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.

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.

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.

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.

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.

Predictive factors for successful sacral nerve stimulation in the treatment of faecal incontinence: results of trial stimulation in 200 patients.

AIM: Sacral nerve stimulation (SNS) has a place in the treatment algorithm for faecal incontinence (FI). However, after implantation, 15-30% of patients with FI fail to respond for unknown reasons. We investigated the effect of SNS on continence and quality of life (QOL) and tried to identify specific predictive factors of the success of permanent SNS in the treatment of FI. METHOD: Two hundred consecutive patients (six men; median age = 60; range 16-81) underwent permanent implantation for FI. The severity of FI was evaluated by the Cleveland Clinic Score. Quality of life was evaluated by the French version of the American Society of Colon and Rectal Surgeons (ASCRS) quality of life questionnaire (FIQL). All patients underwent a preoperative evaluation. After permanent implantation, severity and QOL scores were reevaluated after six and 12 months and then once a year. RESULTS: The severity scores were significantly reduced during SNS (P = 0.001). QOL improved in all domains. At the 6-month follow-up, the clinical outcome of the permanent implant was not affected by age, gender, duration of symptoms, QOL, main causes of FI, anorectal manometry or endoanal ultrasound results. Only loose stool consistency (P = 0.01), persistent FI even though diarrhoea was controlled by medical treatment (P = 0.004), and low stimulation intensity (P = 0.02) were associated with improved short-term outcomes. Multivariate analysis confirmed that loose stool consistency and low stimulation intensity were related to a favourable outcome. CONCLUSION: Stool consistency and low stimulation intensity have been identified as predictive factors for the short-term outcome of SNS.

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.

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.

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.

Nosocomial febrile illness in the elderly: frequency, causes, and risk factors.

BACKGROUND: Although nosocomial febrile illness (NFI) is common in hospitalized patients, it has been less extensively studied in the elderly. OBJECTIVE: To determine the frequency, causes, and risk factors of NFI in elderly inpatients. METHODS: This prospective study involved 608 patients (> or = 65 years of age) admitted in an acute geriatric unit. Investigators followed this cohort until 1 of the following events occurred: development of NFI, discharge from the geriatric unit, or death. The cause of NFI was classified into 3 groups: infectious, noninfectious, and no apparent diagnosis. We systematically studied 17 comorbid conditions, 6 drugs, and 7 invasive procedures. For comparison, the patients were stratified into 2 groups: patients with NFI and patients without NFI. RESULTS: Sixty-six patients (10.9%) with NFI were identified. They were compared with the remaining 542 patients without NFI. In 49 patients (74%) with NFI, the cause was infectious; in 9 (13.5%), it was noninfectious; and in 8 (12.5%), there was no apparent cause. After multivariate analysis, only fecal incontinence (odds ratio [OR], 5.54; 95% confidence interval [CI], 2.13-14.5), congestive heart failure (OR, 2.97; 95% CI, 1.53-5.76), and pressure ulcers (OR, 2.93; 95% CI, 1.19-7.17) were independent risk factors for NFI. The number of invasive procedures preceding the febrile episode was a significant predictor of infection (OR, 3.68; 95% CI, 1.14-9.21). CONCLUSIONS: Nosocomial febrile illness is a common event in elderly hospitalized patients. In 74% of the patients with NFI, an infection is found. Measures to decrease infectious NFI in the elderly require a reduction in the number of invasive procedures.

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.

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.

Plasma 3-methoxy-4-hydroxyphenylglycol and homovanillic acid measurements in deficit and nondeficit forms of schizophrenia.

BACKGROUND: Discrepancies in the biochemical research on negative symptoms in schizophrenia may be ascribed to the lack of differentiation into primary and secondary negative symptoms. We have used Carpenter's criteria to define the deficit syndrome of schizophrenia as the presence of enduring and primary negative symptoms and measured catecholaminergic parameters in deficit as compared with nondeficit schizophrenics. METHODS: We have investigated plasma homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG) concentrations in 34 DSM-III-R neuroleptic-treated schizophrenic patients who were classified into deficit (n = 14) and nondeficit (n = 20) forms of schizophrenia. All these patients were in a stable clinical and therapeutic status for the preceding 12 months. RESULTS: The 14 deficit schizophrenic patients had lower plasma levels of pHVA and higher plasma concentrations of pMHPG from 9 AM to 12 AM as compared with the 20 nondeficit schizophrenic patients. The two groups did not differ on any demographic, therapeutic, or clinical variable considered. CONCLUSIONS: Our data are consistent with the postulated distinct pathophysiological basis for the deficit syndrome of schizophrenia and suggest that opposite alterations in the pHVA or pMHPG levels may reflect specific changes in noradrenergic and dopaminergic functions in these deficit patients.

No evidence for involvement of KCNN3 (hSKCa3) potassium channel gene in familial and isolated cases of schizophrenia.

Several studies have reported in schizophrenia a decrease of age of onset in successive family generations, and this observation is consistent with anticipation. Anticipation is known to result from expansion of CAG repeats in several neurodegenerative disorders. Longer alleles of the KCNN3 gene, which contains a highly polymorphic CAG repeat, and encodes a neuronal small conductance calcium-activated potassium channel, have recently been shown to be over-represented in sporadic cases of schizophrenia. In this report, we tested the hypothesis of an association between longer alleles of CAG repeat in the KCNN3 gene and schizophrenia in 20 families with clinical evidence for anticipation and in 151 unrelated schizophrenic cases. No significant difference in the distributions of allele frequencies was observed between familial cases of schizophrenia and controls, and between unrelated cases and controls. Furthermore, no intergenerational CAG repeat instability was detected in the 20 families. Our results do not support the involvement of the KCNN3 (hSKCa3) gene in the etiology of schizophrenia.

Evidence of a cohort effect for age at onset of schizophrenia.

OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may have introduced a bias into anticipation studies of schizophrenia. METHOD: A retrospective review of the medical records of all admissions for psychotic disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis of schizophrenia and age-at-onset data were included (N=419). For analyses, subjects were placed into one of three successive birth cohorts: 1905-1944 (N=96), 1945-1964 (N=200), and 1965-1984 (N=123). RESULTS: The mean age at first appearance of psychotic symptoms and, similarly, the mean age at first hospitalization significantly decreased over time in successive birth cohorts (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at onset of schizophrenia needs to be incorporated into genetic models.

Is presentation of bacteremia in the elderly the same as in younger patients?

OBJECTIVE: To compare the presentation of bacteremia in young and elderly patients. PATIENTS AND METHODS: Seventy-one elderly (mean age 80.4 years) and 34 younger inpatients (mean age 45.7 years) with bacteremia were prospectively studied. These were compared with a control group of 187 geriatric patients (mean age 81.3 years) with clinical signs of bacteremia but in whom blood cultures were negative. Bacteremia was defined as one or more positive blood cultures showing a pathogenic bacteria in patients with clinical signs of bacteremia. In all 105 patients with bacteremia, 16 common clinical or biological signs of the disease were immediately investigated after blood culture. Patients were classified into three groups: elder patients and young patients with bacteremia and elderly patients without bacteremia. RESULTS: Only three clinical findings of the 16 studied were found in at least 70% of the bacteremic elderly patients: fever, increased erythrocyte sedimentation rate, and a clinical indication of the source of infection. These three signs were found statistically more often in bacteremic elderly compared with nonbacteremic elderly patients (P < 0.01). Seven other signs (hypothermia, altered mental state, leukopenia, and lymphopenia) had a specificity above 80%. On a logistic regression analysis, four variables were significantly and independently associated with bacteremia in the elderly: rapid onset of infection (defined as a period < or = 48 hours between the earliest manifestation of bacteremia and the time of blood blood sample), fever, altered general state, and clinical indication of the source of infection. Younger infected patients had more chills, sweating, alter general state, altered mental state or lymphopenia than did the bacteremic elderly patients. Bacteremic elderly patients had statistically few symptoms than the young infected patients (P < 0.001). CONCLUSIONS: In elderly patients with early stage bacteremia, most of the signs or symptoms that are considered typical in the literature appear irregularly. None appeared pathognomonic. Elderly patients with bacteremia had fewer signs or symptoms than younger infected patients.

Post-stroke changes in cortical 5-HT2 serotonergic receptors.

UNLABELLED: Fluorine-18-setoperone PET imaging was used to investigate serotonergic 5-HT2-specific binding in unlesioned cerebral cortex in stroke patients. METHODS: Seventeen stroke patients (mean age 50 +/- 31 yr) with right (n = 9) or left (n = 8) chronic stroke (middle or anterior cerebral artery territory) underwent [18F]setoperone PET and MR imaging. The distribution volume of the 5-HT2-specific binding at equilibrium (DVSe) was determined in the unlesioned cortical regions. The results were compared with those obtained in 14 age-matched controls. In addition, we investigated the effect of the side of the stroke, lesion volume and its localization. RESULTS: After removing the age effect by covariance analysis, we found a significant DVSe decrease in the temporal (p < 0.05) and frontal (p < 0.05) unlesioned cortices ipsilateral to the stroke. The changes were similar in patients with left and right stroke and did not correlate with the volume of the stroke. However, the localization of the stroke affected the topography of DVSe abnormalities. When the lesion did not extend more medially than the internal capsule, DVSe was significantly reduced in the temporal lobe (-30%, p < 0.05) but not in the frontal lobe (-21%, p = ns). Conversely, when the lesion extended subcortically in the anteromedial region, close to the midline, DVSe was reduced in both temporal (-40%, p < 0.05) and frontal (- 49%, p < 0.05) lobes. CONCLUSION: This study confirms that stroke may alter 5-HT2 receptors in large unlesioned cortical areas and that the changes depend on the subcortical extent of the lesion.