome was the proportion of patients with optimal intravascular attenuation (325–500 HU). Secondary outcomes were mean and standard deviation of intravascular attenuation values (HU), contrast-to-noise ratio (CNR), and subjective image quality with a 4-point Likert scale (1 = poor/2 = sufficient/3 = good/4 = excellent). The t-test for independent samples was used for pairwise comparisons between groups, and a chi-square test (χ2) was used to compare categorical variables between groups. All p values were 2-sided, and a p < 0.05 was considered statistically significant.  To evaluate the performance of three contrast media (CM) injection protocols for cardiac computed tomography angiography (CCTA) based on body weight (BW), lean BW (LBW), and cardiac output (CO). p=0.024). The proportion of patients with optimal intravascular attenuation (325–500 HU) was 83.9%, 84.3%, and 86.9% for groups BW, LBW, and CO, respectively, and between-group differences were small and nonsignificant. Mean CNR was diagnostic (≥10) in all groups. The proportion of scans with good-excellent image quality was 94.6%, 86.1%, and 90.7% in the BW, LBW, and CO groups, respectively. The difference between proportions was significant between the BW and LBW groups.  Mean overall HU and CNR were 423 ± 60HU/14 ± 3 (BW), 404 ± 62HU/14 ± 3 (LBW), and 413 ± 63HU/14 ± 3 (CO) with a significant difference between groups BW and LBW ( Personalization of CM injection protocols based on BW, LBW, and CO, and scan time and tube voltage in CCTA resulted in low variation between patients in terms of intravascular attenuation and a high proportion of scans with an optimal intravascular attenuation. The results suggest that personalized CM injection protocols based on LBW or CO have no additional benefit when compared with CM injection protocols based on BW. Cardiac computed tomography angiography (CCTA) is a valuable tool in ruling out coronary artery disease because of its high negative predictive value 99%) –4. Elect9% –4. ElNowadays, individualization of CM injection protocols based on certain patient parameters is a highly discussed topic. Many different techniques, varying from simple to complicated formulas with differing patient parameters have been suggested, e.g., BW, lean body weight (LBW), and CO . MultiplLBW is a well-known measurement for body composition and is defined as the difference between BW and fatty tissue. Muscle tissue has an increased vascularization compared with fatty tissue . In obesBoth blood volume and CO increase according to BW . A higheThis study addresses the question of whether there are differences in performance between personalized CM injection protocols based on BW, LBW, or CO. The hypothesis is that personalization on either one of these three parameters does not result in a significantly different image quality. Therefore, the aim of this study is to evaluate the performance of three individualized protocols based on BW, LBW, and CO for CCTA.NCT03292354.The local ethical committee and institutional review board approved the study design (METC number: 16-1-110). This single center randomized controlled trial is registered on Clinicaltrials.gov under reference number 2), iodine allergy, age <18 years, and/or no informed consent. All clinically available scan protocols and tube voltages (70–120 kV) were included to simulate daily clinical practice. All patients were weighed just before scanning. After obtaining written informed consent, patients were randomized into one of three study groups: BW, LBW, or CO. Patient characteristics , LBW, and CO) and scan indication were recorded.All patients referred for a standard CCTA were eligible for inclusion. Patients were included after obtaining informed consent. Exclusion criteria were hemodynamic instability, pregnancy, renal insufficiency . Randomization was stratified on age  and weight  categories. Variable random permuted blocks were used to conceal treatment allocation.rd generation dual-source CT scanner .Patients could be scanned with three CCTA protocols, based on their heart rate. The scan protocols are depicted in All dose-related parameters were recorded with dose monitoring software .An 18–22 gauge intravenous injection catheter was inserted in either left or right antecubital vein for CM administration. For flow rates over 7 mL/s, a special 18 gauge needle  was inserted . This nePatients were randomized and enrolled in one of three CM injection protocols  with tailored flow rates and consequtively tailored IDRs. The injection protocols were defined with help of a formula, which has been explained extensively elsewhere  and can (i)∗ kV ∗ BWBW: flow rate = 0.0007976  With BW in kg(ii)∗ kV ∗ LBWLBW according to the Hume formula ∗ BW + 0.33929 ∗L – 29.5336 Man: LBW = 0.32810 ∗ BW + 0.41813 ∗L –43.2933 Woman: LBW = 0.29569 L = length in cm  With BW in kg and LBW: Flow rate = 0.001101 (iii)∗ kV∗ CO (b) CO according to an adapted Katori formula ∗ age) ∗ BSA   CO = (4.874 − 0.023     With age in years and BSA = body surface areaCO: flow rate = 0.008916 The following formulas were used:The formulas shown above determined the flow rates for both test bolus and main bolus. The injection time was fixed for the test bolus (2 s) and the three scan protocols: 8 s for flash and 10 s for adaptive sequence (AS) and helical. The CM volume of the test bolus and main bolus (mL) was then derived by multiplying the calculated flow rate (mL/s) with the injection time (s).All relevant CM injection parameters were recorded by CM monitoring software . The total iodine load (TIL) and IDR were calculated additionally.All CT images were analyzed with multiplanar reconstructions and axial slices on dedicated software . The 17-segment model of the American Heart Association (AHA) was used to assess the segments of all coronary arteries . All outsecondary outcomes). The overall mean (per-patient) intravascular attenuation was defined as the mean of the intravascular attenuation of all present segments. The circumference of the ROIs was kept as large as possible  whilst avoiding arterial walls, intravascular plaques, and stents. In case of a CABG, all segments with an assessable lumen were used to draw ROIs.The primary outcome was defined as the proportion of scans with an intravascular attenuation between 325–500 HU. An intravascular attenuation of ≥325 HU was considered diagnostic , 29. An CNR was determined as intravascular attenuation minus epicardial fat attenuation, divided by the standard deviation of the epicardial fat attenuation. Intravascular attenuation divided by the standard deviation of the intravascular attenuation was used to determine SNR , 21, 30.Both per-patient and per-segment subjective image qualities were assessed by the same, blinded, researcher by using a 4-point Likert scale: Poor—major artifacts and/or low intravascular attenuation; Sufficient—minor artifacts and/or insufficient intravascular attenuation, however still diagnostic for coronary assessment; Good—minimal artifacts and sufficient intravascular attenuation; and Excellent—no artifacts and sufficient intravascular attenuation.χ2) was used to compare categorical variables between groups. The t-test for independent samples was used for pairwise comparisons of continuous variables between groups. All p values were 2-sided, and a p < 0.05 was considered statistically significant.IBM SPSS software  software was used for statistical analysis. Continuous variables are expressed as mean ± standard deviation and categorical variables as absolute numbers and percentages (%). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to assess the robustness of the results. The ITT analysis included randomized patients for whom outcome data were available. The PP analysis included a subset of patients with strict adherence to the assigned CM injection protocol. A chi-square test (n = 286). These patients  received a different protocol for various reasons, e.g., flow rate had to be adjusted because it was not applicable to the needle size.A total of 330 patients were randomly assigned to one of the three experimental study arms between April 2017 and July 2018. Three patients were excluded after randomization; one patient was randomized twice due to randomization software problems, and two patients were excluded because scanning was discontinued after the calcium scoring. Thus, a total of 327 patients remained for the ITT analysis. A total of 41 patients without strict adherence to the assigned CM injection protocol were excluded from the PP analysis , but not between the other pairwise comparisons (The difference in mean intravascular attenuation between groups BW and LBW was significant (parisons . The meaparisons . No signp=0.031) but not between the other groups  were used to create tailored CM injection protocols in CCTA scanning. The use of different patient characteristics for tailoring CM injection protocols resulted in only minor differences in mean intravascular attenuation, with the highest attenuation found in the BW group. With regard to proportion of scans between 325–500 HU and proportion of diagnostic scans , no significant between-group differences were found. However, the higher mean intravascular attenuation value in group BW (compared to the LBW) did result in significantly higher proportions of scans with good to excellent image quality, which can be considered clinically relevant.Previously, the CM injection protocol in our institution was based on BW categories . This protocol resulted in a higher mean intravascular attenuation with a relatively wide standard deviation (464 ± 85 HU). There was a very wide range (186–672 HU) in intravascular attenuation values and an optimal intravascular attenuation between 325–500 HU was observed in 56.4% of patients. The CM injection protocols in the current study resulted in less variation in intravascular attenuation values between patients with standard deviation values around 60 HU and higher proportions of scans within the optimal window of 325–500 HU.All CM injection parameters between groups BW and CO were significantly different. Group BW used a higher CM volume of 5 mL compared with group CO. This increase of 5 mL did not lead to a significant difference in intravascular attenuation nor to significantly more scans. Furthermore, the CM volume between groups LBW and BW did not differ significantly, although a significantly lower attenuation was found in group LBW. However, absence of a significant difference does not mean no difference is present . It is pThe use of BW and LBW in personalization of CM injection protocols has been studied before in varying degrees. Liu et al. showed that BW-adapted injection protocols are feasible in high-pitch prospective CCTA . Liu et The current study has some limitations. Due to lack of correlation with invasive angiography, it could not be verified whether a higher proportion of patients with optimal intravascular attenuation (325–500 HU) resulted in a more accurate diagnosis and decreased underestimation of calcifications. Second, in the current study, CO was calculated with the help of a formula, and CO measurement was not performed.To conclude, personalization of CM injection protocols to BW, LBW, and CO, and scan time and tube voltage in CCTA resulted in low variation in intravascular attenuation between patients in the three groups and a high proportion of scans with an optimal intravascular attenuation. The results suggest that personalized CM injection protocols based on LBW or CO have no additional benefit when compared to CM injection protocols based on BW.