High-fidelity vibrokinetic stimulation induces sustained changes in intercortical coherence during a cinematic experience.

OBJECTIVE: High-fidelity vibrokinetic (HFVK) technology is widely used to enhance the immersiveness of audiovisual (AV) entertainment experiences. However, despite evidence that HFVK technology does subjectively enhance AV immersion, the underlying mechanism has not been clarified. Neurophysiological studies could provide important evidence to illuminate this mechanism, thereby benefiting HFVK stimulus design, and facilitating expansion of HFVK technology. APPROACH: We conducted a between-subjects (VK, N = 11; Control, N = 9) exploratory study to measure the effect of HFVK stimulation through an HFVK seat on electroencephalographic cortical activity during an AV cinematic experience. Subjective appreciation of the experience was assessed and incorporated into statistical models exploring the effects of HFVK stimulation across cortical brain areas. We separately analyzed alpha-band (8-12 Hz) and theta-band (5-7 Hz) activities as indices of engagement and sensory processing, respectively. We also performed theta-band (5-7 Hz) coherence analyses using cortical seed areas identified from the theta activity analysis. MAIN RESULTS: The right fusiform gyrus, inferiotemporal gyrus, and supramarginal gyrus, known for emotion, AV-spatial, and vestibular processing, were identified as seeds from theta analyses. Coherence from these areas was uniformly enhanced in HFVK subjects in right motor areas, albeit predominantly in those who were appreciative. Meanwhile, compared to control subjects, HFVK subjects exhibited uniform interhemispheric decoherence with the left insula, which is important for self-processing. SIGNIFICANCE: The results collectively point to sustained decoherence between sensory and self-processing as a possible mechanism for how HFVK increases immersion, and that coordination of emotional, spatial, and vestibular processing hubs with the motor system may be required for appreciation of the HFVK-enhanced experience. Overall, this study offers the first ever demonstration that HFVK stimulation has a real and sustained effect on brain activity during a cinematic experience.

Lactose malabsorption in systemic sclerosis.

BACKGROUND: There are no studies on systemic sclerosis (SSc) assessing the relationship between food intake, especially lactose, and gastrointestinal dysfunction. AIM: To determine the prevalence of lactose malabsorption, using lactose breath test, in patients with SSc. To evaluate the correlation between lactose malabsorption and gastrointestinal involvement. To predict which SSc patients exhibit lactose malabsorption. METHODS: Seventy-seven consecutive Caucasian patients with SSc and 20 control subjects underwent lactose breath test. All patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. RESULTS: The prevalence of lactose malabsorption was higher in SSc patients than in controls (44.3% vs. 10%; P = 0.004). We observed a marked correlation between the presence of lactose malabsorption and: higher values of GSS (P < 0.0001); severe oesophageal (P = 0.018) and small intestinal (P = 0.04) motor disorders; and joint involvement (P = 0.019). Furthermore, in SSc patients with symptomatic lactose malabsorption, the median value of GSS of digestive symptoms was lower after initiation of lactose-free diet (P < 0.0001). CONCLUSIONS: Our study underscores the fact that lactose malabsorption often occurs in patients with systemic sclerosis. Furthermore, our findings highlight the fact that lactose breath test is a helpful, noninvasive method, by identifying the group of patients with systemic sclerosis with symptomatic lactose malabsorption that may benefit from a reduction in lactose intake.

Long term outcome of patients with low level of cryoglobulin (<0.05g/L).

OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤0.05 g/L. We showed that patients with cryoglobulin level ≤0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level ≤0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level ≤0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry?

BACKGROUND: Anal manometry is the standard technique for evaluating anal sphincter function. However, the functional lumen imaging probe (EndoFLIP(®) ) can be used to measure sphincter distensibility during volume-controlled distensions. Our aims were (i) to assess anal distensibility in patients with fecal incontinence (FI) and in healthy subjects using the EndoFLIP(®) and (ii) to compare the results with anal pressures measured by 3D high-resolution manometry (3D-HRM) to determine whether the EndoFLIP(®) was more sensitive and specific for diagnosing FI than 3D-HRM. METHODS: EndoFLIP(®) and 3D-HRM assessments of 34 female FI patients and 40 healthy female subjects were performed. Anal distensibility was measured as the median cross-sectional area at the narrowest point divided by the corresponding intra-bag pressure at rest and during peak voluntary contraction and was expressed in mm(2) /mmHg. KEY RESULTS: A 40-mL anal distensibility index was selected for further comparisons as it provided the best discrimination between the FI patients and the healthy subjects. The index was significantly higher in the FI patients than in the healthy subjects at rest (p = 1.10(-4) ) and during voluntary contraction (p = 1.10(-4) ). The index at rest and during voluntary contraction appeared to be more appropriate than anal pressures for discriminating between FI patients and healthy subjects. CONCLUSIONS & INFERENCES: The present study confirmed that FI is associated with an abnormally high distensibility index at rest and during voluntary contraction. The ability of the distensibility index to discriminate between FI patients and healthy subjects was significantly better than anal pressure.

Is coracoclavicular stabilisation alone sufficient for the endoscopic treatment of severe acromioclavicular joint dislocation (Rockwood types III, IV, and V)?

BACKGROUND: The primary objective was to evaluate correlations linking anatomical to functional outcomes after endoscopically assisted repair of acute acromioclavicular joint dislocation (ACJD). HYPOTHESIS: Combined acromioclavicular and coracoclavicular stabilisation improves radiological outcomes compared to coracoclavicular stabilisation alone. MATERIAL AND METHODS: A prospective multicentre study was performed. Clinical outcome measures were pain intensity on a visual analogue scale (VAS), subjective functional impairment (QuickDASH score), and Constant's score. Anatomical outcomes were assessed on standard radiographs (anteroposterior view of the acromioclavicular girdle and bilateral axillary views) obtained preoperatively and postoperatively and on postoperative dynamic radiographs taken as described by Tauber et al. RESULTS: Of 116 patients with acute ACJD included in the study, 48% had type III, 30% type IV, and 22% type V ACJD according to the Rockwood classification. Coracoclavicular stabilisation was achieved using a double endobutton in 93% of patients, and concomitant acromioclavicular stabilisation was performed in 50% of patients. The objective functional outcome was good, with an unweighted Constant's score ≥ 85/100 and a subjective QuickDASH functional disability score ≤ 10 in 75% of patients. The radiographic analysis showed significant improvements from the preoperative to the 1-year postoperative values in the vertical plane (decrease in the coracoclavicular ratio from 214 to 128%, p=10(-6)) and in the horizontal plane (decrease in posterior displacement from 4 to 0mm, p=5×10(-5)). The anatomical outcome correlated significantly with the functional outcome (absolute R value=0.19 and p=0.045). We found no statistically significant differences across the various types of constructs used. Intra-operative control of the acromioclavicular joint did not improve the result. Implantation of a biological graft significantly improved both the anatomical outcome in the vertical plane (p=0.04) and acromioclavicular stabilisation in the horizontal plane (p=0.02). The coracoclavicular ratio on the anteroposterior radiograph was adversely affected by a longer time from injury to surgery (p=0.02) and by a higher body mass index (BMI) (p=0.006). High BMI also had a negative effect on the difference in the distance separating the anterior edge of the acromion from the anterior edge of the clavicle between the injured and uninjured sides, as assessed on the axillary views (p=0.009). CONCLUSION: This study demonstrates that acute ACJD requires stabilisation in both planes, i.e., at the coracoclavicular junction and at the acromioclavicular joint. Coracoclavicular stabilisation alone is not sufficient, regardless of the type of implant used. Implantation of a biological graft should be considered when the time from injury to surgery is longer than 10days. The weight of the upper limb should be taken into account, with 6weeks of immobilisation to unload the construct in patients who have high BMI values. LEVEL OF EVIDENCE: II, prospective non-randomised comparative study.

Prognostic factors to succeed in surgical treatment of chronic acromioclavicular dislocations.

INTRODUCTION: Treatment of chronic acromioclavicular joint dislocation (ACJD) remains a poorly known and controversial subject. Given the many surgical options, it is not always easy to determine which steps are indispensable. METHODS: This article reports a multicenter prospective study. The clinical and radiological follow-up involved a comparative analysis of the preoperative and postoperative data at 1 year, including pain (visual analogue scale), subjective functional incapacity (QuickDASH), and the objective Constant score, as well as a comparative analysis of vertical and horizontal movements measured on simple x-rays. RESULTS: Based on a series of 140 operated ACJDs, we included 24 chronic ACJDs. The mean time to surgery was 46 weeks (range, 1 month to 4 years). The patients' mean age was 41 years, with a majority of males (75%), 72% of whom participated in recreational sports. Professionally, 40% of the subjects had jobs involving manual labor. We noted 40% grade III, 24% grade IV, and 36% grade V injury according to the Rockwood classification. In 92% of cases, coracoclavicular stabilization was provided by a double button implant, reinforced with a biological graft in 88% of the cases. In 29%, millimeters to centimeters of the distal clavicle were resected and acromioclavicular stabilization was associated in 54%. We observed complications in 33% of the cases. At 1 year postoperative, 21 patients underwent clinical and radiological follow-up (87.5%). Only 35% of the patients were satisfied or very satisfied, whereas 100% of them would recommend the operation. Full-time work was resumed in 91% of the cases and all sports could be resumed in 86%. The pre- and postoperative values at 1 year changed as follows: the mean Constant score improved from 61 to 87 (p=0.00002); the subjective QuickDASH score decreased from 41 to 9 (p=0.00002); and radiologically significant reduction of the initial displacement was observed in the vertical plane (p<10(-3)) and the horizontal plane (p=0.022). CONCLUSION: In this study, the favorable prognostic factors found were: time to surgery less than 3 months (p=0.02), associated acromioclavicular stabilization, and postoperative immobilization with a sling extended to 6 weeks. However, resection of the distal clavicle did not influence the final result. LEVEL OF PROOF: Level II prospective non-randomized comparative study.

A step towards cinacalcet testing for the diagnosis of primary hyperparathyroidism: comparison with the standardized intravenous calcium loading. A pilot study.

OBJECTIVE: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT. METHODS: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h. RESULTS: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT. CONCLUSION: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC.

Fecal calprotectin in systemic sclerosis and review of the literature.

Fecal calprotectin (FC) is a simple, non-invasive and reproducible test, which has been described to be highly elevated in patients with active inflammatory bowel diseases. Recently, few authors have reported increased levels of FC in SSc patients, although the relationship between FC levels and the degree of gastrointestinal involvement has not yet been determined in patients with SSc. Thus, this prospective study aimed to: 1) determine the prevalence of increased fecal calprotectin (FC) levels in unselected patients with systemic sclerosis (SSc); 2) make prediction about which SSc patients exhibit increased levels of FC; and 3) evaluate the correlation between increased levels of FC and digestive symptoms, and gastrointestinal involvement, including the presence of small intestinal bacterial overgrowth (SIBO) using glucose H2/CH4 breath test. 125 consecutive patients with SSc underwent FC levels and glucose H2/CH4 breath test. All of the patients with SSc also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. 93 (74.4%) patients had abnormal levels of FC (>50 µg/g); 68 patients (54.4%) exhibited highly elevated levels of FC (>200 µg/g). A marked correlation was found between abnormal FC levels and GSS score of digestive symptoms, esophageal involvement and delayed gastric emptying. Moreover, we found a strong association between abnormal levels of FC and the presence of SIBO on glucose H2/CH4 breath test, with the higher correlation between the presence of SIBO and the level of FC ≥275 µg/g with an area under the receiver operating characteristic curve of 0.97 ± 0.001 (CI: 0.93-0.99; p<10(-6)); the sensitivity of FC level ≥275 µg/g for predicting SIBO was as high as 0.93, while the specificity was 0.95. Finally, eradication of SIBO was obtained in 52.4% of the SSc patients with a significant improvement of intestinal symptoms. Finally, after 3 months of rotating courses of alternative antibiotic therapy, eradication of SIBO was associated with significant decrease of FC levels in SSc patients. The current study underscores that abnormal FC levels were correlated with gastrointestinal impairment, especially SIBO. Because FC levels ≥275 µg/g were markedly associated with the presence of SIBO, our findings suggest that FC may be a helpful test in identifying the group of SSc patients at high risk for SIBO requiring glucose breath test to detect SIBO. Finally, we also suggest that FC levels may be helpful in SSc patients to assess SIBO eradication, as long-term antibiotic therapy is costly and carries risks such as the onset of pseudo-membranous colitis and SIBO-related antibiotic resistance.

Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo-controlled pilot study.

AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. RESULTS: There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

Evoked pressure curves from the external anal sphincter following transcranial magnetic stimulation in healthy volunteers and patients with faecal incontinence.

AIM: The hypothesis was tested that evoked pressure curves (EPCs) after transcranial magnetic stimulation (TMS) would provide additional neuropathophysiological information on the descending pathways to the external anal sphincter (EAS) in patients with faecal incontinence (FI). METHOD: Twenty-five healthy subjects and 69 patients with FI were investigated. TMS was applied to the vertex, and EPCs were recorded with a probe placed through the EAS. TMS was performed with the EAS at rest and during contraction (facilitated responses). At least three responses were recorded for each modality. Clinical data and anorectal manometric, electrophysiological perineal and transanal ultrasound recordings were compared with respect to the EPC results. RESULTS: There was no statistically significant difference between the EPCs of healthy subjects and FI patients. Twenty-three per cent of the FI patients had abnormal EPC latencies, with significantly lower voluntary contraction amplitudes (P = 0.03) and significantly higher rectal sensation (P = 0.04) than the other group. We found no significant difference between FI patients with and without abnormal EPC latencies in terms of clinical characteristics and electrophysiological and endoanal ultrasound parameters. There was no difference in the identified causes of the FI between the two groups. CONCLUSION: As abnormal EPC latencies were found in 23% of FI patients with no known central neurological disease, abnormal EPC latencies might reveal undetected lesions of descending pathways in patients with FI.

Clinical manifestations and outcome of anti-PL7 positive patients with antisynthetase syndrome.

BACKGROUND: The aims of the present study were to determine both clinical manifestations and outcome of anti-PL7 patients with antisynthetase syndrome (ASS). METHODS: The medical records of 15 consecutive anti-PL7 patients with biopsy proven ASS were retrospectively analyzed without prior selection. RESULTS: Anti-PL7 patients exhibited polymyositis (n=14) and dermatomyositis (n=1); extra-pulmonary manifestations of ASS included: Raynaud's phenomenon (40%), mechanic's hands (33.3%), joint impairment (26.7%), pericardial effusion (20%) and esophageal/gastrointestinal involvement (20%). The outcome of myositis was as follows: remission/improvement (91.7%) and deterioration (8.3%). Fourteen patients (93.3%) experienced interstitial lung disease (ILD). ILD preceded ASS diagnosis (n=5), was identified concomitantly with ASS (n=8) and occurred after ASS diagnosis (n=1). Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n=1), progressive onset of lung signs (n=11) and asymptomatic patients exhibiting abnormalities consistent with ILD on PFT and HRCT-scan (n=2). No patient had resolution of ILD, whereas 64.3% and 35.7% experienced improvement and deterioration of ILD, respectively. ILD resulted in respiratory insufficiency requiring O2 therapy in 14.3% of cases. Two patients died. Predictive parameters of ILD deterioration were: DLCO<45% at ILD diagnosis and HRCT-scan pattern of usual interstitial pneumonia (UIP). CONCLUSION: Our series mainly underscores that ILD is frequent in anti-PL7 patients, leading to high morbidity. Our study further suggests that patients with predictive factors of ILD deterioration may require more aggressive therapy, especially the group of patients with DLCO<45% at ILD diagnosis and UIP pattern on HRCT-scan.

Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome.

OBJECTIVE: To assess the outcome of interstitial lung disease (ILD) in anti-Jo-1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti-Jo-1 patients with and without ILD. METHODS: Ninety-one anti-Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. RESULTS: Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n = 12), progressive onset of lung signs (n = 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n = 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age ≥55 years. Furthermore, anti-Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. CONCLUSION: Our findings confirm that ILD is a frequent complication in anti-Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti-Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype.

Transcutaneous electrical tibial nerve stimulation in the treatment of fecal incontinence: a randomized trial (CONSORT 1a).

OBJECTIVES: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials. METHODS: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events. RESULTS: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b). CONCLUSIONS: We failed to demonstrate any benefit of TENS on our primary end-point.

[Hypothermia at admission increases the risk of pulmonary contusion's infection in intubated trauma patients]. / L'hypothermie à l'admission augmente le risque d'infection des contusions pulmonaires chez les patients polytraumatisés sous ventilation invasive.

OBJECTIVES: Pulmonary contusion (PC) is common in cases of polytrauma. The aim of this study was to perform a multivariate analysis of risk factors associated with the occurrence of infection in PC and analyze the microbiological epidemiology. PATIENTS AND METHODS: All patients with PC admitted to the intensive care unit (ICU) between January 2002 and December 2006 were included in this retrospective observational study. Patients with penetrating thoracic trauma or those who died in the 48hours following admission to hospital were excluded. Diagnosis of bacterial infection in PC was performed if hyperthermia was associated with a positive quantitative culture (103 colony forming units/mL) on the bronchial sample. Univariate analysis provided statistical difference between variables that were integrated in the multivariate analysis model. Multivariate analysis was then performed to determine the risk factors of bacterial infection in PC. RESULTS: One hundred and seventeen patients were included. The incidence of bacterial infection in PC was 33.3% (39 patients). The most frequently encountered bacteria were Haemophilus sp., Staphylococcus aureus, Enterobacteriaceae, Pseudomonas sp. and Streptococcus sp. According to multivariate analysis, the existence of hypothermia at hospital admission increased the risk of PC infection (OR=2.61; IC 95% [4.2-13.3]). CONCLUSION: In conclusion, PC was infected in 33.3% of cases. The existence of hypothermia was identified as a risk factor. A prospective study is warranted to confirm these results.

Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME).

With the motile sperm organelle morphology examination (MSOME), spermatozoa morphology may be assessed directly on motile spermatozoa at high magnification (up to 6600×). This procedure describes more precisely spermatozoa abnormalities, especially head vacuoles. However, no consensus has been established concerning normal or abnormal MSOME criteria. The aim of our study was to define MSOME vacuole criteria assessed objectively with a digital imaging system software to establish a potential relationship between conventional semen parameters. A total of 440 semen samples were obtained from males consulting in Rouen University Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume, sperm concentration, progressive motility, vitality and morphology) and MSOME assessment {sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head [RVA (%) = [vacuole area (µm(2))/head area (µm(2))] × 100)]} were performed for each semen sample. Among our 440 males, 109 presented normal conventional semen parameters and 331 abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen samples (p < 0.0001). RVA was the most discriminative MSOME criterion between normal and abnormal semen samples according to ROC curves analysis, and was negatively correlated with poor sperm morphology (r = -0.53, p < 0.0001). We concluded to (i) the normal occurrence of vacuoles in sperm head whatever the normality or abnormality of semen parameters, (ii) the discriminative function of the RVA to distinguish semen samples with normal and abnormal parameters, and (iii) the strong correlation between high RVA and poor sperm morphology.

Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome.

The aims of the present study were to: compare the characteristics between antisynthetase syndrome (ASS) patients with anti-Jo1 antibody and those with anti-PL7/PL12 antibody. The medical records of 95 consecutive patients with ASS were reviewed. Seventy-five of these patients had anti-Jo1 antibody; the other patients had anti-PL7 (n=15) or anti-PL12 (n=5) antibody. At ASS diagnosis, the prevalence of myalgia (p=0.007) and muscle weakness (p=0.02) was significantly lower in the group of anti-PL7/PL12-positive patients than in those with anti-Jo1 antibody; median value of CK (p=0.00003) was also lower in anti-PL7/PL12 patients. Anti-Jo1 positive patients developed more rarely myositis resolution (21.3% vs. 46.2%); in addition, the overall recurrence rate of myositis was higher in anti-Jo1 positive patients than in patients with anti-PL7/PL12 antibody (65.9% vs. 19.4%). Anti-Jo1-positive patients, compared with those with anti-PL7/PL12 antibody, more often experienced: joint involvement (63.3%vs. 40%) and cancer (13.3% vs. 5%). By contrast, anti-PL7/PL12 positive patients, compared with those with anti-Jo1 antibody, more commonly exhibited: ILD (90% vs. 68%); in anti-PL7/PL12 positive patients, ILD was more often symptomatic at diagnosis, and led more rarely to resolution of lung manifestations (5.6% vs. 29.4%). Finally, the group of anti-PL7/PL12 positive patients more commonly experienced gastrointestinal manifestations related to ASS (p=0.02). Taken together, although anti-Jo1 positive patients with ASS share some features with those with anti-PL7/PL12 antibody, they exhibit many differences regarding clinical phenotype and long-term outcome. Our study underscores that the presence of anti-Jo1 antibody results in more severe myositis, joint impairment and increased risk of cancer. On the other hand, the presence of anti-PL7/PL12 antibody is markedly associated with: early and severe ILD, and gastrointestinal complications. Thus, our study interestingly indicates that the finding for anti-Jo1 and anti-PL7/PL12 antibodies impacts both the long-term outcome and prognosis of patients with ASS.

Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome.

OBJECTIVE: To report our experience using rituximab as therapy for refractory antisynthetase syndrome (ASS)-associated interstitial lung disease. METHODS: We retrospectively evaluated the medical records of 7 ASS patients with refractory interstitial lung disease, which had previously failed to respond to prednisone and/or other cytotoxic drugs. All 7 patients received rituximab therapy, i.e.: 1 g at days 0 and 14 and at 6-month follow-up. Data on pulmonary symptoms, pulmonary function tests and high resolution computed tomography (HRCT) scan of the lungs were collected: (1) before rituximab initiation; and (2) at 6-month and one-year follow-up after the first infusion of rituximab. RESULTS: At one-year follow-up, ASS patients had resolution (n = 2) or improvement of pulmonary clinical manifestations. Patients also exhibited significant improvement of interstitial lung disease parameters: 1) on pulmonary function tests: FVC (p = 0.03) and DLCO (p = 2 × 10(-5)); 2) and HRCT-scan of the lungs. Due to clinical resolution/improvement of interstitial lung disease, the median daily dose of oral prednisone could be reduced in these 7 ASS patients at one-year follow-up, compared with baseline (20 mg/day vs. 9 mg/day; p = 0.015). CONCLUSION: Our findings suggest that rituximab may be a helpful therapy for refractory interstitial lung disease in patients with ASS.

Risk factors of vitamin K antagonist overcoagulation.

OBJECTIVES: The aims of this prospective study were to identify, in vitamin K antagonist (VKA)-treated patients, factors associated with INR values: (i) greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. METHODS: During a 6-month period, 3090 consecutive patients were referred to our Department of Internal Medicine, including 412 VKA-treated patients. At admission, the medical records of VKA-treated patients were reviewed for type, duration and indication of VKA therapy, previous medical history of VKA-related hemorrhage, comorbidities and concomitant medications. RESULTS: Forty of the 412 VKA-treated patients (9.7%) exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was associated with high morbidity, leading to major bleeding in 27.5% of cases; moreover, 12.5% of these patients died, death being mainly due to major bleeding. Under multivariate analysis, significant factors for VKA-related overcoagulation were as follows: previous medical history of VKA therapy-related hemorrhage (P=0.00001) and INR levels over therapeutic range (P=0.0006), chronic liver disease (P=0.03), therapy with amiodarone (P=0.009); in contrast, statin therapy was found to be a protective factor of VKA overcoagulation (P=0.008). CONCLUSIONS: The knowledge of predictive factors of VKA-related overcoagulation seems of utmost importance to improve patients' management. Our study underlines the fact that the potential of drug interaction should be taken into account when choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6 month) statin therapy may be a protective factor of VKA overcoagulation. Our findings, therefore, suggest that there may be no need to switch long-term users of VKA and statin to a safer alternative therapy.

Hematological malignancy associated with polymyositis and dermatomyositis.

The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin's disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients.

Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients.

OBJECTIVE: This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) and to determine variables predictive of ILD deterioration in PM/DM. METHODS: Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high-resolution computed tomography (HRCT) scan. RESULTS: ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n = 20), patients with progressive-course lung signs (n = 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n = 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid-refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%). CONCLUSION: Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome.