Reduced mortality by meeting guideline criteria before using recombinant activated factor VII in severe trauma patients with massive bleeding.

BACKGROUND: Management of trauma patients with severe bleeding has led to criteria before considering use of recombinant activated factor VII (rFVIIa), including haemoglobin >8 g dl-1, serum fibrinogen ≥1.0 g l-1, platelets >50,000 x 109 l-1, arterial pH ≥ 7.20, and body temperature ≥34 °C. We hypothesized that meeting these criteria is associated with improved outcomes. METHODS: In this prospective cohort study of 26 French trauma centres, subjects were included if they received rFVIIa for persistent massive bleeding despite appropriate care after severe blunt and/or penetrating trauma. RESULTS: After surgery and/or embolization as haemostatic interventions, 112 subjects received a first dose of 103 µg kg-1 rFVIIa (82-200) (median, 25th-75th percentile) at 420 min (285-647) post-trauma. Of these, 71 (63%) "responders" were still alive at 24h post-trauma and had their transfusion requirements reduced by > 2 packed red blood cell units after rFVIIa treatment. Mortality was 54% on day 30 post-trauma. There were 21%, 44% and 35% subjects who fulfilled 0-1, 2-3 or 4-5, respectively, of the guidelines before receiving rFVIIa. Survival at day 30 was 13%, 49% and 64% and the proportion of responders was 39%, 64% and 82%, when subjects fulfilled 0-1, 2-3 or 4-5 conditions, respectively (both P <0.01). CONCLUSIONS: In actively bleeding trauma patients, meeting guideline criteria before considering rFVIIa was associated with lower mortality and a higher proportion of responders to the rFVIIa.

Increased severity of suicidal behavior in impulsive aggressive patients exposed to familial adversities.

BACKGROUND: The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior. METHOD: We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed. RESULTS: Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75-17.5] or physical abuse (OR 5.03, 95% CI 1.50-16.9) in their childhood. CONCLUSIONS: Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.

Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial.

OBJECTIVE: To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. METHODS: Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). MAIN ENDPOINT: The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as > or =19.9 mm on the visual analogue pain scale and/or > or =9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. RESULTS: The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (chi(2)=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. CONCLUSION: For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated.

Analysis of the volatile organic matter of engine piston deposits by direct sample introduction thermal desorption gas chromatography/mass spectrometry.

This article establishes an alternative method for the characterization of volatiles organic matter (VOM) contained in deposits of the piston first ring grooves of diesel engines using a ChromatoProbe direct sample introduction (DSI) device coupled to gas chromatography/mass spectrometry (GC/MS) analysis. The addition of an organic solvent during thermal desorption leads to an efficient extraction and a good chromatographic separation of extracted products. The method was optimized investigating the effects of several solvents, the volume added to the solid sample, and temperature programming of the ChromatoProbe DSI device. The best results for thermal desorption were found using toluene as an extraction solvent and heating the programmable temperature injector from room temperature to 300 degrees C with a temperature step of 105 degrees C. With the use of the optimized thermal desorption conditions, several components have been positively identified in the volatile fraction of the deposits: aromatics, antioxidants, and antioxidant degradation products. Moreover, this work highlighted the presence of diesel fuel in the VOM of the piston deposits and gave new facts on the absence of the role of diesel fuel in the deposit formation process. Most importantly, it opens the possibility of quickly performing the analysis of deposits with small amounts of samples while having a good separation of the volatiles.

Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study.

Essentials Clinical significance of cancer-related isolated distal deep vein thrombosis (iDDVT) is unknown. We studied patients with iDDVT, with and without cancer, and proximal DVT with cancer. Cancer-related iDDVT patients have a much poorer prognosis than iDDVT patients without cancer. Cancer-related iDDVT patients have a similar prognosis to cancer-related proximal DVT patients. SUMMARY: Background Isolated distal deep vein thrombosis (iDDVT) (infra-popliteal DVT without pulmonary embolism [PE]) is a frequent event and, in the absence of cancer, is usually considered to be a minor form of venous thromboembolism (VTE). However, the clinical significance of cancer-related iDDVT is unknown. Methods Using data from the observational, prospective multicenter OPTIMEV cohort, we compared, at 3 years, the incidences of death, VTE recurrence and major bleeding in patients with cancer-related iDDVT with those in cancer patients with isolated proximal DVT (matched 1:1 on age and sex) and patients with iDDVT without cancer (matched 1:2 on age and sex). Results As compared with patients with cancer-related isolated proximal DVT (n = 92), those with cancer-related iDDVT (n = 92) had a similar risk of death (40.8% per patient-year (PY) vs. 38.3% per PY; aHR = 1.0, 95% CI[0.7-1.4]) and of major bleeding (3.8% per PY vs. 3.6% per PY, aCHR = 0.9 [0.3-3.2]) and a higher risk of VTE recurrence (5.4% per PY vs. 11.5% per PY; aCHR = 1.8 [0.7-4.5]). As compared with patients with iDDVT without cancer (n = 184), those with cancer-related iDDVT had a nine times higher risk of death (3.5% per PY vs. 38.3% per PY; aHR = 9.3 [5.5-15.9]), a higher risk of major bleeding (1.8% per PY vs. 3.6% per PY; aCHR = 2.0 [0.6-6.1]) and a higher risk of VTE recurrence (5.0% per PY vs. 11.5% per PY; aCHR = 2.0 [1.0-3.7]). The results remained similar in the subgroup of patients without history of VTE. Conclusion Patients with cancer-related iDDVT seem to have a prognosis that is similar to that of patients with cancer-related isolated proximal DVT and a dramatically poorer prognosis than patients with iDDVT without cancer. This underlines the high clinical significance of cancer-related iDDVT and the need for additional studies.

Long-term risk of venous thromboembolism recurrence after isolated superficial vein thrombosis.

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.

Low incidence of cancer after venous thromboembolism: An update from the French OPTIMEV Cohort.

BACKGROUND: Recent studies have shown lower rates of cancer following venous thromboembolism (VTE) than previously described. OBJECTIVES: To reassess the risk of cancer in patients with clinical symptoms of VTE with or without confirmed VTE. PATIENTS: We used data from OPTIMEV, a French prospective multicenter observational study of patients presenting to hospital and community vascular medicine specialists with suspected VTE. Patients with confirmed VTE (1565) and matched controls without VTE (1847) were followed for 3 years (2006-2009). The main outcome was occurrence of cancer at 3 years, and death was a censoring event. RESULTS: A total of 5.0% [4.0-6.3] of patients with VTE and 3.8% [3.0-4.9] without VTE developed cancer during follow-up. The adjusted hazard ratio (HR) was 1.2 [0.9-1.8] for patients with confirmed VTE (P=0.22). The overall standardized incidence ratio (SIR) was 1.4 [1.1-1.6] for our population, VTE+ and VTE-, compared with the general population, statistically significant (P<0.05). CONCLUSIONS: We found a lower occurrence of cancer after VTE than previously described, with no significant difference between patients whether VTE was confirmed or not. Our results (low incidence and no difference between patients VTE+ or VTE-) provide no argument in favor of an extensive screening for cancer in case of VTE.

Sinus floor elevation with a crestal approach using a press-fit bone block: a case series.

This prospective study aimed to provide detailed clinical information on a sinus augmentation procedure, i.e., transcrestal sinus floor elevation with a bone block using the press-fit technique. A bone block is harvested with a trephine burr to obtain a cylinder. This block is inserted into the antrum via a crestal approach after creation of a circular crestal window. Thirty-three patients were treated with a fixed prosthesis supported by implants placed on 70 cylindrical bone blocks. The mean bone augmentation was 6.08±2.87 mm, ranging from 0 to 12.7 mm. Only one graft failed before implant placement. During surgery and the subsequent observation period, no complications were recorded, one implant was lost, and no infection or inflammation was observed. This proof-of-concept study suggests that the use of a bone block inserted into the sinus cavity via a crestal approach can be an alternative to the sinus lift procedure with the creation of a lateral window. It reduces the duration of surgery, cost of treatment, and overall discomfort.

Increased CRP levels may be a trait marker of suicidal attempt.

Suicide is a leading cause of death worldwide. Identifying biomarkers will help enhance our understanding of suicidal pathophysiology and improve its prevention. Therefore, we investigated CRP levels in 600 depressed inpatients: 520 patients had a lifetime history of suicide attempts and 80 patients did not have any history of suicide attempts. For all patients, we assessed socio-demographic features, lifetime Axis I DSM-IV diagnoses, depression intensity, suicidal ideation, characteristics of suicidal history, and history of childhood trauma. The day following admission, fasting blood tests yielded samples collected for the measurement of high sensitivity hs-CRP. CRP levels were associated with a history of suicide attempts. The risk of suicide attempts increased with higher levels of CRP in a dose-response way before and after adjustments for age, gender, chronic diseases, addiction and anxiety comorbidities, antidepressants use, smoking status and sexual abuse. Noteworthy, the association between CRP levels and history of suicide attempts remained significant after having excluded patients with chronic diseases. There was no significant difference in CRP levels between patients who attempted suicide more or less than a week before plasma sampling, and no significant difference in CRP levels was evidenced between high vs low suicidal ideation. In conclusion, this is the first study suggesting that CRP may be a trait marker for suicidal vulnerability by associating CRP levels and a lifetime history of suicide attempts in depressed inpatients. Therefore, determining the inflammatory marker profile of individuals exhibiting suicidal behaviors could be relevant for anticipating behaviors and refining new therapeutic opportunities.

Prone position affects stroke volume variation performance in predicting fluid responsiveness in neurosurgical patients.

BACKGROUND: Stroke volume variation (SVV) during mechanical ventilation predicts preload responsiveness. We hypothesized that the prone position would alter the performance of this dynamic indicator. METHODS: Two parallel groups of ventilated neurosurgical patients with low tidal volume (6-8 ml.kg-1) were studied before surgical incision. SVV was measured at T0, T15 and T30 min during a fluid volume expansion (250 mL hetastarch 6% over 30 min) with patients in either the supine (N.=29; Supine group) or prone position (N.=23; Prone group). Fluid responsiveness was defined as an increase in the stroke volume index (SVI) of ≥20% at T30. Receiver-operating characteristics (ROC) curves were generated for SVV. RESULTS: Prone positioning significantly increased SVV. Volume expansion in the Prone group increased SVI but led to a decline in SVV from 16% (12-22; median, 25-75th percentile) at T0 to 9% (8-13%) at T30. These effects on SVI and SVV were more pronounced compared to those obtained in the Supine group (P ≤0.05). Fluid responsiveness was predicted by SVV >12% at T0 (sensitivity 88%, specificity 62%) in the Supine group. In the Prone group, the area under the ROC curve of SVV (0.53; 95% confidence interval 0.27-0.79) did not allow the determination of a threshold SVV value. CONCLUSION: In ventilated patients with low tidal volume, a prone position may have a direct effect on the heart that alters the performance of SVV in predicting fluid responsiveness. External factor such as prone position renders difficult the interpretation of SVV as a dynamic indicator of cardiac preload.

Physical exercise during remobilization restores a normal bone trabecular network after tail suspension-induced osteopenia in young rats.

To determine how bone recovers from immobilization-induced bone loss and to specify whether its recovering capacity is improved by physical exercise, 5-week-old male Wistar rats (287.07 g +/- 10.65 SD) were tail suspended for 14 days, then returned to either normal weight-bearing (R) or controlled physical exercise for 28 days (R + E). Bone mineral density (BMD) was measured in three parts of the femur. Using histomorphometric analysis, bone mass and architecture were estimated in the primary (1 degree sp) and secondary spongiosa (2 degrees sp) of the proximal tibial metaphysis. Bone cellular parameters were measured in the 2 degrees sp of the tibia. Tail suspension induced a significant decrease in BMD, 2 degrees sp bone mass, mineral apposition rate, and bone formation rate and marked alterations of the trabecular network. In R rats, BMD was still significantly decreased, except in the distal part of the femur. Long-bone lengthening was significantly altered. The 2 degrees sp bone mass returned to the age-matched control values; however, the trabeculae were still significantly thinner and bone resorption was significantly higher. R + E rats had a normal long bone lengthening and a significant increase in 2 degrees sp bone mass and trabecular thickness when compared with R rats. Bone resorption was significantly depressed, and osteoid surfaces and thickness were significantly increased. Thus, although bone mass returns to normal values in the R group, trabecular alterations persist.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of feasibility of automated osteoblastic line culture in space flight.

There is a large body of evidence that microgravity- or immobilization-induced bone loss is mainly related to osteoblastic cell impairment. Osteoblasts are sensitive to increased mechanical stress and could therefore be responsible for unloading-induced bone changes. However, the nature of osteoblast involvement remains unclear. The effects of the space environment on cells have been studied extensively, but little information about anchorage-dependent cell cultures of the 25 different cell types flown in space has been published. We studied the effects of long-term weightlessness on the cell shape of cultured osteoblasts during the Russian Bion 10 space-flight. This experiment required the development of special automatic culture devices (the plunger-box culture system) finalized with the constructors. Multiple feasibility experiments were performed to allow osteoblast culture for 6 days in microgravity. The study revealed plunger-box biocompatibility; optimization of ROS 17/2.8 (mammalian adherent cells) culture under closed conditions (without gas exchange); and transport of viable cells for 5 days. During the 6 days of microgravity, the growth curves of ground controls and cells in space were roughly similar. Alkaline phosphatase activity was enhanced twofold in microgravity. ROS 17/2.8 cell morphology began to change significantly after 4 days of microgravity; they became rounder and covered with microvilli. At the end of the flight, the cells exhibited mixed morphological types, piling cells, stellar shape, and spread out cells, resembling ground controls or 1g flight controls (centrifuge). We demonstrated that ROS 17/2.8 cells were viable during a 6 day automatic culture in space and were sensitive to space related conditions. They adapted their structure and function to this environment, characterized by loss of mechanical stimuli.

Fat in bone xenografts: importance of the purification procedures on cleanliness, wettability and biocompatibility.

Xenografting is a promising alternative to allografts and autografts. The remaining lipids in bone are known to influence the biocompatibility. A comparative study of wettability was done on standardized blocks of two biomaterials. A highly purified and defatted bovine bone graft (T650) was found to retain more water (2.06 g/block) than a less defatted biomaterial (T360, 0.3 g/block). Wettability, observed in the laboratory, may reflect an important in vivo property: the rapidity for extracellular fluids and blood cells to invade the graft and carry bone forming cells. When implanted in rabbit cancellous bone, T650 appears to be osteoconductive in a manner that allows trabecular architecture to be restored within 6 months.

Histomorphometric analyses of cancellous bone from COSMOS 2044 rats.

The influence of 14 days of spaceflight on cancellous bone of male Wistar rats was assessed by histomorphometric analysis. In proximal tibia, no difference was found between flight, synchronous, vivarium, and basal groups for epiphyseal bone volume or trabecular arrangement. In metaphysis, primary spongiosa width was reduced in flight rats, suggesting an alteration in bone longitudinal growth. In flight rats, secondary spongiosa evidenced a trend toward decreased bone mass, trabecular number and thickness, and osteoid surfaces, whereas there was a tendency toward increased osteoclast number compared with vivarium control but not with synchronous rats. In femoral fossa trochanteri, an area facing deep muscular insertions, no changes in bone volume or structure were noted among the different groups. However, a reduction of osteoid surfaces was seen in flight and synchronous groups compared with the other groups. Resorption activity was increased in flight rats compared with control rats. In thoracic vertebral body, osteoblastic surfaces decreased similarly in flight and synchronous rats. In lumbar vertebral body, decreased osteoblastic surfaces and increased osteoclastic parameters were observed in flight and synchronous rats. The more striking effects of spaceflight were the decrease in tibial primary spongiosa width and the increase in resorption activity of the femoral fossa trochanteri. In all other sites, cellular alterations appeared similar in flight and synchronous rats, suggesting a role for physiological stress. The time course of events would depend on initial growth and turnover rates of bone, its weight-bearing function on earth, and the presence of muscular insertions.

Adverse effects of strenuous exercise: a densitometric and histomorphometric study in the rat.

To investigate the manner in which cancellous bone in different skeletal sites and within a bone site adapts to strenuous training, 5-wk-old male rats were subjected to intensive treadmill running [80% of maximal O2 consumption (VO2max)] for 11 wk. VO2max, tibia length, and bone mineral density were measured. Histomorphometric analysis was performed in the epiphysis, primary spongiosa (1 zero sp) and secondary spongiosa (2 zero sp) of the contralateral proximal tibia, and the 2 zero sp of thoracic and lumbar vertebrae. VO2max was increased by 39%. No changes were observed in vertebrae. Tibia length, 1 zero sp bone volume, and number of trabeculae were significantly decreased, indicating a retarded longitudinal bone growth. Bone mineral density in the proximal tibia was significantly decreased. In the epiphysis, a trabecular thinning and an increase of trabecular number were shown. In the 2 zero sp, bone volume and number of trabeculae were significantly decreased. The increased total eroded surfaces could indicate an early but transient increase in bone resorption activity. Osteoid thickness was reduced, whereas osteoclast number and osteoid surfaces were unchanged, suggesting that the observed bone loss was mostly due to an impaired osteoblastic activity. In conclusion, 1) strenuous training in young rats reduces longitudinal bone growth and induces bone loss, 2) the cancellous bone adaptation is site specific, and 3) the bone loss is mainly due to decreased osteoblastic activity rather than a global adaptation of bone remodeling.

Colorimetric evaluation of cultured osteoblast-like cells (ROS 17/2.8).

We have developed a colorimetric method for evaluating the number of osteoblastic cells in culture without destroying the cells. This assay is based on the staining of basophilic cellular compounds with methylene blue. The dye bound by the cells is released at low pH and measured in a spectrophotometer at 662 nm. Linear correlations exist between the absorbance measured by the methylene blue assay and the number of cells seeded, the total cellular protein content, and thymidine labeling. This colorimetric method has the advantage of preserving cell integrity. After destaining, scanning electron microscopy can be performed on well preserved cell morphology.

Hematology and serum biochemistry values of free-ranging red howler monkeys (Alouatta seniculus) from French Guiana.

One hundred twenty-two wild red howler monkeys (Alouatta seniculus) were translocated during flooding of the forest at a hydroelectric dam site in French Guiana. Blood samples from 103 animals were evaluated for 13 hematologic and/or 22 serum chemistry parameters. Significant age-specific variation was found for white blood cell (WBC), lymphocyte, and platelet counts and for alkaline phosphatase values. Adult males and females had significant differences in red blood cell count, packed cell volume, and hemoglobin, creatinine, cholesterol, and calcium values. In juveniles, amylase and cholesterol levels were significantly lower in males than in females. Significant differences associated with reproductive status were also observed; i.e., lower cholesterol level in pregnant females and higher packed cell volume in lactating females. Chronic stress due to habitat disappearance may have been responsible for significant differences between thin animals and those in good condition. Thin animals had lower WBC, eosinophil, basophil, and monocyte counts and higher platelet counts. Capture stress was probably responsible for high and variable levels of creatine kinase, aspartate aminotransferase, and lactate dehydrogenase.

Crenobalneotherapy (spa therapy) in patients with knee and generalized osteoarthritis: a post-hoc subgroup analysis of a large multicentre randomized trial.

OBJECTIVE: To determine whether the addition of spa therapy to home exercises provides any benefit over exercises and the usual treatment alone in the management of generalised osteoarthritis associated with knee osteoarthritis. METHODS: This study was a post-hoc subgroup analysis of our randomised multicentre trial (www.clinicaltrial.gov: NCT00348777). Participants who met the inclusion criteria of generalized osteoarthritis (Kellgren, American College of Rheumatology, or Dougados criteria) were extracted from the original randomised controlled trial. They had been randomised using Zelen randomisation. The treatment group received 18days of spa treatment in addition to a home exercise programme. Main outcome was number of patients achieving minimal clinically important improvement at six months (MCII) (≥-19.9mm on the VAS pain scale and/or ≥-9.1 points in a WOMAC function subscale), and no knee surgery. Secondary outcomes included the "patient acceptable symptom state" (PASS) defined as VAS pain ≤32.3mm and/or WOMAC function subscale ≤31 points. RESULTS: From the original 462 participants, 214 patients could be categorized as having generalised osteoarthritis. At sixth month, 182 (88 in control and 94 in SA group) patients, were analysed for the main criteria. MCII was observed more often in the spa group (n=52/94 vs. 38/88, P=0.010). There was no difference for the PASS (n=19/88 vs. 26/94, P=0.343). CONCLUSIONS: This study indicates that spa therapy with home exercises may be superior to home exercise alone in the management of patients with GOA associated with knee OA.

Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis.

BACKGROUND: Isolated distal deep vein thrombosis (iDDVT) (i.e. without proximal DVT or pulmonary embolism) represents half of all cases of lower limb DVT. Its clinical significance and management are controversial. Data on long-term follow-up are scarce, especially concerning risk and predictors of venous thromboembolism (VTE) recurrence. METHODS: Using data from the OPTIMEV (OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux) study, a prospective, observational, multicenter study, we compared, 3 years after an index VTE event and after discontinuation of anticoagulants, (i) the incidence and type of recurrence in patients without cancer with a first iDDVT vs. a first isolated proximal DVT (iPDVT) and (ii) predictors of recurrence after iDDVT. RESULTS: Compared with patients with iPDVT (n = 259), patients with an iDDVT (n = 490) had a lower annualized incidence of overall VTE recurrence (5.2% [95% confidence interval 3.6-7.6] vs. 2.7% [1.9-3.8], respectively; P = 0.02) but a similar incidence of pulmonary embolism recurrence (1.0% [0.5-2.3] vs. 0.9% [0.5-1.6], respectively; P = 0.83). An age of > 50 years, unprovoked character of index iDDVT, and involvement of more than one vein in one or both legs each independently tripled the risk of recurrence, with the latter then being ≥ 3% per patient-year. Neither muscular vein nor deep-calf vein location of iDDVT nor clot diameter with compression influenced the risk of recurrence. CONCLUSIONS: After stopping anticoagulants, patients with iDDVT have a significantly lower risk of overall VTE recurrence than did patients with iPDVT but a similar risk of serious recurrent VTE. Age > 50 years, unprovoked iDDVT, and number of thrombosed veins (more than one) influenced the risk of recurrence and may help to define patients at significant risk of recurrence.

Impact of anatomical location of lower limb venous thrombus on the risk of subsequent cancer.

After a proximal deep-vein thrombosis (P-DVT), the risk of diagnosis of a previously unsuspected cancer is high. Isolated distal DVT (iD-DVT; i.e. infra-popliteal DVT without pulmonary embolism [PE]) and isolated superficial-vein thrombosis (iSVT; i.e. without concomitant DVT and PE) are at least as frequent as P-DVT but their association with subsequent cancer is uncertain. We exploited data from the OPTIMEV prospective, observational, multicentre study to i) compare the risk of subsequent cancer three years after a first objectively confirmed iSVT, iD-DVT and iP-DVT in patients without a prior history of cancer or of venous thromboembolism, ii) assess predictors of subsequent cancer in cases of iD-DVT. The overall cumulative rates of cancer among the 304 patients with iSVT, 536 patients with iD-DVT, and 327 patients with iP-DVT were similar (3.4% 95% confidence interval [1.8-6.2], 3.9% [2.5-5.9] and 3.9% [2.3-6.8], respectively), regardless of whether the index venous thromboembolic event was unprovoked or associated with a major transient risk factor. Neither anatomical (muscular vs deep-calf DVT) nor ultrasound scan characteristics (number of thrombosed veins, clot diameter under compression) seemed strongly associated with the risk of cancer in cases of iD-DVT. In patients managed in routine practice, all the different clinical expressions of lower limb venous thromboembolism are associated with a similar risk of subsequent cancer. From a clinical practice point of view, this suggests that cancer screening, without discussing the necessity, or not, of such screening, should not differ between a deep-proximal, deep-distal or superficial location of thrombosis.