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BackgroundUltrasound has demonstrated its interest in the analysis of diaphragm function in patients with respiratory failure. The criteria used to diagnose hemidiaphragm paralysis are not well defined.MethodsThe aim of this observational retrospective study was to describe the ultrasound findings in 103 patients with diaphragm paralysis, previously diagnosed by conventional methods after various circumstances such as trauma or surgery. The ultrasound study included the recording of excursions of both diaphragmatic domes and the measurement of inspiratory thickening.ResultsOn paralyzed hemidiaphragm, thickening was less than 20% in all patients during deep inspiration. Thinning was recorded in 53% of cases. In some cases, the recording of the thickening could be difficult. The study of motion during voluntary sniffing reported a paradoxical excursion in all but one patient. During quiet breathing, an absence of movement or a paradoxical displacement was observed. During deep inspiration, a paradoxical motion at the beginning of inspiration followed by a reestablishment of movement in the cranio-caudal direction was seen in 82% of cases. In some patients, there was a lack of movement followed, after an average delay of 0.4 s, by a cranio-caudal excursion. Finally, in 4 patients no displacement was recorded. Evidence of hyperactivity (increased inspiratory thickening and excursion) of contralateral non-paralyzed hemidiaphragm was observed.ConclusionTo accurately detect hemidiaphragm paralysis, it would be interesting to combine the ultrasound study of diaphragm excursion and thickening. The different profiles reported by our study must be known to avoid misinterpretation.

BackgroundAlthough previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system.MethodsTo determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances.ResultsA total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume.ConclusionThe normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity.

BackgroundSARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown.Materials and methodsThis study was carried out on patients reporting persistent respiratory symptoms 3–4 months after severe COVID-19 pneumonia. The included patients were selected from a medical consultation designed to screen for recovery after acute infection. Respiratory function was assessed by a pulmonary function test, and diaphragm function was studied by ultrasonography.ResultsIn total, 132 patients (85M, 47W) were recruited from the medical consultation. During the acute phase of the infection, the severity of the clinical status led to ICU admission for 58 patients (44%). Diaphragm dysfunction (DD) was detected by ultrasonography in 13 patients, two of whom suffered from hemidiaphragm paralysis. Patients with DD had more frequently muscle pain complaints and had a higher frequency of prior cardiothoracic or upper abdominal surgery than patients with normal diaphragm function. Pulmonary function testing revealed a significant decrease in lung volumes and DLCO and the dyspnea scores (mMRC and Borg10 scores) were significantly increased in patients with DD. Improvement in respiratory function was recorded in seven out of nine patients assessed 6 months after the first ultrasound examination.ConclusionAssessment of diaphragm function by ultrasonography after severe COVID-19 pneumonia revealed signs of dysfunction in 10% of our population. In some cases, ultrasound examination probably discovered an un-recognized pre-existing DD. COVID-19 nonetheless contributed to impairment of diaphragm function. Prolonged respiratory physiotherapy led to improvement in respiratory function in most patients.Clinical trial registration[www.cnil.fr], identifier [#PADS20-207].

Sternum and rib osteomyelitis complicated from breast implant infection is rare. We report a case of early sternum and rib osteomyelitis occurred during breast implant infection managed in an inter-regional referral center for bone/joint infections in the south of France.

Persistence of various symptoms in patients who have recovered from coronavirus disease 2019 (COVID-19) was recently defined as ‘long COVID’ or ‘post-COVID syndrome’ (PCS). This article reports a case of a 58-year-old woman who, although recovering from COVID-19, had novel and persistent symptoms including neurological complications that could not be explained by any cause other than PCS. In addition to a low inflammatory response, persistence of immunoglobulin G anticardiolipin autoantibody positivity and eosinopenia were found 1 year after acute COVID-19 infection, both of which have been defined previously as independent factors associated with the severity of COVID-19. The pathophysiological mechanism of PCS is unknown, but the possibility of persistence of the virus, especially in the nervous system, could be suggested with a post-infectious inflammatory or autoimmune reaction.

Hippo signaling plays an essential role in the development of numerous tissues. Although it was previously shown that the transcriptional effectors of Hippo signaling Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can fine-tune the regulation of sex differentiation genes in the testes, the role of Hippo signaling in testis development remains largely unknown. To further explore the role of Hippo signaling in the testes, we conditionally deleted the key Hippo kinases large tumor suppressor homolog kinases 1 and -2 (Lats1 and Lats2, two kinases that antagonize YAP and TAZ transcriptional co-regulatory activity) in the somatic cells of the testes using an Nr5a1-cre strain (Lats1flox/flox;Lats2flox/flox;Nr5a1-cre). We report here that early stages of testis somatic cell differentiation were not affected in this model but progressive testis cord dysgenesis was observed starting at gestational day e14.5. Testis cord dysgenesis was further associated with the loss of polarity of the Sertoli cells and the loss of SOX9 expression but not WT1. In parallel with testis cord dysgenesis, a loss of steroidogenic gene expression associated with the appearance of myofibroblast-like cells in the interstitial space was also observed in mutant animals. Furthermore, the loss of YAP phosphorylation, the accumulation of nuclear TAZ (and YAP) in both the Sertoli and interstitial cell populations, and an increase in their transcriptional co-regulatory activity in the testes suggest that the observed phenotype could be attributed at least in part to YAP and TAZ. Taken together, our results suggest that Hippo signaling is required to maintain proper differentiation of testis somatic cells.

IntroductionLimited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting.MethodsHIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns.ResultsWe included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6.ConclusionsRAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.

The incidence and significant morbidity of vertebral osteomyelitis are increasing despite the progress of diagnosis competences. Among the 50 cases of vertebral osteomyelitis managed in our centers over the past 5 years, 84% of the cases were in men. The mean age was 55 years. Sixty-two percent of patients had comorbidities and risk factors: diabetes mellitus (24%), malignancy (16%), intravenous drug use (10%) and alcoholism (4%). A source of infection was identified in 66% of cases, including postvertebral surgery infection (18%) and hematogenous infection (48%). The mean time to diagnosis was 36 days. Back pain were occurred in 90% of cases, fever (70%), neurologic deficits (40%), epidural abscesses (32%), completed vertebral bone destruction (26%) and psoas abscess (12%). A single organism was isolated in 92% of cases. Gram-positive bacteria were identified in 76% of cases, while Gram-negative bacilli (GNB) were found in 18% of cases. The presence of GNB was significantly associated with malignancy (p 0.041). The mean duration of antibiotic therapy was 123 days. Surgical treatment was performed in 41 cases: spinal stabilization (26%), drainage of abscesses (32%) and relief of compression (40%). Residual pain was found in 24% of cases, and neurologic sequelae in 22%. Cervical or thoracic localization was a risk factor for neurologic compromise (p 0.042). The epidemiology of vertebral osteomyelitis has changed; an increase in malignancy that was significantly associated with vertebral osteomyelitis due to GNB has been observed. Our study shows that the rate of neurologic complications remains high despite improved diagnostic capabilities and optimal treatment.

Splenic abscess is a rare disease that primarily occurs in patients with splenic trauma, endocarditis, sickle cell anemia, or other diseases that compromise the immune system. This report describes a culture-negative splenic abscess in an immunocompetent patient caused by Campylobacter jejuni, as determined by 16S rRNA gene sequencing.

The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was 500/mm(3). ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting.Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging.