Chemistry of Strigolactones, Key Players in Plant Communication.

Today, the use of artificial pesticides is questionable and the adaptation to global warming is a necessity. The promotion of favorable natural interactions in the rhizosphere offers interesting perspectives for changing the type of agriculture. Strigolactones (SLs), the latest class of phytohormones to be discovered, are also chemical mediators in the rhizosphere. We present in this review the diversity of natural SLs, their analogs, mimics, and probes essential for the biological studies of this class of compounds. Their biosynthesis and access by organic synthesis are highlighted especially concerning noncanonical SLs, the more recently discovered natural SLs. Organic synthesis of analogs, stable isotope-labeled standards, mimics, and probes are also reviewed here. In the last part, the knowledge about the SL perception is described as well as the different inhibitors of SL receptors that have been developed.

SUPPRESSOR OF MAX2 1-LIKE (SMXL) homologs are MAX2-dependent repressors of Physcomitrium patens growth.

SUPPRESSOR OF MAX2 (SMAX)1-LIKE (SMXL) proteins are a plant-specific clade of type I HSP100/Clp-ATPases. SMXL genes are present in virtually all land plant genomes. However, they have mainly been studied in angiosperms. In Arabidopsis (Arabidopsis thaliana), 3 functional SMXL subclades have been identified: SMAX1/SMXL2, SMXL345, and SMXL678. Of these, 2 subclades ensure endogenous phytohormone signal transduction. SMAX1/SMXL2 proteins are involved in KAI2 ligand (KL) signaling, while SMXL678 proteins are involved in strigolactone (SL) signaling. Many questions remain regarding the mode of action of these proteins, as well as their ancestral roles. We addressed these questions by investigating the functions of the 4 SMXL genes in the moss Physcomitrium patens. We demonstrate that PpSMXL proteins are involved in the conserved ancestral MAX2-dependent KL signaling pathway and negatively regulate growth. However, PpSMXL proteins expressed in Arabidopsis cannot replace SMAX1 or SMXL2 function in KL signaling, whereas they can functionally replace SMXL4 and SMXL5 and restore root growth. Therefore, the molecular functions of SMXL proteins are conserved, but their interaction networks are not. Moreover, the PpSMXLC/D clade positively regulates SL signal transduction in P. patens. Overall, our data reveal that SMXL proteins in moss mediate crosstalk between the SL and KL signaling pathways.

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments.

BACKGROUND: In 2017, a new treatment by nusinersen, an antisense oligonucleotide delivered by repeated intrathecal injections, became available for patients with spinal muscular atrophy (SMA), whereas clinical trials had mainly involved children. Since 2020, the oral, selective SMN2-splicing modifier risdiplam has been available with restrictions evolving with time. In this peculiar context of lack of data regarding adult patients, many questions were raised to define the indications of treatment and the appropriate follow-up in this population. To homogenize access to treatment in France, a national multidisciplinary team meeting dedicated to adult SMA patients, named SMA multidisciplinary team meeting, (SMDTs) was created in 2018. Our objective was to analyze the value of SMDTs in the decision-making process in SMA adult patients and to provide guidelines about treatment. METHODS: From October 2020 to September 2021, data extracted from the SMDT reports were collected. The primary outcome was the percentage of cases in which recommendations on validating treatment plans were given. The secondary outcomes were type of treatment requested, description of expectations regarding treatment and description of recommendations or follow-up and discontinuation. Data were analyzed using descriptive statistics. Comparisons between the type of treatment requested were performed using Mann-Whitney test or the Student t test for quantitative data and the Fisher's exact test or the χ2 test for qualitative data. RESULTS: Cases of 107 patients were discussed at the SMDTs with a mean age of 35.3 (16-62). Forty-seven were SMA type 2, and 57 SMA type 3. Twelve cases were presented twice. Out of 122 presentations to the SMDTs, most of requests related to the initiation of a treatment (nusinersen (n = 46), risdiplam (n = 54), treatment without mentioning preferred choice (n = 5)) or a switch of treatment (n = 12). Risdiplam requests concerned significantly older patients (p = 0.002), mostly SMA type 2 (p < 0.0001), with greater disease severity in terms of motor and respiratory function compared to requests for nusinersen. In the year prior to presentation to the SMDTs, most of the patients experienced worsening of motor weakness assessed by functional tests as MFM32 or other meaningful scales for the most severe patients. Only 12% of the patients discussed had a stable condition. Only 49/122 patients (40.1%) expressed clear expectations regarding treatment. The treatment requested was approved by the SMDTs in 72 patients (67.2%). The most common reasons to decline treatment were lack of objective data on the disease course prior discussion to the SMDTs or inappropriate patient's expectations. Treatment requests were more likely to be validated by the SMDTs if sufficient pre-therapeutic functional assessment had been performed to assess the natural history (55% vs. 32%) and if the patient had worsening rather than stable motor function (p = 0.029). In patients with approved treatment, a-priori criteria to define a further ineffectiveness of treatment (usually after 14 months of treatment) were proposed for 67/72 patients. CONCLUSIONS: In the context of costly treatments with few controlled studies in adults with SMA, in whom assessment of efficacy can be complex, SMDTs are 'real-world observatories' of great interest to establish national recommendations about indications of treatment and follow-up.

Effect of oxygen therapy duration on cognitive impairment 12 months after hospitalization for SARS-COV-2 infection.

OBJECTIVE: To identify predictors of persistent cognitive impairment at 12 months after hospitalization due to COVID-19 (SARS-CoV-2) infection. DESIGN: Retrospective, single-centre study. SUBJECTS: All consecutive patients assessed in physical and rehabilitation medicine consultations at 3 months with a neuropsychiatric testing (NPT) at 6 months. METHODS: A Mini Mental State Examination (MMSE) was performed at 3 months and NPT at 6 and 12 months, exploring global cognitive efficiency, attention and processing speed, short-term memory and executive function. Logistic regression and receiver operating characteristic curves were used to identify predictors of persistent cognitive impairment. RESULTS: Among 56 patients, 64.3% and 53.6% had 1 or more impaired cognitive functions at 6 and 12 months, respectively, attention and processing speed being the most represented (41.1% at 12 month). Duration of oxygen therapy (odds ratio 0.926 [0.871-0.985], p = 0.015) and MMSE score at 3 months (odds ratio 0.464 [0.276-0.783], p = 0.004) were associated with cognitive impairment at 12 months by multivariable analysis (R² 0.372-0.497). CONCLUSIONS: Half of patients have cognitive impairment 12 months after acute SARS-CoV-2 infection requiring hospitalization. The duration of oxygen therapy in acute care could be a protective parameter. Systematic evaluation with the MMSE at 3 months after infection might be an effective tool to detect risk.

Histone Deacetylases Regulate MORE AXILLARY BRANCHED 2-Dependent Germination of Arabidopsis thaliana.

Under specific conditions, the germination of Arabidopsis thaliana is dependent on the activation of the KARRIKIN INSENSITIVE 2 (KAI2) signaling pathway by the KAI2-dependent perception of karrikin or the artificial strigolactone analogue, rac-GR24. To regulate the induction of germination, the KAI2 signaling pathway relies on MORE AXILLARY BRANCHED 2- (MAX2-)dependent ubiquitination and proteasomal degradation of the repressor protein SUPPRESSOR OF MAX2 1 (SMAX1). It is not yet known how the degradation of SMAX1 proteins eventually results in the regulation of seed germination, but it has been hypothesized that SMAX1-LIKE generally functions as transcriptional repressors through the recruitment of co-repressors TOPLESS (TPL) and TPL-related, which in turn interact with histone deacetylases. In this article, we show the involvement of histone deacetylases HDA6, HDA9, HDA19 and HDT1 in MAX2-dependent germination of Arabidopsis, and more specifically, that HDA6 is required for the induction of DWARF14-LIKE2 expression in response to rac-GR24 treatment.

Effects of Whole-Body Vibration Exercise on Athletes with Ankle Instability: A Systematic Review.

OBJECTIVE: Chronic Ankle Instability (CAI) or Functional Ankle Instability (FAI) is a condition characterized by laxity and mechanical instability in the ankle joint. This instability interferes with the activities and physical-functional parameters of athletes, which leads to repetitive ankle sprains. The current systematic review was carried out to identify the effects of whole-body vibration exercise (WBVE) in athletes with CAI. METHODS: We conducted electronic searches in Pubmed, the Cochrane Library, Embase, Web of Science, Scopus, Science Direct, Allied Health Literature (CINAHL) and Academic Search Premier (ASP) (EBSCO) databases on 26 February 2022. Registers were identified, and studies were selected for inclusion according to the eligibility criteria. The methodological quality was assessed by the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Seven studies were included with a mean methodological quality score of 5.85, considered 'regular' quality on the PEDro scale. WBVE interventions in athletes with CAI showed that this exercise contributes to a better response on parameters of neuromuscular performance, muscle strength and consequently in balance and postural control, variables that are for the management of CAI. CONCLUSION: WBVE interventions in sports modalities promote physiological responses that may lead to positive effects in several parameters. The protocols proposed in each modality can be carried out in practice and are considered effective additional exercise and training methods beyond traditional types of training for athletes. However, more studies are needed on athletes with this condition, with specific protocols, to highlight the possible physiological and physical-functional responses. Protocol study registration: PROSPERO (CRD42020204434).

Therapeutic Approach of Whole-Body Vibration Exercise on Wound Healing in Animal Models: A Systematic Review.

Human skin wounds pose a gathering threat to the public health, carrying an immense epidemiologic and financial burden. Pharmacological and non-pharmacological (NP) treatments have been proposed to the management of wound healing. Physical exercise is a strong NP intervention considered for patients in wound healing. Particularly, a type of exercise intervention known as whole-body vibration (WBV) exercise has gained increasing interest. WBV exercise is generated due to the transmission of mechanical vibrations, produced by a vibrating platform, to the body. The aim of this review was to summarize studies in experimental animal models using WBV exercise in wound healing. Searches were performed in EMBASE, PubMed, Scopus and Web of Science including publications on 21 November 2022 using the string "whole body vibration" AND "wound healing" (animal or mice or mouse or rat or rodent). The SYRCLE tool was used to assess the risk of bias (RoB). From 48 studies, five studies met the inclusion criteria. RoB indicated that none of the studies fulfilled all methodological analyzed criteria, resulting in possible biases. The studies were homogeneous, and results suggest beneficial effects of WBV exercise in wound healing, mainly related to enhancing angiogenesis, granulation tissue formation, reducing the blood glucose level and enhancing blood microcirculation, by increasing myofiber growth and rapid re-epithelialization. In conclusion, the various biological effects of the response to the WBV exercise indicate the relevance of this intervention in wound healing in animals. Moreover, considering the translation approach, it is possible to speculate that the beneficial effects of this non-pharmacological therapy might justify clinical trials for wound healing also in humans, after criterion evaluation.

Post-Intensive Care Syndrome Prevalence Six Months after Critical Covid-19: Comparison between First and Second Waves.

OBJECTIVE: To explore the impact of improved intensive care for COVID-19 patients on the prevalence of post-intensive care syndrome (PICS). DESIGN: Ambispective cohort study. PATIENTS: Post-intensive care unit COVID-19 patients from the first and second waves of COVID-19. METHODS: Patients were evaluated at 6 months after infection. PICS was defined as the presence of a 1-min sit-to-stand test (1STS) score < 2.5th percentile or a Symbol Digit Modalities Test (SDMT) below the 2 standard deviation cut-off, or a Hospital Anxiety and Depression Scale score ≥ 11. RESULTS: A total of 60 patients were included (34 from wave 1 and 26 from wave 2). Intensive care unit management improved between waves, with shorter duration of orotracheal intubation (7 vs 23.5 days, p = 0.015) and intensive care unit stay (6 vs 9.5 days, p = 0.006) in wave 2. PICS was present in 51.5% of patients after wave 1 and 52% after wave 2 (p = 0.971). Female sex and diabetes were significantly associated with PICS by multivariate analysis. CONCLUSION: Approximately half of post-intensive care unit COVID-19 patients have 1 or more impairments consistent with PICS at 6 months, with an impact on quality of life and participation. Improved intensive care unit management was not associated with a decrease in the prevalence of PICS. Identification of patients at risk, particularly women and diabetic patients, is essential. Further studies of underlying mechanisms and the need for rehabilitation are essential to reduce the risk of PICS.

Noncanonical Strigolactone Analogues Highlight Selectivity for Stimulating Germination in Two Phelipanche ramosa Populations.

Strigolactones (SLs) are plant hormones exuded in the rhizosphere with a signaling role for the development of arbuscular mycorrhizal (AM) fungi and as stimulants of seed germination of the parasitic weeds Orobanche, Phelipanche, and Striga, the most threatening weeds of major crops worldwide. Phelipanche ramosa is present mainly on rape, hemp, and tobacco in France. P. ramosa 2a preferentially attacks hemp, while P. ramosa 1 attacks rapeseed. The recently isolated cannalactone (14) from hemp root exudates has been characterized as a noncanonical SL that selectively stimulates the germination of P. ramosa 2a seeds in comparison with P. ramosa 1. In the present work, (-)-solanacol (5), a canonical orobanchol-type SL exuded by tobacco and tomato, was established to possess a remarkable selective germination stimulant activity for P. ramosa 2a seeds. Two cannalactone analogues, named (±)-SdL19 and (±)-SdL118, have been synthesized. They have an unsaturated acyclic carbon chain with a tertiary hydroxy group and a methyl or a cyclopropyl group instead of a cyclohexane A-ring, respectively. (±)-SdL analogues are able to selectively stimulate P. ramosa 2a, revealing that these minimal structural elements are key for this selective bioactivity. In addition, (±)-SdL19 is able to inhibit shoot branching in Pisum sativum and Arabidopsis thaliana and induces hyphal branching in the AM fungus Rhizophagus irregularis, like SLs.

Characteristics of COVID-19 Inpatients in Rehabilitation Units during the First Pandemic Wave: A Cohort Study from a Large Hospital in Champagne Region.

Background: Data describing patients hospitalized in medical rehabilitation wards after the acute phase of COVID-19 could help to better understand the rehabilitation needs in the current pandemic situation. Methods: Cohort including all patients with COVID-19 hospitalized in a single, large university hospital in Northeast France from 25 February to 30 April 2020. Results: 479 patients were admitted with COVID-19 during the study period, of whom 128 died (26.7%). Among the 351 survivors, 111 were referred to rehabilitation units, including 63 (17.9%) referred to physical and rehabilitation medicine (PRM) units. The median age of patients referred to rehabilitation units was 72 years. Patients who had been in intensive care, or who had had a long hospital stay, required referral to PRM units. Two biomarkers were associated with referral to rehabilitation units, namely, elevated troponin (p = 0.03) and impaired renal function (p = 0.03). Age was associated with referral to PRM units (p = 0.001). Conclusions: Almost one-third of COVID-19 patients required post-acute care, but only one-fifth had access to PRM units. The optimal strategy for post-acute management of COVID-19 patients remains to be determined. The need for rehabilitation wards during a pandemic is a primary concern in enabling the long-term functioning of infected patients.

MAX2-dependent competence for callus formation and shoot regeneration from Arabidopsis thaliana root explants.

Although the division of the pericycle cells initiates both lateral root development and root-derived callus formation, these developmental processes are affected differently in the strigolactone and karrikin/KARRIKIN INSENSITIVE 2 (KAI2) ligand signalling mutant more axillary growth 2 (max2). Whereas max2 produces more lateral roots than the wild type, it is defective in the regeneration of shoots from root explants. We suggest that the decreased shoot regeneration of max2 originates from delayed formation of callus primordium, yielding less callus material to regenerate shoots. Indeed, when incubated on callus-inducing medium, the pericycle cell division was reduced in max2 and the early gene expression varied when compared with the wild type, as determined by a transcriptomics analysis. Furthermore, the expression of the LATERAL ORGAN BOUNDARIES DOMAIN genes and of callus-induction genes was modified in correlation with the max2 phenotype, suggesting a role for MAX2 in the regulation of the interplay between cytokinin, auxin, and light signalling in callus initiation. Additionally, we found that the in vitro shoot regeneration phenotype of max2 might be caused by a defect in KAI2, rather than in DWARF14, signalling. Nevertheless, the shoot regeneration assays revealed that the strigolactone biosynthesis mutants max3 and max4 also play a minor role.

Epstein-Barr Virus (EBV) Is Mostly Latent and Clonal in Angioimmunoblastic T Cell Lymphoma (AITL).

The Epstein-Barr virus (EBV) is associated with angioimmunoblastic T cell lymphoma (AITL), a peripheral T lymphoma of poor prognosis in at least 90% of cases. The role of EBV in this pathology is unknown. Using next-generation sequencing, we sequenced the entire EBV genome in biopsies from 18 patients with AITL, 16 patients with another EBV-associated lymphoma, and 2 controls. We chose an EBV target capture method, given the high specificity of this technique, followed by a second capture to increase sensitivity. We identified two main viral strains in AITL, one of them associated with the mutations BNRF1 S542N and BZLF1 A206S and with mutations in the EBNA-3 and LMP-2 genes. This strain was characterized in patients with short post-diagnosis survival. The main mutations found during AITL on the most mutated latency or tegument genes were identified and discussed. We showed that the virus was clonal in all the AITL samples, suggesting that it may be involved in this pathology. Additionally, EBV was latent in all the AITL samples; for one sample only, the virus was found to be latent and probably replicative, depending on the cells. These various elements support the role of EBV in AITL.

Expansion of the Strigolactone Profluorescent Probes Repertory: The Right Probe for the Right Application.

Strigolactones (SLs) are intriguing phytohormones that not only regulate plant development and architecture but also interact with other organisms in the rhizosphere as root parasitic plants (Striga, Orobanche, and Phelipanche) and arbuscular mycorrhizal fungi. Starting with a pioneering work in 2003 for the isolation and identification of the SL receptor in parasitic weeds, fluorescence labeling of analogs has proven a major strategy to gain knowledge in SL perception and signaling. Here, we present novel chemical tools for understanding the SL perception based on the enzymatic properties of SL receptors. We designed different profluorescent SL Guillaume Clavé (GC) probes and performed structure-activity relationship studies on pea, Arabidopsis thaliana, and Physcomitrium (formerly Physcomitrella) patens. The binding of the GC probes to PsD14/RMS3, AtD14, and OsD14 proteins was tested. We demonstrated that coumarin-based profluorescent probes were highly bioactive and well-adapted to dissect the enzymatic properties of SL receptors in pea and a resorufin profluorescent probe in moss, contrary to the commercially available fluorescein profluorescent probe, Yoshimulactone Green (YLG). These probes offer novel opportunities for the studies of SL in various plants.

Convergence of patient- and physician-reported outcomes in the French National Registry of Facioscapulohumeral Dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent muscular dystrophies and currently has no treatment. Clinical and genetic heterogeneity are the main challenges to a full comprehension of the physiopathological mechanism. Improving our knowledge of FSHD is crucial to the development of future therapeutic trials and standards of care. National FSHD registries have been set up to this end. The French National Registry of FSHD combines a clinical evaluation form (CEF) and a self-report questionnaire (SRQ), filled out by a physician with expertise in neuromuscular dystrophies and by the patient, respectively. Aside from favoring recruitment, our strategy was devised to improve data quality. Indeed, the pairwise comparison of data from 281 patients for 39 items allowed for evaluating data accuracy. Kappa or intra-class coefficient (ICC) values were calculated to determine the correlation between answers provided in both the CEF and SRQ. RESULTS: Patients and physicians agreed on a majority of questions common to the SRQ and CEF (24 out of 39). Demographic, diagnosis- and care-related questions were generally answered consistently by the patient and the medical practitioner (kappa or ICC values of most items in these groups were greater than 0.8). Muscle function-related items, i.e. FSHD-specific signs, showed an overall medium to poor correlation between data provided in the two forms; the distribution of agreements in this section was markedly spread out and ranged from poor to good. In particular, there was very little agreement regarding the assessment of facial motricity and the presence of a winged scapula. However, patients and physicians agreed very well on the Vignos and Brooke scores. The report of symptoms not specific to FSHD showed general poor consistency. CONCLUSIONS: Patient and physician answers are largely concordant when addressing quantitative and objective items. Consequently, we updated collection forms by relying more on patient-reported data where appropriate. We hope the revised forms will reduce data collection time while ensuring the same quality standard. With the advent of artificial intelligence and automated decision-making, high-quality and reliable data are critical to develop top-performing algorithms to improve diagnosis, care, and evaluate the efficiency of upcoming treatments.

A structural homologue of the plant receptor D14 mediates responses to strigolactones in the fungal phytopathogen Cryphonectria parasitica.

Strigolactones (SLs) are plant hormones and important signalling molecules required to promote arbuscular mycorrhizal (AM) symbiosis. While in plants an α/ß-hydrolase, DWARF14 (D14), was shown to act as a receptor that binds and cleaves SLs, the fungal receptor for SLs is unknown. Since AM fungi are currently not genetically tractable, in this study, we used the fungal pathogen Cryphonectria parasitica, for which gene deletion protocols exist, as a model, as we have previously shown that it responds to SLs. By means of computational, biochemical and genetic analyses, we identified a D14 structural homologue, CpD14. Molecular homology modelling and docking support the prediction that CpD14 interacts with and hydrolyses SLs. The recombinant CpD14 protein shows α/ß hydrolytic activity in vitro against the SLs synthetic analogue GR24; its enzymatic activity requires an intact Ser/His/Asp catalytic triad. CpD14 expression in the d14-1 loss-of-function Arabidopsis thaliana line did not rescue the plant mutant phenotype. However, gene inactivation by knockout homologous recombination reduced fungal sensitivity to SLs. These results indicate that CpD14 is involved in SLs responses in C. parasitica and strengthen the role of SLs as multifunctional molecules acting in plant-microbe interactions.

Structural and functional analyses explain Pea KAI2 receptor diversity and reveal stereoselective catalysis during signal perception.

KAI2 proteins are plant α/ß hydrolase receptors which perceive smoke-derived butenolide signals and endogenous, yet unidentified KAI2-ligands (KLs). The number of functional KAI2 receptors varies among species and KAI2 gene duplication and sub-functionalization likely plays an adaptative role by altering specificity towards different KLs. Legumes represent one of the largest families of flowering plants and contain many agronomic crops. Prior to their diversification, KAI2 underwent duplication resulting in KAI2A and KAI2B. Here we demonstrate that Pisum sativum KAI2A and KAI2B are active receptors and enzymes with divergent ligand stereoselectivity. KAI2B has a higher affinity for and hydrolyses a broader range of substrates including strigolactone-like stereoisomers. We determine the crystal structures of PsKAI2B in apo and butenolide-bound states. The biochemical, structural, and mass spectra analyses of KAI2s reveal a transient intermediate on the catalytic serine and a stable adduct on the catalytic histidine, confirming its role as a bona fide enzyme. Our work uncovers the stereoselectivity of ligand perception and catalysis by diverged KAI2 receptors and proposes adaptive sensitivity to KAR/KL and strigolactones by KAI2B.

Impact of resistance training on the 6-minute walk test in individuals with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to assess functional improvement, measured by the 6-minute walk test (6MWT) after the application of a resistance training (RT) protocol in people with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: The search involved the databases ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, EMBASE, PubMed and Scopus from the beginning of inception to September 1, 2019. Randomized controlled trials evaluating the functional impact of RT were included. The quality of the trials was assessed with the Physiotherapy Evidence Database (PEDro) scale. Calculations were performed according to mean difference (MD) for differences between pre- and post-intervention in 6MWT distance and according to the standardized mean difference (SMD) for post-treatment results of the 6MWT and quadriceps muscle strength (QMS) improvement. RESULTS: In total, 23 studies (690 patients) met the inclusion criteria. Meta-analysis was used to compute the best improvement on the 6MWT with an analysis of improvement pre- versus post-treatment (MD 37.3, 95% confidence interval [CI] 9.8; 64.8, I2 = 86%, p = 0.008) versus post-treatment alone, intervention versus control group (MD 15.5, 95% CI -7.7; 38.6, I2 = 71%, p = 0.19). QMS was significantly improved (SMD 2.9, 95% CI 1.1; 4.7, I2 = 91%, p = 0.002). CONCLUSION: The results of the meta-analysis show a significant improvement in walking ability and performance measured by the 6MWT and an improvement in QMS for people with COPD responding to the therapy. The main limitation of this review is the significant heterogeneity across the study results. Furthermore, the statistical significance does not totally coincide with the clinical significance. RT is recommended to reduce muscle dysfunction and seems useful when combined with endurance training.

Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations.

BACKGROUND: Adjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews. OBJECTIVE: To assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process. METHODS: Four electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs. RESULTS: We included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n=9), joint posture procedures (JPPs, n=11), and active ATs (n=14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score=7 [6-8]) but moderate (n=2) or poor (n=2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (>3months after botulinum toxin injections), particularly when performed at a high-intensity (>3h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended. CONCLUSIONS: JPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life. REVIEW REGISTRATION: PROSPERO (CRD42018105856).