bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two whole-body computer tomography protocols for polytrauma patients
Authors: van Veelen N , Studer S , van de Wall B , Babst R , Link B -C , Knobe M , Beeres F
Published: May 2021

Objective

The use of whole-body computed tomography (CT) is an established standard primary diagnostic method in the work up of polytrauma patients. The protocols used for such CTs however vary between trauma centers. In our Level 1 trauma Centre the protocol was changed from a three phase to a two phase protocol with different positioning of the patient. The primary aim of this study was to compare the estimated radiation dose and scan duration of the two protocols. The secondary aim was to evaluate whether the revision of the CT protocol led to a reduction of required additional imaging of the upper extremities.

Methods

For this retrospective, cross-sectional study two groups of consecutive trauma patients, which were treated in a level 1 trauma center in Switzerland and received a whole-body CT were analyzed. Group A consisted of patients, who presented between January and August 2016. These patients received a three-phased CT in which a repositioning of the arms from the side of the torso to above the head between phases two and three was needed. Group B consisted of those, who presented between January and July 2017. These patients received a CT according to a revised protocol, which was performed in two phases with the arms positioned ventral on a pillow to the torso throughout the entire CT. Scan duration, estimated radiation dose, number of upper extremity injuries, number of addition imaging (xray and CT) of the upper extremities within 24 hours of initial CT.

Results

A total of 182 patients were included in group A and 218 in group B. Baseline characteristics didn't differ, except for there being more males in group B (p 0.006). The estimated radiation dose was lower (15.0 mSv vs 22.9 mSv, p < 0.001) and the scan duration shorter (4 vs 7 minutes, p < 0.001) in group B. No difference could be shown in the number of upper extremity injuries detected. Further, the number of additional images of the upper extremities needed within 24 hours of the initial CT did not differ between the groups.

Conclusion

Both the estimated radiation dose and the scan duration of a whole-body CT scan in trauma patients can be reduced when a two phase protocol in which the arms are positioned on a pillow ventral to the torso is used instead of a three phase protocol with repositioning of the arms. The amount of additional imaging of the upper limb could not be reduced by having the arms visible on the scan.
Stress related growth after severe trauma: Investigating long-term psychiatric outcomes and coping mechanisms 20+ years after injury
Authors: Kalbas Y , Halvachizadeh S , Luidl A T , Zelle B , Pfeifer R , Pape H -C
Published: May 2021

Objective

There is limited research on the long-term psychiatric outcomes of severely injured patients. Those studies existing, focus on the negativ effects like post-traumatic stress disorder, anxiety and depression. Yet, also psychiatric improvements can be noticed in patients after severe trauma, mainly focused on stress related growth. In our study we investigated coping mechanisms in multiply injured patients at least 20 years after trauma.

Methods

631 patients, who suffered a severe injury between 1971 and 1990 were contacted 20 or more years later. All patients were 3 to 60 years of age when injured and were attended to at the same institution. 36 questions inspired by the stress related growth scale (SRGS) and the post-traumatic growth inventory (PGI) were enquired via a questionnaire. Questions touched on 5 specific topics relating to growth: 1) relationships to others, 2) personal strengths, 3) appreciation of life, 4) new possibilities and 5) spiritual change. Each question quantified improvements in specific areas: Possible answers were „None at all“, „some“ and „a great deal“.

Results

A total of 338 patients returned the questionnaire and could be included in our study. Gender distribution was 114 females (33,8%) to 223 males (66,8%). 96,5% of patients reported improvements regarding at least one of the 36 questions. Approximately a third of patients noticed distinct improvements regarding their relationship to others (29,2%) and their appreciation of life (36,2%). Furthermore, 32,5% of patients registered overall positive attitudes towards new possibilities. Referring to spiritual changes, only 20,5% of patients reported positive changes, while 55,7% reported no changes at all. Regarding personal strengths, 23,4% indicated overall positive changes compared with 35% indicating no changes at all.

Statistical analysis showed women to adapt significantly better (p < 0,01) in every aspect besides spiritual changes. Furthermore, we noticed weak positive correlations between positive changes and age at injury (r = 0.26) as well as injury severity (r = 0.152). We saw, however no correlation with general health.

Conclusion

20 years after severe trauma, patients report improvements in their relationship with others, appreciation of life and attitude towards new possibilities. Such coping mechanisms, as results of stress related growth, should be identified and fostered in clinical practice.
ORIF versus nailing for humeral shaft fractures: A meta-analysis and systematic review of randomised clinical trials and observational studies
Authors: van de Wall B , van Veelen N , Babst R , Link B , Knobe M , Beeres F
Published: May 2021

Objective

This meta-analysis aims to compare open reduction and internal fixation with a plate (ORIF) versus nailing for humeral shaft fractures in terms of healing, complications, general quality of life and shoulder/elbow function.

Methods

PubMed/Medline/Embase/CENTRAL/CINAHL was searched for both randomised clinical trials (RCT) and observational studies comparing ORIF with nailing for humeral shaft fractures. Effect estimates were pooled across studies using random effects models and presented as weighted odds ratio (OR) or risk difference (RD) with corresponding 95% confidence interval (95%CI). Subgroup analysis was performed stratified by study design (RCTs and observational studies).

Results

A total of ten RCT's (525 patients) and eighteen observational studies (4906 patients) were included. The effect estimates obtained from observational studies and RCT's were similar in direction and magnitude. More patients treated with nailing required re-intervention (RD: 2%; OR 2.0, 95%CI 1.0 – 3.8) with shoulder impingement being the most predominant indication (17%). Temporary radial nerve palsy secondary to operation occurred less frequently in the nailing group (RD: 2%; OR 0.4, 95% CI 0.3 – 0.6). Notably, all but one of the radial nerve palsies resolved sponta-neously in each groups. Nailing leads to a faster time to union (mean difference: -1.9 weeks, 95%CI -2.9 – -0.9), lower infection rate (RD: 2%; OR: 0.5, 95%CI 0.3 – 0.7) and shorter operation duration (mean difference: -26 minutes, 95%CI -37 – -14). No differences were found regarding non-union, general quality of life, functional shoulder scores, and total upper extremity scores.

Conclusion

Nailing carries a lower risk of infection, postoperative radial nerve palsy, shorter operation duration, and time to union. Absolute differences, however, are small and almost all patients with radial nerve palsy recovered spontaneously. Satisfactory results can be achieved with both treatment modalities and both techniques have their inherent pros and cons.
MIPO vs. nail for extra-articular distal tibia fractures and the effect of intra-operative alignment control
Authors: Bleeker N J , van Veelen N , van de Wall B , Link B -C , Babst R , Knobe M , Beeres F
Published: May 2021

Objective

Definitive treatment of distal extra-articular fractures of the tibia is challenging and both minimal invasive plate osteosynthesis (MIPO) and intramedullary nailing (IMN) are considered feasible surgical modalities with their own implant-specific merits and demerits. This retrospective study was designed to compare MIPO versus IMN in terms of fracture healing, complications, functional and radiological outcomes and to assess the efficacy of intra-operative alignment control in order to reduce the rate of malalignment after definitive fixation of distal extra-articular fractures of the tibia.

Methods

All consecutive adult patients with extra-articular distal meta- or diaphyseal tibia fractures that were treated in a level 1 trauma center in Switzerland between January 2012 and September 2019 either with plating or IMN were included. Outcome measures included fracture healing, complications (infection, malalignment, subsequent sur-geries), functional and radiological outcomes. Intra-operative alignment control encompassed bilateral draping of the lower extremities.

Results

A total of 135 patients were included out of which seventy-two patients (53%) were treated with MIPO and 63 patients (47%) underwent IMN. There was a significantly higher incidence of non-union for fractures treated with an IMN (13 (22%) vs. 4 (6%), p = 0.037). There was no significant difference between both groups in terms of rotational malalignment (4% vs. 9%) and angular malalignment (4% vs. 5%). The incidence of malalignment in both groups was lower than reported in literature. A significantly higher rate of infection was found after MIPO (13% vs. 6%, p = 0.028). No differences were found in subsequent surgeries or functional outcomes.

Conclusion

Both MIPO and IMN are reliable surgical techniques. IMN is associated with higher rates of non-union whereas MIPO results in a higher risk for infection. The incidence of malalignment was surprisingly low endorsing the utility of the intra-operative alignment control.
Cement augmentation for trochanteric femur fractures: A meta-analysis and systematic review of randomized clinical trials and observational studies
Authors: Rompen I F , Knobe M , Link B -C , Beeres F J P , Baumgärtner R , Diwersi N , Migliorini F , Nebelung S , Babst R , van de Wall B J M
Published: May 2021

Objective

To date, it is unclear what the clinical benefit of cement augmentation in fixation for trochanteric fractures is. The aim of this meta-analysis is to compare cement augmentation to no augmentation in fixation of trochanteric femur fractures in the elderly patients (>65 years) following low energy trauma.

Methods

PubMed/Medline/Embase/CENTRAL/CINAHL were searched for both randomized clinical trials (RCT) and observational studies comparing both treatments. Effect estimates were pooled across studies using random effects models. Subgroup analysis was performed stratified by study design (RCTs and observational studies). The primary outcome is overall complication rate. Secondary outcomes include re-operation rate, mortality, operation duration, hospital stay, general quality of life, radiologic measures and functional hip scores.

Results

A total of four RCT's (437 patients) and three observational studies (293 patients) were included. The effect estimates of RCTs were equal to those obtained from observational studies. Cement augmentation has a significantly lower overall complication rate (28.3% versus 47.2%) with an odds ratio (OR) of 0.3 (95%CI 0.1-0.7). The occurrence of device/fracture related complications was the largest contributing factor to this higher overall complication rate in the non-augmented group (19.9% versus 6.0%, OR 0.2, 95%CI 0.1-0.6). Cement augmentation also carries a lower risk for re-interventions (OR 0.2, 95%CI 0.1- 0.7) and shortens the hospital stay with 2 days (95%CI -2.2 to -0.5 days). The mean operation time was 7 minutes longer in the augmented group (95%CI 1.3-12.9). Radiological scores (lag screw/blade sliding mean difference -3.1mm, 95%CI -4.6 to -1.7, varus deviation mean difference -6.15°, 95%CI; -7.4 to -4.9) and functional scores (standardized mean difference 0.31, 95%CI 0.0-0.6) were in favor of cement augmentation. Mortality was equal in both groups (OR 0.7, 95%CI 0.4-1.3) and cement related complications were rare.

Conclusion

Cement augmentation in fixation of trochanteric femoral fractures leads to fewer complications, re-operations and shorter hospital stay at the expense of a slightly longer operation duration. Cementation related complications occur rarely and mortality is equal between treatment groups. Based on these results, cement augmentation should be considered for trochanteric fractures in elderly patients.
Multicenter observational study of the gore excluder conformable endograft for endovascular abdominal aortic repair: Initial results
Authors: Roesti A , Isaak A , Gemayel G , Mujagic E , Briner L , Wolff T , Deslarzes-Dubuis C , Corpataux J -M , Déglise S
Published: May 2021

Objective

Endovascular repair (EVAR) has become the standard of care for treatment of abdominal aortic aneurysms. However, a significant number of EVAR remains outside the IFU, especially in cases of severe proximal angulation (>60 degrees), resulting in failure. The new device GORE EXCLUDER Conformable AAA Endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz) has been designed to accommodate neck angulation, due to conformability and angulation control. The aim of this multicenter study is to report the initial results of this device.

Methods

From March 2019 to January 2021, the data of all consecutive patients with AAA treated with the Gore Excluder Conformable endograft at 4 vascular centers were reviewed. Patients were followed using a standardized protocol, with CT-scan at 1, 6 and 12 months, and then yearly. The primary endpoint was technical success and secondary outcomes were postoperative morbidity, rate of endoleak (EL) and any aneurysm-related re-interventions during follow-up.

Results

Among the 32 patients included, most were men with a mean age of 77 years old (range 60-92). Half of patients were smokers and 72% had hypertension. The mean diameter of AAA was 62 mm (47-90). The mean length of aortic neck was 26 mm (10-69), the mean diameter 23 mm (16-31) and the median neck angulation was 81 degrees (range 40-110). The mean procedural duration was 102 min (54-153) with a mean time of scopy of 24 min (8-47) and a total volume of contrast of 101 ml (40-165). Thirteen iliac branch device have been used in 7 patients. The technical success was 97% with 1 type Ia EL (3%). In the post-operative period, 4 medical and 3 surgical complications were observed. Two reinterventions were needed with an iliac stenting for a stenosis and a correction of a femoral false aneurysm. During the mean follow-up of 7 months, 2 type Ia ELs were observed. One spontaneously resolved and the other one was followed. One distal limb extension was succesfully implanted at 3 months for a type Ib EL for a total rate of reintervention of 9%. No migration was observed. No death occured.

Conclusion

The use of the Gore Excluder Conformable endograft seems to be safe and effective in difficult anatomies and especially high angulation. It allows for precise deployment without the need for additional contrast or operation time. Longer follow-up and more patients are required to confirm these excellent initials results.
Outcome after cervical debranching for proximal landing zone extension in thoracic endovascular aortic repair
Authors: Makaloski V , Lutz E , Bühlmann R , Weiss S , Schmidli J
Published: May 2021

Objective

Aim of this study was to assess perioperative and long-term outcome after cervical debranching for proximal landing zone extension in thoracic endovascular aortic repair (TEVAR).

Methods

Retrospective analysis of all patients undergoing left-sided carotid-subclavian bypass (CSB) and subclavian-carotid transposition (SCT) with simultaneous or staged TEVAR between 2010 and 2019. Endpoints were patency and re-intervention due to the debranching, postoperative stroke, cranial nerve injury and mortality at 30 days and during follow-up.

Results

Forty-eight patients (66 ± 12 years, 81 % male) had 25 (52%) CSB and 23 (48%) SCT. TEVAR was performed simultaneously in 39 (81%). Eleven (23%) patients had simultaneous emergency debranching and TEVAR. There were eight (17%) re-interventions within 30 days: four due to local hematoma, one for bypass occlusion, two for stenosis (of which one was not confirmed intraoperatively), and one after initially abandoned SCT with subsequent CSB on the next day. Thirty-day mortality was 2 %; one patient died on the first postoperative day after combined CABG surgery and multiorgan failure. Four (8%) patients suffered postoperative strokes; three occurred after simultaneous emergency procedures and none was fatal. Seven (15%) patients had postoperative ipsilateral cranial nerve lesions: two occurred after CSB and five after SCT. Two patients had recurrent laryngeal nerve palsy, two had phrenic nerve injury and three had Horner syndrome. All patients had mild symptoms and recovered mostly.

During a mean follow-up of 31±29 months with a Follow-up Index of 0.77, there were no reinterventions or occlusions, and no graft infections. Primary patency was 94%, primary assisted patency 96%, and secondary patency 100%. 9 patients died during follow-up after a mean of 30±29 months (range 0-82) all of them with patent cervical debranching.

Conclusion

Cervical debranching for proximal landing zone extension in TEVAR is a safe procedure with an acceptable rate of early re-interventions. There is a higher risk for postoperative stroke during simultaneous emergency debranching and TEVAR. Cranial nerve injuries and hematomas remain relevant periprocedural complications. During follow-up, excellent patency can be expected.
Management of malignant pleural effusion. A retrospective study comparing efficiency and outcomes of VATS talcum pleurodesis, insertion of tunneled pleural catheter (PleurX®), and a combination of both
Authors: Figueiredo L F Azenha , Deckarm S , Kocher G
Published: May 2021

Objective

The management of malignant pleural effusion is a common problem in thoracic surgery. Patients are often polymorbid and are usually referred at a terminal stage of their oncological disease. Our objective was to compare the efficiency and outcomes after different treatment strategies of malignant pleural effusion.

Methods

We retrospectively reviewed the charts of a total of 416 patients treated during the period of 2010 to 2020 who underwent thoracoscopic pleurodesis with or without implantation of tunneled pleural catheter (TPC) as well as patients who underwent the implantation of TPC alone. Primary outcome was postoperative survival and secondary outcome was length of stay (LOS). In addition, we documented the recurrence of ipsilateral pleural effusion and the need for reintervention as well as the pulmonary reexpansion of the lung on postoperative chest x-ray. Inclusion criteria were malignant pleural effusion and documented follow-up until time of death. Exclusion criteria were treatment for mesothelioma, pneumothorax and emphysema.

Results

A total of 199 patients were included for analysis. Median LOS of patients treated with implantation of TPC alone in analgosedation (n = 28) was 1 day (range:1-4 days). Median LOS of patients who received video-assisted talcum pleurodesis (n = 65) without implantation of a TPC was 6 days (range 1-38 days). Median LOS of patients who received VATS talcum pleurodesis and TPC (n = 106) was 3 days (range 1-34 day). The difference in LOS was statistically significant (p < 0.05). Median overall survival was 108 days (range 3-3001 days). There was no statistically significant difference in survival between the different treatment groups (p = 0.47).

Conclusion

The primary goal when treating patients with malignant pleural effusion is relief of dyspnea and/or pain and to keep the duration of the inpatient treatment to a minimum. In patients with a considerable surgical risk due to comorbidities and their underlying oncological disease and who don’t require the sampling of histological material, a conservative treatment option with implantation of a TPC can be sufficient. The additional insertion of a TPC not only reduces the length of stay, but also has a positive effect on the efficacy of the pleurodesis in terms of less recurrence. We therefore recommend the routine use of TPC when performing VATS talcum pleurodesis in patients with malignant pleural effusion.
Ex vivo analysis of graft viability using 31P magnetic resonance imaging spectroscopy
Authors: Longchamp A , Klauser A , Agius T , Songeon J , Nastasi A , Ruttiman R , Meier R P H , Buhler L , Allagnat F , Corpataux J -M , Lazeyras F
Published: May 2021

Objective

Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]) in order to face the chronic shortage of kidneys for transplantation. However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable non-invasive means to determine kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. However, the reliability of pMRI to predict kidney energy state, and its viability before transplantation remain also unknown.

Methods

To mimic DCD, pig kidneys underwent 0, 30 min or 60 min of warm ischemia, before oxygenated hypothermic machine perfusion (HMP). During the ex vivo perfusion, we assessed energy metabolites and Gadolinium elimination using pMRI. Each sample underwent histopathological scoring.

Results

Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury.

Conclusion

ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft viability and patient's survival.
Optimal liver metabolism and proliferation require the tight junction protein claudin-3
Authors: Baier F A , Sanchez-Taltavull D , Gómez Castellà C , Jebbawi F , Keogh A , Dias M , Deutsch U , Engelhardt B , Furuse M , Odriozola A , Zuber B , Odermatt2 A , Candinas D , Stroka D
Published: May 2021

Objective

The expression of hepatic tight junction proteins and their contribution to homeostasis and regeneration remained largely unexplored. Here, we determine the cell type specific expression of tight junction genes in murine livers. We further explore the regulation and functional importance of the transmembrane protein CLDN3 in normal and regenerating livers.

Methods

Murine livers were used for tissue- and single cell RNA-seq. CLDN3 localization was determined by immunofluorescence. CLDN3+/+ or CLDN3-/- livers were analysed by electron microscopy, fluorescence-activated cell sorting and liquid chromatography mass spectrometry. Lipid content was quantified with oil-red. Mice were subjected to 2/3 partial hepatectomy. Proliferation was quantified with Ki67 and pHH3 stainings. Cell cycle gene expression was determined by RT-qPCR. Barrier impairments were assessed with total bile acid measurements. Differential gene expression was analysed by tissue RNAseq with DESeq2.

Results

We determined the profile of tight junction gene expression the main liver cell types, showing that tight junction transcripts can be found in hepatocytes and cholangiocytes but also on non-parenchymal cell populations. CLDN3 was among the highly expressed- and regulated genes in native and regenerating livers. CLDN3 had a zonated expression pattern. CLDN3-/- mice had microscopically intact tight junctions, but showed significantly downregulated hepatic energy metabolism and suboptimal cell proliferation in the regeneration model.

Conclusion

Our data suggests a functional role of CLDN3 for maintenance of energy homeostasis and optimal regeneration, proving that the function of hepatic tight junction proteins extends beyond basic membrane sealing.
Intrapleural hyperthermic chemotherapy induces pro-immunogenic e-selectin expression in the vasculature of malignant pleural mesothelioma
Authors: Hao Y , Chriqui L -E , Gattlen C , Gonzalez M , Krueger T , Krueger T , Dyson P , Cavin S , Perentes J
Published: May 2021

Objective

Malignant pleural mesothelioma (MPM) is a deadly disease with dismal prognosis. Prior studies combining surgery with intrapleural hyperthermic chemotherapy (IPHC) have shown improved survivals in selected patients with MPM. However, the mechanisms by which IPHC acts on MPM and its microenvironment remains unknown. Here we focus on tumor endothelial adhesion molecule expression patterns.

Methods

First, we determined the impact of IPHC on MPM tumor and vascular compartments in vitro using a novel bioincubater for hyperthermic cell culture. The cytotoxicity of normo (37 °C) / hyperthermic (42 °C for 60 minutes) cisplatin/carboplatin therapies were evaluated on four MPM (MSTO211H, H-Meso, AE17 and AB12) and one endothelial (EC-RF24) cell lines at a minimum of 24 hours using a presto-blue assay. Second, we treated endothelial cells with IPHC (60 min, 42 °C at optimized cytotoxic concentrations) and determined its impact on pro-immunogenic adhesion molecule (E-selectin, VE-cadherin, VCAM and Connexin-43) expression at 24 hours by Western blot.

Results

Tumor and endothelial cell viability decreased with increasing doses of both chemotherapeutics but was not affected by hyperthermia (IC50 with or without hyperthermia of each cell line at 24 hours reported in Figure 1A). Interestingly, endothelial cell line IC50 was much higher than that of MPM tumor cells for both chemotherapeutics (Figure 1A). Pro-immunogenic adhesion molecule E-Selectin was increased at 24 hours by IPHC with both chemotherapeutics while VE-Cadherin, VCAM and Connexin-43 were not affected (Figure 1B).

Conclusion

Hyperthermia adds no cytotoxicity to intrapleural chemotherapy. However, IPHC favors pro-immunogenic endothelial E-selectin expression. The latter could help induce patient immunity against their MPM and improve survival. Confirmation of these findings in vivo is mandatory.
Outcome measurement in trauma surgery with a fracture database and clinical and patient-reported outcome measures (PROMs)
Authors: Bilici M , Morgenstern M , Frank C , Alispahic N , Müller A , Sauermann M , Eckardt H , Rikli D
Published: May 2021

Objective

Patient-Reported Outcome Measures (PROMs) gain growing attention. The Food and Drug Administration suggested in 2009 to have PROMs for every new treatment and technology. The use of PROMs was further promoted by the Patient Protection and Affordable Care Act of 2010 in the USA. Recommendations from other national and international organizations include the OECD's Project of Patient-Reported Indicator Surveys (PaRIS) and the International Consortium for Health Outcomes Measurement (ICHOM). Our development and initiation of a Fracture Database started early in 2018. We orientated our database on the role model of the Swedish Fracture Registry.

Methods

REDCap (Research Electronic Data Capture) is a web interface for a SQL (Structured Query Language)-Database. We used it to program the Fracture Registry. We collect data about demographics, diagnosis, treatment, adverse events, clinical outcomes, and PROMs. The PROMS are recorded with the Software 'Heartbeat ONE' vs. 6.15.4. Inclusion criteria are all patients with fractures of the upper and lower extremity, including the pelvis and multiple injuries, treated surgically. Excluded are all patients with fractures of the hand as monotrauma and non-surgical treatment. We established questionnaire sets for each anatomical region. Every hospitalized patient is screened for inclusion criteria to get the baseline PROMs. Follow-up PROMs are collected at 3-months and 12-months in our outpatient clinic.

Results

In five months of collecting PROMs, we have evaluated 599 patients, 521 fulfilling the inclusion criteria. 329 (63%) questionnaire sets were completed. The mean time for answering the questions was 11-20 minutes. The input rate of 63% for PROMs accounts for the start of the process, with 22 (4%) patients being dismissed before answering the questionnaires. 93 (18%) patients denied participation. 52 (10%) patients were not able to participate (dementia, delirium). Other causes for missing data were language barriers (n = 28; 5%), medical reasons like polytraumatized patients (n = 4; 0.8%), and deceased patients (n = 15; 2.9%).

Conclusion

Most Orthopaedic Trauma centers publish data about PROMs from surgically treated patients. Starting in the first quarter of 2021, we will include non-surgically treated patients. We have optimized the process of including patients. Our aim is a response rate of more than 80% within this year to get representing data.
Impact of autism genetic risk on brain connectivity: a mechanism for the female protective effect
Authors: Lawrence Katherine E , Hernandez Leanna M , Fuster Emily , Padgaonkar Namita T , Patterson Genevieve , Jung Jiwon , Okada Nana J , Lowe Jennifer K , Hoekstra Jackson N , Jack Allison , Aylward Elizabeth , Gaab Nadine , Van Horn John D , Bernier Raphael A , McPartland James C , Webb Sara J , Pelphrey Kevin A , Green Shulamite A , Bookheimer Susan Y , Geschwind Daniel H , Dapretto Mirella ,   GENDAAR Consortium, Aylward Elizabeth , Bernier Raphael A , Bookheimer Susan Y , Dapretto Mirella , Gaab Nadine , Geschwind Daniel H , Jack Allison , McPartland James C , Nelson Charles A , Pelphrey Kevin A , Van Horn John D , Webb Sara J , Ankenman Katy , Corrigan Sarah , Depedro-Mercier Dianna , Guilford Desiree , Gupta Abha R , Jacokes Zachary , Jeste Shafali , Keifer Cara M , Libsack Erin , Lowe Jennifer K , Kresse Anna , MacDonnell Erin , McDonald Nicole , Naples Adam , Neuhaus Emily , Sullivan Catherine A W , Tsapelas Heidi , Torgerson Carinna M , Ventola Pamela , Welker Olivia , Wolf Julie
Published: May 2021

The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains.

To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8–17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder.

The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls.

These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.
Aberrant Claustrum Microstructure in Humans after Premature Birth
Authors: Hedderich Dennis M , Menegaux Aurore , Li Hongwei , Schmitz-Koep Benita , Stämpfli Philipp , Bäuml Josef G , Berndt Maria T , Bäuerlein Felix J B , Grothe Michel J , Dyrba Martin , Avram Mihai , Boecker Henning , Daamen Marcel , Zimmer Claus , Bartmann Peter , Wolke Dieter , Sorg Christian
Published: May 2021

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum’s development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons.

Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ.

This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.
DOP17 In high-risk Crohn’s Disease patients, anastomosis configuration types have similar rates of endoscopic recurrence
Authors: Bachour S , Shah R , Lyu R , Rieder F , Cohen B , Qazi T , Lashner B , Lipman J , Regueiro M , Lightner A , Holubar S , Click B
Published: May 2021

Background

There is conflicting data on the influence of surgical anastomosis configuration on endoscopic postoperative recurrence (POR) of Crohn’s disease (CD) following ileocolonic resection (ICR). Furthermore, whether this relationship differs by preoperative risk factors for POR has not been studied. We aimed to assess the role of ileocolonic anastomosis type on the rate and time to POR by preoperative POR risk.

Methods

Retrospective cohort study of adult CD patients who underwent ICR between 2009–2020 at a quaternary IBD referral center. Patients with a primary or secondary anastomosis and ≥1 postoperative colonoscopy were included. Endoscopic activity was assessed by modified Rutgeerts’ scoring. POR was defined as Rutgeerts’ ≥ i2b. Patients were categorized by anastomosis type: end-to-end (ETE), end-to-side (ETS), or side-to-side (STS). High-risk CD patients were defined by ≥1: age ≤ 30 years, active smoker, or ≥2 ICR for penetrating disease.

Results

548 CD patients (52.6% female, age 35 y, 15.5% > 1 prior ICR, 19.7% on biologic prophylaxis, 74.8% high-risk for POR) were included in the study (Figure 1). The majority received a STS (52.0%, N=285), 27.2% ETS, and 20.8% ETE. Patients with an ETE were diagnosed with CD at a younger age (p=0.04), had more penetrating disease (p=0.01), hand-sewn anastomoses (p <0.001), and diverting loop ileostomies (p=0.02). There were no differences in prior ICR, smoking, biologic prophylaxis, or in median time from ICR to first post-operative colonoscopy (388.5 days, p=0.41) or POR detection (905 days, p=0.8) by anastomosis type. ETS patients had a shorter median follow-up time (3.9 y, p=0.02). The majority (55.7%) of all patients experienced POR (57% ETS; 55.4% STS; 54.4% ETE). Overall, there was no significant association between anastomosis type and POR rate (p=0.91) or time to POR (p=0.32). However, in high-risk CD patients, ETS was significantly associated with more rapid time to POR on log-rank (p=0.03) and multivariable Cox modeling (HR=1.51; p=0.04). Postoperative prophylactic biologic therapy initiated within 3 months of ICR significantly delayed POR in the overall cohort (HR=0.64; p=0.012) and the high-risk CD subgroup (HR=0.67; p=0.047). High-risk CD patients on prophylactic biologics had no difference in time to POR by anastomosis type (p=0.66).

Conclusion

In post-operative CD patients, there is no difference in rates of endoscopic recurrence by anastomosis configuration regardless of risk stratification. In high-risk patients, ETS was associated with more rapid endoscopic recurrence compared to other configurations, however prophylactic postoperative biologics may protect against this effect.

Figure 2: KM Survival analysis of time (days) to POR
DOP20 Genetic of vitamin D as predictor of response to adalimumab in Crohn’s Disease
Authors: Cusato J , Ribaldone D G , Bertani L , Antonucci M , Tomasello C , Caviglia G P , Dibetto S , Mangia M , Astegiano M , D’Avolio A
Published: May 2021

Background

Personalised medicine is the direction towards are converging many efforts of experts in inflammatory bowel diseases (IBDs). The advent of biological drugs, with anti-TNF as first category, have revolutionized the managements of these patients. Unfortunately, several unmet needs are present, like an efficacy in about two third of the patients, onset of side effects like infections, paradoxical IMIDs. Being able to treat with these drugs only patients who will respond would avoid losing time without disease improvement and possible side effects.

Vitamin D is important for several biological functions, such as regulation of the immune response and modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. Vitamin D is activated by cytochrome (CYP) 27B1, inactivated by CYP24A1, transported in kidney by Vitamin D binding protein (VDBP, encoded by GC gene) and carries out its activities through its receptor (VDR).

No data are available concerning vitamin D genetics and response to anti-TNF drug adalimumab.

The aim of this study was to describe the relationship between vitamin D pathway-related gene single nucleotide polymorphisms (SNPs) and adalimumab clinical outcome in a cohort of patients affected by Crohn’s disease.

Methods

We performed a multi-centre prospective study including patients affected by Crohn’s disease who started adalimumab therapy. SNPs in CYP27B1, CYP24A1, GC and VDR genes were analysed. Clinical outcome was considered as clinical response and remission at 3 months of therapy.

Results

We enrolled 69 patients. Median age was 40 (IQR 31–56) years, males were 40 (58%). Median basal calprotectin was 396 (IQR 188–851) mg/Kg, and 36 (53.7%) had a positive PCR value.

We documented the following associations: CYP27B1 + 2838 CT/TT with perianal disease (p= 0.002), basal calprotectin (p= 0.018) and T3 calprotectin (p= 0.035), figure 1; CYP27B1-1260 GT/TT with perianal disease (p= 0.006), basal calprotectin (p= 0.036) and T3 calprotectin (p= 0.024); VDR ApaI CA/AA with basal calprotectin (p= 0.014) and T3 calprotectin (p= 0.036); VDR BsmI GA/AA with perianal disease (p= 0.036), and GC 1296 TG/GG with basal calprotectin (p= 0.014), figure 2.

GC 1296 TG/GG genotype polymorphism (p= 0.044, figure 3) predicted clinical remission at multivariate analysis.

Finally, median concentrations adalimumab trough levels at 3 months were 7.4 (IQR 5.5; 11.7) ug/mL. CYP24A1 3999 (p=0.025) and VDR TaqI (p=0.016) SNPs affected these levels.

Conclusion

This is the first study reporting the association between vitamin D pathway-related genetics and adalimumab treatment in a cohort of patients affected by IBD. Further studies in different and larger cohorts are needed to clarify these aspects.
DOP41 Temporal Trends in the epidemiology of Inflammatory Bowel Diseases in the public healthcare system in Brazil: A large population-based study
Authors: Quaresma A B , Damiao A O M C , Coy C S R , Magro D O , Valverde D A , Panaccione R , Coward S B , Ng S C , Kaplan G G , Kotze P G
Published: May 2021

Background

Background: Population-based data on incidence and prevalence of Inflammatory Bowel Diseases (IBD) in newly industrialized countries such as Brazil are scarce. This study aims to define temporal trends of estimated incidence and prevalence rates of Crohn’s disease (CD) and ulcerative colitis (UC) in Brazil using unique public healthcare datasets.

Methods

Methods: All IBD patients (UC and CD) from the unique public healthcare national system (DATASUS) were included from January 2012 to December 2020 and identified according to ICD codes, medication use or IBD-relates procedures. Data extraction was performed with the platform “TT Disease Explorer” (Techtrials Healthcare Data Science, Brazil) and checked by 2 independent reviewers. The platform collects publicly available data from the ministry of health via electronic algorithms (ETLs and Webcrawlers) with automatic updates. The population of Brazil was calculated according to the national Brazilian Geographics and Statistics Institute (IBGE). Average Annual Percent Change (AAPC) and 95% confidence intervals (CI) were calculated using poisson (or negative binomial) regression for incidence and log binomial regression for prevalence.

Results

Results: A total of 212,026 IBD patients (UC: n=140,705; CD: n=92,326) were included, There was a higher proportion of females as opposed to males, and age at health system entry was similar to developed countries (figure 1). Estimated incidence rates of IBD were 9.41 per 100,000 in 2012 and 9.57 per 100,000 in 2020 (AAPC=0.80%; CI -0.37–1.99; p=0.18); for UC, incidence increased from 5.69 per 100,000 to 6.89 per 100,000 (AAPC=3.04; CI 1.51–4.58; p<0.001) and for CD incidence dropped from 3.71 per 100,000 to 2.68 per 100,000 (AAPC=-3.24%; CI -4.45- -2.02; p<0.001) in the same time period (figure 2). Estimated prevalence rates of IBD increased significantly from 30.01 per 100,000 in 2012 to 100.13 per 100,000 in 2020 (AAPC=14.87%; CI 14.78–14.95; p<0.001); For UC, from 17.4 per 100,000 to 66.45 per 100,000 (AAPC=16.51%; CI 16.41–16.62; p<0.001) and for CD from 14.24 per 100,000 to 43.6 per 100,000 (AAPC=13.49%; CI13.37-13.61; p<0.001) in the same time period (figure 3).

Conclusion

Conclusions: Estimated incidence rates of IBD have remained stable from 2012–2020. Incidence of CD is significantly decreasing whereas of UC is significantly increasing. There was a significant increase in estimated prevalence rates of CD and UC. This massive rise in prevalence can support planning for future strategies for public healthcare providers in our country towards better IBD care. This is the largest IBD epidemiological study from newly industrialized countries to date.
DOP66 The effect of exclusive enteral nutrition on circulating inflammatory protein levels in paediatric patients with Crohn’s Disease
Authors: Pidoux M , Logan M , Milling S , Ijaz U Z , Hansen R , Russell R K , Gerasimidis K
Published: May 2021

Background

Exclusive enteral nutrition (EEN) is the recommended first line treatment for active paediatric Crohn’s disease (CD). The mechanism of action and immunological effects of EEN remain unclear. This study compared circulating inflammatory proteins of patients with CD and ulcerative colitis (UC) with non-inflammatory bowel disease (non-IBD) controls and explored the effect of EEN in children with active CD.

Methods

Patients with CD were treated with EEN for 8 weeks, with plasma samples collected prior to EEN start and upon EEN completion. Levels of 92 inflammatory proteins were quantified using Olink Inflammation panel. Paired faecal samples were collected to measure faecal calprotectin (FC) levels by ELISA. Patients in which FC decreased >50% during EEN were classed as FC responders; whereas patients who had a <50% decrease in FC were classed as FC non-responders.

Results

84 patients were recruited (CD:54, UC:11, non-IBD:19). Paired plasma samples were collected from 18 patients with CD receiving EEN. Of these 18 patients, 72% achieved clinical remission by the end of EEN (wPCDAI <12.5 points).

Prior to EEN start, 29 proteins were significantly different between patients with CD compared to non-IBD; and 25 proteins were significantly different between UC and non-IBD, Fig 1. EEN lead to the significant alteration of 23 proteins. This included 5 proteins, CCL23, CXCL10, IL6, IL24, and MMP-1 which were higher in patients with CD prior to EEN start compared to non-IBD, Fig 2.

In patients who achieved clinical remission during EEN, 22 proteins significantly changed from their EEN start levels by the end of EEN, Fig 3. FC responders had a similar pattern of protein changes, in which 22 proteins changed significantly during EEN, Fig 4. 16/22 (72%) of the proteins that changed significantly in the FC responder group during EEN, also changed during EEN in patients who entered clinical remission including significant reductions in several innate immune proteins such as IL-6 and IL-18.

Patients who did not achieve clinical remission did not have significant reductions in these proteins. Despite being higher in patients with CD prior to treatment compared to non-IBD, the level of 17 proteins, including IL17a and oncostatin M, did not change in FC responders during EEN.

Conclusion

EEN leads to alteration of multiple inflammatory proteins, in keeping with a reduction in innate immune pro-inflammatory activity and improvement in clinical response, although some inflammatory proteins remain elevated.

Figure 1: Venn diagram of proteins significantly different

Figure 2: Effect of EEN on protein levels

Figure 3: Effect of EEN on protein levels, stratified based on clinical response during EEN

Figure 4: Effect of EEN on protein levels, stratified based on FC response
DOP67 Comparison of the pharmacokinetics of CT-P13 between Crohn’s Disease and Ulcerative Colitis in biologic-naïve patients; a prospective multi-center observational study of the KASID
Authors: Kim E S , Park D I , Kim H J , Lee Y J , Koo J S , Kim E S , Yoon H , Lee J H , Kim J W , Shin S J , Kim H W , Kim H S , Park Y S , Kim Y S , Kim T O , Lee J , Choi C H , Han D S , Chun J , Kim H S
Published: May 2021

Background

We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes.

Methods

This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose.

Results

267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p<0.001) and clinical response (75.6% vs. 47.5%, p<0.001) at 54-week were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to 14-week (2-week, 19 vs. 15, p<0.001; 6-week, 13 vs. 9, p<0.001; 14-week, 3 vs. 2, p=0.001, Fig 1). The median ADA level (AU/mL) was significantly lower in CD than in UC at 2-week (6 vs. 7, p=0.046), 30-week (8 vs. 12, p=0.007) and 54-week (9 vs. 12, p=0.032, Fig 1). The difference in drug and ADA levels between CD and UC remained significant after adjustment for confounders in repeated measures analysis. Cox proportional hazard analysis showed that CD over UC (adjusted hazard ratio (aHR) 0.78, 95% confidence interval (CI) 0.62–0.95, p=0.016, Fig 2) and no immunomodulator (aHR 1.55, 95% CI 1.07–2.25, p=0.02) were independent risk factors for the development of ADA. The development of ADA at 2-week (adjusted odds ratio (aOR) 0.12, 95% CI 0.03–0.6, p=0.009) and CD over UC (aOR 1.85, 95% CI 1.33–2.56, p=0.0002) were independent predictors of clinical remission at 54-week.

Conclusion

CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.