Evaluation of ostium size following endoscopic dacryocystorhinostomy as a predictive factor of outcome: A prospective study.

INTRODUCTION: Endonasal dacryocystorhinostomy (DCR) is a surgical procedure that aims to increase tear drainage to treat epiphora caused by nasolacrimal obstruction by creating a bypass through the bone between the lacrimal sac and the nasal cavity. A silicone stent is temporarily put in place for 2 months to avoid early obstruction of the rhinostomy. One of the causes of surgical failure is related to progressive stenosis of intranasal ostium, due to fibrosis and new bone growth, inducing a relapse of epiphora and/or dacryocystitis. Few studies have described changes in the size of the intranasal ostium on direct post-DCR measurement or kinetics of its shrinkage. The purpose of this study is to determine whether changes in the size of intranasal ostium might be a predictor of final functional efficacy. MATERIALS AND METHODS: A prospective cohort of eighteen consecutive patients undergoing endonasal DCR for chronic epiphora or chronic dacryocystitis between January 2017 and April 2018 was analyzed. Eight patients who underwent bilateral DCR, and twenty-six intranasal ostia were finally analyzed. Follow-up took place every two months for 1 year, with the silicone tube removed at 2 months. Functional success was defined as absence of recurrent epiphora or dacryocystitis. Ostium size was systematically measured on photos taken during intranasal endoscopy performed every 2 months for 1 year. RESULTS: At 2 months after endonasal DCR, 23 of the 26 ostia (88.5%) were functional, but only 19 (73.1%) of them were directly measurable. The mean horizontal diameter at 2 months was 1.44 (SD 0.61) mm, and the mean vertical diameter was 0.86 (SD 0.37) mm, which corresponded to a mean area of 10 (SD 0.84)mm2. We noted a statistically significant decrease in ostium size and area between 2 and 4 months after the procedure (P -0.001), followed by a stabilization period with no statistical correlation between the size of the ostium and its final functional efficacy. At 6 months after DCR, of the 7 ostia that were not initially measurable, 3 were immediately non-functional at 2 months, 3 had a relapse of epiphora at 4 months, and 1 had a relapse of dacryocystitis at 6 months, i.e., 100% clinical failures at 6 months. The other procedures all remained functional after 1 year of follow-up. CONCLUSION: The intranasal ostium of an endonasal DCR shrinks significantly within the 2 months after removal of the silicone tube and remains stable thereafter. There is no correlation between the size or area of intranasal ostium and its final functional efficacy. However, when the ostium is not measurable at the time of 2-month stent removal, all patients experienced a relapse of epiphora or dacryocystitis within 6 months.

[Evaluation in clinical practice of the quality of life of patients with VADS cancer: an ethical justification or a fad?]. / Evaluation en pratique clinique de la qualité de vie des patients atteints de cancers des V.A.D.S.: une démarche éthique justifiée ou un effet de mode?

Now that the treatment of head and neck cancer has been perfectly standardized and the complications and sequelae are well known, many authors have started to investigate health-related quality of life (QoL). The use of generic and cancer-specific QoL instruments remains limited to the field of research, but can this approach be transposed to clinical oncology? This study was designed to answer this question by identifying the ethical problems related to QoL assessment. The methodology used is based on a questionnaire survey of a cohort of 40 volunteer patients, conducted some time after their initial treatment in order to optimally assess their expectations and questions in relation to these aspects. The validity of the instrumental approach cannot be guaranteed due to conceptual limits, and the sociocultural level and cognitive state of the target population. A more subtle approach to QoL assessment in routine clinical practice would consist of a mixed approach harmoniously combining quantitative and qualitative aspects based on questionnaire and interview.

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran.

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.

The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study.

BACKGROUND: Ximelagatran and its subcutaneous (s.c.) form melagatran are novel direct thrombin inhibitors for the prevention and treatment of thromboembolic disease. METHODS: In a double-blind study, 2835 consecutive patients undergoing total hip or knee replacement were randomized to either melagatran/ximelagatran or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d. beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was started 12 h before surgery. Both treatments were continued for 8-11 days. The main efficacy outcome measures were major venous thromboembolism (VTE); [proximal deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death where PE could not be ruled out], and total VTE (proximal and distal DVT; PE; death from all causes). DVT was detected by mandatory bilateral ascending venography at the end of the treatment period or earlier if clinically suspected. The main safety outcome was bleeding. RESULTS: The rates of major and total VTE were significantly lower in the melagatran/ximelagatran group compared with the enoxaparin group (2.3% vs. 6.3%, P = 0.0000018; and 20.3% vs. 26.6%, P < 0.0004, respectively). Fatal bleeding, critical site bleeding and bleeding requiring reoperation did not differ between the two groups. 'Excessive bleeding as judged by the investigator' was more frequent with melagatran/ximelagatran than with enoxaparin. CONCLUSIONS: In patients undergoing total hip or knee replacement, preoperatively initiated s.c. melagatran followed by oral ximelagatran was significantly more effective in preventing VTE than preoperatively initiated s.c. enoxaparin.

The European experience with laparoscopic cholecystectomy.

A retrospective survey of 7 European centers involving 20 surgeons who undertook 1,236 laparoscopic cholecystectomies was performed. The procedure was completed in 1,191 patients. Conversion to open cholecystectomy was necessary in 45 patients (3.6%) either because of technical difficulty (n = 33), the onset of complications (n = 11), or instrument failure (n = 1). There were no deaths reported, and the total postoperative complication rate was 20 of 1,203 (1.6%), with 9 being serious complications requiring laparotomy. The total incidence of bile duct damage was 4 of 1,203. The median hospital stay was 3 days (range: 1 to 27 days) and the median time to return to full activity after discharge was 11 days (range: 7 to 42 days).

[The oral direct thrombin inhibitor Ximelagatran Prophylaxis of venous thromboembolism in hip and knee replacement]. / Der orale direkte Thrombininhibitor Ximelagatran.

AIM: The efficacy and safety of the new oral, direct and selective thrombin inhibitor Ximelagatran and its active form Melagatran was analysed in patients undergoing total hip or knee replacement. METHODS AND PATIENTS: Methro II, a randomised, double-blind controlled dose-finding study, involved 1876 patients. Melagatran (1, 1.5, 2.25 or 3 mg; twice daily; start: immediately before surgery) was given subcutaneously, followed by orally administered Ximelagatran (8, 12, 18 or 24 mg, twice daily, day after surgery) and compared to subcutaneously administered dalteparin (5000 IE, once daily). Methro III was a randomised, double blind controlled study involving 2788 patients. The fixed dose of 3 mg Melagatran was given (start: 4-12 hours postoperatively) followed by oral Ximelagatran (24 mg, twice daily, day after surgery) compared to subcutaneous enoxaparin (40 mg, once daily). In both studies, dalteparin or enoxaparin was applied at the evening before operation; the treatment lasted 8 to 11 days. A bilateral venography was performed at the last day of treatment. RESULTS: In the Methro II study, 1270 patients underwent total hip, 606 total knee replacement. In both groups the thromboembolism rate was reduced depending on the dose of Ximelagatran/Melagatran. Compared to dalteparin, it was significantly lower for the Ximelagatran/Melagatran group with the highest dose. In the Methro III study 1923 patients underwent a total hip, 865 a total knee replacement. The thromboembolism rate was 31% for the Ximelagatran/Melagatran group compared to 27% for the enoxaparin group. In both studies blood loss and transfusion requirement were in the same range as with low weight molecular heparins. CONCLUSIONS: A fixed subcutaneously given dose of Melagatran, followed by orally administered Ximelagatran is effective and well tolerated as prophylaxis against venous thromboembolism.

[Obstruction of the small intestine and celioscopic viscerolysis]. / Occlusion du grêle et viscérolyse coelioscopique.

The authors treated 16 patients with small bowel obstruction by 19 laparoscopy (3 patients underwent 2 laparoscopies). The operation was performed 4 times as an emergency and in 15 cases after resolution of the obstruction in patients who had already experienced such attacks. Adhesiolysis was complete in 14 cases and incomplete in 5 cases. Conversion in laparotomy was necessary in one patient to cure a total obstruction. 2 operative complications were reported (bowel perforation during enterolysis); one of which required conversion into laparotomy). This patient also developed post-operative complications whereas the post-operative course was uneventful for the other patients. Five patients developed an obstructive recurrence which required laparotomy in 2 cases and laparoscopy in the other 3 cases; but for two patients, initial enterolysis had been incomplete and a laparotomy was performed on another patient. Laparoscopic viscerolysis seems to be attractive but, the long-term outcome, and the frequency of adhesion recurrence need to be defined.

[Pyolaryngocele: case report of an uncommon laryngeal disease]. / La pyolaryngocèle: une pathologie rare du larynx. A propos d'une observation.

Laryngocele is an unusual laryngeal disease caused by an abnormal dilatation of the saccule of the laryngeal ventricule. Infection results in laryngopyocele. We report a case of laryngopyocele discovered in a patient presenting with fever, an inflammatory mass, dysphagia and minimal respiratory distress. Diagnosis was established from direct laryngoscopy and CT-scan. Early treatment consisted in antibiotics and needle aspiration followed by external excision. Laryngopyocele can sometimes be revealed by an episode of acute respiratory distress requiring tracheotomy. If there is no respiratory distress and if the infection is cured, endoscopic treatment with or without laser can be performed for internal laryngocele. The cervical approach can only be recommended for external or combined laryngocele.

[Cervical branchiomeric paraganglioma. Report of 21 cases]. / Paragangliomes branchiomériques cervicaux. A propos de 21 cas.

Over the last 24 years the authors operated 21 branchiomeric paragangliomas in 18 patients. They emphasize the difficulty of making the diagnosis and the importance of completing a thorough work-up before deciding surgery. Adequate imaging is particularly important (neck sonography, computed tomography, arteriography) to avoid making the diagnosis by exploratory neck dissection and to assess the vascular risk. Biological studies have regained importance, especially in the context of complex neuro-cristopathy. Treatment is essentially surgical and must be considered with prudence in patients with bilateral lesions. The surgical removal of branchiomeric paragangliomas necessitates preparation of a small saphenous vein bypass in case it is not possible to avoid sacrificing the internal carotid artery.

[Malformations of the bony labyrinth and deafness]. / Malformations du labyrinthe osseux et surdités.

17 new cases of malformation of the bony labyrinth detected radiologically (tomography, CT) and associated with perceptive or composite deafness are reported. 2 cases discovered in spontaneous or traumatic recurrent meningitis are described, as well as 1 case discovered after the occurrence of total deafness following stapedial surgery. The malformations were unilateral in 7 cases, bilateral in 10. Deafness was of the composite type in 6 cases. An associated malformation of the middle or external ear was noted in 4 cases. 5 cases were included in a context of multiple malformations, including 1 case of otobranchiorenal syndrome, 1 case of Apert's syndrome and 3 cases of craniostenosis. Referring to the classification given by Mrs Vignaud and Jardin, we have encountered 1 case of stage I malformation, 9 cases of stage II, pseudo-Mondini malformation, 1 case of stage III or true Mondini malformation, 1 case of stage IV malformation, 3 cases of malformation of the aqueduct of the vestibule, ie. stage V. We have also encountered 2 isolate cases of stenosis of the internal auditory canal. On the basis of these cases, we report a few physiopathogenetic hypotheses and various classifications currently described in the literature. We also list the various associated external and middle ear malformations and the multiple-malformation syndromes that are commonly described. Stress is laid on the fact that these malformations often go undetected in congenital deafness, as well as on the usual course of these types of deafness for which there is no medical or surgical treatment.

[Is hepatic ultrasonography necessary in the initial check-up of patients with squamous cell carcinoma of the upper respiratory and digestive tract?]. / L'échographie hépatique a-t-elle une place dans le bilan d'extension initial des patients atteints d'un carcinome malpighien des voies aéro-digestives supérieures (VADS)?

PURPOSE OF THE STUDY: The purpose of our study was to determine the position and value of ultrasound scan of the liver in the initial check-up of patients treated for a squamous cell carcinoma of the upper respiratory and digestive tract. MATERIAL AND METHODS: Our study is based on a retrospective review of 267 patients (249 males and 18 females) managed in the E.N.T. Department of Grenoble universitary hospital from 1993 to 1995 for a upper respiratory and digestive tract malignant tumor. No patient has been previously treated. The site of the primary tumor was: the oropharynx (108 cases), the hypopharynx (88 cases), the oral cavity (44 cases), the larynx (20 cases), the rhinopharynx (6 cases) and the cervical oesophagus (1 case). Endoscopic procedure with biopsy was performed for all the patients. Histologic examination revealed an invasive squamous cell carcinoma in all the cases. The complete check up included a ultrasound scan of the liver and a chest X-ray for all the patients. RESULTS: Ultrasound scan of the liver revealed one or several metastases in 4 cases (1.5%). The primary tumor was hypopharyngeal in 3 cases (2 stages III, 1 stage IV) and oropharyngeal in 1 case (stage III). In three cases, carcinoma was poorly differentiated. Ultrasound scan of the liver was doubtful for 8 patients (3%). The primary tumor was oropharyngeal in 6 cases (1 stage I, 3 stages III, 2 stages IV), laryngeal in 1 case (stage III) and hypopharyngeal in case (stage IV). In six cases carcinoma was well differentiated. All the complementary examinations concluded to a benign liver disease, with a mean diagnosis delay of 4 weeks for the 8 patients. The mean follow-up duration of the 8 patients was 22 months (range 9 to 42 months). None presented any metastases during the follow up. CONCLUSION: Our results compared with those of the literature revealed that ultrasound scan of the liver is a few specific examination which may be recommended for hypopharyngeal tumors, or for a large cervical adenopathy (N2 or N3), a poor differentiated tumor wherever the site of the primary tumor is.

Liposarcoma of the hypopharynx. A case report and review of the literature.

A new case of well differentiated hypopharyngeal liposarcoma is reported. The author reviews the literature about the clinical and histologic features of these tumors. From the 93 head and neck liposarcomas reported 13 are located in the hypopharynx. The mean age of presentation is 61 years and males are largely predominant. Etiology is still unknown. Tumor size does not seem to affect the prognosis. Usually patients do not present with cervical lymph node metastasis nor distant metastasis. Histologic diagnosis according to Enzinger and Weis's classification could be difficult especially to distinguish between lipoma and well differentiated liposarcoma. The main prognostic factor is histologic grade but early recognition combined with a complete surgical excision can result in a decreased local recurrence rate and high survival rate. Low grade tumors often recur locally but distant metastases are rare. From the 8 well differentiated tumors reviewed 6 presented a local recurrence 2 months to 20 years after surgery but only 1 patient died without disease. High grade tumors are much more aggressive locally and metastasize frequently. Radiotherapy and chemotherapy are proposed in selected cases without evidence to be of value.

[Primary and recovery transmaxillar buccopharyngectomy in buccopharyngeal cancers]. / La buccopharyngectomie transmaxillaire en première intention et en rattrapage dans les cancers buccopharyngés latéraux.

From january 1976 to december 1986, 78 patients were treated surgically for squamous cell carcinoma of the lateral buccopharyngeal junction without chemotherapy at first. 36 patients were treated by primary surgery with post-operative radiotherapy and 31 patients were treated by recovery surgery. Post-operative course was uncomplicated in 41% of cases (39% in primary surgery, 43% in recovery surgery); in 14% of cases serious local complications were observed (11% in primary surgery, 17% in recovery surgery). Carcinological failures appeared in 46% of cases in primary surgery and in 70% of cases in recovery surgery. Three years and five years actuarial survival rate were 45% and 39% respectively in recovery surgery. Prognostic factors are studied: resection quality, histological metastasis in lymph nodes. The authors emphasize on the best control of the big tumors in primary surgery and on the best results with small ulcerated infiltrant carcinoma.

[Malignant cervical epithelial adenopathy from unknown primary source. Apropos of a series of 54 cases]. / Les adénopathies cervicales malignes épithéliales en apparence primitives. A propos d'une série de 54 cas.

Fifty four patients with cervical lymph node metastasis from an unknown primary tumor underwent treatment from 1969 to 1988. Fourty five underwent radical neck dissection. 69% had node capsular effraction and 36% perinodal vascular embolism. Thirty four patients underwent postoperative radiotherapy including rhinopharynx, cervical oesophagus and all the bilateral cervical nodes. The primary tumor appeared after treatment in 7 cases. Total survival rate is 36% 5 years after treatment. Vascular embolism aggravates the prognosis. Radiosurgical association allow effective control of loco-regional cancer but does not improve survival rate. Prognosis is aggravated by metastases arising (18%).

[First-intention surgical treatment of thyroglossal duct cysts in children: apropos of 99 cases]. / Traitement chirurgical de première intention des kystes du tractus thyréoglosse chez l'enfant: à propos de 99 cas.

INTRODUCTION: Thyroglossal duct cyst (TGDcs) is the most common malformation of the neck. The risk of infection and malignant transformation impose its treatment. OBJECTIVES: The purpose of our study were: 1) to specify some points about the symptomatology and preoperative evaluation necessary for TGDcs diagnosis; 2) to analyse the factors who can explain an unsuccessful surgical treatment. PATIENTS AND METHODS: Our study is based on a retrospective review of cases and a review of the literature. From 1981 to 2000, 99 children with a mean age of five years were treated for a TGDcs with a surgical procedure in the Grenoble University Hospital. 3 excision and 96 Sistrunck's procedure were performed. In all cases a histological study was made. RESULTS: Ultrasonography was the most frequent preoperative evaluation. We have had 7 complications: 3 haematoma, 2 abscess and 2 desunited scar. 6 children have had recurrent disease. Among these 6 children, 3 have had an excision and 3 a Sistrunck's procedure. No case of malignant transformation was reported. CONCLUSION: Ultrasonography is the first preoperative evaluation to obtain before surgical treatment of a TGDcs. Sistrunck's procedure is the best surgical treatment with a value of recurrence from 1% to 10%. Areas of surgical failure included breaking of cyst during the dissection, inadequate hyoïd bone resection, an anatomical variation with many ductuli in the base of tongue, inadequate muscles of tongue resection.

[Postoperative treatment, rehabilitation and expert assessment of patients with endoprostheses of the hip joint]. / Postoperative Behandlung, Rehabilitation und gutachterliche Beurteilung von Endoprothesenträgern des Hüftgelenks.

The main demands on a total hip replacement are to reduce pain or achieve painlessness and to recover or improve mobility and walking ability. Today more younger patients were operated replacing a destroyed hip joint: the reintegration in professional and sportive activities is a major part of the rehabilitation process. The postoperative management especially in physical therapy can be standardized inspite of the use of various models. Usually full weight bearing is accepted after 3 months. A review of consecutive treatment methods and professional and sportive rehabilitation measures are presented. Hip replacement leads to restrictions in activity in general. The evaluation, in relation to the different indemnifying, is differentiated.

Aerobic capacities and exercise tolerance in neuromuscular diseases: a descriptive study.

INTRODUCTION: Up until now, there has been little description of the test exercises carried out in patients with neuromuscular diseases. However, prescription of physical therapy by exercise requires rigorous individualized assessment of the patient's physical endurance parameters. OBJECTIVE: To describe exercise tolerance and external limitation factors in a sample group of adult patients suffering from neuromuscular diseases. MATERIALS AND METHODS: A descriptive retrospective study of exercise tests realized at the Reims university hospital for patients divided into three groups according to their pathologies: CMT hereditary neuropathies, muscular dystrophies, metabolic myopathies. RESULTS: Forty-four (44) tests were analyzed. Cessation was occasioned on 63.6% of the cases by muscular symptomatology, with no possibility of maintaining the cycling frequency in 29.5% of the overall population. Insufficient lung volume recruitment was involved in 61.4% of the patients, final oxygen pulse (VO2/heart rate) was 80% lower than the theoretical pulse in 50% of the patients, and there existed an early first ventilatory threshold in 54.5% of the cases. Peripheral deconditioning was highly severe in 18% of the population and significantly greater in the subjects suffering from dystrophies (VT1 at 31% of the maximum theoretical O2, P<0.001). DISCUSSION: The main limitation factor in exercise tests is peripheral. Ventilatory and cardiovascular limitations can nonetheless be added on; while they are absent when the patient is at rest, they are unmasked in effort situations. Exercise tests could be of great interest in screening and managing the relevant pathologies. Multicenter studies on homogeneous populations could facilitate definition of the procedures specific to exercise tests for patients suffuring from neuromuscular diseases.

Extended venous thromboembolism prophylaxis in patients undergoing hip fracture surgery - the SAVE-HIP3 study.

There is currently limited information available on the benefits and risks of extended thromboprophylaxis after hip fracture surgery. SAVE-HIP3 was a randomised, double-blind study conducted to evaluate the efficacy and safety of extended thromboprophylaxis with the ultra-low molecular-weight heparin semuloparin compared with placebo in patients undergoing hip fracture surgery. After a seven- to ten-day open-label run-in phase with semuloparin (20 mg once daily subcutaneously, initiated post-operatively), patients were randomised to once-daily semuloparin (20 mg subcutaneously) or placebo for 19 to 23 additional days. The primary efficacy endpoint was a composite of any venous thromboembolism (VTE; any deep-vein thrombosis and non-fatal pulmonary embolism) or all-cause death until day 24 of the double-blind period. Safety parameters included major and clinically relevant non-major bleeding, laboratory data, and treatment-emergent adverse events (TEAEs). Extended thromboprophylaxis with semuloparin demonstrated a relative risk reduction of 79% in the rate of any VTE or all-cause death compared with placebo (3.9% vs 18.6%, respectively; odds ratio 0.18 (95% confidence interval 0.07 to 0.45), p < 0.001). Two patients in the semuloparin group and none in the placebo group experienced clinically relevant bleeding. TEAE rates were similar in both groups. In conclusion, the SAVE-HIP3 study results demonstrate that patients undergoing hip fracture surgery benefit from extended thromboprophylaxis.

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE.

BACKGROUND: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. OBJECTIVES: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). PATIENTS/METHODS: All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). RESULTS: In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. CONCLUSIONS: Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles.