Health professional students frequently use alcohol and narcotics. The potential impact on academic performance and professional behaviour is concerning.This study aimed to determine self-reported use of alcohol, illicit substances , prescription medication and smoking habits, correlating academic performance.Faculty of Health Sciences, University of the Free State.An observational, descriptive, cross-sectional study design was used. Information was obtained using a self-administered questionnaire, capturing demographics, self-reported academic performance, drinking and smoking habits, and substance use. Coded responses were analysed using the Remark Office OMR 8 Software System. Descriptive statistics were calculated for categorical variables.Completed questionnaires comprised 171 students. A total of 78.4% of second year and 82.8% of third year students reported using alcohol. Twenty-two per cent of second year and 24.1% of third year students reported cannabis use. In the second year group, three (2.7%) students reported using magic mushroom, two (1.8%) reported cocaine, two (1.8%) reported ecstasy and one (0.9%) reported using methamphetamine. Only third year students reported using LSD or ‘crack’. Cigarette smoking was common – 31.5% and 35.1% in both groups, respectively. Smokeless tobacco devices were used by 8.5% of second year and 7.1% of third year students. Almost 40% of both groups reported that they had smoked a water pipe. Academic performance achieved was mostly 60% – 69% (38.9%) among second year students and 70% – 79% (46.6%) among third year students.Self-reported use of alcohol and drugs and smoking among medical students is alarming. Additional student support, early identification and referral for management and/or rehabilitation should be a priority at tertiary institutions responsible for training future healthcare professionals. Alcohol abuse among students nationally and internationally is rising and alcohol has generally been identified as the most commonly used substance among students . The target population included all second and third year undergraduate medical students, aged 18 years and older, registered in the Faculty’s medical (MBChB) programme. These students are all involved in structured lectures presented by the School of Medicine and were willing to participate in a research project. First year students were excluded from this specific project in order to rule out possible other reasons or causes for using alcohol, other illicit drugs and/or smoking which might be specific to first year students only, for example, adjusting to a new social environment or adapting to the academic load and responsibilities. Medical students in their clinical years are again exposed to different daily responsibilities and stressors in comparison to the preclinical years of studying. They were therefore not included in this study, but might be included in similar future studies.Students were approached after a lecture. The principal investigators organised data collecting sessions with the presenting lecturer involved and were present at all times. The necessary information pertaining to the study and information regarding participation was given to the students at each of these sessions, whereafter they were free to choose to participate or not. Questionnaires were then handed to the participating students to complete individually at their own pace. Participation was voluntary and questionnaires were completed anonymously. Completed questionnaires were collected and kept safe for data collection and analyses by the investigators.The questionnaire used in this study was compiled by using information from various internationally validated questionnaires, with Cronbach’s alpha scores ranging between 0.74 and 0.90 . This includes authorisation from the responsible and applicable academic, research and student bodies involved. Participants received an information leaflet and the principal investigators explained the research objectives to them. Confidentiality was assured as no identifying data were recorded. The participants gave written consent before questionnaires were handed out for completion during a scheduled contact session.n = 70, 62.0%), whereas in the third year half of the participants were females .The age range for the second year students was between 19 and 26 years (77.0% in the age group of 19–20 years).The age range for the third year students was between 19 and 25 years (86.2% in the age group of 20–22 years).A total of 171 students participated in the study. The response rate was 96.6% (113/117) for second year and 46.8% (58/124) for third year students. In the second year, participants were mostly females (As shown in There were six (5.4%) and nine (8.2%) second year students who reported using sedatives and tranquilisers with and without a prescription, respectively, while eight (13.8%) and four (6.9%) third year students reported using sedatives and tranquilisers with and without a prescription, respectively. These results are summarised in Three (2.7%) second year students and one (1.8%) third year student reported using glue and other solvents over a period of 12 months.None of the second year students reported using synthetic cannabis (‘spice’), while 14 (24.1%) third year students reported its use. Twenty-five (22.3%) second year and 14 (24.1%) third year students reported cannabis use. This included 11 (9.8%) second year and 5 (8.6%) third year students who reported using cannabis between 3 and 39 times over a period of 12 months, and 1 (0.9%) second year and 2 (3.5%) third year students who reported using cannabis more than 40 times over a period of 12 months.In the second year group, three (2.7%) students reported the use of magic mushroom, two (1.8%) reported cocaine, two (1.8%) reported ecstasy and one (0.9%) reported methamphetamine use. None of the second year students reported lysergic acid diethylamide (LSD) or ‘crack’ use. In the third year group, one (1.8%) student reported the use of magic mushroom, three (5.2%) reported the use of cocaine, one (1.8%) reported the use of ecstasy and two (3.5%) reported the use of methamphetamine. Three (5.2%) indicated the use of LSD and two (3.5%) reported the use of ‘crack’.None of the second or third year students used ketamine, while one (0.9%) second year student reported heroine and benzodiazepine use, respectively, between one and two times during the past 1 year.n = 34, 30.1%) and 34.5% (n = 20) of the third year students bought their alcohol from a liquor store.As shown in A total of 87 (78.4%) second year and 48 (82.8%) third year students reported the use of alcohol. In the second year group, 10 (9.0%) students reported using alcohol 20–39 times and 25 (22.5%) students reported using alcohol more than 40 times in the previous year. In the third year group, there were 8 (13.8%) students who reported using alcohol 20–39 times and 17 (29.3%) students who reported using alcohol more than 40 times in the previous year.The use of alcohol combined with an energy drink was reported by 47 (42.7%) second year and 28 (49.1%) third year students in the past 1 year. Nine (8.1%) second year students used an energy drink with alcohol between 20 and ≥ 40 times. Four (7.0%) third year students combined an energy drink with alcohol with a frequency of between 20 and ≥ 40 times.Eighteen (15.9%) second year and nine (15.5%) third year students reported using cannabis and alcohol together. Only one (0.9%) second year student reported using cannabis and alcohol together between 20 and 39 times over a period of 12 months, and none more than 40 times. None of the third year students reported using cannabis and alcohol more than 20 times over a period of 12 months.n = 35) of second year and 35.1% (n = 20) of third year students reported cigarette smoking over a period of 12 months. Nine (8.5%) second year and four (7.1%) third year students reported using smokeless tobacco devices, and 45 (40.9%) second year and 23 (39.7%) third year students reported smoking a water pipe over a period of 12 months.The participants’ smoking habits are illustrated in Fifteen (13.3%) second year students reported that they had started smoking over a period of 12 months compared to the nine (15.5%) participants in the third year group.n = 16) of the students reported average marks of 80% – 89%; 25.7% (n = 29) reported average marks of 70% – 79%, 38.9% (n = 44) reported average marks of 60% – 69% and 20.4% (n = 23) reported average marks of < 60%. As far as the third year group was concerned, 8.6% (n = 5) of the students reported average marks of 80% – 89%; 46.6% (n = 27) reported average marks of 70% – 79%, 41.4% (n = 24) reported average marks of 60% – 69% and 3.5% (n = 2) reported obtaining marks between 50% and 59%.According to students’ responses in the questionnaire, their self-perceived perception was that their social habits, including use of alcohol, drugs and/or smoking, did not negatively affect their academic performance.This study confirmed that the self-reported prevalence of the use of alcohol and other substances of abuse, as well as smoking, among a group of undergraduate medical students is similar to findings in international literature. All types of drugs and alcohol are becoming more easily accessible and are used by populations much younger than it was in the past  between the use of methylphenidate and the rate at which alcohol, tobacco, cannabis, hard drugs and prescription medication were used.In this study, methylphenidate use with and without prescription was higher among third year students than among second year students. A previous study among medical students across all 5 years of the MBChB curriculum at the UFS reported that 9.8% of students used methylphenidate, and about one-third of these students were diagnosed with ADHD. Most students reported using stimulants to improve their ability to study as well as academic performance  third year students reported using LSD or ‘crack’. Four (2.3%) of the second and third year students also reported using glue and other solvents. Although these results are lower than figures reported in other international studies  and third year (82.8%) students reported using alcohol over a period of 12 months. Of concern was the reported alcohol use (more than 40 times over a period of 12 months) that was reported by 22.5% of second year and 29.3% of third year students. This is in line with international findings by Leinwand , indicatWelcome et al.  indicateFewer students reported smoking cigarettes than using alcohol, with approximately one-third of second and third year students reporting cigarette smoking. About 40% of second and third year students reported using a water pipe device, while less than 10% of second and third year students reported using smokeless tobacco devices. While cigarette smoking and tobacco use are detrimental to health, regular smoking is associated with other lifestyle choices and/or risky behaviours, such as drinking heavily, the use of cannabis and having multiple sexual partners  among undergraduate medical students in order to ensure that they are able to function without impairment as future healthcare professionals.The response rate in the third year group was lower than expected because these students were preparing off campus for assessments at the time of completion of the questionnaires.Surveys may be biased because participants must recall past experiences. The self-reported and sensitive nature of the information gathered in this questionnaire may have inhibited students and contributed to bias in findings, in spite of assurances of confidentiality and privacy.Participants may not have responded fully in fear of potential repercussions. This could have resulted in under-representation of substance use. The small number of participants in this study limits the generalisability of the findings. It would be valuable to expand this study to other healthcare professions students at this institution, as well as to other institutions across South Africa.The high self-reported use of alcohol, drugs and cigarette and water pipe smoking among second and third year undergraduate medical students in this study is of great concern. Prevention, early identification and remediation of risky behaviour of future healthcare professionals should be an urgent priority.This study emphasises the need for follow-up studies to identify and address the driving factors responsible for the concerning prevalence of alcohol and drug use among medical students. Additionally, a holistic approach that includes prevention, early identification and emotional as well as social support programmes must be developed and incorporated in the curriculums of health sciences students.The focus for alcohol and drug abuse prevention programmes should rather be on social and enhancement motives that resonate more with university students than emphasising the negative consequences of alcohol and drug use.


To assess the safety and clinical outcomes of multi-probe stereotactic radiofrequency ablation (SRFA) for very large (≥8 cm) primary and metastatic liver tumors with curative treatment intent. A retrospective, single center study carried out between 01.2005 and 06.2018. 34 consecutive patients had a total of 41 primary and metastatic liver tumors with a median size of 9.0 cm (8.0–18.0 cm) at initial SRFA. Patients were treated under CT guidance using a 3D navigation system. Endpoints consisted of (i) technical efficacy; primary - requiring one treatment, and secondary – requiring two treatments (ii) complication and mortality rates (iii) local and distant recurrence (LR), (iv) disease free survival (DFS), (v) overall survival (OS). 33/41 tumors were successfully ablated at initial SRFA ). Four tumors required repeat ablation, resulting in a secondary technical efficacy (STE) rate of 90.2%. Local tumor recurrence (LR) developed in 4 of 41 tumors (9.8%). The 30-day perioperative mortality was 2.3% (1/ 44 ablations). The total major complication rate was 20.5% (9 of 44 ablations). Three of nine (33.3%) major complications, such as pleural effusion, pneumothoraces or perihepatic hemorrhages were relatively easy to treat. The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 87.1%, 71.8%, and 62.8% for patients with hepatocellular carcinoma (HCC) and 87.5%, 70.0% and 70.0% for patients with intrahepatic cholangiocarcinoma (ICC) respectively. Patients with metastatic disease had OS rates of 77.8% and 22.2% at 1- and 3- years. The clinical results of SRFA in this study are encouraging and warrant a prospective multicenter study. SRFA may become one of the best therapeutic choices for a growing number of patients with primary and metastatic liver cancer. Whilst hepatic resection (HR) is still the preferred treatment in patients with preserved liver function, in clinical practice less than one-third of the patients are eligible for HR at diagnosis4. Historically, the reported local recurrence rates after conventional RF ablation are relatively high and vary from 10% to 39.1% by 5 years, depending on tumor size and number6. It has been shown that an ablation zone ‘safety margin’ is required around tumors by at least 5 mm to achieve local control and good clinical outcome7. However, achieving adequate treatment margins may be challenging in large and irregularly shaped tumors or in situations where the target tumor is either difficult to visualize, awkward to access, or adjacent to vulnerable structures. Similar considerations apply to HR, with larger tumors more likely to be unresectable due to small future liver remnant and close relationship with the major vessels or hepatic hilum8.Radiofrequency (RF) ablation has been increasingly accepted as a curative and cost-effective treatment for small liver tumors10 and whilst a survival benefit has been demonstrated11, it is considered a palliative treatment12.Transarterial chemoembolization (TACE) is currently the recommended treatment method in patients with impaired liver function and large (>5 cm) hepatocellular carcinoma (HCC)16. However, conventional multi-probe RF ablation using ultrasound or CT-fluoroscopy guidance lacks reliability for accurate three-dimensional RF probe placement and thus complete tumor coverage. Stereotaxy has proven useful for planning and executing complex or challenging ablations where access routes can be specifically facilitated and more precise coverage of the target tumor and safety margins can be accomplished18.To overcome limitations in RF ablation zone size, other thermal ablation strategies have been developed including use of microwave (MW) energy and placement of multiple RF electrodes19, although its role in very large lesions remains undefined.We have previously shown that SRFA is a viable treatment option in HCCThe purpose of the current study was to assess the safety and clinical outcomes of multi-probe SRFA for very large (≥8 cm) primary and metastatic liver tumors, treated with curative intent. Specifically, our endpoints are primary (requiring one treatment) and secondary (requiring two treatments) technical efficacy, complication rates, recurrence, disease free and overall survival.The Institutional Review Board of the Medical University of Innsbruck approved this single-center, retrospective study. All participants gave their informed consent to collect their data. All treatment plans were consensually agreed in multidisciplinary tumor board meetings.Between 01.2005 and 06.2018, 943 consecutive patients were treated by SRFA. Seventy-seven patients with portal venous invasion, extensive tumor with subsequent palliative intention to treat, or benign liver tumors were excluded  or double vacuum fixation technique . For image-to-patient registration, 10–15 fiducials,  are broadly attached to the skin of the thorax and upper abdomen. A contrast-enhanced planning CT  is obtained with 3 mm slice thickness. To enable precise stereotactic conditions, the endotracheal tube (ETT) is temporarily disconnected during the planning CT, during each stereotactic needle placement and for the final control CT. The CT dataset is transferred to an optical-based navigation system . Multiple SRFA probe trajectories with an interprobe spacing of 1.5–2 cm are planned by using multiplanar and 3D reconstructed images.The method of SRFA has previously been reported in detailAfter registration and a registration accuracy check, the probe of the navigation system is introduced into the ATLAS aiming device . After alignment of the probe axis with the planned virtual trajectory by using the guidance software of the navigation system, 15G/17.2 cm coaxial needles  are sequentially advanced through the adjusted targeting device without real-time imaging control. The depth from the aiming device to the target is automatically calculated by the navigation software. For verification of correct needle placement, a native control CT is performed and fused with the planning CT. In cases with lack of histological confirmation, a 16G coaxial biopsy sample is obtained. Thereafter, three 17G RF-electrodes  are introduced through the coaxial needles for serial tumor ablation. RF ablation is carried out using the unipolar Cool-tip RF generator , including the Cool-tip_RF switching controller. The standard ablation time for three electrodes is 16 minutes. However, if a significant increase of impedance is observed  the ablation process is finished. Track ablation is performed during every repositioning and final removal of the RF-electrodes to reduce bleeding and tumor seeding.For verification of the ablation zone and for assessment of complications, a final contrast-enhanced CT scan is superimposed onto the planning CT.Example images from multi-probe SRFA of very large liver tumors are shown in Figs. (I).Technical success was defined as accurate electrode placement, with a deviation <1 cm at the needle tip, according to predefined plans. Primary technical efficacy, requiring one treatment with complete ablation, and secondary technical efficacy, requiring more treatments for complete ablation, were determined by follow-up contrast-enhanced CT or MR scans performed at 1- month. The imaging tests were evaluated by two board certified abdominal radiologists by consensus.(II).23. Mortality was defined as death within 30 days after SRFA treatment.Considering the complexity of the procedures and for better comparison to surgery, the study endpoint major complications were defined according to the Clavien-Dindo classification (Grade III+)(III).Local recurrence was specified as appearance of new enhancing nodules  within or directly adjacent to the initially tumor-free ablation zone. New enhancing nodules distant to the ablation zone and or to the initial tumor location were specified as distant tumor recurrence.(IV). Survival was calculated from the date of initial SRFA to the date of death attributable to malignancy or other causes  or to the most recent follow-up visit .The endpoints of the study consisted of (i) technical success and efficacy rates, (ii) complication and mortality rates, (iii) local and distant recurrence rates, (iv) DFS and (v) OS.The statistical analysis was performed with IBM SPSS version 24 . The Kolmogorov-Smirnov-Test, tested normality of distribution. Data were expressed as total numbers, median and range. Survival data (OS and DFS) were analyzed with the Kaplan Meier method. The X² test was used to determine differences between categorical variables, and the Mann-Whitney U test between independent continuous variables. A two-tailed p-value of <0.05 was considered as statistically significant.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.Consent for publication was obtained for every individual person’s data included in the study.34 Patients, 7 females and 27 males, with a median age of 66 years (range 27–81) underwent 44 SRFA treatments of 41 very large primary or metastatic liver tumors Table The histopathological results from the biopsies obtained during SRFA (in 18 patients) were positive for malignancy in all cases.Major perioperative complications are presented in Table One patient developed acute liver failure after treatment of 3 HCCs (largest tumor 8 cm) requiring salvage liver transplantation. Thermal injuries of the bowel (1 patient) and gallbladder (1patient) had to be surgically treated. One liver abscess required CT guided drainage. Other complications included transient liver failure (1 patient) and pleural effusions (3 patients) requiring thoracoenteses respectively. Additionally, two perihepatic hemorrhages and one pneumothorax were treated within the same session by embolization and chest drain which did not influence the postoperative course. 3/9 (33%) major complications were successfully treated by the interventional radiologist within the next days by placing a pleural drainage in case of major pleural effusions (3 patients).The median hospital stay after the ablation was 7 days, ranging from 3–21 days. The median number of inserted coaxial needles per tumor was 12 (6–31).SRFA was successfully completed according to plan in all 41 tumors  Table A sub analysis based on tumor type  showed the highest PTE rates for HCC tumors with 88.2% (15/17) and the lowest for ICC with 75% (9/12). However, the differences between groups were non-significant (p = 0.607).During a median imaging follow-up of 9.4 months (range 1–133 months) local tumor recurrence developed in 4 of 41 tumors  showed the lowest LR rates for HCC at 5.9% (1/16) and the highest for ICC at 16.7% (2/12). However, the differences between groups were non-significant (p = 0.600).For HCC, the median OS and OS rates Fig.  at 1-, 3Among patients with metastatic disease, the OS rates at 1- and 3- years were 77.8% and 22.2% with a median OS of 22.8 months (95% CI 17.4–36.2).There was a difference, however, non-significant between groups based on tumor entity (p = 0.15).The disease-free (DFS) rates Fig.  at 1-, 3There was no significant difference between groups based on tumor entity (p = 0.72).4, meaning other curative treatment options are required.The main finding of our study is that SRFA is a feasible and effective treatment strategy for tumors >8 cm. To the best of our knowledge, there are no reports available dealing with thermal ablation of this tumor size, partially because HR remains the recommended treatment in large tumors with preserved liver function. However, the minority of patients are suitable for resection26, it has been incorporated into international guidelines for small tumors29. However, early studies demonstrated that complete cure falls to 40–70%31 for medium HCCs (up to 5 cm) and to 23–45% for large HCCs32 respectively, which is very likely to reflect the size limitations of RF ablation zones and the difficulties in producing overlapping ablations. To overcome size limitations, two main strategies were implemented. Firstly, increasing energy transfer in the form of microwave energy, and secondly using multiple RF probes to create overlapping ablation zones. More recent studies have consequently shown better PTE rates up to 86–97% in medium and large HCCs up to 10 cm34.Since RFA results in complete cure for small HCCs (<3 cm) and colorectal liver metastases (CRLM) in greater than 90% of cases35, this higher thermal energy might injure adjacent vulnerable structures or create unnecessarily large ablation zones36. Whilst the lower energy transferred in RFA may result in more predictable ablation zones, the greater number of probes required considerably increases the complexity and difficulty of the procedure.Whilst MWA can produce larger ablation zones faster and with less ‘heat-sink’ effect  than RFA37 facilitate precise path needle and probe placement17. Immediate post ablation contrast-enhanced CT fusion with the planning CT allows for rapid, reliable intraoperative judgment of the ablation results with the option for re-ablation within the same session. In a recent histopathological validation study in explanted livers after bridging therapy with SRFA, we found no viable tumor in 183 of 188 treated lesions (97.3%) and in 50 of 52 lesions >3 cm (96.2%).Accurate three-dimensional probe alignment to create sufficiently overlapping ablation zones demands a high level of operator experience using conventional US- and CT- guidance. However, SRFA offers three-dimensional ablation planning to achieve an optimal configuration of RF probes and create multiple overlapping coagulation volumes. Usage of an aiming device and triggering of respiratory motion38.Despite our inclusion of tumors up to 18 cm in diameter in the present study, LR developed in only 4 of 41 tumors (9.8%). In contrast, best results from the US- or CT- guided multiprobe thermal ablation literature with ‘freehand’ targeting quote LR rates of 15.9–19.7% after thermal ablation of large HCCs  and other large liver tumors up to 8 cm (mean tumor size 2.8 cm)et al.34 reporting lower OS rates than in our study - specifically 65.5%, 36.3% and 21% at 1-, 3- and 5- years, respectively. Several retrospective studies compared HR and TACE in solitary HCC >5 cm, and reported 5-year OS of 43–65% and 17.5–49.6% for HR and TACE respectively41. Two studies regarding HR in HCC >5 cm by Zhao et al.42 and Hwang et al.43 reported OS of 75%, 59% and 44% and 78.4%, 58.8% and 49.3% at 1-, 3- and 5- years, respectively. For HCC (>10 cm), Zhou et al.44 showed OS of 60.7%, 34% and 28.6% at 1-, 3- and 5- years respectively. Data are sparse for HR of large CRLM with Nomit et al.45 reporting OS at 1-, 3- and 5- years of 87.2%, 56.1% and 35.4% respectively after laparoscopic HR.OS rates in our study at 1-, 3-, and 5- years from first SRFA were 87.1%, 71.8%, 62.8%, and 87.5%, 70.0%, 70.0% for patients with HCC and ICC, respectively whereas patients with metastatic disease had OS rates of 77.8% and 22.2% at 1- and 3-years. Data are sparse regarding RF ablation of tumors >5 cm with Ma 46 and micrometastases47, and are line with the surgical literature at 57.1–82.4%44.In the present study, distant tumor recurrence was found in 70.6% of patients and median DFS rates were 4.4–7.1 months. These unfavourable prognostic indicators despite high levels of effective local tumor control (90.8%) might be explained by large lesions having a greater chance of vascular invasionet al.34 and Laeseke et al.32 who reported a major complication rate of 16% following RFA for HCC >5 cm. One of the main reasons for that could be the high number of needles used (median 12 per tumor). However, our mortality rate compares favorably to Filmann et al.48 who reported a mortality of 9.1–25.5% after major HR in large outcome analysis of 110 332 procedures. Zhou et al.44 also published a systematic review after HR of large HCC (>10) a median perioperative morbidity of 29.2% (13.6–72%) and mortality of 3.5% (0–18.2%) and Nomit et al.45 reported a major complication rate of 50.0% after laparoscopic HR of large CRLM.Our major complication rate of 20.5% is higher than in the study of Ma Study limitations include the retrospective design, heterogeneity of previous unsuccessful loco treatments (TACE or HR), and single treatment center bias. Comparisons with previous related studies are limited as stereotactic navigation systems were not employed in prior reports.In summary, although all patients in this study were considered to be inoperable, we report lower mortality rates, lower complication rates and similar survival to the curative literature meaning SRFA may represent an important tool in the treatment of very large liver tumors.


Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities.DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60 months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score.This is a retrospective observational study with 105 patients with type 2 diabetes (p < 0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60 months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes.Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (2.Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI ≥ 35 kg/m Obesity is a worldwide health problem, affecting children, adolescents as well as adults , being a2 but pre-diabetes is not included yet. Bariatric/metabolic surgery has shown to achieve high rates of type 2 diabetes remission in retrospective as well as prospective studies, thus reducing cardiovascular risk factors in patients with obesity [Type 2 diabetes is considered a criterion for bariatric surgery in patients with BMI > 35 kg/m obesity . ConsideThis retrospective observational study included morbidly obese patients. For analysis, we reviewed the electronic medical record of 105 patients with type 2 diabetes or pre-diabetes of a cohort of 313 obese patients, who had undergone Roux -en-Y Gastric Bypass (RYGB) surgery between June 2000 and November 2011 at Hospital Universitario y Politécnico La Fe, with a follow-up of 5 years. 70 of 105 patients completed a 5-year follow-up.2, or above 35 kg/m2 with associated comorbidities  who had previously tried lifestyle changes to control their obesity. All eligible subjects were aged 18–60 years and had passed a psychological evaluation . All surgical interventions had been performed by the same surgical team at our hospital and all patients signed an informed consent form before undergoing surgery.Inclusion criteria were BMI > 40 kg/mData were collected from electronic medical records at baseline (between 1 and 3 months prior to surgery) and at every follow-up visit . The following data were collected: blood pressure, anthropometric parameters , obstructive sleep apnea (OSA), and blood parameters , plasma insulin and c-peptide). Normal or pathological values were based on cut-off parameters.An oral glucose tolerance test in patients with unknown type 2 diabetes was done at baseline. Diabetes and cardiovascular medications were also considered.All procedures in studies involving human participants were performed in accordance with the ethical standards of the institutional review board of Hospital Universitario y Politécnico La Fe and with the principles of the Declaration of Helsinki 2013. For this type of study formal consent was not required. This study was approved by the Ethics Committee of the Hospital Universitario y Politécnico La Fe.The primary end point was to compare CVD risk between patients with type 2 diabetes and subjects with pre-diabetes before and 1 year after RYGB. To calculate the predicted 10-year risk of cardiovascular disease we used the Framingham Risk Score (FRS) , which rSecondary end points were to describe the evolution of glycemic control, hypertension, dyslipidemia, OSA and weight parameters individually, for 5 years after surgery.2 and weight loss was expressed as total weight loss percentage (%TWL): follow-up weight - preoperative weight/ 100.BMI was calculated as Kg/mExcess weight loss percentage (%EWL) was calculated with the following formula: × 100.2 was used. An EWL ≥ 50% was considered successful weight loss [To calculate ideal body weight the equivalent to a BMI of 25 kg/mght loss .Body fat percentage was measured by bio-electrical bio-impedance (Bodystar® 1500) once a year. Body fat percentage > 25% in men and > 33% in women was considered elevated .Blood pressure was taken collecting the mean of three determinations in a seated state. Hypertension  was defiOSA was diagnosed through polysomnography before surgery. Improvement/resolution was considered after performing a new polysomnography and indicating the discontinuation of CPAP by the physician pneumologist after surgery. Remission of comorbidities was defined as the absence of disease according to the above criteria.DMbaseline) or pre-diabetes (preDMbaseline) prior to surgery.Information for relevant variables is shown at baseline and 6,12, 36 and 60 months. Follow-up data after surgery is presented according to diagnosis of type 2 diabetes  and mean waist was 137.3 (15.2). Mean percentage body fat was 50.8% (7.3) and 100% of the patients had a high percentage of body fat.The study included 105 patients (18 men and 87 women) who had undergone RYGB, 70 of whom (10 men and 60 women) had completed a 5 -year -follow-up. A summary of the most relevant baseline characteristics of our sample is presented in Table DMbaseline group and 15 of the preDMbaseline group). 20% (21) of the patients were smokers.Other comorbidities, such as OSA, were present in 32.4% of the patients  of the patients had a high CVD risk (a 10-year risk of a CVD event > 20%).Prior to surgery, 48 patients (45.7%) had type 2 diabetes. A total of 23 patients were diagnosed of type 2 diabetes at baseline (16 of whom after a glucose tolerance test). 50% of the patients with diabetes took medications (18 patients took 1 drug and 6 took 2 drugs). Metformin was the most common prescribed, and only 3 patients required insulin.Fifty-seven (54.2%) patients of the cohort had pre-diabetes. A HOMA-IR index > 3.8 was detected in 77.1% (81) of all of patients. C-peptide levels were similar in both groups.Other comorbidities, such as hypertension, were present in 81.9% (86) of the patients at baseline. 57% of the patients took 1 antihypertensive drug, and about 20% of the patients took 2 or 3 medications. Only 1 patient was treated with 4 drugs.62.9% (66) of the patients had dyslipidemia, and 19.7% (13) of whom took treatment prior to intervention.p < 0.001) and the effect. The difference between baseline and month 12 was also statistically significant . Nevertheless, after the intervention all patients reached similar levels of CVD risk regardless of their previous status. Therefore, patients with higher fasting glucose levels are the ones that benefit the most from the intervention regarding CVD risk .The primary end point was assessed in 105 patients. Progression of CVD risk over time and its association with fasting glucose levels were studied using a beta regression model. The model showed a clear effect of fasting glucose levels on the different progression of CVD risk over time .The main analysis was performed using fasting glucose levels as a continuous numerical variable, but the same analysis was also performed after classifying patients with type 2 diabetes or pre-diabetes. Results of this analysis were similar to those obtained using the continuous fasting glucose levels: patients with type 2 diabetes experienced a clear benefit after the intervention compared to pre-diabetes  12 months after surgery, compared to their baseline risk. Nevertheless, at that time point (month 12), patients with type 2 diabetes showed a larger reduction in CVD risk than those with pre-diabetes .DMbaseline group and the preDMbaseline group. Median and quartiles of evolution of parameters described at baseline are shown in Table In order to gain more insight into the different outcomes related to the intervention in this type of patients, the trends over time for eight different parameters were studied . These trends are depicted in Fig. DMbaseline group, and 15.8% (6) of patients of the preDMbaseline group. Only 2 subjects of our cohort took lipid-lowering treatment at 60 months.Seventy patients completed the 5-year-follow up. Among them, dyslipidemia was present in 9.4% (3) of patients of the DMbaseline group, and 57.9% (22) of the preDMbaseline group. 18 patients of our cohort took antihypertensive treatment (13 of the DMbaseline group and 5 of the preDMbaseline group). Most of them were treated with 1 drug. Hypertension worsened in one patient (treatment with 5 drugs).Hypertension resolved in 50% (16) of patients of the DMbaseline group, and 5  in the preDMbaseline group.According to the Framingham Risk Score, 3.2% (2) of the patients maintained a high CVD risk (a 10-year risk of a CVD event > 20%) five years after surgery. Median of %FRS was 5  in the preDMbaseline group, and 6.3% (2) of the DMbaseline group.OSA was present in 7.9% (3) of the DMbaseline group and 34 and 69.5 in the preDMbaseline group, respectively, one year after surgery. We did not find statistically significant differences in mean %TWL and %EWL between both groups 1 and 5 years after surgery. Successful weight loss was achieved in 71.9% (23) of the DMbaseline group and 83.3% (32) of the preDMbaseline group.Regarding weight parameters, mean %TWL and %EWL were 32.8 and 63.4 in the DMbaseline group). The type 2 diabetes remission rate was 92% (29/32). The mean decrease in HbA1c was 2.05 in the DMbaseline group and 0.37 in the preDMbaseline group. No patient of the preDMbaseline group developed type 2 diabetes. Medications were reduced after intervention and only 2 subjects continued to take hypoglycemic drugs.At 60 months, only 4 patients had type 2 diabetes and 20 patients had pre-diabetes . As previously shown, the higher the fasting plasma glucose, the higher the CVD risk. After intervention, the CVD risk decreased in both groups (type 2 diabetes and pre-diabetes) 12 months after surgery with a clear benefit in type 2 diabetes compared to pre-diabetes  with a sharp decrease during the first year and a flat trend until 60 months after surgery. The potential mechanisms involve a reduction in systemic inflammation and the restoration of a normal adipokine secretory profile [The assessment of individual cardiovascular risk factors (hypertension and dyslipidemia) after bariatric surgery also confirms the beneficial effects of metabolic surgery. An improvement was observed in both groups  and were diagnosed with type 2 diabetes or pre-diabetes in the pre-surgery evaluation. The DMbaseline group had an acceptable glycemic control, likely to lead to a high diabetes remission after surgery. Moreover, 35 patients had been referred to their local hospitals, which resulted in the loss of their data.This study has a few limitations: as other longitudinal studies, this is a retrospective observational study. In our cohort, median BMI was elevated in both groups, especially in the 2.Our results support the beneficial effects of metabolic surgery decreasing cardiovascular risk in type 2 diabetes as well as pre-diabetes, and improving glycemic control and obesity comorbidities in both groups. A greater benefit among subjects with diabetes as compared to those with pre-diabetes was observed in our study. More studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI ≥ 35 kg/m


To explore the relationship between FABP4 and FABP6 expression and the pathogenesis of colorectal cancer (CRC) and their potential as biomarkers in the diagnosis of CRC.In total, 100 CRC patients and 100 controls were enrolled. The serum levels of FABP4 and FABP6 were detected by enzyme-linked immunosorbent assay (ELISA) before and 2 weeks after radical resection of CRC. The protein expressions of FABP4 and FABP6 were observed in colorectal tumor tissues and adjacent tissues by immunohistochemistry and western blot, respectively. The diagnostic performance of FABP4 and FABP6 in patients with CRC was evaluated by receiver operating characteristic (ROC) curve analysis.P < 0.001), and significantly decreased at 2 weeks after operation (P < 0.001). Immunohistochemistry showed that FABP4 and FABP6 were mainly distributed in the cytoplasm of human colorectal tumor tissues, and only a small amount distributed in adjacent tissues. Western blot revealed that the protein expressions of FABP4 and FABP6 were significantly higher in tumor tissues than in adjacent tissues . Tumors with high and low FABP4 and FABP6 expression have no significant correlation in tumor size, tumor site, distant organ and lymph node metastasis, histologic grade, lymphatic permeation, neurological invasion, vascular invasion, and Duke’s and TNM classification. Multivariate logistic regression analysis showed that FABP4 and FABP6 were independent risk factors for CRC ; P < 0.001, respectively). In discriminating CRC from the normal control, the optimal sensitivity of FABP4 and FABP6 were 93.20% (95%CI 87.8–96.7) and 83.70% (95%CI 76.7–89.3), respectively, while the optimal specificity of FABP4 and FABP6 were 48.8% (95%CI 39.8–57.9) and 58.4% (95%CI 49.2–67.1), respectively. When combined detection of serum carcinoembryonic (CEA) and FABP4 and FABP6, the optimal sensitivity and specificity were 61.33% (95%CI 53.0–69.2) and 79.82% (95%CI 71.3–86.8), respectively.The serum levels of FABP4 and FABP6 in patients with CRC were higher than the levels in the controls before surgery (Increased expression of FABP4 and FABP6 not only were strong risk factors for the development of CRC but could also represent a potential biomarker for CRC diagnosis in Chinese patients. Combined detection of CEA with FABP4 and FABP6 could improve the diagnostic efficacy of CRC. Worldwide, the incidence of colorectal cancer (CRC) ranks third in malignant tumors and ranks second in terms of mortality . In 2014Fatty acid-binding proteins (FABPs) are a group of low-molecular-weight proteins involved in the transport of long-chain bioactive fatty acids in cells. Since FABPs were discovered in 1972, 12 different types (FABP1-12) have been confirmed, nine (FABP1–FABP9) are expressed in humans. According to the current literature, FABPs are expressed differently in different types of cancer or in different cell lines of the same cancer. FABP4 is mainly expressed in differentiated adipocytes and macrophages , and preFABP6 is highly expressed in the ileum and is an intracellular transporter of bile acids in ileal epithelial cells, which helps catalyze and metabolize cholesterol. Fecal bile acid concentrations, particularly secondary bile acids, are known to be higher in colon adenomas or CRC patients –11, wherRecent studies have shown that FABPs may play an important role in cells proliferation , 14, sugSo far, fewer clinical studies concerning the association between FABP4 and FABP6 and CRC are reported , 19, 20.In all, 100 consecutive Chinese patients of Han nationality with pathologically or biopsy-diagnosed CRC who had not received surgery, radiotherapy, or chemotherapy, between September 2017 and December 2018, at the First Affiliated Hospital of Anhui Medical University, were enrolled in this study. Of the 100 patients, 38 had colon cancer, and the remainder had rectal cancer. The control subjects were 100 consecutive Chinese subjects of Han nationality without colorectal polyp or inflammatory bowel disease, who underwent a total colonoscopy after a voluntary health check-up or occult fecal blood loss at the same hospital. Each control was matched with one case for gender, age, BMI and time to the admission of the corresponding case (± 1 month). The exclusion criteria were patients with familial adenomatous polyposis, hereditary non-polyposis CRC, previous gastrointestinal tract surgery, inflammatory bowel disease, serious liver and renal dysfunction, and acute and chronic infectious disease. Patients with CRC were treated with radical resection of CRC, and TNM staging was performed on the post-operative pathology results according to the criteria  to assess the extent of cancer invasion. According to tumor localization, samples were classified as “right-sided”  and “left-sided” (set in the descendant or sigmoid colon or in the rectum). According to tumor size, two groups were identified: the first comprised tumors ≤ 5 cm in size, and the second consisted of tumors > 5 cm in size. Local invasion was also classified into two groups, pT1-T2 and pT3-T4, respectively. Moreover, cases were subdivided into two groups based on their histological grade, the first group comprising grade 1 and grade 2 cases, and the second group consisting of grade 3 adenocarcinomas. This study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University in March 2017 and has been registered in the Clinical Drug Evaluation Center of Anhui Medical University as CDEC000002712. Statement of consent to participate in this study was obtained in advance from all participants.All subjects fasted for 10 h and then were measured for height, weight, waist circumference (WC), hip circumference, diastolic blood pressure (DBP), and systolic blood pressure (SBP). Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and a questionnaire about their smoking habits, alcohol intake, medications  and family history of CRC were completed. Any person who had smoked an average of more than five cigarettes every day for a year was defined as a regular smoker, whereas those who had stopped smoking for more than a year previously were counted as ex-smokers. Any person who drank an average of more than 25 g of alcohol daily for 1 year was defined as a regular alcohol drinker. A family history of CRC was defined as a first-degree relative with CRC, respectively .Two hundred subjects had 8 ml of blood drawn from the cubital vein in the morning after fasting for 10 h. Of the 100 patients with CRC, 8 ml of blood was again taken under the same conditions after surgery (2 weeks). The collected blood samples were centrifuged, and the serum was aspirated and stored in a − 80 °C refrigerator until analysis. Blood glucose and blood lipids were measured using an automatic biochemical analyzer . Among them, fasting plasma glucose (FPG) was detected by glucose oxidase method. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected by enzymatic method. CEA and CA19-9 were detected by electrochemiluminescence . The serum levels of FABP4 and FABP6 were measured by ELISA kits based on the double antibody sandwich technique , and the sensitivity of interval assay was 0.1 pg/ml. Intra- and inter-assay variability should be less than 9% and 15%, respectively. Standards, controls, and samples were evaluated at a wavelength of 450 nm. Three measurements were made in a single experiment and determined by comparing the absorbance  of the sample to a standard curve. Referring to previous research , in the 2O2 was added to the tissue and incubated . The samples were washed three times with phosphate-buffered saline (PBS), and the sections were dried. An appropriate amount (~ 100 μl) of primary antibody  was added and incubated . After rinsing, 100 μl or an appropriate amount of secondary antibody  was added dropwise and incubated again . After washing, add diaminobenzidine (DAB) coloring agent was added, the color development time under the microscope  was controlled (there is a positive termination color development), and the color development was stopped and rinsed with distilled water. Finally, the stained sections were stained for 1 min in hematoxylin staining solution, differentiated with 1% hydrochloric acid alcohol for several seconds, and washed again. After washing, the expression and distribution of FABP4 and FABP6 were observed under a microscope . The average optical density value  was calculated by immunohistochemical morphological analysis software to quantitatively compare the difference between the protein expressed by the positive cells in the cancer tissue and the adjacent tissues. In addition, we deal positive control tissues sections (confirmed homologous tissue sections containing FABP4 and FABP6 antigens) and experimental tissues sections of this study with the same treatment and immunostaining to confirm the effectiveness of the immunohistochemical staining procedure and to exclude false negatives.The embedded tissue was trimmed, the slicer was placed in a 4-μm section, and the oven was dewaxed and hydrated overnight. Three times xylene (Shanghai Susie) and 100%–95%–80% ethanol were passed in sequence for 15 min. The slices were placed together with the staining rack into the beaker and rinsed with tap water slowly until the slices were clean and transparent. A pressure cooker was used to hold 2 L of double distilled water, and 40 ml of pH 8.0 ethylenediaminetetraacetic acid (EDTA) repair solution was added and heated to boiling on the induction cooker. Then, the slices were put together with the dyeing rack into the repair solution, fixed after boiling for 2 min, and allowed to cool naturally. Next, 3% Hg, 10 °C for 10 min), and the supernatant was retained. Protein samples were separated by 10% sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to a nitrocellulose membrane. After blocking 5% skim milk in Tris-buffered saline containing 0.05% Tween-20 (TBS-T) for 2 h, the membrane was incubated with primary antibody against FABP4 and FABP6 at room temperature overnight ; then, the secondary antibody was added and incubated at room temperature for 60 min  and washed. Finally, antibody detection was performed by ECL chemiluminescence .Total protein was isolated from the ground tissue samples using radioimmunoprecipitation assay (RIPA) buffer. Briefly, a 100-mg sample was mechanically comminuted and resuspended in 1 ml RIPA buffer (100 mg tissue/ml). The resuspended sample was sonicated on ice, the insoluble matter was removed by centrifugation  and their 95%CI using a conditional logistic regression model. In the logistic regression analysis, FABP4 and FABP6 and other variables were all analyzed as categorical variables and were classified into two categories based on the cutoff value, and potential confounding factors were adjusted. ROC curves were established to explore if FABP4 and FABP6 could be potential biomarkers for CRC. The optimal sensitivity and specificity from ROC curves were determined by commonly used methods [P values are two-sided and less than 0.05 were considered statistically significant.Excel 2013 was used for data aggregation, and the SPSS statistical software package and Medcalc 15.2 software of Windows vers.17.0  were used for statistical analysis. Data were expressed as mean ± SD , LDL-C (P = 0.001), FABP4 (P < 0.001), FABP6 (P < 0.001), CEA (P = 0.001), CA19-9 (P = 0.004), and the distribution of the numbers of family history of CRC (P = 0.03) were all higher, but HDL-C was (P = 0.006) lower compared with the control group. In addition, compared with preoperative levels, the patients’ BMI and WC (2 weeks after surgery) decreased slightly, but there were no statistical difference. However, the serum levels of FABP4 and FABP6 were significantly reduced ; the decrease amplitude was 11.3% and 13.8%, respectively, whereas, it still higher than those in the control group . Moreover, in consistence with the changes of the serum levels of FABP4 and FABP6, the serum levels of CEA and CA-199 were all significantly decreased after surgery in the CRC group   , tumor site , distant organ and lymph node metastasis , histologic grade , lymphatic permeation , neurological invasion , vascular invasion , and Duke’s  and TNM classification . or high (≥ the median) according to a cutoff value calculated from the median of the values observed in the CRC subjects. Tumors with high and low FABP4 and FABP6 expression have no significant correlation in tumor size  and FABP6 levels were positively associated with BP . When restricted to the control group, we can merely find FABP4 levels were positively correlated with BMI and WHR . We did not observe any significant correlations of FABP4 and FABP6 levels with age, sex, FPG, TCH, HDL-C, LDL-C, CEA, and CA19-9 in the CRC and control groups. In addition, among patients with CRC, FABP4 levels were not significantly associated with BP, and FABP6 levels were not significantly associated with BMI, WHR, and TG. Similarly, among the control group, FABP6 levels were not significantly associated with BMI or WHR.Spearman correlation coefficients for associations between FABP4 and FABP6 levels and metabolic and anthropometric variables and other parameters among cases and control participants are shown in Table P < 0.001; adjusted odds ratio 2.162; 95%CI 1.046, 1.078); P < 0.001, respectively) , SBP , DBP , WHR , TCH , TG , LDL-C , HDL-C , FPG , FABP4 , FABP6 , CEA , CA19-9 , and family history of CRC  as independent variables. Univariate logistic regression analysis indicated that WHR, LDL-C, FABP4, FABP6, CEA, and family history of CRC were risk factors for CRC, and HDL-C was a protective factor. According to the results of univariate logistic regression and the previous studies about the impact of metabolic syndrome on CRC [61.2–74.5) and 85.9% (95%CI 75.6–93.0), respectively. Similarly, the optimal sensitivity and specificity obtained by movement of the cutoff value of serum FABP6, which was 347.26 pg/ml, were 83.70% (95%CI 76.7–89.3) and 58.4% (95%CI 49.2–67.1) in discriminating CRC from the normal control and PPV and NPV were 70.3% (95%CI 62.9–76.9) and 75.9% (95%CI 65.5–83.5), respectively. The optimal sensitivity and specificity obtained by movement of the cutoff value of serum CEA, which was 7.5 ng/ml, were 53.06% (95%CI 44.7–61.3) and 77.60% (95%CI 69.3–84.6) in discriminating CRC from the normal control, and PPV and NPV were 73.6% (95%CI 64.1–81.7) and 58.5% (95%CI 50.5–66.0); the optimal sensitivity and specificity obtained by movement of the cutoff value of serum CA19-9, which was 14.24 U/ml, were 46.26% (95%CI 38.0–54.7) and 68.80% (95%CI 59.9–76.8) in discriminating CRC from the normal control, and PPV and NPV were 63.6% (95%CI 53.7–72.6) and 52.1% (95%CI 44.2–59.9), respectively. When combined detection of FABP4, FABP6, and CEA, the area of ROC curves is 0.746 (95% CI 0.689–0.798), and the optimal sensitivity and specificity were 61.33% (53.0–69.2) and 79.82% (71.3–86.8), and PPV and NPV were 80.0% (95%CI 71.5–86.9) and 61.1% (95%CI 52.8–68.9), respectively, and the diagnostic efficiency was higher than any single index (P < 0.05) , 0.683 (95%CI 0.624–0.738), 0.689 (95%CI 0.631–0.744), and 0.592 (95%CI 0.531–0.651), respectively. The optimal sensitivity and specificity obtained by movement of the cutoff value of serum FABP4, which was 223.35 pg/ml, were 93.20% (95%CI 87.8–96.7) and 48.8% (95%CI 39.8–57.9) in discriminating CRC from the normal control and positive predictive value (PPV) and negative positive predictive value (NPV) were 68.2%  of CRC. Therefore, the results of this study suggest that increased levels of FABP4 and FABP6 not only were strong risk factors for CRC but also could represent potential biomarkers for diagnosis of CRC in Chinese patients.FABPs are structurally conserved intracellular lipid transporters that bind unesterified long-chain fatty acids and other ligands with nanomolar affinity and a molecular weight of approximately 15 kDa . These tIt is well known that FABP4 is primarily expressed in adipocytes and macrophages. In recent years, studies have found that FABP4 may play an important role in metabolic syndrome and the pathogenesis of liver cancer caused by obesity . ThompsoOhmachi et al. revealed that tumors with high FABP6 expression were smaller in size, more often in the left colon and had shallower invasion into the bowel wall compared with those with low expression, and there was no significant difference in histologic type, lymph node, or liver metastasis, Dukes’ classification, and prognosis (13). However, we did not find a link between serum levels of FABP4 and FABP6 and the clinicopathologic features of CRC. The reasons why our findings are inconsistent with those of Ohmachi et al. may include race, sample size, and so on. Therefore, further verification is worth conducting in the future to elucidate association between expressions of FABP4, FABP6, and the clinicopathologic features of CRC.Interestingly, in this study, immunohistochemistry and western blot analysis showed that FABP4 and FABP6 were mainly expressed in the cells from tumor tissues, and only a small amount distributed in adjacent tissues. Meanwhile, compared with preoperative levels, the serum levels of FABP4 and FABP6 at 2 weeks after surgery were significantly reduced. However, we found that the above decrease amplitude of FABP4 and FABP6 was merely 11.3% and 13.8%, respectively, both FABP4 and FABP6 levels in CRC group after surgery were still higher than those in the control group. These results suggested the causes of high serum levels of FABP4 and FABP6 in patients with CRC are complicated. Tumor-induced secretion may only be one of the reasons for the increase of FABP4 and FABP6 in peripheral serum. This may explain why the serum levels of FABP4 and FABP6 in CRC patients cannot be completely reversed after surgical removal of tumor tissue. However, the partial results of our study were inconsitent with previous studies. Shen et al. and Sayagués et al. explored the expression of FABP4 in patients with CRC by microarray analysis, the former studies showed that decreased FABP4 gene expression was identified from tumor samples compared with adjacent non-cancerous controls , the latIdeal biomarkers should be highly differentiated from other lesions, such as cancer, normal lesions, or adenomas, and are continuously released into the lumen or circulation and disappear or reduce after the lesion is removed or treated. In our preliminary observational study (data unpublished), we found that serum concentrations of FABP4 and FABP6 increased before operation and gradually reduced postoperatively in patients with CRC, consistent with changes of serum levels of CEA and CA19-9 which are well known biomarkers of CRC. The present study further confirmed our previous finding. Thus, we consider that FABP4 and FABP6 may be suitable biomarkers for diagnosing relatively early CRC and/or assessing anticancer therapy. Regrettably, the ROC curves showed that the area under the curves (AUC) of each of the four indicators  was lower than 0.7. Compared with CEA and CA199, FABP4 and FABP6 are more sensitive but less specific. CEA combined with FABP4 and FABP6 have higher diagnostic efficacy than any single indicator. Therefore, it is clinically possible to jointly detect FABP4 and FABP6 with CEA to improve the diagnosis rate of early CRC. Excitingly, the recent study reported by Long et al. showed that several genes involved in cellular energetic could be candidate for diagnostic, prognostic, and predictive biomarkers of CRC by high-throughput omics and statistical learning integration , and theA correlation analysis showed that FABP4 was positively associated with BMI and WHR among subjects both in CRC group and control group. Moreover, FABP4 was positively associated with TG and FABP6 levels were positively correlated with SBP and DBP in CRC group, respectively. In adipocytes, FABP4 activates hormone-sensitive lipase (HSL) to regulate lipolysis of adipocytes, and lipid metabolism disorder and chronic inflammatory response are two important characteristics of obesity. Studies , 34 haveIn addition, in the present study, we revealed a significant increased OR of WHR, LDL-C, CEA, and CRC family history and a significant decreased OR of HLD-C in patients with CRC by univariate regression analysis, which is consistent with previous studies –38. As wThe current molecular mechanism between FABP4 and FABP6 and the onset of CRC are unclear. Some scholars believed that there is a potential link between FABP4 and hyperlipidemia, hyperinsulinemia, and insulin resistance , which iNotwithstanding, this study also has several shortcomings, such as the relatively small sample size; the levels of FABP4 and FABP6 were measured only 2 weeks after surgery; a longer-term dynamic follow-up measurement on patient’s treatment, treatment effect, survival time, and FABPs levels were not performed; without using the more sensitive PCR methods to determine the mRNA expressions of FABP4 and FABP6. Thus, the relationship between FABP4 and FABP6 expression levels and treatment response and prognosis survival in CRC patients has remained unknown.In conclusion, this study found that serum levels of FABP4 and FABP6 were significantly increased in patients with CRC, and the increased expressions of FABP4 and FABP6 were associated with the development of CRC. We also revealed that serum FABP4 and FABP6 may represent potential biomarkers for CRC diagnosis in Chinese patients. Combined detection of CEA with FABP4 and FABP6 could improve the diagnostic efficacy of CRC. However, this study is still unable to determine the causal relationship between FABP4 and FABP6 and the onset of CRC, which is to be confirmed by in vitro cell studies and animal experiments.


There is a foreseeable trend that life expectancy is on the rise in many parts of the world. More and more patients will present with colorectal cancer at extreme old age and advanced age is a well-known risk factor for adverse outcomes after surgery. The aim of this study is to evaluate the outcomes of colorectal cancer surgery in patients aged 90 or above.A retrospective analysis of consecutive patients aged 90 or above who underwent operations for colorectal cancer between January 1996 and December 2015 was performed. The primary outcomes were the complications rate, 30-day and 180-day mortality rates.A total of 57 patients were included in the analysis. The majority of them were women (64.9%). The median age was 92 years. Most of the surgery was of curative intent (77.2%), performed under elective setting (57.9%) and with open approach (78.9%). 36.8% of patients had postoperative complications, with pneumonia being the commonest. The 30-day and 180-day mortality rate was 7 and 31.6% respectively. History of ischemic heart disease and surgery under emergency setting were predictors of postoperative complications. Pneumonia, preoperative leukocytosis and Charlson comorbidity score ≥ 9 were predictors of 180-day mortality. The one and two-year survival rate for elective surgery was 69.7 and 54.5% respectively.The outcomes of colorectal cancer surgery for nonagenarians could be favorable in a selected group of patients. Future study on better risk profiling and ways to improve outcomes is warranted. Life expectancy is rising worldwide, and according to statistics from the United Nations in 2015, 0.8% of the populations in developed countries were aged 90 or above . With imColorectal cancer is the leading malignancy in many countries and is especially common in elderly individuals . The decThis study aimed to evaluate the outcomes of colorectal cancer surgery for nonagenarian patients, i.e. patients who were between 90 and 99 years old at the time of surgery, in a tertiary referral center over a 20-year period.This was a retrospective observational study approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority UW 18–229). Between January 1996 and December 2015, all patients who suffered from histologically proven adenocarcinoma of the colon and rectum and underwent surgery were entered into a prospectively maintained database. Patients who were lost to follow-up or had incomplete data were excluded. Patients who were aged 90 or above at the time of surgery were reviewed. All patients received broad spectrum antibiotics on induction, covering common colonic microbes such as gram negative bacilli and anaerobes. Bowel preparation was administered to patients undergoing elective surgery unless the tumor was partially obstructing and as a result patients were unable to tolerate the iso-osmotic bowel cleansing agent. The following baseline demographics were retrieved: ASA score, Eastern Cooperative Oncology Group (ECOG) performance status [–229. Bet2 test where appropriate. Continuous variables were analyzed using the independent sample t-test. All comparisons were two-sided, and a p value of < 0.05 was considered statistically significant. Multivariate analysis was performed to identify the predictors for overall complications, and 30-day and 180-day mortality, using a forward stepwise model. Variables with significant univariate association, defined by a p value of < 0.1, were included in the multivariate analysis. The survival rates of the elective and emergency surgery groups were estimated with the Kaplan-Meier curve. Statistical analysis was performed by SPSS version 20 .Univariate analysis was performed on various clinical parameters. Categorical variables were analyzed using the Fisher exact test and the χDuring the study period, there were a total of 68 patients who were aged 90 or above at the time of surgery. After excluding those with incomplete data, 57 patients were included in the analysis; the majority of them (64.9%) were female. The age of patients ranged from 90 to 101 years, with a median age of 92 years; 42.1, 52.6, and 5.3% of the patients were ASA 2, 3, and 4, respectively  developed postoperative complications, the majority of which was pneumonia (14.0%). Four patients developed respiratory failure requiring tracheostomy after surgery. Four patients (7.0%) developed paralytic ileus, and all resolved with conservative treatment. Five patients (8.8%) suffered from myocardial infarction or arrhythmia. Two patients (3.5%) suffered from urinary tract infections and were managed with antibiotics. One (1.8%) suffered from stroke and was treated with aspirin. Two patients (3.5%) underwent re-operations within the same admission. One of them had anastomotic leakage and intra-abdominal collection after an elective palliative bypass for a cecal tumor. The other developed recurrent inguinal hernia with strangulation after an emergency right hemicolectomy and synchronous bilateral inguinal herniorrhaphy for cancer of the transverse colon; 86% of the patients were discharged home after various period of rehabilitation. The overall complication rates were 24.2 and 50.0% for elective and emergency operations, respectively.Four patients died within the first 30 postoperative days, and three were operated under the emergency setting. The 30-day mortality rate was 3% (1/33) for elective surgery and 12.5% (3/24) for emergency surgery. The overall 30-day mortality rate was 7%, with postoperative pneumonia being the cause of death in all  for elective surgery and 58.3% (14/24) for emergency surgery. The most common cause of death was pneumonia (42.9%), followed by terminal malignancy (21.4%). There were only three more deaths from 6 months to 1 year after surgery, and they were all attributed to terminal malignancy.The 1 and 2-year survival rates for elective surgery were 69.7% (23/33) and 54.5% (18/33), respectively. The 1 and 2-year survival rates for emergency surgery were 54.2% (13/24) and 37.5% (9/24), respectively , history of ischemic heart disease (p = 0.017), colon cancer (p = 0.031), and those who underwent emergency surgery (p = 0.044) were at significantly higher risk of developing complications. ASA 4 (p = 0.002), history of ischemic heart disease (p = 0.031), and emergency surgery (p = 0.059) were also associated with postoperative respiratory complications (data not shown).The factors associated with postoperative complications are shown in Table p = 0.011), CCI score ≥ 9 (p = 0.042), serum albumin level (p = 0.041), pneumonia (p ≤ 0.001), and overall complications (p = 0.012) had a significant association with 30-day mortality. All of these, together with preoperative leukocytosis (p = 0.021) were also associated with 180-day mortality.ASA 4  and a history of ischemic heart disease  were predictors of postoperative complications. Pneumonia , preoperative leukocytosis , and CCI score of ≥9  were independent predictors of 180-day mortality  incidence of pneumonia . These eThis study was a retrospective analysis of patients from a single tertiary center with a relatively small number of patients. One major limitation was that the results were subjected to selection bias. The patients selected for surgery were regarded as having a reasonably good risk. A median follow-up period of 15.9 months was relatively short, but this was related to the limited lifespan of the patients who were senile to begin with. Moreover, only morbidity and mortality information were available, the quality of life and functional outcomes were not reported. Also, the study included a span of 20 years, in which some of the clinical practices had changed. For example, there was an increase in the use of laparoscopic approach since the year 2002, and the adoption of enhanced recovery after the surgery protocol in the year 2007.Advanced age alone should not preclude surgery in patients with colorectal cancer. A comprehensive risk profiling taking into account the co-morbidities, ASA, and CCI score is crucial. Nutritional status should be optimized, and measures should be taken to prevent postoperative pneumonia. A favorable outcome could be achieved in a selected group of nonagenarian patients.


The aim was to assess personalised contrast media (CM) protocols—based on patient’s blood volume (BV) and automated tube voltage selection (ATVS)—in coronary computed tomography angiography (CCTA).rd-generation dual-source CT with 70-120kV (ATVS) and 330mAsqual.ref. CM was adapted to BV, scan time (s) and kV. Image quality (IQ) was assessed in a 17-segment coronary model using attenuation values (HU), contrast-to-noise (CNR), signal-to-noise ratio (SNR) (objective IQ) and a Likert scale (subjective IQ: 1 = poor/2 = sufficient/3 = good/4 = excellent). igA total of 114 consecutive patients received an ECG-triggered or ECG-gated helical scan on a 3Patient distribution was: n = 60 for 70kV, n = 37 80kV and n = 17 90kV. Mean BV was 5.4±0.6L for men and 4.1±0.6L for women. Mean CM volume (300 mg I/mL) and flow rate were: 30.9±6.4mL and 3.3±0.5mL/s (70kV); 40.8±7.1mL and 4.5±0.6mL/s (80kV); 53.6±8.6mL and 5.7±0.6mL/s (90kV). Overall mean HU was >300HU in 98.2% (112/114) of patients. Overall mean attenuation was below 300HU in two scans (70kV) due to late scan timing. Of 1.661 segments, 95.4% was assessable. Mean CNR was 14±4(70kV), 13±3(80kV) and 14±4(90kV); mean SNR was 10±2(both 70kV+80kV) and 9±2(90kV). Objective IQ was comparable between kV settings, protocols and sex. Subjective IQ was diagnostic in all scans and excellent-sufficient in 95.4% of segments.Personalisation of CCTA CM injection protocols to BV and ATVS is a promising technique to tailor CM administration to the individual patient, while maintaining diagnostic IQ. Cardiac diseases are the leading cause of death in the western world . GrowingThe relation between computed tomographic angiography (CTA) and the development of contrast-induced nephropathy (CIN) has recently been a topic of discussion . PatientTo our knowledge, the feasibility of using BV in this context has not previously been investigated. Therefore, the aim of our study is to assess the diagnostic image quality when adjusting CM injection protocols to estimated BV of the individual patient and automated tube voltage selection (ATVS).The personalised injection protocol was incorporated in standard clinical care for patients receiving CCTA. The local ethical committee and institutional review board approved the study design and a waiver of written informed consent was obtained .2).All patients who underwent CCTA between July and October 2016 were eligible for inclusion. Inclusion criteria were: patients over 18 years old and referral for a contrast enhanced CCTA. Exclusion criteria: patients with previous severe adverse reaction to CM , BV, heart rate  and sex) and scan indications were prospectively collected and analysed.rd-generation dual-source CT scanner . Patients received either a prospectively ECG-triggered (‘high-pitch’ or ‘adaptive sequence’ [AS]) CCTA depending on the HR of the patient . The scans were performed with tube voltage settings set by automated tube voltage selection  with 100 kVref.qual, slider position 11 and 330 mAsref.qual . For patients with a pacemaker, a tube voltage of 120 kV was chosen by the technician to avoid artefacts caused by the leads. Slice collimation of 2*192*0.6 mm (high pitch) or 2*160*0.6 mm (AS) was used, 0.25 s rotation time and pitch value 3.2 (high pitch). Test bolus technique was used to determine scan delay. Because of the shorter scan times, especially with the prospective ‘high pitch’ protocol, the chance of missing the bolus increases. When the bolus tracking technique would be used, there is a chance the peak attenuation would be missed. Therefore, the test bolus technique was chosen. Image reconstruction was performed using 0.6 mm slice thickness and an (overlapping) increment of 0.4 mm. A Bv40 kernel (strength 2) was used for high pitch and Bv36 (strength 3) for AS (Advanced Modelled Iterative Reconstruction (ADMIRE), Siemens). Dose monitoring software  was used to record all dose-related parameters. This software automatically calculates the effective (organ) radiation dose (mSv), with help of Monte Carlo simulations, according to the latest guidelines of the International Commission on Radiological Protection .Where necessary, patients were prepared with beta blockade . All patients received sublingual nitro-glycerine . All scans were performed on a 3Iopromide  was pre-warmed (37 ˚C) and administered using a dual-head CT power injector  via an 18–22 gauge intravenous injection catheter in either the left or right antecubital vein. All patients received an injection protocol based on their BV. First, a formula was developed to calculate the hypothetical concentration of contrast media in the blood of the patient :c; mg I/mL), the cardiac output , the volume of CM that remains in the heart , the time of injection  and the patient factor for patient variability (e). This formula was then adapted to achieve an intravascular attenuation of ± 300 Hounsfield units (HU) in the coronary arteries. The known relation of intravascular attenuation (HU) and concentration of CM in the blood  [This formula accounts for the flow rate of the CM injected , the concentration of the CM used (Ionstant) , 17 and onstant)  was usedkvp to ensure safe margins for reaching the diagnostic attenuation. The formula was then rewritten to calculate the flow rate (F) for each individual patient. The modified formula calculates the required flow rate for the individual patient and adjusts for BV and kV setting. With BV = (0.3669*h3) + (0.03219*w) + 0.6041 for men and BV = (0.3561*h3)+ (0.03308*w) + 0.1833 for women (w = BW in kg and h = height in cm):In this formula BV, calculated using the Nadler formula , was choFig 1).The CM volume was then determined with the calculated flow rate (mL/s) and the known scan time (s) of the scan protocols (8 s for high pitch protocol and 10 s for AS protocol). An Excel file was assembled with the formulas to make sure the technicians only had to choose the right protocol and change the patient parameters accordingly . The total iodine load (TIL) injection duration (ID) and IDR were additionally calculated.All relevant CM injection parameters were recorded by CM monitoring software  was used to analyse all CT images with multi-planar reconstructions and axial slices. In the applied workflow protocol (Cardiac) centrelines were automatically drawn in the right coronary artery (RCA), left main (LM), left anterior descending artery (LAD) and circumflex artery (Cx). The 17-segment model of the American Heart Association (AHA) was used to assess the coronary arteries [Dedicated software  by using the 4-point Likert scale: 1 = poor, non-diagnostic image quality: major artefacts and/or low attenuation; 2 = sufficient image quality: minor artefacts and/or insufficient attenuation, however still diagnostic; 3 = good image quality: minimal artefacts and sufficient attenuation; 4 = excellent image quality: no artefacts and sufficient attenuation.2) was used to test differences between groups. Correlations were calculated using Spearmans’ correlation. All p-values were 2-sided and a p-value below 0.05 was considered statistically significant.Statistical analysis of the data was performed using the Statistical Package for Social Sciences . Categorical variables were expressed as absolute numbers and percentages; continuous variables are expressed as mean ± SD. The data was tested for normal distribution. In case of normally distributed data, the independent samples T-test was used to compare means between the different scan protocols. One-way ANOVA was used to compare means between groups. In case of a significant difference, a post hoc Tukey test or non-parametric Kruskal-Wallis test was used to compare means between different kV settings in the two scan protocols. For categorical variables, chi-square (χTable 1).Between July and October 2016, a total of 141 consecutive patients were eligible for inclusion. A total of 114 patients were included in the statistical analysis (48.2% men). A total of 27 patients were excluded from further statistical analysis because group sizes were too small; 3 patients scanned at 100 kV, 9 patients at 120 kV and 15 patients scanned with a retrospective ECG-gated helical protocol. Of the 114 patients, no patient had a CABG in their case history, one patient underwent PCI in the RCA with stent placement. No significant difference was found in most patient characteristics between the two scan protocols, except for age (p = 0.040) and HR (p < 0.001) (Table 1). Table 2 shows all scan parameters for the different scan protocols. Except for mAseff (p = 0.237) in the AS protocol, significant differences were found in all scan parameters  between the different kV settings.In 81 (71.1%) scans, a high pitch protocol was used; an AS protocol was used in 33 (28.9%) scans. ATVS selected 70 kV in 60 (52.6%), 80 kV in 37 (32.5%), and 90 kV in 17 (14.9%) patients . Mean attenuation for men was 369 ± 40 HU for high pitch and 374 ± 42 HU for AS. For women, this was 365 ± 46 HU for high pitch and 343 ± 28 HU for AS. Mean overall CNR was 14 ± 4 (70 kV), 13 ± 3 (80 kV) and 14 ± 4 (90 kV) for the high pitch protocol and 16 ± 4 (70 kV), 17 ± 4 (80 kV) and 18 ± 2 (90 kV) for the AS protocol. No significant difference was found in parameters between the kV settings. When comparing attenuation and CNR levels between men and women for both scan protocols at different kV settings, no significant difference was found. Fig 2 shows the attenuation profile in the RCA for the two scan protocols (high pitch A-C and AS D-F) and different kV settings.Overall mean attenuation of all coronary arteries was diagnostic in 98.2% of all scans (112/114 patients). Mean attenuation for kV settings was 378 ± 48 HU (70 kV), 358 ± 37 HU (80 kV), 360 ± 38 HU (90 kV) for the high pitch protocol and 354 ± 33 HU (70 kV), 375 ± 52 HU (80 kV) and 336 ± 44 HU (90 kV) for the AS protocol  for different kV settings were diagnostic (> 300 HU), except for the scans of two women in the high-pitch group at 70 kV. One scan was regarded as diagnostic (263 HU), the other as non-diagnostic (264 HU). However, no extra scan was made, since the clinical query could be answered.Fig 3C and 3D); 4 scans in both the 70 kV and 80 kV groups, 1 scan in the 90 kV group for the high pitch protocol, and 2 scans in the 70 kV group for the AS protocol. All these scans were considered diagnostic with regard to subjective image quality.CNR levels were below 10 in 11 scans , except for men scanned with the high pitch protocol. No correlation was significant. Correlation between BV and CNR showed slight negative trend for men scanned with the high pitch and AS protocol, as for women scanned with the AS protocol, although no correlation was significant. CNR and BV showed no correlation for women scanned with the high pitch protocol.Correlation between BV and HU for men and women and the two scan protocols showed a negative trend between HU and BV  of these segments were assessable. A total of 4.6% of segments were not assessable due to bolus timing, movement artefacts or small arteries. The segments not assessable most often were the distal segments: segment 4 of the RCA (6.1% of 114 scans), segments 9 and 10 of the LAD (10.5% and 7.9%) and segments 12, 13 and 14 of the Cx . Mean attenuation was ≥ 300 HU in 88.7% of all segments. Segmental attenuation was < 300 HU due to multiple potential causes such as bolus timing, movement artefacts and/or small arteries. A low attenuation was mostly seen in the distal segments: intravascular attenuation was below 300 HU in only 8 proximal segments . However, although the attenuation was below 300 HU in some coronaries, these could still be (adequately) assessed for the presence of plaques by the cardiac radiologist.CNR was below 10 in 10.8% of all segments, 12.9% in the high pitch protocol and 5.6% in the AS protocol. A CNR < 10 was mostly seen in the LAD side branches (segment 9 and 10), the distal Cx and side branch (segment 14 and 15) and the ramus intermedius (segment 17).No scan was overall graded with a non-diagnostic overall subjective image quality. For high pitch, 4 scans were graded with Likert score 2 (4.9%), 29 scans with Likert score 3 (35.8%) and 48 scans with Likert score 4 (59.3%). The AS protocol resulted in 5 scans with Likert score 2 (15.2%), 14 scans with Likert score 3 (42.4%) and 14 scans with Likert score 4 (42.4%). No significant difference in subjective image quality between the high pitch and AS protocol (p = 0.366) was found. Furthermore, no significant difference in subjective image quality between men and women was found for the high pitch protocol (p = 0.828) or AS protocol (p = 0.667).st obtuse marginal Cx) and 14  for the high pitch and segment 10  and 14 for the AS protocol were scored as 1 most frequently. In only 5 segments , 2 in high pitch and 3 in AS, subjective image quality was scored as 1 in the proximal segments due to movement artefacts (3 scans) and a small Cx artery (2 scans). Other reasons for a non-diagnostic subjective image quality were low attenuation, movement artefacts and small arteries. One patient (scanned with a high pitch protocol and 90 kV) had a stent in the RCA (segment 2), this segment was assessable and graded as excellent image quality .A Likert score of 4 was applicable in 44.9% of segments , Likert score 3 in 34.0%  and Likert score 2 in 16.4%  of segments. In all above-mentioned non-assessable segments, subjective image quality was scored as 1 (4.6%). This was mostly seen in the distal and side branch segments. Segments 12 . Segmental intravascular attenuation was ≥ 300 HU in 71.5% of all segments and in 85.7% of proximal segments. Overall diagnostic subjective image quality was reached in all scans and in 95.4% of coronary segments.The use of personalised injection protocols adapted to patient’s BV and ATVS resulted in diagnostic overall intravascular attenuation in 98.2% scans, and in a CNR ≥ 10 in 90.4% scans  showed no significant difference between men and women. Thus, with a lower amount of CM volume , a similar HU and CNR level can be reached in the different kV settings for both men and women. When testing for a correlation between BV and HU and BV and CNR, almost all correlations showed a slightly negative trend. Surprisingly, the correlation between HU and blood volume showed a slight positive trend for men in the AS protocol. The small group sizes have to be taken into account here (13 men in the AS group). With such small group sizes, small differences alter a slope. However, not any of the correlations was significant, and the positive trend can also be seen as a coincidence.The CNR levels . Image quality in CCTA scanning is susceptible to multiple factors. Intravascular attenuation, motion artefacts, vessel diameter and scan parameters are all factors that could influence the image and diagnostic quality of a scan. The 300 HU threshold was no guarantee for an assessable coronary artery, illustrating that setting a definite attenuation threshold for (non-)diagnostic image quality is difficult and up for discussion.The scanner and test bolus would ideally correct for HR to prevent late scan timing. Unfortunately, irregular HR during the scanning process can still result in a suboptimal image quality due ‘missed’ peak attenuation (scanning either too late or too early). It is known that with a decreased CO the intravascular attenuation peak is delayed due to decreased circulation of CM . PerhapsThe individualisation of CM injection protocols is gaining more interest in the overall transition to personalised medicine. Especially in patients with cardiovascular diseases, the concern of development of CIN still exists. Although the relation between CIN and CTA has been called into question , personaFig 1).The current study assessed the feasibility of further adaptation (besides tube voltage) of CM injection protocols to BV. The advantage of adapting CM protocols to BV is that the estimated BV in litres is calculated differently for men and women. Previously, the CM injection protocol was adapted to BW categories in our department . With that method, no distinction between sex or kV setting was made. The intravascular attenuation for different weight groups between men and women showed a wider standard deviation for women, with attenuation values of up to 900 HU. This shows that some women received a CM bolus that was too high for their body habitus. Moreover, borderline patients (patients of e.g. 61 kg or 69 kg) would also receive either too much or too little CM volume. When adapting for BV, a distinction between sex is made and a more continuous measurement is used, therefore this problem should not occur. A continuous adaptation scale of the injection protocols to BW could also be feasible, however a correction for sex of the patient will not be made. Therefore, BV based CM volumes can be considered more patient specific compared to BW. Lastly, the formula used was implemented in a locked Excel file and could easily be adapted and implemented in daily clinical practice for other scanners in other hospitals (This study has some limitations; no direct comparison between the current method and BW adapted protocols could be made, since the BW adapted protocols did not take tube voltage into account. However, this study was a feasibility study and did not focus on a direct comparison. A second limitation is that the sample sizes in the higher kV levels and helical scan protocol were so small, that statistical analysis was not possible. It would be interesting to see if the formula works in the higher kV levels and helical scan protocol as well.To conclude, adaptation of CM injection protocols to the patient’s BV and ATVS in CCTA results in an overall and segmental diagnostic image quality in almost all scans. It is easy to use, making this a promising and feasible technique.