Conquering new grounds: plant organellar C-to-U RNA editing factors can be functional in the plant cytosol.

Plant mitochondrial and chloroplast transcripts are subject to numerous events of specific cytidine-to-uridine (C-to-U) RNA editing to correct genetic information. Key protein factors for this process are specific RNA-binding pentatricopeptide repeat (PPR) proteins, which are encoded in the nucleus and post-translationally imported into the two endosymbiotic organelles. Despite hundreds of C-to-U editing sites in the plant organelles, no comparable editing has been found for nucleo-cytosolic mRNAs raising the question why plant RNA editing is restricted to chloroplasts and mitochondria. Here, we addressed this issue in the model moss Physcomitrium patens, where all PPR-type RNA editing factors comprise specific RNA-binding and cytidine deamination functionalities in single proteins. To explore whether organelle-type RNA editing can principally also take place in the plant cytosol, we expressed PPR56, PPR65 and PPR78, three editing factors recently shown to also function in a bacterial setup, together with cytosolic co-transcribed native targets in Physcomitrium. While we obtained unsatisfying results upon their constitutive expression, we found strong cytosolic RNA editing under hormone-inducible expression. Moreover, RNA-Seq analyses revealed varying numbers of up to more than 900 off-targets in other cytosolic transcripts. We conclude that PPR-mediated C-to-U RNA editing is not per se incompatible with the plant cytosol but that its limited target specificity has restricted its occurrence to the much less complex transcriptomes of mitochondria and chloroplast in the course of evolution.

Comparative analysis of surgical treatment modalities for a popliteal pterygium: a meta-analysis.

INTRODUCTION: Popliteal pterygium syndrome is a rare congenital disorder characterized by orofacial, cutaneous, musculoskeletal, and genital anomalies. The popliteal pterygium (PP) affects ambulation due to severe knee flexion contracture and equinovarus deformities. Surgical treatment aims to correct these deformities while preserving limb sensibility. However, due to its rarity, surgical guidelines are lacking. MATERIALS AND METHODS: A meta-analysis according to PRISMA guidelines was conducted to summarize and compare surgical methods for PP. 183 paper were identified in PubMed and data from 32 articles were analyzed, including patient demographics, treatment modalities (Ilizarov fixator, femoral osteotomy, skin/soft tissue procedures, hamstring release, nerve surgery, and amputation), pre- and post-operative abilities to walk, knee joint parameters, complications, and recurrent contractions. RESULTS: Among 58 patients (87 limbs), Ilizarov fixator demonstrated improved knee and ankle mobility postoperatively, but showed a relatively high surgical session count and complication rates. Femoral osteotomy achieved successful knee posture correction with fewer sessions and no complications. Isolated skin/soft tissue procedures improved flexion contracture and mobility, though they required several procedures. Hamstring release achieved notable contracture reduction but also necessitated multiple interventions. Nerve surgery and amputation had limited data, warranting further investigation. CONCLUSION: The management of PP demands a comprehensive approach, considering individual patient characteristics and treatment outcomes. While different surgical modalities offer distinct benefits, a classification or guideline to treat this deformity is still lacking. Further research is essential to validate findings, refine treatment approaches, and enhance the quality of life for individuals with PP.

Mechanisms, interventions at risk and clinical presentation of iatrogenic nerve lesions in trauma patients.

BACKGROUND: Iatrogenic nerve lesions during surgical interventions are avoidable complications that may cause severe functional impairment. Hereby, awareness of physicians and knowledge of structures and interventions at risk is of utmost importance for prevention. As current literature is scarce, we evaluated all patients treated surgically due to peripheral nerve injuries in our specialized nerve center for the presence of iatrogenic nerve lesions. METHODS: We evaluated a total of 5026 patients with peripheral nerve injuries treated over a time period of 8 years in our facility for the prevalence of iatrogenic nerve injuries, their clinical presentations, time to treatment, mechanisms and intraoperative findings on nerve continuity. RESULTS: A total of 360 (6.1%) patients had an iatrogenic cause resulting in 380 injured nerves. 76.6% of these lesions affected the main branch of the injured nerve, which were mainly the radial (30.5%), peroneal (13.7%) and median nerve (10.3%). After a mean delay of 237 ± 344 days, patients presented 23.2% with a motor and 27.9% with a mixed sensory and motor deficit. 72.6% of lesions were in-continuity lesions. Main interventions at risk are displayed for every nerve, frequently concerning osteosyntheses but also patient positioning and anesthesiologic interventions. DISCUSSION: Awareness of major surgical complications such as iatrogenic nerve injuries is important for surgeons. An often-seen trivialization or "watch and wait" strategy results in a huge delay for starting an adequate therapy. The high number of in-continuity lesions mainly in close proximity to osteosyntheses makes diagnosis and treatment planning a delicate challenge, especially due to the varying clinical presentations we found. Diagnostics and therapy should therefore be performed as early as possible in specialized centers capable of performing nerve repair as well as salvage therapies.

Single incision thenar muscle reconstruction using the free functional pronator quadratus flap.

BACKGROUND: Injuries to the thenar muscle mass or the thenar branch of the median nerve and resulting loss of thumb opposition lead to a massive impairment of hand function. For decades, reconstructive approaches were based on tendon transfers. To broaden the reconstructive repertoire, we present the free functional pronator quadratus flap as a viable alternative for functional reconstruction and provide a specification for its indication. We demonstrate our surgical technique to a single incision reconstruction using the free functional pronator quadratus flap. Based on a series of three patients, which were analyzed for hand function using Kapandji's score and the angle of Bourrel, grip strength and nerve conduction velocity in a two year follow up, we present an indication algorithm. RESULTS: After successful reinnervation of all flaps, we found an improvement of Kapandji's score from 4.3 ± 0.94 preoperatively, to 8.7 ± 0.47 after two years. Accordingly, the angle of Bourrel decreased from 75.75 ± 3.45 degrees to 36.96 ± 3.68 degree. Grip strength also improved from 14 ± 2.2 kg to 26.2 ± 1.2 kg. No impairment of wrist pronation was observed. CONCLUSION: We found excellent functional recovery of thumb opposition and strength, showing similar or even superior results compared to results from tendon transfers. With the benefit of a single incision surgery and therefore minimal donor site morbidity, this free functional muscle transfer is a viable alternative to classic tendon transfers.

Long-term muscle changes after hamstring lengthening in children with bilateral cerebral palsy.

AIM: To evaluate short-term (1y postoperatively; E1) and long-term (at least 4y postoperatively; E2) changes in hamstring muscle-tendon length (MTL) and lengthening velocity after hamstring lengthening in children with bilateral cerebral palsy (CP). METHOD: Three-dimensional gait analysis was performed in 19 children (16 males, 3 females; 36 limbs; mean age at surgery 9y [SD 3y]; range 6-10y) with flexed knee gait, preoperative ankle dorsiflexion lower than 20 degrees, and CP before bilateral hamstring lengthening (E0), at E1 and E2. Hamstring MTL (normalized by leg length) and velocity were assessed via OpenSim software. RESULTS: MTL increased from E0 to E1 (p=0.004) and decreased from E1 to E2 (p<0.020). Hamstring lengthening velocity did not change. In the subgroup with short, not slow hamstrings, the increase in MTL was maintained at E2. INTERPRETATION: Hamstring lengthening is an efficient procedure to lengthen short and/or slow hamstrings short-term. The desired outcome with maintenance of the postoperative changes in hamstring MTL is only achieved for preoperatively short, not slow hamstrings. WHAT THIS PAPER ADDS: Surgical hamstring lengthening can be confirmed via musculoskeletal modelling in OpenSim software. Surgical hamstring lengthening in cerebral palsy does not change hamstring lengthening velocity. Short, not slow hamstrings present a long-lasting muscle-tendon length (MTL) increase after hamstring lengthening. Changes in MTL after hamstring lengthening cannot be maintained for slow hamstrings. MTL does not change after hamstring lengthening for neither short nor slow hamstrings.

CAMBIOS MUSCULARES A LARGO PLAZO DESPUÉS DEL ALARGAMIENTO DE LOS ISQUIOTIBIALES EN NIÑOS CON PARÁLISIS CEREBRAL BILATERAL: OBJETIVO: Evaluar los cambios a corto plazo (un año después de la operación; E1) y a largo plazo (al menos cuatro años después de la operación; E2) de la longitud del tendón muscular de los isquiotibiales (LT) y la velocidad de alargamiento después del estiramiento en niños con parálisis cerebral bilateral (PC). MÉTODO: Se realizó un análisis tridimensional de la marcha en 19 niños (16 varones, tres mujeres; 36 extremidades; edad media en la cirugía 9 años [DS 3 años]; rango 6-10 años) con la marcha en flexión de la rodilla, dorsiflexión preoperatoria del tobillo inferior a 20 grados, antes del alargamiento bilateral de los isquiotibiales (E0), en E1 y E2. El LT de los músculos isquiotibiales (normalizado por la longitud de la pierna) y la velocidad fueron evaluadas mediante el OpenSim. RESULTADOS: El LT aumentó de E0 a E1 (p = 0,004) y disminuyó de E1 a E2 (p<0,020). La velocidad de alargamiento de los isquiotibiales no cambió. En el subgrupo con isquiotibiales cortos, pero no lentos, el aumento de la LT se mantuvo en E2. INTERPRETACIÓN: El alargamiento de los isquiotibiales es un procedimiento eficiente para los isquiotibiales cortos y/o lentos a corto plazo. El resultado deseado con el mantenimiento de los cambios postoperatorios en la longitud de los isquiotibiales solo se logra para los isquiotibiales cortos no lentos antes de la operación.

ALTERAÇÕES MUSCULARES A LONGO PRAZO APÓS ALONGAMENTO DE ISQUIOTIBIAIS EM CRIANÇAS COM PARALISIA CEREBRAL BILATERAL: OBJETIVO: Avaliar a curto (um ano de pós-operatório; E1) e longo prazo (no mínimo quatro anos de pós-operatório; E2) alterações no comprimento do tendão do músculo (CTM) isquiotibial e a velocidade de estiramento após alongamento do isquiotibial em crianças com paralisia cerebral bilateral (PC). MÉTODO: Foi realizada a análise tridimensional da marcha em 19 crianças (16 meninos, três meninas; 36 membros; média de idade de cirurgia de 9 anos [DP 3 anos]; variação de 6-10 anos) com marcha com flexão de joelho, ângulo de dorsiflexão de tornozelo menor que 20o no pré-operatório, e PC antes do alongamento bilateral dos isquiotibiais (E0), em E1 e E2. CTM dos isquiotibiais (normalizado pelo comprimento da perna) e a velocidade foram avaliados pelo OpenSim. RESULTADOS: CTM aumentou de E0 para E1 (p=0,004) e diminuiu de E1 para E2 (p<0,020). A velocidade de estiramento do isquiotibial não mudou. No subgrupo com isquiotibial encurtado e não lento, o aumento no CTM foi mantido em E2. INTERPRETAÇÃO: O alongamento do músculo isquiotibial é um procedimento eficiente para alongar isquitotibiais encurtados e/ou lentos a curto prazo. O resultado desejado com a manutenção das alterações no pós-operatório no CTM do isquiotibial é atingida somente para isquiotibial curto e não lento no pré-operatório.

Supracondylar femoral rotation osteotomy affects frontal hip kinetics in children with bilateral cerebral palsy.

AIM: To evaluate the influence of supracondylar femoral derotation osteotomy (FDO) on hip abduction muscle force and frontal hip moments in children with bilateral cerebral palsy. METHOD: For this retrospective cohort study 79 children (36 females, 43 males; mean age at surgery 11y [SD 3y]; range 4-17y) with bilateral cerebral palsy and preoperatively and 1-year postoperatively documented frontal hip moments who received supracondylar FDO in 134 limbs were included. The control group consisted of eight children (two females, six males; mean age 11y [SD 4y]; range 5-17y) who received single-event multi-level surgery without FDO. RESULTS: Hip joint impulse (p<0.001) and the first peak of frontal hip moments (p=0.003) increased, whereas the second peak decreased (p<0.001) from preoperatively to postoperatively. Hip abductor strength improved (p=0.001) from preoperatively to postoperatively. INTERPRETATION: Despite the compensatory mechanism, frontal hip moments are decreased preoperatively. Supracondylar FDO results in increased frontal hip moments. Changes in anteversion directly influence hip kinetics, although no direct change of the proximal bony geometry is performed. WHAT THIS PAPER ADDS: Internal rotation gait cannot fully restore the frontal hip moment. Supracondylar femoral derotation osteotomy (FDO) influences frontal hip kinetics in children with bilateral cerebral palsy. Supracondylar FDO changes the curve progression of frontal hip moments. Supracondylar FDO restores the hip abductor moment arm. Supracondylar FDO leads to an increase in hip abductor muscle force.

[Nerve Transfers in Peripheral Nerve Lesions]. / Nerventransfers bei peripheren Nervenläsionen.

BACKGROUND: Lesions of peripheral nerves of the upper extremities often lead to persistent, serious limitations in motor function and sensory perception. Affected patients suffer from both private and professional restrictions associated with long-term physical, psychological and socioeconomic consequences. INDICATION: An early indication for a nerve transfer shortens the reinnervation distance and improves the growing of motor and sensory axons into the target organ to facilitate early mobility and sensitivity. When planning the timepoint of the surgical procedure, the distance to be covered by reinnervation as well as the morbidities of donor nerves must be considered individually. RESULTS: Nerve transfers can achieve earlier and safer reinnervation to improve motor and sensory functions after nerve injuries in the upper extremity.

Hopeless Neuroma-The Neurotized Free Flap Tissue Augmentation as Salvage Therapy-A Concept and Clinical Demonstration.

Therapy-resistant neuroma pain is a devastating condition for patients and surgeons. Although various methods are described to surgically deal with neuromas, some discontinuity and stump neuroma therapies have anatomical limitations. It is widely known that a neurotizable target for axon ingrowth is beneficial for dealing with neuromas. The nerve needs "something to do". Furthermore, sufficient soft tissue coverage plays a major role in sufficient neuroma therapy. We aimed, therefore, to demonstrate our approach for therapy of resistant neuromas with insufficient tissue coverage using free flaps, which are sensory neurotized via anatomical constant branches. The central idea is to provide a new target, a new "to do" for the painful mislead axons, as well as an augmentation of deficient soft tissues. As indication is key, we furthermore demonstrate clinical cases and common neurotizable workhorse flaps.

Peripheral nerve injuries in children-prevalence, mechanisms and concomitant injuries: a major trauma center's experience.

BACKGROUND: Peripheral nerve injuries are severe conditions with potential lifelong impairment, which is especially meaningful for the pediatric population. Knowledge on prevalence, injury mechanisms and concomitant injuries is, therefore, of utmost importance to increase clinician awareness and enable early diagnosis and treatment. As current literature on pediatric nerve lesions and concomitant injuries is scarce, we aimed to analyze all details of our patient population. METHODS: A total of 110 667 patients treated at our level 1 trauma center from 2012 to 2021 were evaluated for pediatric peripheral nerve injuries, causes, concomitant injuries and assessed for lesion classification (in continuity, partial lesion, dissection) and further relevant intraoperative findings. RESULTS: We found 5026 patients of all ages with peripheral nerve lesions, whereof 288 were pediatric, resulting in a prevalence of 5.7% of pediatric patients with nerve injuries. Mean age was 12.4 ± 4.6 years. Most common lesions were digital nerves (48.2%), followed by median (14.9%), ulnar (14.6%), radial (8.8%), peroneal nerve (5.2%) and brachial plexus injuries (2.1%). Of all pediatric nerve injuries, 3.8% were iatrogenic, only 30.2% had preserved continuity and 47.3% a concomitant vessel injury. Fractures were accompanied in 22.6%. DISCUSSION: We observed that a large proportion of injures had complete transections, often accompanied by concomitant vessel injuries especially in distally located injuries, highlighting the importance of early surgical exploration. Radial, ulnar and lower extremity nerve injuries were often associated with fractures. Early surgical nerve repair is key to improve motor and sensory outcomes. Knowledge on mechanisms and concomitant injuries facilitates timely diagnosis and treatment, thereby potentially preventing lifelong impairment.

Effects of artificially induced bilateral internal rotation gait on gait kinematics and kinetics.

BACKGROUND: Bilateral internal rotation gait is a common gait abnormality in children with bilateral cerebral palsy, but still not fully understood. RESEARCH QUESTION: The aim of this clinical study was to analyze the effects of artificially induced bilateral internal rotation gait on kinematics and kinetics. Our hypothesis was, that the internal rotation gait defined as increased dynamic internal hip rotation itself causes significant alterations in gait kinematics and kinetics. METHODS: 30 typically developing children with a mean age of 12 (SD 3) years (range 8 - 16) performed three-dimensional gait analysis in two different conditions: with unaffected gait and with artificially induced bilateral internal rotation gait with two rotation bandages worn in order to internally rotate the hips. Kinematic and kinetic changes between these two conditions were calculated and compared using a mixed linear model with "gait condition" as fixed effect and both "limb" and "patient" as random effects. RESULTS: The rotation bandages induced a significant increase in internal hip rotation and foot progression angle towards internal without affecting pelvic rotation. The peak hip internal rotator moment during loading response and the peak hip external rotator moment during the first half of stance phase increased significantly and the peak hip internal rotator moment during the second half of stance phase decreased significantly. Anterior pelvic tilt, hip flexion, knee flexion and ankle dorsiflexion increased significantly. The first peak of the frontal hip moment decreased, and the second increased significantly. The second peak of the frontal knee moment decreased significantly, while the first didn't change significantly. SIGNIFICANCE: The data suggest, that the bilaterally increased dynamic internal hip rotation itself has a relevant impact on frontal hip moments. The increased anterior pelvic tilt, hip and knee flexion may be either induced by the pull of the rotation bandage or a secondary gait deviation.

Pain in Adults With Cerebral Palsy After Single-Event Multilevel Surgery.

OBJECTIVE: The aim of the investigation was to assess the contribution of pain to functional, social, and health-related quality-of-life outcomes in adults with cerebral palsy. DESIGN: This monocentric, prospective study included long-term data for ambulant adults with cerebral palsy and at levels I-III in the Gross Motor Function Classification System who had received orthopedic multilevel surgery in adulthood and in whom preoperative and postoperative three-dimensional gait analysis was conducted, including the Gait Profile Score. A questionnaire including the Visual Analog Scale, Oswestry Disability Index, and European Quality of Life 5 Dimensions 3 Level was analyzed. RESULTS: Twenty-four adults at a mean age of 38.0 yrs were included. Sixteen patients (66.7%) indicated that they experienced pain and 10 patients (41.7%) had pain for more than 6 mos. Overall, 13 patients (54%) experienced both pain and anxiety. There was no correlation of the Gait Profile Score with pain, Gross Motor Function Classification System, and Oswestry Disability Index. The Oswestry Disability Index showed a positive correlation with the Gross Motor Function Classification System (r = 0.39, P = 0.05) and pain (r = 0.57, P = 0.004). CONCLUSIONS: Pain and anxiety represent relevant comorbidities in adults with cerebral palsy. The occurrence of pain correlates with the Oswestry Disability Index and is higher than in children with cerebral palsy.

An Algorithm for Elective Amputation Combined with Targeted Muscle Reinnervation in Complex Regional Pain Syndrome-A Perspective.

Complex regional pain syndrome (CRPS) can result in a devastating condition. For a small number of patients, there is a non-response to any existing multimodal therapies and they ultimately request amputation. Such a drastic and final decision is not easy to take for both the patient and the surgeon and requires careful and interdisciplinary assessments and considerations. Furthermore, new surgical procedures, such as targeted muscle reinnervation (TMR) and hybrid prosthetic fitting, and multidisciplinary board advice should be included when considering amputation. In order to help other therapeutic teams in decision making for such rare but more than demanding cases, we aimed to propose an advanced algorithm for amputation indications in CRPS patients combining all these new factors. This algorithm consists of extensive pre-operative psychiatric assessment, diagnostic hybrid prosthetic fitting including fMRI analyses, multidisciplinary board advice as well as targeted muscle reinnervation and amputation procedures with final prosthetic fitting and rehabilitation. By involving multiple disciplines, this algorithm should provide optimized and individualized patient treatment on the one hand and a reliable base for decision making for therapists on the other.

An Epidemiological and Etiological Analysis of 5026 Peripheral Nerve Lesions from a European Level I Trauma Center.

BACKGROUND: Peripheral nerve lesions are associated with debilitating long-term consequences. Albeit being essential for evidence-based clinical decision making, epidemiological and etiological data are scarce. We therefore aimed to comprehensively analyze epidemiological and etiological factors of peripheral nerve lesions in one of the largest cohorts. METHODS: We screened a total of 110,667 patients treated at our level I trauma center between January 2012 and July 2020 for nerve lesions. Subsequently, demographics, etiologies, concomitant injuries, and lesion characteristics were analyzed. RESULTS: A total of 5026 patients, predominantly young males suffering from non-work-related nerve injuries, were treated. Proximal levels of injury were more likely to be accompanied by fractures, whereas more distal injuries with concomitant vessel or tendon injury. Main causes were 54.6% lacerations. Acute traumatic nerve injury was treated within 24 h in 55.9% of cases. CONCLUSIONS: Given the young age of affected patients, early diagnosis and treatment in specialized centers may facilitate their early return to work and improve long-term functional outcomes. The data show the importance of a special attention on nerve injuries, which may be masked by large accompanying injuries. New findings on lesion characteristics of selected subgroups and accompanying circumstances can support a change in treatment strategies.

3D motion analysis of latissimus dorsi tendon transfer in patients with posterosuperior rotator cuff tears: Analysis of proprioception and the ability to perform ADLS.

BACKGROUND: Massive irreparable posterosuperior rotator cuff tears may result in a loss of external rotation. Most of these patients lose their ability to perform activities of daily living (ADLs), especially where external rotation and abduction are needed. Latissimus dorsi tendon transfer (LDTT) is a method to restore abduction and external rotation in patients with posterosuperior rotator cuff tears. There are no objective data concerning whether LDTT can restore range of motion (ROM), especially in performing ADLs and if proprioception changes after LDTT. METHODS: We examined 12 patients 4.2 years (1-9 years) after LDTT with simultaneous 3D motion analysis; the opposite, nonaffected side was assessed as control. The measurement protocol included maximum values in flexion/extension, abduction/adduction, internal/external rotation in 0° and in 90° flexion and in 90° abduction. To evaluate competences, we measured seven activities of daily life and examined the proprioceptive ability using an active angle reproduction test. RESULTS: In total, 4.2 years (1-9 years) after LDTT there was no significant difference in flexion/extension and abduction/adduction compared to the healthy side. Maximum external rotation was significantly reduced compared to the opposite side. Eleven patients (85%) were able to perform all ADL. Proprioceptive ability did not differ from the healthy side. CONCLUSION: LDTT cannot fully restore a patient's ability for external rotation after a posterosuperior rotator cuff tear. However, 4.2 years after surgery, 85% of the patients are able to perform all ADLs. Proprioceptive ability is not affected by the transfer.