Quadriceps strength in intensive care unit survivors: Variability and influence of preadmission physical activity

BackgroundMuscle weakness is common in patients who survive a stay in the intensive care unit (ICU). Quadriceps strength (QS) measurement allows evaluation of lower limb performances that are associated with mobility outcomes.ObjectivesThe objective of the study was to characterise the range of QS in ICU survivors (ICUS) during their short-term evolution, by comparing them with surgical patients without critical illness and with healthy participants. The secondary aim was to explore whether physical activity before ICU admission influenced QS during that trajectory.MethodsPatients with length of ICU stay ≥2 days, adults scheduled for elective colorectal surgery, and young healthy volunteers were included. Maximal isometric QS was assessed using a handheld dynamometer and a previously validated standardised protocol. The dominant leg was tested in the supine position. ICUSs were tested in the ICU and 1 month after ICU discharge, while surgical patients were tested before and on the day after surgery, as well as 1 month after discharge. Healthy patients were tested once only. Patients were classified as physically inactive or active before admission from the self-report.ResultsThirty-eight, 32, and 34 participants were included in the ICU, surgical, and healthy groups, respectively. Demographic data were similar in the ICUS and surgical groups. In the ICU, QS was lower in the ICU group than in the surgical and healthy groups (3.01 [1.88–3.48], 3.38 [2.84–4.37], and 5.5 [4.75–6.05] N/kg, respectively). QS did not significantly improve 1 month after ICU discharge, excepted in survivors who were previously physically active (22/38, 56%): the difference between the two time points was ?6.6 [?27.1 to ?1.7]% vs 20.4 [?3.4 to 43.3]%, respectively, in physically inactive and active patients (p = 0.002).ConclusionsPatients who survived an ICU stay were weaker than surgical patients. However, a huge QS heterogeneity was observed among them. Their QS did not improve during the month after ICU discharge. Physically inactive patients should be early identified as at risk of poorer recovery.     

Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study

OBJECTIVE: To assess the prevalence and severity of peripheral enthesitis among the different subtypes of spondylarthropathy (SpA) by using ultrasonography (US) in B mode with power Doppler. METHODS: One hundred sixty-four consecutive patients with SpA (according to the criteria of the European Spondylarthropathy Study Group) and 64 control patients (34 with mechanical low back pain [MBP] and 30 with rheumatoid arthritis [RA]) underwent US examination of major entheses of their limbs. Particular attention was given to the detection of vascularization at the following sites: cortical bone insertion of entheses, junction between tendon and entheses, body of tendon, and bursa. RESULTS: Abnormal US findings consistent with at least one enthesitis were observed in 161 of 164 SpA patients (98%), affecting 1,131 of 2,952 entheses examined (38%). In contrast, only 132 of 1,152 entheses (11%) were found to be abnormal in 33 of 64 control patients (52%). US enthesitis was most commonly distributed in the distal portion of the lower limbs, irrespective of SpA subtype and of skeletal distribution of clinical symptoms. None of the abnormal entheses in control patients showed vascularization, compared with 916 of 1,131 abnormal entheses in SpA patients (81%), where it was always detected at the cortical bone insertion and sometimes also in the bursa. In SpA patients, the US pattern depended on the clinical presentation, with a higher prevalence of the most severe stages in those with peripheral forms. CONCLUSION: US in B mode combined with power Doppler allowed the detection of peripheral enthesitis in a majority of SpA patients, but not in MBP or RA patients. The presence of entheseal involvement was independent of SpA subtype, but its degree of severity appeared to be greater in peripheral forms. US could be very useful for both the diagnosis and the assessment of SpA activity.     

Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders

OBJECTIVE: Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects. METHODS: Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting. RESULTS: Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus. CONCLUSION: No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.     

In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

The in vitro activity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32 Acinetobacter baumannii (including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) and 35 Pseudomonas aeruginosa (including 18 VIM and 3 IMP carbapenemase producers) strains and compared to the activities of standard antibiotics. Overall, both species collections showed MIC_50/90 values of 8/8 μg/ml and minimum bactericidal concentrations at which 50% or 90% of strains tested are killed (MBC_50/90) of 8/8 μg/ml. G3KL is a promising molecule with antibacterial activity against multidrug-resistant and extensively drug-resistant A. baumannii and P. aeruginosa isolates.     

Release of cardiac bio-markers during high mechanical index contrast-enhanced echocardiography in humans.

BACKGROUND: Recent experimental data have shown that the combined exposure of rodent hearts to high acoustic pressure and ultrasound contrast agents can induce vascular injury and cell damage. The aim of the present work was to test whether similar effects can be observed in humans. METHODS AND RESULTS: Twenty patients underwent simultaneous arterial and coronary sinus blood sampling during contrast-enhanced echocardiography using Perfluorocarbon-enhanced Sonicated Dextrose Albumin. Control subjects were compared to groups of patients exposed to either high mechanical index (MI = 1.5) triggered second harmonic (1.3-2.6 MHz) imaging or low mechanical index (MI = 0.2) real-time power modulation imaging for 15 min. No significant changes arterio-venous differences in lactate, total creatine kinase (CK) and myoglobin occurred over time in the three groups. Similarly, the arterio-venous difference in CK-MB and troponin I remained stable over time in control and low-MI patients. By contrast, these two parameters progressively increased over time in the high-MI group (P < 0.05 vs. baseline and vs. controls). CONCLUSION: Our data suggest that high-MI contrast-enhanced echocardiography can cause subclinical release of cardiac bio-markers in humans, while low-MI real-time imaging appears to be safer.     

Gemcitabine combined with oxaliplatin is safe and effective in patients with previously untreated advanced pancreatic adenocarcinoma

AIM: The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1% with a 12.5% complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. CONCLUSION: These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patients with locally-advanced disease.     

Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules

OBJECTIVE The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied In patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary Iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels. PATIENTS A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied. MEASUREMENTS In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with Increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery. RESULTS All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma In 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive In the former patient but also In the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative In the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC. CONCLUSIONS This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels.     

Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with features overlapping with the Saethre–Chotzen syndrome. TCF12 molecular testing should be considered in patients with unilateral- or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in FGFR3.