Applications of ultrasound elastography to hand and upper limb disorders.

Ultrasound elastography is a recently developed method for accurate measurement of soft tissue stiffness in addition to the clinician's subjective evaluation. The present review briefly describes the ultrasound elastography techniques and outlines clinical applications for tendon, muscle, nerve, skin and other soft tissues of the hand and upper limb. Strain elastography provides a qualitative evaluation of the stiffness, and shear-wave elastography generates quantitative elastograms superimposed on a B-mode image. The stiffness in degenerative tendinopathy and/or tendon injury was significantly lower than in a normal tendon in several studies. Elastography is also a reliable method to evaluate functional muscle activity, compared to conventional surface electromyography. The median nerve is consistently stiffer in patients with carpal tunnel syndrome than in healthy subjects, on whatever ultrasound elastography technique. Elastography distinguishes normal skin from scars and can be used to evaluate scar severity and treatment. Elastography has huge clinical applications in musculoskeletal tissues. Continued development of systems and increased training of clinicians will expand our knowledge of elastography and its clinical applications in the future.

Isocitrate dehydrogenase wt and IDHmut adult-type diffuse gliomas display distinct alterations in ribosome biogenesis and 2'O-methylation of ribosomal RNA.

BACKGROUND: High-grade adult-type diffuse gliomas (HGGs) constitute a heterogeneous group of aggressive tumors that are mostly incurable. Recent advances highlighting the contribution of ribosomes to cancer development have offered new clinical perspectives. Here, we uncovered that isocitrate dehydrogenase (IDH)wt and IDHmut HGGs display distinct alterations of ribosome biology, in terms of rRNA epitranscriptomics and ribosome biogenesis, which could constitute novel hallmarks that can be exploited for the management of these pathologies. METHODS: We analyzed (1) the ribosomal RNA 2'O-ribose methylation (rRNA 2'Ome) using RiboMethSeq and in-house developed bioinformatics tools (https://github.com/RibosomeCRCL/ribomethseq-nfandrRMSAnalyzer) on 3 independent cohorts compiling 71 HGGs (IDHwt n = 30, IDHmut n = 41) and 9 non-neoplastic samples, (2) the expression of ribosome biogenesis factors using medium throughput RT-qPCR as a readout of ribosome biogenesis, and (3) the sensitivity of 5 HGG cell lines to RNA Pol I inhibitors (CX5461, BMH-21). RESULTS: Unsupervised analysis demonstrated that HGGs could be distinguished based on their rRNA 2'Ome epitranscriptomic profile, with IDHwt glioblastomas displaying the most significant alterations of rRNA 2'Ome at specific sites. In contrast, IDHmut HGGs are largely characterized by an overexpression of ribosome biogenesis factors compared to non-neoplastic tissues or IDHwt glioblastomas. Finally, IDHmut HGG-derived spheroids display higher cytotoxicity to CX5461 than IDHwt glioblastoma, while all HGG spheroids display a similar cytotoxicity to BMH-21. CONCLUSIONS: In HGGs, IDH mutational status is associated with specific alterations of the ribosome biology and with distinct sensitivities to RNA Pol I inhibitors.

The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context.

Nutrient availability is a key determinant of tumor cell behavior. While nutrient-rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor general control non-derepressible 2 (GCN2; also known as eIF-2-alpha kinase 4) represses the expression of the precursor of ribosomal RNA (rRNA), 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53-mediated apoptosis in patient-derived models of colon adenocarcinoma (COAD). In nutrient-rich conditions, a cell-autonomous GCN2 activity supports cell proliferation by stimulating 47S rRNA transcription, independently of the canonical integrated stress response (ISR) axis. Impairment of GCN2 activity prevents nuclear translocation of methionyl-tRNA synthetase (MetRS), resulting in nucleolar stress, mTORC1 inhibition and, ultimately, autophagy induction. Inhibition of the GCN2-MetRS axis drastically improves the cytotoxicity of RNA polymerase I (RNA pol I) inhibitors, including the first-line chemotherapy oxaliplatin, on patient-derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls ribosome biogenesis according to the nutritional context. Furthermore, pharmacological co-inhibition of the two GCN2 branches and RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically stressed COAD cells.

[Diagnostic and therapeutic guidelines of trigger fingers for general practitioner]. / Conduite diagnostique et thérapeutique du médecin traitant face au ressaut digital.

The jumping finger is commonly found clinical finding in various pathologies. However, trigger finger is the main cause. Therefore, the general practitioner should be aware of the differential diagnoses of jumping finger and the multiple presentation of trigger finger. This article aim is to guide the general practitioner diagnose and cure trigger finger.

Le ressaut digital est un signe clinique présent dans de multiples pathologies. Le doigt à ressort en est de loin la cause la plus fréquente. Le médecin traitant ne doit pas ignorer les nombreuses pathologies pouvant mimer ce diagnostic et les multiples formes de doigt à ressort. Le but de cet article est d'orienter le médecin traitant dans sa conduite diagnostique et thérapeutique face à un ressaut digital.

[Osteoarticular surgery of the hand in rheumatoid patients]. / Chirurgie ostéoarticulaire de la main dans le cadre des pathologies inflammatoires rhumatismales.

Surgical treatment of hands in rheumatoid arthritis is adapted to functional and aesthetical needs of the patient. In dialogue between the patient, rheumatologist and general practitioner, the hand surgeon tailors the solution in each case. During last 20 years, the biological drugs have revolutionized the medical treatment, in parallel the hand surgery developed mostly in the domain of arthroplasty. This article reviews the therapeutic options a hand surgeon can offer his patients with inflammatory diseases with a focus on recent development.

La prise en charge chirurgicale des maladies rhumatismales au niveau de la main repose essentiellement sur les besoins fonctionnels et esthétiques du patient. L'enjeu du chirurgien de la main est de proposer une solution chirurgicale adaptée à chaque cas, après avoir effectué une concertation avec le patient, le rhumatologue et le médecin traitant. En discussion avec ces derniers, le chirurgien de la main peut proposer une solution chirurgicale adaptée à chaque cas. Si le traitement médical a révolutionné, aujourd'hui, la prise en charge des pathologies inflammatoires rhumatismales, l'éventail des options thérapeutiques chirurgicales a également évolué, notamment dans le domaine de l'arthroplastie, depuis une vingtaine d'années. Cet article propose un aperçu de ces options thérapeutiques chirurgicales.

RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells.

Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitry that coordinates gene expression at multiple levels from chromatin to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis, yet the underlying molecular mechanisms remain largely unknown. Here, we identified RSL24D1 as highly expressed in both mouse and human pluripotent stem cells. RSL24D1 is associated with nuclear pre-ribosomes and is required for the biogenesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors and of components from the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact on differentiation, RSL24D1 depletion significantly alters ESC self-renewal and lineage commitment choices. Altogether, these results demonstrate that RSL24D1-dependant ribosome biogenesis is both required to sustain the expression of pluripotent transcriptional programs and to silence PRC2-regulated developmental programs, which concertedly dictate ESC homeostasis.

New Insights into Boxer's Knuckle Injury of the Little Finger.

BACKGROUND: The original description of boxer's knuckle injury of the fifth ray mentions that the injury occurs between the extensor digitorum communis (EDC) and the extensor digiti minimi (EDM). Subsequent reports claim similar findings. Anatomical studies show that the EDC of the fifth ray is absent in most patients, while the EDM is generally composed of two slips. We present a modification of the current description of boxer's knuckle injury of the little finger based on the correlation between advanced preoperative 3D imaging and intraoperative findings. METHODS: Five patients were investigated preoperatively using high-resolution ultrasound and 3D tendon reconstruction-based MR arthrography. Surgical exploration identified the lesion site relative to the EDM and EDC. RESULTS: All patients had two slips of the EDM and no EDC to the fifth ray. The injury appeared as a longitudinal tear of the EDM between its two slips. The mean gap was 7.8 mm (range 4.5-10 mm) on the pathological side vs. 1.3 mm (range 1-2 mm) on the healthy contralateral side. CONCLUSIONS: We believe that previous descriptions of boxer's knuckle of the fifth ray are inaccurate. High-resolution ultrasound and 3D reconstructions based on MR arthrography are reliable diagnostic tools allowing to locate the injury with precision.

Diagnosis of ulnar nerve entrapment anterior to the medial epicondyle by ultrasound elastography and diffusion tensor imaging with fiber tractography: a case report.

Ulnar/cubital tunnel syndrome is the second most common compressive neuropathy of the upper limb. Permanent location of the ulnar nerve anterior to the medial epicondyle is extremely rare, with only five cases reported in the literature. Using ultrasound elastography and diffusion tensor imaging with fiber tractography, we diagnosed a case in which ulnar nerve entrapment was associated with anterior nerve location. Surgical release confirmed the diagnosis and the patient was symptom free 3 months after surgery.

Three-dimensional CT for the diagnosis and management of bipartite scaphoids: a report of four cases in three patients.

We investigated the role of three-dimensional (3-D) CT in the diagnosis and management of four bipartite scaphoids in three patients. We computed the volume ratio, moment of inertia ratio and direction vector from the centroid of the scaphoid to the os centrale carpi. We found that the os centrale carpi was always smaller than the scaphoid and showed an elongated shape in the scaphoid longitudinal axis. Its position was always posterior compared with the scaphoid anteroposterior axis. The main morphological feature of bipartite scaphoids was the continuity of the scaphoid from its proximal to distal aspect along the longitudinal axis. These criteria from 3-D imaging should be considered useful in the diagnosis of bipartite scaphoid as it allows differentiation from nonunion. 3-D single-photon emission computed tomography (SPECT)/CT was helpful in the surgical decision-making when the patient was symptomatic. 3-D imaging was also used for the preoperative simulation and planning of bone fusion as it simplifies surgery and makes it more accurate. Here we provide clear criteria for diagnosing bipartite scaphoids and for the planning when surgery is deemed necessary.

Periosteal medial femoral condyle free flap for metacarpal nonunion.

BACKGROUND: Metacarpal nonunion is a rare condition. The osteogenic capacity of periosteal free flap was investigated in five patients with metacarpal nonunion and impaired bone vascularization. PATIENTS AND METHODS: Surgery was performed between 64 and 499 days after the initial bone osteosynthesis. The average age was 27.6 (range 16-32) years. Nonunion was caused by excessive periosteal removal in two patients, extensive open trauma in three. Four nonunions were diaphyseal, one metaphyseal. A periosteal medial femoral condyle free flap was raised on the descending genicular artery for four patients, the superomedial genicular artery for one. After osteosynthesis with a plate, the flap was wrapped around the metacarpal, overlapping the bone proximally and distally. The recipient vessel were the dorsal branch of the radial artery and a vena comitans in the anatomical snuffbox in four patients, at the base of the first webspace in one. RESULTS: The flap size ranged from 5 × 3.5 cm to 8 × 4 cm. No postoperative complication occurred. Radiological bone union was achieved 3 to 8 months after surgery. One patient had a full range of motion, one a slight extension lag of the proximal interphalangeal joint, two moderate joint stiffness of the proximal interphalangeal or metacarpophalangeal joint (one requiring plate removal and extensor tenolysis), one severe stiffness that allowed using a hook grip which was the aim of the surgery. CONCLUSION: In case of metacarpal nonunion with impaired bone vascularization, the periosteal medial femoral condyle free flap provides an effective and biomimetic approach to bone healing.

Three-Dimensional Comparative Study of Human Bipartite Scaphoids and the Os Centrale of the Wrist in Neandertals and Non-Human Anthropoid Primates.

In humans, bipartite scaphoid still does not differentiate clearly from traumatic non-union of the scaphoid. To aid diagnosis, we sought to analyze the main geometrical similarities among bipartite scaphoids from primate species with fused and unfused scaphoid centrales. Four human embryos, four cases of adult humans with bipartite scaphoid, twelve adult specimens of other extant anthropoid primates, and two Neandertal scaphoid specimens were included in this study. Three-dimensional polygon models of the scaphoid and os centrale were generated from CT scan, micro-CT scan, or histological sections. A 3D comparative study of the morphological and morphometrical parameters was performed using the MSC Patran software. The os centrale was smaller than the scaphoid in all specimens and its shape was elongated in the anteroposterior scaphoid direction. The position of the os centrale centroid compared to the scaphoid using direction vectors had a strong orientation along the proximodistal axis in all species. The main morphological feature of bipartite scaphoid was the continuity of the scaphoid from its proximal pole to its tubercule along the anteroposterior axis. In all specimens, if the os centrale was removed, the scaphoid still appeared normal and whole. The bipartite scaphoid in adult humans shares geometrical analogies with monkeys and orangutans, human embryos, and Neandertals. Morphological and morphometrical features identified in this study are useful to differentiate bipartite scaphoid from scaphoid pseudarthrosis. All other criteria suggested in the past lead to misdiagnosis.

Post-Operative Assessment of Ulnar Nerve Tension Using Shear-Wave Elastography.

BACKGROUND: Ulnar nerve compression at the elbow level is the second-most common entrapment neuropathy. The aim of this study was to use shear-wave elastography for the quantification of ulnar nerve elasticity in patients after ulnar nerve decompression with anterior transposition and in the contralateral non-operative side. METHOD: Eleven patients with confirmed diagnosis and ulnar nerve decompression with anterior transposition were included and examinations were performed on an AixplorerTM ultrasound system (Supersonic Imagine, Aix-en-Provence, France). RESULTS: We observed significant differences at 0-degree (p < 0.001), 45-degree (p < 0.05), 90-degree (p < 0.01) and 120-degree (p < 0.001) elbow flexion in the shear elastic modulus of the ulnar nerve in the operative and non-operative sides. There were no statistically significant differences between the elasticity values of the ulnar nerve after transposition at 0-degree elbow flexion and in the non-operative side at 120-degree elbow flexion (p = 0.39), or in the ulnar nerve after transposition at 120-degree elbow flexion and in the non-operative side at 0-degree elbow flexion (p = 0.09). CONCLUSION: Shear-wave elastography has the potential to be used postoperatively as a method for assessing nerve tension noninvasively by the estimation of mechanical properties, such as the shear elastic modulus.

2'O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases.

Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2'O-ribose methylation (2'Ome), intrinsically occur in many organisms. In the last 5 years, accumulating reports have illustrated that rRNA 2'Ome varies in human cell lines but also in living organisms (yeast, plant, zebrafish, mouse, human) during development and diseases. These rRNA 2'Ome variations occur either within a single cell line, organ, or patient's sample (i.e., intra-variability) or between at least two biological conditions (i.e., inter-variability). Thus, the ribosomes can tolerate the absence of 2'Ome at some specific positions. These observations question whether variations in rRNA 2'Ome could provide ribosomes with particular translational regulatory activities and functional specializations. Here, we compile recent studies supporting the heterogeneity of ribosome composition at rRNA 2'Ome level and provide an overview of the natural diversity in rRNA 2'Ome that has been reported up to now throughout the kingdom of life. Moreover, we discuss the little evidence that suggests that variations of rRNA 2'Ome can effectively impact the ribosome activity and contribute to the etiology of some human diseases.

Spiral Oblique Retinacular Ligament Procedure Using Flexor Digitorum Profundus Hemi-Tendon Transfer: Anatomical Basis and Clinical Application.

PURPOSE: The spiral oblique retinacular ligament (SORL) procedure acts as a dynamic tenodesis to restore distal interphalangeal joint (DIP) extension and restrain proximal interphalangeal hyperextension. Despite the ingenious technique based on the oblique retinacular ligament anatomy, obtaining strong internal fixation remains an issue during the SORL procedure. We present a modified technique using the flexor digitorum profundus (FDP) hemi-tendon transfer. METHODS: We dissected 5 fresh cadaveric specimens to evaluate morphometric parameters of the SORL procedure using the hemi-FDP. The volar groove of the FDP tendon was identified in zone I of the flexor sheath and the tendon was divided into radial and ulnar bundles. The selected hemi-tendon was divided at the proximal edge of the A1 pulley and a SORL procedure was performed through a transosseous tunnel in the distal phalanx. This technique was used in 3 patients with swan neck deformity. RESULTS: The optimal distance between the DIP joint and the anterior drill hole of the transosseous tunnel was 7.6 mm (range, 6.8-8.5 mm). The relative loss of length of the tendon owing to the SORL path was 25.8 mm (range, 19.6-29.9 mm). In the clinical cases, the procedure improved DIP joint extension lag and prevented proximal interphalangeal joint hyperextension. Preserving one-half of the FDP allowed complete flexion of the DIP joint. CONCLUSIONS: The procedure is technically feasible. Its main advantages are that a distal suture is not required and that the substantial length of the tendon allows sturdy proximal internal fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1.

Altered expression of the translation factor eIF3e is associated with breast cancer occurrence. We have previously shown that eIF3e deficiency leads to an impaired DNA damage response with a marked decrease in DNA repair by homologous recombination. Here, we explored the possibility to exploit this DNA repair defect in targeted cancer therapy using PARP inhibitors. Surprisingly, eIF3e-deficient breast cancer cells are resistant to these drugs, in contrast to BRCA1-deficient cells. Studying this, we found that eIF3e-depleted cells synthesize lowered amounts of PARP1 protein, due to a weakened translation of the corresponding mRNA, associated with a strong decrease in cellular poly(ADP-ribosyl)ation. Additionally, we discovered that the mTORC1 signaling pathway is aberrantly activated in response to eIF3e suppression. Together, these PARP1 and mTORC1 dysfunctions upon eIF3e depletion are causally linked to induction of cellular senescence associated with a pro-inflammatory secretory phenotype. This study provides mechanistic insights into how eIF3e protects against breast cancer, with potential novel cancer therapeutic opportunities. While PARP inhibitors appear as inappropriate drugs for eIF3e-deficient breast tumors, our findings suggest that such cancers may benefit from senolytic drugs or mTORC1 inhibitors.

Morphological and functional assessment of the flexor carpi radialis brevis using conventional ultrasound and elastography.

PURPOSE: The flexor carpi radialis brevis (FCRB) is a supernumerary musculotendinous structure of the wrist that has been the focus of some interest in the last decade. While its anatomy is well known, its in vivo function remains unknown as it has never been studied. METHODS: Eleven cases of FCRB underwent a multimodal ultrasound consisting of B-mode, color Doppler and shear wave elastography. RESULTS: A pennate shape was observed in all cases and the mean value of the cross-sectional area was 0.8 cm2 (SD 0.3 cm2). Young's modulus was significantly (p < 0.01) different between the resting position and active flexion or passive extension. CONCLUSION: Our study demonstrates that the FCRB shows biomechanics of a typical skeletal muscle and is voluntarily controlled by flexing the wrist. Absent in other vertebrate taxa, the FCRB probably plays a role in active stability of the wrist in Human.

Could Spectral CT Have a Potential Benefit in Coronavirus Disease (COVID-19)?

OBJECTIVE. The purpose of this study is to evaluate the potential benefit of spectral imaging, notably electron density imaging, in patients with suspected or confirmed coronavirus disease (COVID-19), by retrospectively reviewing the cases of four patients who each underwent two chest CT scans for confirmed COVID-19. CONCLUSION. The use of spectral CT with electron density imaging could improve the assessment of lung lesion extent in patients with early-stage COVID-19.