Further characterisation of ARX-related disorders in females due to inherited or de novo variants.

The Aristaless-related homeobox (ARX) gene is located on the X chromosome and encodes a transcription factor that is essential for brain development. While the clinical spectrum of ARX-related disorders is well described in males, from X linked lissencephaly with abnormal genitalia syndrome to syndromic and non-syndromic intellectual disability (ID), its phenotypic delineation in females is incomplete. Carrier females in ARX families are usually asymptomatic, but ID has been reported in some of them, as well as in others with de novo variants. In this study, we collected the clinical and molecular data of 10 unpublished female patients with de novo ARX pathogenic variants and reviewed the data of 63 females from the literature with either de novo variants (n=10), inherited variants (n=33) or variants of unknown inheritance (n=20). Altogether, the clinical spectrum of females with heterozygous pathogenic ARX variants is broad: 42.5% are asymptomatic, 16.4% have isolated agenesis of the corpus callosum (ACC) or mild symptoms (learning disabilities, autism spectrum disorder, drug-responsive epilepsy) without ID, whereas 41% present with a severe phenotype (ie, ID or developmental and epileptic encephalopathy (DEE)). The ID/DEE phenotype was significantly more prevalent in females carrying de novo variants (75%, n=15/20) versus in those carrying inherited variants (27.3%, n=9/33). ACC was observed in 66.7% (n=24/36) of females who underwent a brain MRI. By refining the clinical spectrum of females carrying ARX pathogenic variants, we show that ID is a frequent sign in females with this X linked condition.

Radiologic Evolution after Scapholunate Dorsal Capsulodesis for Chronic Tears.

Background Many debates are still ongoing for the management of chronic scapholunate (SL) injuries. We have proposed an arthroscopic technique of dorsal capsulodesis with good clinical results. We now propose a radiological follow-up. Purpose To determine if arthroscopic dorsal capsulodesis can improve the radiographic SL angle and maintain this correction over time. Methods From January 2020 to January 2021, we included every patient with an SL instability and sorted them according to the European Wrist Arthroscopy Society (EWAS) classification. All patients had bilateral X-rays with a measurement of the radiolunate (RL) and SL angles for both the pathologic and healthy side. We also included patients with lunotriquetral or triangular fibrocartilage complex lesions. The exclusion criteria were the presence of arthritis and persistent intraoperative SL instability after capsulodesis. An arthroscopic dorsal capsulodesis was performed in all patients as originally described by Mathoulin. The RL and SL angles were then again measured on the immediate postoperative X-ray, and then again at 3, 6, and 12 months postoperatively. The statistical analysis was done using a paired Student's t -test with 145 degrees of freedom and α = 0.05. Results We included a total of 146 patients with a 1-year follow-up. Both the RL angle and the SL angles approach the healthy side at 12 months postoperatively. The RL angle has increased from -7.23 degrees to 4.37 degrees; the difference is still statistically significative, but it is almost equal to the healthy side (5.16 degrees). The SL angle has lowered from 74.55 to 54.95; the difference is still statistically and radiologically significative (6.788 degrees) but has been lowered by 74.3%. Conclusion This study shows that this technique can normalize the dorsal intercalated segment instability (DISI) over time without the need for any pinning or invasive ligament reconstructive surgery. Level of Evidence Level IV, cohort study. Clinical Relevance Dorsal capsulodesis should be considered in all reducible SL injuries, even when DISI is present.

Lunate Pseudarthrosis: Our Clinical Experience.

Background: Lunate pseudarthrosis is a complication of lunate fractures and few cases are described in the literature. We designed a case series of lunate pseudarthrosis, to acknowledge this topic and to show our clinical experience. Methods: Four patients were included in this study. Three went through surgical treatment of lunate nonunion. Results: At 2 years' follow-up, patients had slight improvement of range of motion (ROM) and Quick-DASH score compared to preoperative measures, though two patients developed scaphocapitate, radiolunate or midcarpal osteoarthritis. The fourth patient is asymptomatic and is being followed up. Conclusions: Surgical options depend on the localization of the pseudarthrosis in the lunate. Fragment excision can be a good option when the fragment is small, preserving scapholunate (SL) stability. Caution must be taken with dorsal pole pseudarthrosis, regarding midcarpal osteoarthritis. Level of Evidence: Level IV (Therapeutic).

Treatment of scaphoid nonunion by arthroscopic cancellous bone grafting.

INTRODUCTION: In order to avoid Scaphoid Nonunion Advanced Collapse (SNAC) type osteoarthritis, which progressively affects the radial and midcarpal joints, several vascularized and non-vascularized grafting techniques have been described. Over the past decade, there has been growing interest in arthroscopic cancellous bone grafts for scaphoid nonunion. The aim of this novel prospective study was to assess the healing rate of scaphoid grafts under arthroscopy, and the prognostic factors for healing. MATERIAL AND METHODS: This prospective study was carried out across 10 centers between September 2019 and April 2021, in patients aged 16 to 65. Scaphoid nonunion grafting was performed arthroscopically. Union was assessed on CT scans and displacement correction angles were measured preoperatively and then at 3 and 6months. We assessed mobility, Jamar wrist strength, functional results as per the Patient Related Wrist Score (PRWE) and the Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH) score. Risk factors for nonunion were assessed. RESULTS: We included 77 patients with a mean age of 24years (18 to 55years) with a mean time between trauma and treatment of nonunion of 34.8months (6 to 180months). The population was represented by 46 manual workers and 20 were smokers. In 42 cases, the nonunion was proximal, in Schernberg zone I or II. At the last follow-up of 12.9months on average (Standard Deviation: 8.7months), union was achieved in 72 patients (93.5%). The average duration of union was 3.4months (Standard Deviation 1.6). Among the 5 patients who did not heal, grafting was performed in addition to the fixation. We did not identify any contributory factors for nonunion. CONCLUSION: This study demonstrated the effectiveness of arthroscopic treatment of scaphoid nonunion with a union rate at least equivalent to pedicled vascularized grafts. Smoking and delayed treatment were no longer considered unfavorable prognostic factors in the context of arthroscopic treatment. LEVEL OF EVIDENCE: III.

Jersey finger type IV: a case report.

Avulsion of the flexor digitorum profundus, usually known as jersey or rugby finger, is a rare condition that can only be treated surgically. It is mostly reported in sports injuries, in which the diagnosis is easily made. It is less frequent in household accidents, but should not be ignored because good results are time-dependent. Type IV jersey finger is the combination a fracture of the volar base of the distal phalanx and avulsion of the flexor digitorum profundus. This is a rare variety, and the surgical approach has not been discussed in detail. We introduce here a case report describing the clinical aspect, diagnostic approach, surgical technique and results at 6 months.

Wide arthroscopic dorsal capsuloligamentous repair in patients with severe scapholunate instability.

A conventional arthroscopic capsuloligamentous repair is a reliable surgical solution in most patients with scapholunate instability. However, this repair does not seem to be sufficient for more advanced injuries. The aim of this study was to evaluate the functional results of a wide arthroscopic dorsal capsuloligamentous repair (WADCLR) in the management of severe scapholunate instability. This was a prospective single-centre study undertaken between March 2019 and May 2021. The primary outcome was the evaluation of the reduction of the radiological deformity and the functional outcomes after WADCLR. A secondary outcome was the evaluation of the effectiveness of this technique in patients with the most severe instability (European Wrist Arthroscopy Society (EWAS) stage 5). The patients were reviewed postoperatively at three, six, and 12 months. The study included 112 patients (70 male and 42 female). Their mean age was 31.6 years (16 to 55). A total of three patients had EWAS stage 3A injuries, 12 had stage 3B injuries, 29 had stage 3C injuries, 56 had stage 4 injuries, and 12 had stage 5 injuries. There was a significant improvement of the radiological signs in all patients with a return to normal values. There was also a significant improvement in all aspects of function except for flexion, in which the mean increase was negligible (0.18° on average). There was also a significant improvement in all criteria for patients with a stage 5 injury, except for some limitation of extension, flexion, and radial and ulnar deviation, although these showed a trend towards improvement (except for flexion). WADCLR is a minimally invasive, easy, and reproducible technique with few complications, offering a clear improvement in function and a reduction in the radiological deformity at one year postoperatively.

Hyperselective neurectomy for the treatment of upper limb spasticity in adults and children: a prospective study.

Hyperselective neurectomy (HSN) procedures in the spastic upper limb aim to reduce tone by excising some branches of the involved peripheral motor nerves, at the point of entry of each motor ramus into the target muscle. In this prospective study, 42 patients with upper limb spasticity were treated by HSN for the muscles of elbow flexion, forearm pronation and wrist flexion and evaluated for their short-term results (average 6 months) and long-term outcomes (average 31 months). Results at both time points showed an effective reduction of the spastic tone, with no decrease of muscle strength in the operated spastic muscles. Comparison of results between the two time points showed durability of the improvement, which remained statistically significant despite a slight relapse in spasticity. The results of HSN compare favourably with the other techniques of partial neurectomy; however, the technique requires a detailed knowledge of upper limb motor anatomy.Level of evidence: II.

How to improve clinical research in a department of radiation oncology.

INTRODUCTION: Radiation therapy is a core modality for cancer treatment. Around 40% of cancer cures include the use of radiotherapy, either as a single strategy or combined with other treatments. In the past decade, substantial technical advances and novel insights into radiobiological properties have considerably improved patients' outcomes. This study overviewed the landscape of clinical research at our radiotherapy department. METHODS: We surveyed our institutional database of clinical trials to collect information for completed or ongoing radiation therapy clinical trials, from 2005 to December 2017 at the Lucien Neuwirth cancer institute. RESULTS: A total of 31 clinical trials were undertaken during the study period, of which 4 studies (12.9%) were industry-sponsored and 3 studies (9.7%) were launched by our radiotherapy unit. The vast majority of clinical trials (83.9%) were dedicated to unique organ localization, especially urological cancer (prostate or bladder) (42%). We also observed a shift towards more phase II trials during the study period as well as a special focus on elderly population. Over the last decade, the number of included patients increased by a 5.3 fold input, with 135 inclusions before 2011 and 720 inclusions after 2011. DISCUSSION: This study provided an observational and comprehensive analysis of radiotherapy research. From a monocentric point-of-view, these results reflected the on-going progress of worldwide radiotherapy research. Based on a 13-years' experience, this study aimed at highlighting essential cues to ensure efficient and perennial research.

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.

Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.

Art Therapy Sessions for Cancer Patients: A Single-Centre Experience.

INTRODUCTION: Cancer and anti-cancer therapies are often associated with pain, loss of self-worth, anxiety, and depression. Alternative therapies such as art therapy are available to improve patients' quality of life, by reducing asthenia, depression, anxiety and pain. OBJECTIVE: The aim of this study was to assess the effectiveness of art therapy, namely theatre and plastic art workshops, on well-being and quality of life of participants in the Lucien Neuwirth Cancer Institute. METHODS: A prospective study was conducted at the Lucien Neuwirth Cancer Institute (France), between April 2018 and July 2018. Cancer patients followed at the Institute have been asked to participate in 10 2-h sessions, once a week, based on theatre and plastic art workshops. Self-report questionnaires were used to evaluate both psychological and quality of life domains, but also satisfaction and well-being, before (pre-test) and after the last session (early post-test), as well as 1-month post-experimentation (late post-test). RESULTS: Among the 14 patients who were enroled, the QLQ-C30 questionnaire revealed a pre-test median score of 50.0, an early post-test score of 51.5, and the late post-test revealed a score of 48.0. The anxiety test revealed median scores of 8.0 (pre-test), 6.0 (early post-test) and 6.0 (late post-test), respectively. The depression test reported median scores of 4.0 (pre-test), 5.0 (early post-test) and 6.0 (late post-test), respectively. The median well-being score difference observed between the beginning and the end of sessions is +2.13. The minimum satisfaction score observed is 3.50 out of 10, and the maximum is 10 out of 10. The median is between 7.00 and 10.00. CONCLUSIONS: Art therapy sessions had an impact on patients' welfare. We also reported a trend towards amelioration of quality of life that could probably be confirmed in a larger population, and potentially with a different methodology.

Role of wrist arthroscopy in scapholunate dissociation.

Scapholunate ligament tear is most frequently encountered in the aftermath of trauma in supination and extension of the wrist. It generates chronic instability, leading to osteoarthritis. It may be associated with fracture of the distal epiphysis of the radius or of the scaphoid. These lesions are often difficult to diagnose, especially in early stages. Treatment of chronic scapholunate ligament lesions before onset of osteoarthritis is a challenge for the surgeon. To date, recommendations are for open reconstruction or repair, which can improve pain and grip strength, but very often at the cost of wrist stiffness. The advent of arthroscopy has completely changed the understanding and treatment of these lesions. The present review focuses on recent contributions to the anatomy of the scapholunate complex and the anatomopathology of these dissociations, and explores classical treatments and the emerging role of arthroscopy. We shall seek to answer five questions: (1) What are the anatomical bases of the scapholunate complex, (2) What is the initial clinical and paraclinical work-up for scapholunate dissociations, and how are they to be classified, (3) What are the classical treatments for scapholunate dissociation, (4) What are the technical principles and results of arthroscopic treatment, (5) What are the limits and perspectives of arthroscopic treatment?

Use of Complementary and Alternative Medicines among Cancer Patients: A Single-Center Study.

PURPOSE: It is usual for cancer patients to use complementary and alternative medicines (CAMs) and yet the literature evaluating their efficacy in cancer patients is very limited. The objective of the present study was to report on the nature, frequency of use, and patient-reported outcome of CAMs in a single-center study. METHODS: All the consecutive patients treated between November 2017 and June 2018 at the Lucien Neuwirth Cancer Institute (France) were screened. Their reasons for using CAMs and their usage habits were collected. Patients evaluated their benefit. RESULTS: Of the 209 patients screened, 200 patients were included. CAMs ranged from osteopathy, homeopathy, acupuncture, healing touch, magnetism, naturopathy, suction cups, Chinese medicine, reflexology, to hypnosis. CAMs were widely used (n = 166, 83%), the first being osteopathy (n = 99, 49.5%), the second homeopathy (n = 78, 39.0%), and finally acupuncture (n = 76, 38.0%). Whatever the CAM, high satisfaction rates were reported (median satisfaction: 61-81%). CAMs were mainly used to prevent/treat side effects of anticancer treatments (81.2% for healing touch), increase well-being (55.4% for naturopathy), improve the immune system (16.9% for homeopathy), and treat cancer (n = 3, 5.1% for homeopathy). Patients could easily consider using CAMs, as up to 50.8% would have accepted a consultation. CONCLUSIONS: The reasons for using CAMs differed among patients. They praised CAMs and kept asking for more information although there is limited evidence about their efficacy in the literature. Thus, prospective randomized controlled trials exploring the safety and efficacy of CAMs in cancer patients are needed.

[Complementary and alternative medicines in cancer patients]. / Les médecines alternatives complémentaires en oncologie.

Complementary and alternative medicines (CAMs) play more and more a significant role both in France and all over the world. Yet, their definition and their role in cancer treatments legitimately raise concerns. This article aims at establishing a picture of the CAMs admitted by the French Medical Board as well as those which are new or in common medical practices in France. We start with a brief reminder of their origin, their status and how they are used. Then, we review the literature about some of the best clinical trials using CAMs in cancer patients. To finish, we try to understand what makes CAMs so thrilling, but also why they create controversy and which common points they may have with conventional medicine.

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2.

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs.awx326media15680039660001.

Arthroscopic Management of Dorsal and Volar Wrist Ganglion.

Dorsal and volar wrist ganglions are benign tumors; most of them are asymptomatic. They can disappear spontaneously. Arthroscopic resection can be performed for pain or cosmetic concern. Dorsal ganglion is more common (70%). The hypothesis of the origin is the result of mucoid dysplasia in association with intracapsular and extrasynovial ganglia that occur at the level of the dorsal scapholunate complex. Volar wrist ganglia are less common (20%) and occur mainly in the radiocarpal joint. They are due to capsular destruction at the volar insertion of the SL ligament and arise from the interval between radio scaphocapitate and long radiolunate ligament.

Treatment of Avascular Necrosis of the Proximal Pole of the Scaphoid by Arthroscopic Resection and Prosthetic Semireplacement Arthroplasty Using the Pyrocarbon Adaptive Proximal Scaphoid Implant (APSI): Long-Term Functional Outcomes.

Fractures of the proximal pole of the scaphoid with associated avascular necrosis and nonunion are well known to be problematic. Many techniques for fixation and reconstruction of the proximal pole of the scaphoid have been reported, often with poor results. One of the newer modalities of treatment for these difficult cases is excision of the proximal pole and replacement with a pyrocarbon implant. The ovoid shape of the implant acts as a spacer and repositions itself throughout the range of motion of the wrist. The procedure can be performed arthroscopically, thus reducing the morbidity and allowing the procedure to be a day case. Satisfactory results have been reported in elderly patients, but there is a paucity of literature regarding the outcomes in younger patients. This multicenter retrospective study evaluates the clinical, radiologic, and functional outcomes in patients under the age of 65 years with a minimum follow up of 5 years. There were 14 patients with scaphoid nonunion advanced collapse (SNAC) grade I, II, or III wrists, with a mean age of 53 years and mean follow up of 8.7 years. There were improvements in all of the patient related variables including VAS pain scores (7.5 to 0.7), extension (45° to 60°), flexion (32° to 53°), and grip strength (15.8 to 34.6 kg). Complications included volar subluxation of the implant, which was acutely surgically corrected (1), volar subluxation of the implant, with persistent pain that required a four-corner fusion (2), and secondary radial styloidectomy (3). This technique is an attractive, minimally invasive alternative for nonunion and avascular necrosis resulting from fractures of the proximal pole of the scaphoid. The authors provide details of the technique, including technical suggestions for performing the procedure.