Anatomical risk factors for aseptic loosening of full hinge knee prosthesis in primary and revision TKAs.

INTRODUCTION: Risk factors (RF) associated with aseptic loosening (AL) in total knee arthroplasty (TKA) are poorly understood. Therefore, the aim of this study was to investigate the anatomical shape variations in relation to the inner-diameter of the femur and the tibia as prognostic RF for AL of full hinge prosthesis (FHP) in primary and revision TKA. MATERIALS AND METHODS: We retrospectively examined all patients, who underwent revision surgery (2003-2018) due to AL of the FHP in primary (n = 38) and revision TKA (n = 46). Diagnosis-appropriate controls without AL at minimum follow-up of 24 months were randomly collected for each group. Besides other risk factors, we also measured the inner diameter of the femur according to the Citak classification and of the tibia on anteroposterior radiographies. RESULTS: RF for AL are younger age in primary and revision as well as > 1 previous surgeries in revision TKA. The femoral index was shown to be a RF for AL in revision TKA (p = 0.001), but not in primary TKA. The novel tibial index was associated with AL in primary with AUC 0.776 (95% CI 0.67, 0.88), 65.8% sensitivity, 86.6% specificity and in revision TKA with AUC 0.817 (95% CI 0.73, 0.91), 82.6% sensitivity and 71.7% specificity. CONCLUSION: This is the first study to calculate the tibial measurements and the tibial index according to Citak et al. and to identify them as prognostic RF for AL of the full hinge knee prosthesis in TKA and confirm the femoral index as a RF for AL also in revision full hinge knee prosthesis. Therefore, the preoperative radiological evaluation should include the analysis of the anatomical shape variants in order to select the appropriate prosthesis design with a possibly enhanced prognosis.

Impact of preoperative body mass index and weight loss on morbidity and mortality following colorectal cancer-a retrospective cohort study.

PURPOSE: Body weight and preoperative weight loss (WL) are controversially discussed as risk factors for postoperative morbidity and mortality in colorectal cancer surgery. The objective of this study is to determine whether body mass index (BMI) or WL is associated with a higher postoperative complication rate. METHODS: In this retrospective cohort study, data analysis of 1241 consecutive patients undergoing colorectal cancer surgery in an 11-year period was performed. The main outcome measures were wound infections (WI), anastomotic leakages (AL), and in-house mortality. RESULTS: A total of 697 (56%) patients with colon and 544 (44%) with rectum carcinoma underwent surgery. The rate of WI for each location increased with rising BMI. The threshold value was 28.8 kg/m2. Obese patients developed significantly more WI than normal-weight patients did following rectal resection (18.0% vs. 8.2%, p = 0.018). Patients with preoperative WL developed significantly more AL following colon resections than did patients without preoperative WL (6.2% vs. 2.5%, p = 0.046). In-house mortality was significantly higher in obese patients following colon resections than in overweight patients (4.3% vs. 0.4%, p = 0.012). Regression analysis with reference to postoperative in-house mortality revealed neither increased BMI nor WL as an independent risk factor. CONCLUSIONS: Increased preoperative BMI is associated with a higher WI rate. AL rate after colon resection was significantly higher in patients showing preoperative WL. Preoperative BMI and WL are therefore risk factors for postoperative morbidity in this study. Nevertheless, this has to be further clarified by means of prospective studies. Trial registration DRKS00025359, 21.05.2021, retrospectively registered.

Early postoperative endoscopic evaluation of rectal anastomoses: a prospective cross-sectional study.

BACKGROUND: Reported incidence of anastomotic leakage (AL) of rectal anastomoses is up to 29% with an overall mortality up to 12%. Nevertheless, there is no uniform evidence-based diagnostic procedure for early detection of AL. The objective of this prospective clinical trial was to demonstrate the diagnostic value of early postoperative flexible endoscopy for rectal anastomosis evaluation. METHODS: Flexible endoscopy between 5 and 8th postoperative day was performed consecutively in 90 asymptomatic patients. Sample size calculation was made using the two-stage Simon design. Diagnostic value was measured by management change after endoscopic evaluation. Anastomoses were categorized according to a new classification. Study is registered in German Clinical Trials Register (DRKS00019217). RESULTS: Of the 90 anastomoses, 59 (65.6%) were unsuspicious. 20 (22.2%) were suspicious with partial fibrin plaques (n = 15), intramural hematoma and/or local blood coagulum (n = 4) and ischemic area in one. 17 of these anastomoses were treated conservatively under monitoring. In three a further endoscopic re-evaluation was performed and as consequence one patient underwent endoscopic vacuum therapy. 11 (12.2%) AL were detected. Here, two could be treated conservatively under monitoring, four with endoscopic vacuum therapy and five needed revision surgery. No intervention-related adverse events occurred. A change in postoperative management was made in 31 (34.4%) patients what caused a significant improvement of diagnosis of AL (p < 0.001). CONCLUSIONS: Early postoperative endoscopic evaluation of rectal anastomoses is a safe procedure thus allows early detection of AL. Early treatment for suspicious anastomoses or AL could be adapted to avoid severe morbidity and mortality.

[Laparoscopic Heller Myotomy in the Treatment of Achalasia]. / Laparoskopische Heller-Myotomie zur Therapie der Achalasie.

BACKGROUND: Achalasia refers to a primary oesophageal motility disorder characterised by the absence of peristalsis and incomplete or complete lack of relaxation of the lower oesophageal sphincter. The cardinal symptom is dysphagia. The therapeutic goal is surgical or interventional repair of the oesophageal outflow tract at the level of the oesophagogastric junction. INDICATION: We present the case of a 24-year-old patient with dysphagia accompanied by regurgitations, odynophagia as well as an unintentional weight loss over two years. METHODS: The video describes the preoperative imaging as well as endoscopic findings and demonstrates the technique of laparoscopic Heller myotomy followed by Dor fundoplication. CONCLUSIONS: Concerning the therapy of classic achalasia, laparoscopic Heller myotomy followed by Dor fundoplication - despite controversies regarding peroral endoscopic myotomy as an alternative therapeutic option - can be considered as an established standard procedure.

Learning curves, potential and speed in training of laparoscopic skills: a randomised comparative study in a box trainer.

BACKGROUND: The effectiveness of practical surgical training is characterised by an inherent learning curve. Decisive are individual initial starting capabilities, learning speed, ideal learning plateaus, and resulting learning potentials. The quantification of learning curves requires reproducible tasks with varied levels of difficulty. The hypothesis of this study is that the use of three-dimensional (3D) vision is more advantageous than two-dimensional vision (2D) for the learning curve in laparoscopic training. METHODS: Forty laparoscopy novices were recruited and randomised to a 2D Group and a 3D Group. A laparoscopy box trainer with two standardised tasks was used for training of surgical tasks. Task 1 was a positioning task, while Task 2 called for laparoscopic knotting as a more complex process. Each task was repeated at least ten times. Performance time and the number of predefined errors were recorded. 2D performance after 3D training was assessed in an additional final 2D cycle undertaken by the 3D Group. RESULTS: The calculated learning plateaus of both performance times and errors were lower for 3D. Independent of the vision mode the learning curves were smoother (exponential decay) and efficiency was learned faster than precision. The learning potentials varied widely depending on the corresponding initial values and learning plateaus. The final 2D performance time of the 3D-trained group was not significantly better than that of the 2D Group. The final 2D error numbers were similar for all groups. CONCLUSIONS: Stereoscopic vision can speed up laparoscopic training. The 3D learning curves resulted in better precision and efficiency. The 3D-trained group did not show inferior performance in the final 2D cycle. Consequently, we encourage the training of surgical competences like suturing and knotting under 3D vision, even if it is not available in clinical routine.

[Robotic Assisted Proctocolectomy with Ileal Pouch-Anal Anastomosis in a Case of Suspected Hereditary Polyposis]. / Roboterassistierte Proktokolektomie mit ileopouchanaler Anastomose bei Verdacht auf hereditäre Polyposis.

BACKGROUND: Various forms of hereditary polyposis have been described in the literature. Classical familial adenomatous polyposis (FAP) is a rare, autosomal dominantly inherited disease which is caused by a germline mutation in the adenomatous polyposis coli gene (APC). Patients with this diagnosis successively develop multiple polyps of the colon. Left untreated, FAP almost inevitably leads to malignant transformation. INDICATION: We present the case of a 37-year-old patient with histologically confirmed, stenotic adenocarcinoma of the descending colon and an initially suspected hereditary polyposis due to multiple polyps in the descending and sigmoid colon. METHODS: The video describes the preoperative imaging as well as endoscopic findings and demonstrates the technique of a two-stage, robotically assisted proctocolectomy with ileal pouch-anal anastomosis (IPAA) and the creation of a temporary loop ileostomy. CONCLUSIONS: With respect to the surgical treatment of classic FAP, restorative proctocolectomy (RPC) with ileal J-pouch construction can be regarded as an established standard procedure, despite controversy regarding various technical aspects. Minimally invasive strategies should be considered as an equivalent option compared to conventional techniques.

Therapy of pessary-induced rectovaginal fistula and pelvic organ prolapse in elderly patients by vaginal approach and modified LeFort colpocleisis: a case series.

PURPOSE: Pelvic organ prolapse (POP) presents a common benign condition in women associated with reduced quality of life (QoL). The use of pessaries is considered a first-line treatment of POP. However, pessaries can cause perforations into adjacent organs resulting in fistulas. We present a series of three cases of rectovaginal fistulas (RVF) due to pessary perforation. METHODS: Three consecutive cases of pessary-induced RVF in patients with POP stage IV were assessed between September 2016 and September 2019. Consensus for therapeutic strategy was reached by an interdisciplinary board. RESULTS: The RVF were located in the posterior vaginal wall and had a diameter of up to 60 mm. In one of three patients, a two-step approach was chosen with the ostomy being performed at the same time as fistula closure and modified LeFort colpocleisis. It was followed by ostomy closure 3 months later. In two patients, a three-step approach was chosen with the ostomy performed separately due to a local tissue inflammation around RVF. Neither fistula nor POP recurrences have occurred so far. CONCLUSION: Combined temporary gastrointestinal diversion, RVF closure and POP therapy can be performed as a two- or three-stage approach. Lack of evidence and standardized algorithms in RVF therapy make further clinical studies essential. We encourage the preoperative assessment of any case of complex rectovaginal fistula by an interdisciplinary board for determining an individualized treatment.

Enterocutaneous fistula in severely active Crohn's disease: preoperative anti-TNF alpha treatment to limit bowel resection-report of a case.

PURPOSE: Strategies for limiting the extent of bowel resection in cases of enterocutaneous or interenteric fistulas in severely active Crohn's disease are urgently necessary. Anti-inflammatory therapy with tumor necrosis factor alpha (anti-TNF alpha) inhibitors has positive impact on fistulizing Crohn's disease. We describe a case of a 32-year-old male suffering from enterocutaneous fistula in severely active Crohn's disease. METHODS: The patient's clinical course and data of therapy monitoring before bowel resection were reviewed and compared to the pretherapeutic findings. In addition, the reports of surgery and histopathological workup were evaluated and a clinical follow-up was performed. The literature on anti-TNF alpha treatment in fistulizing Crohn's disease was surveyed. RESULTS: A 32-year-old male with an 8-year history of Crohn's disease and condition after previous ileocecal and sigmoid resection at the age of 28 presented with increasing pain in the middle-right abdomen. Laboratory and radiologic assessment detected elevated C-reactive protein and presence of a conglomerate of inflammatory thickened and narrowed small intestine involving the neoterminal ileum and enteroenteric fistulas. Ileocolonoscopy showed a stenosing inflammation of the neoterminal ileum. After initial anti-infective therapy, as a result of an interdisciplinary decision, preoperative anti-TNF alpha treatment was performed to achieve limited bowel resection. After declining of inflammation, limited bowel resection was carried out successfully. CONCLUSIONS: Preoperative therapy with anti-TNF alpha might potentially reduce inflammation to subsequently limit the extent of bowel resection in selected cases of enterocutaneous or interenteric fistulas in severely active Crohn's disease. We describe an impressive case in which such therapeutic approach was carried out.

[First Robotic Assisted Resection of a Retrorectal Tailgut Cyst - Video Case Report of a 27-Year-Old Female Patient]. / Roboterassistierte Resektion einer retrorektalen Tailgut-Zyste ­ erstbeschreibender Videofallbericht einer 27-jährigen Patientin.

PURPOSE: Tailgut cysts are a rare form of retrorectal tumours. They are also referred to as cystic hamartomas and predominantly affect female patients. Malignant transformation is thought to occur in 2 - 10% of cases, but there is scant further evidence. Besides the risk of malignant transformation, the feared complications include infection, difficulties in defecation, or potential dystocia necessitating in sano resection. INDICATION: We describe the case of a 27-year-old female patient presenting with a prolapsing round structure during defaecation. MRI, endosonography and transrectal drainage were carried out to exclude malignancy. We performed resection of the retrorectal tailgut cyst by robotic surgery. To the authors knowledge, this access has not previously been described for tailgut cyst resection. METHOD: Our video shows preoperative diagnostic testing, endoscopic drainage and robotic resection of the tailgut cyst. An intraoperative lesion of the dorsal rectum was successfully closed by suture. CONCLUSIONS: Different surgical techniques have been described for tailgut cyst resection. That with the widest application is posterior/sacral access, followed by abdominal and transrectal techniques. There are no published reports of robotic resection. We chose the robotic approach, as this is the surgeon's preferred technique for minimally invasive surgery of the pelvis.

Heart transplantation in patients with previous malignancy. An overview.

INTRODUCTION: A history of malignancy has been considered as a contraindication for heart transplantation. The number of patients with prior malignancy needing transplantation is increasing due to improved survival and to cardiotoxic cancer treatment. However, this reluctance for transplantation can be challenged by the already available results. METHODS: A systematic literature search was performed in electronic databases. After exclusion of cardiac sarcomas, three case reports, thirteen series of which three are paediatric, two database searches and one article with specific design have been found. The larger series are of more recent origin. The study design of the manuscripts differed to some degree. RESULTS: The preoperative profile and the postoperative results are reviewed. The preoperative profile includes demographics, interval between treatment of malignancy and transplantation, indication of transplantation and differences between patients with and without prior malignancy. An important observation is the increase of transplantation in patients with chemotherapy-related cardiomyopathy over time. The postoperative results.show that hospital mortality and long-term survival do not differ significantly between patients with and without pre-transplant malignancy. This seems also to be true for post-transplant recurrence.The disease-free pre-transplant interval has a major effect on both outcomes. Patients with haematologic malignancies and after splenectomy have a worse prognosis. Use of LVAD (left ventricular assist device) as bridge-to-transplant and rapamycin as immune suppression, holds some promises. CONCLUSIONS: This review has some limitations since the published series are not comparable. It seems that transplantation in patients with prior malignancy can be justified in some cases, especially when the interval between malignancy and transplantation exceeds five years.

Diagnostic accuracy of hyperbilirubinaemia in anticipating appendicitis and its severity.

BACKGROUND: Hyperbilirubinaemia is reported to be a positive predictor in diagnosing appendicitis and especially appendiceal perforation. We, therefore, analysed the diagnostic accuracy of serum bilirubin in anticipating appendicitis and its severity. METHODS: All consecutive patients undergoing appendectomy for suspected appendicitis from May 2009 to August 2011 were analysed. Patients were classified based on final histopathological findings into the groups: no appendiceal inflammation, non-perforated appendicitis and perforated appendicitis. Primary outcome was the diagnostic accuracy of serum bilirubin levels in discriminating between no appendiceal inflammation and any appendicitis (perforated and non-perforated appendicitis) and non-perforated and perforated appendicitis. RESULTS: Of 493 analysed patients, 125 (25%) had no appendiceal inflammation, 312 (64%) had non-perforated appendicitis and 56 (11%) had perforated appendicitis. The proportion of patients with bilirubin elevation (>1.1 mg/dL) was different between those with no appendiceal inflammation (14%) and any appendicitis (36%) (p<0.0001), and between non-perforated appendicitis and perforated appendicitis 48% (p=0.04). However, the positive and negative likelihood ratios (LRs) for an elevated bilirubin were poor at discriminating the groups: no appendiceal inflammation versus any appendicitis (LR+ 2.62 (95% CI 1.65 to 4.16) and LR- 0.75 (95% CI 0.67 to 0.83)) and non-perforated appendicitis versus perforated appendicitis (LR+ estimate 1.74 (95% CI 1.28 to 2.38) and LR- 0.72 (95% CI 0.55 to 0.93)). CONCLUSIONS: Hyperbilirubinaemia is present in acute appendicitis but has a low diagnostic accuracy in discriminating between any appendicitis versus no appendiceal inflammation and perforated versus non-perforated appendicitis and is, therefore, of limited value in clinical routine. TRIAL REGISTRATION NUMBER: NCT01698099.

Arthroscopic pubic symphysis debridement and adductor enthesis repair in athletes with athletic pubalgia: technical note and video illustration.

We elaborately describe our novel arthroscopic technique of the symphysis pubis in athletes with osteitis pubis and concomitant adductor enthesopathy who fail to conservative treatment modalities. The symphysis pubis is debrided arthroscopically and the degenerated origin of adductor tendon (enthesis) is excised and reattached. With our surgical procedure the stability of the symphysis pubis is successfully preserved and the adductor longus enthesopathy simultaneously addressed in the same setting.

Synthesis, characterization, and antibacterial activity studies of two Co(II) complexes with 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid as a ligand.

Two new Cobalt(II) complexes 12 and 13 have been synthesized from 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid (11) as a novel ligand. These three new compounds were characterized on the basis of their powder X-Ray Diffraction, UV-Vis, IR, NMR, elemental analysis and MS spectral data. DFT/B3LYP mode of calculations were carried out to determine some theorical parameters of the molecular structure of the ligand. The purity of the azoic ligand and the metal complexes were ascertained by TLC and melting points. The analysis of the IR spectra of the polyfunctionalized azo compound 11 and its metal complexes 12 and 13, reveals that the coordination patterns of the ligand are hexadentate and tetradentate respectively. Based on the UV-Vis electronic spectral data and relevant literature reports, the ligand and derived complexes were assigned the E (trans) isomer form. Likewise, octahedral and square-planar geometries were respectively assigned to the cobalt(II) complexes. The broth microdilution method was used for antibacterial assays through the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The ligand 11 displayed moderate antibacterial activity (MIC = 32-128 µg/mL) against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa and Klebsiella pneumoniae 22. The octahedral cobalt(II) complex 12 showed moderate activity against Pseudomonas aeruginosa (MIC = 128 µg/mL) and Klebsiella pneumoniae 22 (MIC = 64 µg/mL) and none against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922, whereas the square-planar complex 13 displayed moderate activity only on Klebsiella pneumoniae 22 (MIC = 64 µg/mL).

Food Restriction in Anorexia Nervosa in the Light of Modern Learning Theory: A Narrative Review.

Improvements in the clinical management of anorexia nervosa (AN) are urgently needed. To do so, the search for innovative approaches continues at laboratory and clinical levels to translate new findings into more effective treatments. In this sense, modern learning theory provides a unifying framework that connects concepts, methodologies and data from preclinical and clinical research to inspire novel interventions in the field of psychopathology in general, and of disordered eating in particular. Indeed, learning is thought to be a crucial factor in the development/regulation of normal and pathological eating behaviour. Thus, the present review not only tries to provide a comprehensive overview of modern learning research in the field of AN, but also follows a transdiagnostic perspective to offer testable explanations for the origin and maintenance of pathological food rejection. This narrative review was informed by a systematic search of research papers in the electronic databases PsycInfo, Scopus and Web of Science following PRISMA methodology. By considering the number and type of associations (Pavlovian, goal-directed or habitual) and the affective nature of conditioning processes (appetitive versus aversive), this approach can explain many features of AN, including why some patients restrict food intake to the point of life-threatening starvation and others restrict calorie intake to lose weight and binge on a regular basis. Nonetheless, it is striking how little impact modern learning theory has had on the current AN research agenda and practice.

Evaluation of different setting configurations with a new developed telemedical interface of a parallel kinematic robotic system - An experimental development study.

BACKGROUND: For development of a minimally invasive intracorporal micromanipulator, a master-slave telemanipulation system was required. METHODS: Different input positions for a tablet-based input device with a heads-up centred screen were evaluated. Personal preference was assessed using a questionnaire. Then, the most ergonomic and intuitive position was compared to a surgical reference position based on laparoscopic sigmoid resection. RESULTS: After comparing a 45°, 75° (pitch) and 60°/20° (pitch/yaw) to a 60° reference position no significant differences in processing time and number of failures could be demonstrated. Study participants indicated the 60°/20° position as the most comfortable in the questionnaire. This was therefore compared with the laparoscopic reference position, both sitting and standing. Here, the laparoscopic sitting position was perceived to be the most ergonomic. CONCLUSIONS: The developed input device offers a maximum of flexibility and individualisation to reach ergonomic and intuitive conditions. General recommendations regarding an optimal setting cannot be given, based on our results.

Enhancing the radiological classification system from the distal femur to the proximal tibia.

OBJECTIVES: This study aims to identify anatomical variants of the proximal tibia shaft and to develop a novel classification system for proximal tibia. PATIENTS AND METHODS: Between October 2019 and April 2020, a total of 200 patients with standard knee anteroposterior radiographs were included in this study. We measured the inner diameter of the tibia 16 cm distally from the tibial plateau and 3 cm distally from the tibial spine. The ratio between these two measurements was applied as the novel index ratio. RESULTS: A total number of 197 patients (100 males and 97 females) with a median age of 68 years (range, 21 to 89 years) were included in the final analysis. According to the 25th and 75th percentiles, three groups were clustered for each sex. A higher distribution of the type B pattern was found in female and male patients. However, type A with a narrow inner diaphyseal diameter was less common in female patients. The median intraobserver reliability for rater 1 was 0.998. The inter-observer reliability was high (intraclass correlation coefficient: 0.998). There was a moderate correlation between the anteroposterior (AP) diameter and height (r=0.568) and a low correlation between the AP diameter and weight (r=0.376). The novel index shows no significant correlation between the index ratio and height (r=0.082), weight (r=0.014) or body mass index (r=-0.038). CONCLUSION: The novel classification presents three different types of tibia for each sex: type C has a wider inner diaphyseal diameter compared to type A with a narrow inner diaphyseal diameter. Type B has the widest distribution among the subjects.

Detection of adverse events leading to inadvertent injury during laparoscopic cholecystectomy using convolutional neural networks.

Uncontrolled movements of laparoscopic instruments can lead to inadvertent injury of adjacent structures. The risk becomes evident when the dissecting instrument is located outside the field of view of the laparoscopic camera. Technical solutions to ensure patient safety are appreciated. The present work evaluated the feasibility of an automated binary classification of laparoscopic image data using Convolutional Neural Networks (CNN) to determine whether the dissecting instrument is located within the laparoscopic image section. A unique record of images was generated from six laparoscopic cholecystectomies in a surgical training environment to configure and train the CNN. By using a temporary version of the neural network, the annotation of the training image files could be automated and accelerated. A combination of oversampling and selective data augmentation was used to enlarge the fully labeled image data set and prevent loss of accuracy due to imbalanced class volumes. Subsequently the same approach was applied to the comprehensive, fully annotated Cholec80 database. The described process led to the generation of extensive and balanced training image data sets. The performance of the CNN-based binary classifiers was evaluated on separate test records from both databases. On our recorded data, an accuracy of 0.88 with regard to the safety-relevant classification was achieved. The subsequent evaluation on the Cholec80 data set yielded an accuracy of 0.84. The presented results demonstrate the feasibility of a binary classification of laparoscopic image data for the detection of adverse events in a surgical training environment using a specifically configured CNN architecture.

Reducing Degrees of Freedom in Surgical Suturing: Implications for Minimally Invasive Device Development-A Prospective Experimental Study.

Open surgery allows the use of all 6 degrees of freedom (DOF; x-y-z and roll-pitch-yaw), whereas laparoscopy requires working under limitation to 4 axes. We present a prospective experimental study evaluating translational and rotational DOF restriction in surgical suturing tasks. An experimental platform included a kinematic structure that limited the maneuverability of the surgical instruments. The subjects (n=20) worked in a randomized order using (1) 6DOF, (2) 4DOF with 3 translational and 1 rotational DOF (4TRANS), and (3) 4DOF with 1 translational and 3 rotational DOF (4ROT). The time required to perform each task was recorded. Suturing and knot tying were significantly faster under 6DOF compared with 4ROT (both P<0.001) and 4TRANS (both P<0.001). Assessment of subjective difficulty and impairment showed most favorable results for 6DOF. The advantage of rotational compared with translational DOF should be considered in the development of future surgical devices.

TuThor: an innovative new training model for video-assisted thoracic surgery.

OBJECTIVES: Video-assisted thoracic surgery (VATS) is a complex technique requiring dedicated surgical training. Platforms for such training are scarce and often rely on the use of live animals, which raises ethical concerns. The objective of this study was to develop a box trainer that is dedicated for VATS training and able to reproduce bleeding scenarios. METHODS: The developed Tuebingen Thorax Trainer comprises 5 components that are mounted on a human anatomy-like thoracic cavity containing a porcine organ complex. Any standard thoracoscopic instrument can be used. The organ complex is attached to a perfusion module. We assessed the applicability of the system in four 1-day VATS training courses at the Tuebingen Surgical Training Center. Assessment was performed using a questionnaire handed out to all participants. RESULTS: Forty participants have been trained with the Tuebingen Thorax Trainer at our institution since November 2016. Thirty-five (87.5%) participants stated that the Tuebingen Thorax Trainer is an adequate model for VATS training. The ex vivo organ complex was reported to be realistic with regards to the level of detail and scale (76%). A large proportion of participants (27.5%) were experienced with VATS and reported having performed >50 procedures before taking the training course. CONCLUSIONS: This new training device allows realistic training for VATS procedures. 'Stagnant hydrostatic perfusion' permits simulation of reproducible bleeding scenarios. The device is low in production costs and offers a strong resemblance to the clinical scenario. It reduces the use of animal models and contributes to the efforts in making surgical skills training for VATS more accessible.

Leflunomide-hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome (RepurpSS-I): a placebo-controlled, double-blinded, randomised clinical trial.

BACKGROUND: Primary Sjögren's syndrome is a systemic autoimmune disease characterised by secretory gland dysfunction, for which no effective therapy is available. Based on the complementary properties of leflunomide and hydroxychloroquine in inhibiting activation of key immune cells in primary Sjögren's syndrome, we aimed to evaluate the clinical efficacy and safety of leflunomide-hydroxychloroquine combination therapy in patients with primary Sjögren's syndrome. METHODS: We did a placebo-controlled, double-blinded, phase 2A randomised clinical trial in patients with primary Sjögren's syndrome at the University Medical Center Utrecht (Utrecht, Netherlands). Eligible patients were aged 18-75 years, had a European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) score of 5 or higher, and a lymphocytic focus score of 1 or higher in labial salivary gland biopsy specimens. Patients were randomly assigned (2:1) with block randomisation (block size of six) to receive leflunomide 20 mg and hydroxychloroquine 400 mg daily or placebo for 24 weeks. The primary endpoint was the between-group difference in change in ESSDAI scores from 0 to 24 weeks, adjusted for baseline ESSDAI score. Patients were analysed according to the intention-to-treat principle. This study is registered with EudraCT, 2014-003140-12. FINDINGS: Between March 7, 2016, and Nov 30, 2017, 37 patients were screened, of whom 29 patients (28 women and one man) were enrolled. 21 patients were assigned to receive leflunomide-hydroxychloroquine and eight patients were assigned to receive placebo. One patient in the placebo group required high-dose prednisone to treat polymyalgia rheumatica at week 13 and was excluded from the primary analysis. From 0 to 24 weeks, the mean difference in ESSDAI score, adjusted for baseline values, in the leflunomide-hydroxychloroquine group compared with the placebo group was -4·35 points (95% CI -7·45 to -1·25, p=0·0078). No serious adverse events occurred in the leflunomide-hydroxychloroquine group and two serious adverse events occurred in the placebo group (hospital admission for pancreatitis and hospital admission for nephrolithiasis). The most common adverse events in the leflunomide-hydroxychloroquine group were gastrointestinal discomfort (11 patients [52%] vs two [25%] in the placebo group), modest transient increases in alanine aminotransferase (ten [48%] vs one [13%]), and short episodes of general malaise and shivering (nine [43%] vs one [13%]). INTERPRETATION: Leflunomide-hydroxychloroquine was safe and resulted in a clinical response in patients with primary Sjögren's syndrome. These results warrant further evaluation of leflunomide-hydroxychloroquine combination therapy in larger clinical trials. FUNDING: ZonMw.