The hamstrings are more impacted than the quadriceps after severe ankle sprain

Ankle sprains (AS) are common in the military population, with a prevalence 5 to 8 times higher than that for civilians. The aim of this study was to evaluate in patients with severe AS the impact of disuse on thigh muscle induced by unloading and immobilization due to care. This study focused on muscle trophicity and dynamometric strength. In this observational prospective study, assessments were repeated at 3 visits: close to injury, 15 and 30 days following the sprain. The injured limb was compared to the contralateral limb. A dynamometer assessment was used to monitor changes in strength and fatigue of the thigh muscles of both limbs. Isometric and isokinetic concentric evaluation of peak torque (PTiso and PTdyn), total work (Wt), and peak torque time integral (IPT) of thigh muscles. Full follow-up was obtained in 30 subjects. The injured limbs showed significant deficits in the mean (SD). The quadriceps PTiso and IPT deficits were −12.6% ± 1.9% (P < .0001) and −13.27% ± 1.8% (P < .0001), respectively. The quadriceps PTdyn showed a significant deficit since V2 (−12.2.5% ± 2.0). The quadriceps Wt presented a significant deficit of −4.2% ± 2.4 (P < .0007) at 1 month. The hamstring PTdyn deficit presented a mean loss of −16.5% ± 2.4% (P < .0001). The hamstring Wt deficit was −13.7% ± 2.3% (P < .001). The analysis of variance showed that the grade of the sprain had a significant effect on the quadriceps PTq deficit (P < .016) but not the type of discharge. Our study showed that disuse leads to a significant deficit in the strength of knee muscles within 1 month. It is noteworthy that the hamstrings are more affected than the quadriceps. The rehabilitation protocol to prevent the risk of iterative ankle injuries and secondary knee injuries should incorporate early training of both quadriceps and hamstrings.     

High prevalence of unusual KRAS,NRAS, and BRAF mutations in POLE ‐ hypermutated colorectal cancers

Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1–2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE‐mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE‐mutated tumors were identified, most frequently in microsatellite (MMR)‐proficient young (< 70 years) male patients, with left‐sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE‐mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE‐mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE‐mutated cases had a high CD8⁺ tumor‐infiltrating lymphocyte (TIL) infiltration. These clinicopathological and molecular criteria may help to identify edPOLE mutations associated with a high TMB in CRC, and improve the selection of patients who could benefit from immunotherapy.     

IL‐7 is expressed in malignant mesothelioma and has a prognostic value

Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL‐7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL‐7R/IL‐7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL‐7R, IL‐7 had no effect on their intracellular signaling. Accordingly, the addition of IL‐7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL‐7 concentration was not a good diagnostic biomarker. However, we observed that high IL‐7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL‐7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL‐7R/IL‐7 signaling pathway is not functional in MPM cells, IL‐7 expression in PEs may have prognostic value in MPM patients.     

Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

An auto-controlled prospective comparison of two embryos culture media (G III series versus ISM) for IVF and ICSI treatments

Purpose

To compare the effects of 2 different media on embryo morphology and development at days 2/3.

Method

Six hundred seventy-six attempts from 512 couples were included in this prospective auto-controlled study. Sibling oocytes of all couples undergoing an IVF (n?=?286) or ICSI (n?=?390) attempt were randomly assigned to either GIII series (Vitrolife) or ISM (Medicult) media. Primary end points were fertilization and embryo morphology rates.

Results

Fertilization rates in GIII series and ISM (IVF: 59.9 vs 62.0% and ICSI: 65.7 vs 66.8%) respectively were not different. GIII series showed an increase, compared to ISM, of early cleavage rate, (IVF: 25.8 vs 16.2% (p?=?0.005); ICSI: 40.8 vs 25.5% (p?<?0.0001), and good embryo morphology rate at day 2 [IVF: 64.6 vs 57.3% (p?=?0.01); ICSI: 74.2 vs 69.4 (p?=?0.03)] and at day 3 [IVF: 57.5 vs 49.0% (p?=?0.02); ICSI: 67.2 vs 61.6% (p?=?0.01)].

Conclusions

Embryo morphology at days 2/3 was significantly enhanced when the embryos were cultured in GIII series.     

Revised Definitions of Tuberculosis Resistance and Treatment Outcomes,France, 2006–2019

Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre–XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006–2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events.     

Diagnostic accuracy of myocardial perfusion imaging with single photon emission computed tomography and positron emission tomography: a comparison with coronary angiography

Objective The aim of this study was to compare the diagnostic accuracy of myocardial perfusion imaging (MPI) by positron emission tomography (PET) with the diagnostic accuracy of MPI by single photon emission computed tomography (SPECT) in two comparable patient cohorts, using coronary angiography (CA) as the standard of reference. Methods A “SPECT-group” of 80 patients (15 female, 65 male; mean age 60 ± 9 years) and a “PET-group” of 70 patients (14 female, 56 male; mean age 57 ± 10 years) underwent a one day stress/rest examination either with attenuation-corrected ¹³N-ammonia PET or attenuation-corrected ²⁰¹TlCl SPECT or ^99mTc-hexakis-methoxy-isobutyl-isonitril (MIBI) SPECT. PET and SPECT results were semiquantitatively graded using a 6-segment heart model. All patients underwent CA, and stenoses were graded as a diameter reduction ≥50%. Results Coronary findings between both groups did not significantly differ at CA. For the SPECT-group overall sensitivity and specificity for localisation of stenoses was 77% and 84%. Respective values for the PET-group were 97% and 84%. The specificity of MPI by SPECT in the detection of ischemia was 74% and 91% for MPI by PET. The diagnostic accuracy of MPI improves when the individual coronary dominance and previous coronary revascularisations are taken into account. Conclusion MPI by ¹³N-ammonia PET is more sensitive in the detection and localisation of coronary stenoses, and more specific in the detection of ischemia than MPI by ²⁰¹TlCl/^99mMIBI SPECT.