Metatarsal lengthening by distraction osteogenesis for brachymetatarsia in paediatric patients: is it safe and effective?

PURPOSE: The primary aim is to assess the efficacy of the surgical callus distraction technique of the metatarsus in paediatric patients. Secondary objectives are to assess complications and treatment duration. We have also described the details of our surgical technique. MATERIALS AND METHODS: A case series review of paediatric patients who had metatarsal lengthening at our unit between 2014 and 2022. Patient demographics, duration of time in frame, complications and metatarsal length achieved were recorded. The AOFAS Midfoot and the MOXFQ were taken pre-operatively and at final follow-up. RESULTS: Sixteen metatarsals in 8 patients (14 feet) underwent lengthening between 2014 and 2022 using the MiniRail OrthoFix 100 (Orthofix Medical Inc, Lewisville, TX, USA). The mean age was 13.3 (12-17) years. The average duration between surgery and implant removal was 5.2 months. According to Paley's classification, there was one obstacle encountered in a patient who required a revision of their osteotomy and one problem in another patient who had an infected metatarsophalangeal joint stabilising k-wire treated with oral antibiotics. The Mean AOFAS Midfoot score improved from 53.10 to 86.40 (p < 0.0001) and the Mean MOXFQ improved from 32.5000 to 12.1250 (p < 0.05); these were statistically significant. CONCLUSION: Gradual metatarsal lengthening using the MiniRail external fixator is a safe and effective method to treat brachymetatarsia in paediatric patients. This preliminary report describes and supports metatarsal lengthening in appropriate patients. Holistic care in terms of a pre-operative assessment, psychological support and preparation for the extended rehabilitation period are vital.

Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime-treated Pseudomonas aeruginosa acute pneumonia.

Pseudomonas aeruginosa (PA) remains one of the leading causes of nosocomial acute pneumonia. The array of virulence factors expressed by PA and the intense immune response associated with PA pneumonia play a major role in the severity of these infections. New therapeutic approaches are needed to overcome the high resistance of PA to antibiotics and to reduce the direct damage to host tissues. Through its immunomodulatory and anti-virulence effects, azithromycin (AZM) has demonstrated clinical benefits in patients with chronic PA respiratory infections. However, there is relatively little evidence in PA acute pneumonia. We investigated the effects of AZM, as an adjunctive therapy combined with ceftazidime (CAZ), in a murine model of PA acute pneumonia. We observed that the combined therapy (i) reduces the weight loss of mice 24 h post-infection (hpi), (ii) decreases neutrophil influx into the lungs at 6 and 24 hpi, while this effect is absent in a LPS-induced pneumonia or when PA is pretreated with antibiotics and mice do not receive any antibiotics, and that (iii) AZM, alone or with CAZ, modulates the expression of PA quorum sensing regulators and virulence factors (LasI, LasA, PqsE, PhzM, ExoS). Our findings support beneficial effects of AZM with CAZ on PA acute pneumonia by both bacterial virulence and immune response modulations. Further investigations are needed to clarify the exact underlying mechanisms responsible for the reduction of the neutrophils influx and to better discriminate between direct immunomodulatory properties of AZM, and indirect effects on neutrophilia resulting from bacterial virulence modulation.

Clostridial prosthetic joint infections: A series of 16 cases and literature review.

OBJECTIVES: Prosthetic joint infections (PJIs) due to the Clostridium species have not been widely investigated. We aimed to characterize these uncommon infections. METHODS: We conducted a retrospective study between 2003 and 2020 in six French hospitals combined with a review of the literature. RESULTS: The main conclusions obtained from the 16 patients included were reinforced by the literature analysis: (i) Clostridium perfringens was the most frequently involved species, (ii) patients presented an advanced age at the time of prosthesis placement and infection, (iii) most of the infections were early- or delayed-onset, (iv) the prognosis for these PJIs remains poor, (v) when performed (n = 5), DAIR with 12-week antimicrobial therapy led to a favorable outcome in 80% of cases. CONCLUSIONS: Given the low incidence of this infection, our work represents the largest series of clostridial PJIs reported to date and highlights some specificities of these infections. Further prospective studies are needed to confirm these results.

Magnetically localized and wash-free fluorescence immunoassay (MLFIA): proof of concept and clinical applications.

Immunoassays are used for many applications in various markets, from clinical diagnostics to the food industry, generally relying on gold-standard ELISAs that are sensitive, robust, and cheap but also time-consuming and labour intensive. As an alternative, we propose here the magnetically localized and wash-free fluorescence immunoassay (MLFIA): a no-wash assay to directly measure a biomolecule concentration, without mixing nor washing steps. To do so, a fluorescence no-wash measurement is performed to generate a detectable signal. It consists of a differential measurement between the fluorescence of fluorophores bound to magnetic nanoparticles specifically captured by micro-magnets against the residual background fluorescence of unbound fluorophores. Targeted biomolecules (antibodies or antigens) are locally concentrated on micro-magnet lines, with the number of captured biomolecules quantitatively measured without any washing step. The performance of the MLFIA platform is assessed and its use is demonstrated with several biological models as well as clinical blood samples for HIV, HCV and HBV detection, with benchmarking to standard analyzers of healthcare laboratories. Thus, we demonstrated for the first time the versatility of the innovative MLFIA platform. We highlighted promising performances with the successful quantitative detection of various targets (antigens and antibodies), in different biological samples (serum and plasma), for different clinical tests (HCV, HBV, HIV).

Bartonella quintana infective endocarditis in a homeless man with unexpected positive blood culture.

Bartonella species represent important causative agents of blood culture-negative infective endocarditis (IE). Their diagnosis represents a challenge for microbiologists and often relies on serological and molecular tools. However, even if the sensitivity of blood culture remains low, it should not be definitely ruled out. Indeed, we report the unusual case of a 22 year-old Guinean homeless man diagnosed with an IE due to Bartonella quintana. Unexpectedly, conventional blood cultures were positive after 13 days of incubation. Subculture was obtained on blood and chocolate agar, after 15 days of incubation in a 5 % CO2 atmosphere. Bacterial identification was obtained up to the species level using molecular tools (16S rRNA gene amplification and sequencing). A literature review of B. quintana blood culture-positive IE was conducted and revealed eighteen similar reported cases on a 25-year period. This case illustrates that, despite low sensitivity, Bartonella IE may be diagnosed thanks to prolonged blood culture.

Investigating the Stability of Six Phenolic TMZ Ester Analogues, Incubated in the Presence of Porcine Liver Esterase and Monitored by HPLC.

Previous published data from our group showed the encouraging in vitro activities of six phenolic temozolomide (TMZ) ester analogues (ES8-ES12 and ES14) with up to a five-fold increase in potency compared to TMZ against glioblastoma multiform cell lines and TMZ-resistant O6-methylguanine-DNA methyl transferase (MGMT)-positive primary cells. This study investigated the stabilities of the six phenolic TMZ ester analogues in the presence of porcine liver esterase (PLE) as a hydrolytic enzyme, using high-performance liquid chromatography (HPLC), monitored by a diode-array detector (DAD). Determining the rates of hydrolysis of the esters provided a useful insight into the feasibility of progressing them to the next phase of drug development. Fifty percent of TMZ esters consisting of para nitro, chloro, phenyl and tolyl groups (ES9, ES10, ES12 and ES14) were hydrolysed within the first 4.2 min of PLE exposure, while the TMZ esters consisting of para methoxy and nitrile groups (ES8 and ES11) demonstrated increased stability, with 50% hydrolysis achieved in 7.3 and 13.7 min, respectively. In conclusion, the survival of these phenolic TMZ esters on route to the target site of a brain tumor would be a challenge, mainly due to the undesirable rapid rate of hydrolysis. These findings therefore pose a question regarding the effectiveness of these esters in an in vivo setting.

COVID-19 Pandemic: The Importance of Supporting Civilian and Military Transition-to-Practice Programs to Avert Current and Future Nursing Shortages.

Registered nurses (RNs) are national assets who provide quality patient care, especially during the corona virus disease 2019 pandemic. Currently, healthcare organizations are overwhelmed with ill patients who require RNs with specialty experiences. Curtailment and cancellation by healthcare organizations of civilian and military transition-to-practice programs for newly licensed RNs are at risk. If this phenomenon continues, current and future nursing shortages will prevail.

Accuracy of gradient diffusion method for susceptibility testing of dalbavancin and comparators.

OBJECTIVES: This multicenter study aimed to assess the performances of gradient diffusion (GD) method in comparison to broth microdilution (BMD) method for susceptibility testing of dalbavancin, daptomycin, vancomycin, and teicoplanin. METHODS: Minimum Inhibitory Concentrations (MICs) were retrospectively determined concomitantly by BMD and GD methods, for 93 staphylococci and enterococci isolated from clinical samples. BMD was considered as the gold standard. Essential (EA) and categorical agreements (CA) were calculated. Discordant categorical results were categorized as major (ME) and very major errors (VME). RESULTS: EA and CA were 95.7% and 96.8%, 82.8% and 100%, 97.8% and 96.8%, and 94.6% and 95.7% for dalbavancin, daptomycin, vancomycin, and teicoplanin respectively. Concerning dalbavancin, 3 ME without any VME were observed and discrepancies were low (≤ to 2 two-fold dilutions) between both methods. VME were noted in 1 and 3 cases for vancomycin and teicoplanin, respectively, and resulted from 1 two-fold dilution discrepancy in each case. EA was lower for daptomycin. When they were discrepant, BMD MICs were systematically higher than GD ones. Nevertheless, no categorical discrepancy was noted. CONCLUSIONS: GD appears as an acceptable and convenient alternative for dalbavancin, vancomycin, and teicoplanin MICs determination. Our study also emphasizes how achieving accurate daptomycin MICs remains challenging.

[Artificial intelligence, radiomics and pathomics to predict response and survival of patients treated with radiations]. / Intelligence artificielle en radiothérapie : radiomique, pathomique, et prédiction de la survie et de la réponse aux traitements.

Artificial intelligence approaches in medicine are more and more used and are extremely promising due to the growing number of data produced and the variety of data they allow to exploit. Thus, the computational analysis of medical images in particular, radiological (radiomics), or anatomopathological (pathomics), has shown many very interesting results for the prediction of the prognosis and the response of cancer patients. Radiotherapy is a discipline that particularly benefits from these new approaches based on computer science and imaging. This review will present the main principles of an artificial intelligence approach and in particular machine learning, the principles of a radiomic and pathomic approach and the potential of their use for the prediction of the prognosis of patients treated with radiotherapy.

The association of socioeconomic deprivation and paediatric open tibia fractures.

The primary aim of this study is to test the association of open tibial fractures (OTF), in a paediatric age group, with socioeconomic deprivation. The secondary objectives are to more clearly define the epidemiological characteristics of these high-energy injuries. A consecutive series of patients with OTF presenting to a major trauma centre at a children's hospital in Liverpool had age, gender, fracture pattern, mechanism, timing of the injury and their postcode of residence recorded. Those cases outside Liverpool, Sefton and Knowsley local authorities were excluded from incidence calculations. Postcodes were used to generate deprivation scores (Index of Multiple Deprivation, 2010) based on census data (2011). Cases were ranked and allocated to deprivation quintiles. A comparison to the normal population within Merseyside was undertaken using regression analysis. There were 71 cases over a 9-year period. Fifty cases resided within the geographical limits of Merseyside and were included in the incidence calculations. The annual incidence of paediatric OTF is 3.09 per 100 000 children (0-16 years). The median age at injury was 11 years (range 2-16) and this occurred most usually during term-time between 3 and 5 p.m. from road traffic collisions. Paediatric OTFs are strongly associated with socioeconomic deprivation. The association with deprivation reflects an exposure to unsafe roads in busy urban areas with limited access to safe playing spaces. Socioeconomically deprived men are most at risk from this injury. The links between deprivation and outcomes of treatment or long-term prospects are unclear.

Low prevalence of Cutibacterium acnes in prostatic tissue biopsies in a French hospital.

We evaluated the Cutibacterium acnes prevalence in prostatic biopsies and characterized the strains at a molecular level. 18 out of 36 biopsies (50%) were sterile after seven days in culture. C. acnes was observed in only two biopsies. Its prevalence was low (5.6%). Finally, the molecular characterization revealed diverse clusters including phylotypes IA1, IB and II.

Prevalence and risk factors of geohelminthiasis among the rural village children in Kota Marudu, Sabah, Malaysia.

Geohelminthiasis is a worldwide problem, especially in low-income countries. Children from rural areas and those living in poverty, lacking basic health amenities and having poor environmental sanitation are likely to be affected. Adverse effects such as anemia, protein malnutrition, colitis are common which can affect both the children's physical and mental growing development. A cross-sectional study on geohelminthiasis was conducted among children from 238 households in 13 villages in Kota Marudu of northern Sabah, East Malaysia. The study involved interviewing villagers using questionnaires to collect demographic and socio-economic data, getting faecal samples from the children, collecting soil samples and identifying parasite eggs with microscopy and molecular methods. A total of 407 children (6 months-17 years old) enrolled in the study. Geohelminthiasis was detected in the faecal samples of children from 54% (7/13) of the villages with mean prevalence of infection per village of 9.0% (0%-34.9%). On a household basis, 18% (43/238) of the households sampled had infected children, with mean prevalence rate per household of 11% (0%-43%). The prevalence was for Ascaris lumbricoides: 9.6% (39/407), Trichuris trichiura: 2.7% (11/407) and hookworms (Necator americanus and Ancylostoma sp.): 2.7% (11/407). The overall mean infection rate of the children examined was 14.3%. Significantly higher prevalence was recorded for the children of mothers who did not have any formal education (p = 0.003); household income of less than USD119 (RM500) (p<0.001); children from homes without proper sanitation facilities (p<0.001); children who usually go about barefoot (p<0.001) and not washing feet before entering the house (p = 0.017). Soil samples were found to have geohelminth eggs or larvae which could be due to unhygienic sanitation practices. This study shows the geohelminthiasis is prevalent in the villages, and the risk factors are lack of maternal education, low income, poor sanitation facilities and irregular deworming practice. Expanding deworming coverage in the study region may help reduce the worm infections in these communities, so that the mental and physical development of the children would not be affected by geohelminthiasis. The data on the prevalence of geohelminthiasis in this study would contribute to better public health monitoring and operation to reduce the infection in rural areas.

Correction to: Androgen receptor regulates expression of skeletal muscle-specific proteins and muscle cell types.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

EEG dynamics and neural generators of psychological flow during one tightrope performance.

Psychological "flow" emerges from a goal requiring action, and a match between skills and challenge. Using high-density electroencephalographic (EEG) recording, we quantified the neural generators characterizing psychological "flow" compared to a mindful "stress" state during a professional tightrope performance. Applying swLORETA based on self-reported mental states revealed the right superior temporal gyrus (BA38), right globus pallidus, and putamen as generators of delta, alpha, and beta oscillations, respectively, when comparing "flow" versus "stress". Comparison of "stress" versus "flow" identified the middle temporal gyrus (BA39) as the delta generator, and the medial frontal gyrus (BA10) as the alpha and beta generator. These results support that "flow" emergence required transient hypo-frontality. Applying swLORETA on the motor command represented by the tibialis anterior EMG burst identified the ipsilateral cerebellum and contralateral sensorimotor cortex in association with on-line control exerted during both "flow" and "stress", while the basal ganglia was identified only during "flow".

Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis.

OBJECTIVES: To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis. METHODS: We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success. RESULTS: Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6-12 g) and 12 g (range 10-13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure. CONCLUSIONS: Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication.

Catheter-related bloodstream infection due to Tsukamurella pulmonis identified by MALDI-TOF spectrometry, 16S rRNA gene sequencing, and secA1 gene sequencing in an immunocompromised child: a case report and literature review.

Tsukamurella species are Gram-positive bacilli related to aerobic Actinomyces. Originally reported from the environment, Tsukamurella species have also been described in human infections, especially in bacteremia. A literature review analysis revealed that Tsukamurella spp. are often initially considered as contaminant microorganisms, especially due to bacterial identification issues. Here, we report a catheter-related bloodstream infection in an immunocompromised child caused by Tsukamurella pulmonis. Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF) mass spectrometry allowed rapid genus-level identification and contributed to better patient care. However, accurate species-level identification required 16S rRNA gene sequencing and secA1 gene sequencing. Considering the increased number of Tsukamurella infections, the implementation of new Tsukamurella species in MALDI-TOF databases is required to be more discriminant.

Propionibacterium/Cutibacterium species-related positive samples, identification, clinical and resistance features: a 10-year survey in a French hospital.

A 10-year retrospective study of Propionibacterium/Cutibacterium-positive samples gathered from hospitalized patients was conducted at Nantes University hospital. A total of 2728 Propionibacterium/Cutibacterium-positive samples analyzed between 2007 and 2016 were included. Due to the implementation of MALDI-TOF identification in 2013, most non-Cutibacterium acnes isolates were identified a second time using this technology. Over that period, Cutibacterium acnes remained the most predominant species accounting for 91.5% (2497/2728) of the isolates, followed by Cutibacterium avidum (4.2%, 115/2728) and Cutibacterium granulosum (2.4%, 64/2728). Regarding the origin of samples, the orthopaedic department was the main Cutibacterium sample provider representing 51.9% (1415/2728) of all samples followed by the dermatology department (11.5%, 315/2728). Samples were recovered from various tissue locations: 31.5% (858/2728) from surgery-related samples such as shoulder, spine or hip replacement devices and 19.1% (520/2728) from skin samples. MALDI-TOF method revealed misidentification before 2013. Cutibacterium avidum was falsely identified as C. granulosum (n = 33). Consequently, MALDI-TOF technology using up-to-date databases should be preferred to biochemical identification in order to avoid biased species identification. Regarding antibiotic resistance, 14.7% (20/136) of C. acnes was resistant to erythromycin. 4.1% (41/1005) of C. acnes strains, 17.9% (12/67) of C. avidum strains and 3.6% (1/28) of C. granulosum strains were found resistant to clindamycin.

Accessible laparoscopic liver resection performed in low volume centers: Is it time for democratization?

INTRODUCTION: Laparoscopic liver resection (LLR) has been developed and is daily practiced by many expert teams. However, very few data are available on the experience of low volume centres. The aim of our study was to report and discuss the operative results of LLR performed in three low volume centres. METHODS: Records of patients who underwent a LLR in three low volume centres in France between May 2014 and November 2017 were collected. Endpoints studied were indications, intra and postoperative outcomes as well as short-term outcomes. RESULTS: A total of 46 patients (57 specimen resected) underwent a LLR during this period, representing 29.6% of total liver resections. Indications of LLR were benign lesions in 26%, primitive malignant lesions in 32.6% and metastatic tumours in 41.3%. Median size of lesions was 22mm (range 11-100). Most liver resections were non-anatomic (64.7%), while left lateral sectionectomies represented 19.2%. Five patients required conversion and there were at the end 3 specimen with margins inferior to 1mm resected laparoscopically. Postoperative mortality was nil and morbidity rate was 17.3%. Median hospital stay was 6 days (3-15). CONCLUSION: Although LLR have gained acceptance in surgeons' arsenal, it remains concentrated in referral centres. Our results suggest the feasibility of LLR in non-academic centres when it comes to small accessible lesions. Further studies would provide data about the long-term safety of this procedure in those centres.