A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair.

JOURNAL/nrgr/04.03/01300535-202501000-00036/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal regeneration following surgical nerve repair is slow and often incomplete, resulting in poor functional recovery which sometimes contributes to lifelong disability. Currently, there are no FDA-approved therapies available to promote nerve regeneration. Tacrolimus accelerates axonal regeneration, but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery. The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site, with suitable properties for scalable production and clinical application, aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure. Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days. Size and drug loading are adjustable for applications in small and large caliber nerves, and the wrap degrades within 120 days into biocompatible byproducts. Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80% compared with systemic delivery. Given its surgical suitability and preclinical efficacy and safety, this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Revealing digital nerve lesions-A comprehensive analysis of 2084 cases of a specialized center.

BACKGROUND: Finger nerve injuries have a significant impact on hand function and can result in reduced sensation, pain and impaired coordination. The socioeconomic implications of these injuries include decreased workplace productivity, reduced earning potential, and financial burdens associated with long-term medical treatment and rehabilitation. However, there is a lack of comprehensive literature regarding the incidence, mechanisms, and associated injuries of finger nerve lesions. METHODS: A retrospective analysis was conducted on patients treated at our institution from January 2012 to July 2020. Cases of peripheral finger nerve lesions were identified using the digital hospital information system and ICD-10 Classification. Exclusion criteria included injuries to the median nerve at the carpal tunnel level or superficial branch of the radial nerve. Data were collected using a pseudonymized approach, and statistical analyses were performed using SPSS Statistics (Version 27). RESULTS: A total of 2089 finger nerve lesions were analyzed, with a majority of cases occurring in men. Most injuries97.4 % were caused by trauma, predominantly cut/tear injuries. Isolated finger nerve injuries were more common than multiple nerve injuries, with the index finger being the most frequently affected. Concomitant tendon and vascular injuries were observed in a significant proportion51.7 % of cases. Surgical management included direct nerve coaptation, interposition grafting and neurolysis. DISCUSSION: Finger nerve injuries are the most prevalent type of nerve injury, often resulting from small lacerations. These injuries have substantial societal costs and can lead to prolonged sick leave. Understanding the epidemiology and etiology of finger nerve injuries is crucial for implementing effective preventive measures. Accompanying tendon injuries and the anatomical location of the nerve lesions can impact sensory recovery and treatment outcomes. Proper management of peripheral finger nerve lesions is essential for optimizing functional outcomes and minimizing the impact on daily activities. Treatment options should be tailored to the severity and underlying cause of the nerve injury.

Corneal Neurotization: Preoperative Patient Workup and Surgical Decision-making.

Background: The use of sensory nerve transfers to the anesthetic cornea has transformed the treatment of neurotrophic keratopathy by restoring ocular surface sensation and activating dysfunctional epithelial repair mechanisms. However, despite numerous reports on surgical techniques, there is a scarcity of information on the interdisciplinary management, preoperative assessment, and surgical decision-making, which are equally critical to treatment success. Methods: This Special Topic presents a standardized, interdisciplinary preoperative workup based on our 10-year experience with corneal neurotization in 32 eyes of patients with neurotrophic keratopathy. Results: Our assessment includes a medical history review, ophthalmic evaluation, and systematic facial sensory donor nerve mapping for light touch and pain modalities. This approach enables evidence-based patient selection, optimal surgery timing, and suitable donor nerve identification, including backup options. Conclusions: Based on a decade-long experience, this special topic highlights the importance of interdisciplinary collaboration and provides a practical roadmap for optimizing patient selection and surgical decision-making in patients undergoing corneal neurotization.

The Role of Sensory Innervation in Homeostatic and Injury-Induced Corneal Epithelial Renewal.

The cornea is the window through which we see the world. Corneal clarity is required for vision, and blindness occurs when the cornea becomes opaque. The cornea is covered by unique transparent epithelial cells that serve as an outermost cellular barrier bordering between the cornea and the external environment. Corneal sensory nerves protect the cornea from injury by triggering tearing and blink reflexes, and are also thought to regulate corneal epithelial renewal via unknown mechanism(s). When protective corneal sensory innervation is absent due to infection, trauma, intracranial tumors, surgery, or congenital causes, permanent blindness results from repetitive epithelial microtraumas and failure to heal. The condition is termed neurotrophic keratopathy (NK), with an incidence of 5:10,000 people worldwide. In this report, we review the currently available therapeutic solutions for NK and discuss the progress in our understanding of how the sensory nerves induce corneal epithelial renewal.

Advancing Nerve Regeneration: Translational Perspectives of Tacrolimus (FK506).

Peripheral nerve injuries have far-reaching implications for individuals and society, leading to functional impairments, prolonged rehabilitation, and substantial socioeconomic burdens. Tacrolimus, a potent immunosuppressive drug known for its neuroregenerative properties, has emerged in experimental studies as a promising candidate to accelerate nerve fiber regeneration. This review investigates the therapeutic potential of tacrolimus by exploring the postulated mechanisms of action in relation to biological barriers to nerve injury recovery. By mapping both the preclinical and clinical evidence, the benefits and drawbacks of systemic tacrolimus administration and novel delivery systems for localized tacrolimus delivery after nerve injury are elucidated. Through synthesizing the current evidence, identifying practical barriers for clinical translation, and discussing potential strategies to overcome the translational gap, this review provides insights into the translational perspectives of tacrolimus as an adjunct therapy for nerve regeneration.

Avoiding scar tissue formation of peripheral nerves with the help of an acellular collagen matrix.

INTRODUCTION: Extensive scar tissue formation after peripheral nerve injury or surgery is a common problem. To avoid perineural scarring, implanting a mechanical barrier protecting the nerve from inflammation processes in the perineural environment has shown promising results for functional recovery. This study investigates the potential of an acellular collagen-elastin matrix wrapped around a peripheral nerve after induction of scar tissue formation. MATERIALS AND METHODS: In the present study, 30 Lewis rats were separated into three groups and sciatic nerve scarring was induced with 2.5% glutaraldehyde (GA-CM) or 2.5% glutaraldehyde with a supplemental FDA-approved acellular collagen-elastin matrix application (GA+CM). Additionally, a sham group was included for control. Nerve regeneration was assessed by functional analysis using the Visual Statisc Sciatic Index (SSI) and MR neurography during the 12-week regeneration period. Histological and histomorphometry analysis were performed to evaluate the degree of postoperative scar tissue formation. RESULTS: Histological analysis showed an extensive scar tissue formation for GA-CM. Connective tissue ratio was significantly (p < 0.009) reduced for GA+CM (1.347 ± 0.017) compared to GA-CM (1.518 ± 0.057). Similarly, compared to GA+CM, MR-Neurography revealed extensive scar tissue formation for GA-CM with a direct connection between nerve and paraneural environment. Distal to the injury site, quantitative analysis presented significantly higher axon density (p = 0.0145), thicker axon diameter (p = 0.0002) and thicker myelinated fiber thickness (p = 0.0008) for GA+CM compared to GA-CM. Evaluation of functional recovery revealed a significantly faster regeneration for GA+CM. CONCLUSION: The supplemental application of an acellular collagen-elastin matrix showed beneficial effects in histological, radiological, and functional analysis. Therefore, applying a collagen-elastin matrix around the nerve after peripheral nerve injury or surgery may have beneficial effects on preventing scar tissue formation in the long run. This represents a feasible approach to avoid scar tissue formation in peripheral nerve surgery.

Effect of Surgical Release of Entrapped Peripheral Nerves in Sensorimotor Diabetic Neuropathy on Pain and Sensory Dysfunction-Study Protocol of a Prospective, Controlled Clinical Trial.

BACKGROUND: Nerve entrapment has been hypothesized to contribute to the multicausal etiology of axonopathy in sensorimotor diabetic neuropathy. Targeted surgical decompression reduces external strain on the affected nerve and, therefore, may alleviate symptoms, including pain and sensory dysfunction. However, its therapeutic value in this cohort remains unclear. AIM: Quantifying the treatment effect of targeted lower extremity nerve decompression in patients with preexisting painful sensorimotor diabetic neuropathy and nerve entrapment on pain intensity, sensory function, motor function, and neural signal conduction. STUDY DESIGN: This prospective, controlled trial studies 40 patients suffering from bilateral therapy-refractory, painful (n = 20, visual analogue scale, VAS ≥ 5) or painless (n = 20, VAS = 0) sensorimotor diabetic neuropathy with clinical and/or radiologic signs of focal lower extremity nerve compression who underwent unilateral surgical nerve decompression of the common peroneal and the tibial nerve. Tissue biopsies will be analyzed to explore perineural tissue remodeling in correlation with intraoperatively measured nerve compression pressure. Effect size on symptoms including pain intensity, light touch threshold, static and moving two-point discrimination, target muscle force, and nerve conduction velocity will be quantified 3, 6, and 12 months postoperatively, and compared (1) to the preoperative values and (2) to the contralateral lower extremity that continues non-operative management. CLINICAL SIGNIFICANCE: Targeted surgical release may alleviate mechanical strain on entrapped lower extremity nerves and thereby potentially improve pain and sensory dysfunction in a subset of patients suffering from diabetic neuropathy. This trial aims to shed light on these patients that potentially benefit from screening for lower extremity nerve entrapment, as typical symptoms of entrapment might be erroneously attributed to neuropathy only, thereby preventing adequate treatment.

Optical Tissue Clearing Enables Three-Dimensional Morphometry in Experimental Nerve Regeneration Research.

Novel optical tissue clearing techniques enable three-dimensional imaging of entire organs at a subcellular resolution while preserving tissue architecture and fluorescence. In conjunction with computational image segmentation and automated analysis, these techniques provide fast and precise three-dimensional morphometry. Here, we present a tissue clearing protocol adapted to nerves and their motor and sensory targets in experimental rat models. Given their rapid processing times, low costs, and wide-ranging applicability, these techniques are likely to be a key technology for future nerve repair studies.

Objective Burn Scar Assessment in Clinical Practice Using the Cutometer©: Introduction and Validation of a Standardized Measurement Protocol.

An objective burn scar assessment is essential to informed therapeutic decision-making and to monitor scar development over time. However, widely employed scar rating scales show poor inter-rater reliability. For this study we developed a standardized measurement protocol for the Cutometer© applicable for objective burn scar assessment in everyday clinical practice. We developed a measurement protocol for the Cutometer© MPA 580 including a scar site relocation technique based on anatomical landmarks. The protocol emerged through several steps: Identifying key factors for valid and reliable measurements, preliminary testing, specification of technical details, refining the protocol and final testing. Consecutively, the protocol was validated for inter-rater reliability by assessing 34 burn scars in 17 patients by four clinicians and computing an Intra-class Correlation Coefficient (ICC). Parameter R0, representing scar pliability, was identified as the best suited output parameter yielding excellent inter-rater reliability for average measures (ICC 0.92 [95% CI 0.86; 0.96]) and acceptable reliability for single measures (ICC: 0.74 [0.61; 0.84]). The pressure applied on the measuring probe was identified as an influential confounding factor for reliable measurements. Rater gender did not influence reliability of measurements. The introduced standardized measurement protocol for the Cutometer© MPA 580 enables an objective and reliable burn scar assessment for clinical as well as research purposes.

Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation.

Purpose: Corneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats. Methods: A compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate-urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation. Results: Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release. Conclusions: Locally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure. Translational Relevance: Topically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.

Sensor-Based Nerve Compression Measurement: A Scoping Review of Current Concepts and a Preclinical Evaluation of Commercial Microsensors.

Background: Chronic nerve compression is the most common indication for nerve surgery. However, the clinical diagnosis still relies on surrogate parameters since devices for direct nerve compression pressure measurement (DNCPM) are clinically unavailable yet. Objectives: To review previous approaches to DNCPM and evaluate presently available microsensor systems for their feasibility and reliability in preclinical nerve compression models. Methods: A scoping literature review was conducted in accordance with the PRISMA-ScR guidelines. A subsequent market research aimed at identifying commercially available sensor systems potentially suitable for DNCPM. Sensors were evaluated for feasibility and safety of perineural sensor positioning, tissue compatibility and measurement reliability in a synthetic nerve compression model and an ex-vivo chicken leg model. Results: A scoping literature review identified 197 potentially eligible studies of which 65 were included in the analysis. Previous approaches to DNCPM predominantly used pressure sensing catheters designed for fluid- or intra-compartmental pressure measurement. A market research identified two piezoresistive sensor systems (IntraSense, SMi, United States; Mikro-Cath, Millar, United States) as potentially suitable for intraoperative DNCPM. In both preclinical models, the detected compression pressure differed significantly between sensors and systems showed substantial measurement variability with a median percent coefficient of variation between 15.5% and 32%. Sensor position was accountable for up to 99.1% of the variance. Conclusion: Measurement variability caused by unreliable sensor positioning is a key limitation of presently available sensors when applied for nerve compression measurements. Redesigned systems with small, flat-shaped and longitudinally oriented sensors and dedicated introducers would facilitate sensor positioning and therefore may allow for reliable measurements.

[Differential therapeutic Approaches in Treatment of Carpal Tunnel Syndrome]. / Differentialtherapeutische Herangehensweisen zur Behandlung des Karpaltunnelsyndroms.

Carpal tunnel syndrome (CTS) is one of the most common compression neuropathies. The therapeutic concept should be tailored to each patient individually, with initial non-surgical treatment being the standard of care for early CTS. Primary surgical intervention should be considered in more advanced diseases stages, in case of concomitant pathologies (including space-occupying lesions, complex regional pain syndrome or diabetic neuropathy), if non-surgical strategies have failed or in pregnancy-related CTS. This work aims to discuss common surgical approaches, their clinical application as well as benefits and disadvantages in a pragmatic style. Further, we highlight surgical strategies to address recurrent CTS following failed primary surgery. In view of the recently updated S3 guidelines "Diagnosis and Therapy of Carpal Tunnel Syndrome", this topic is timely and relevant for hand and nerve surgeons.

Foretinib mitigates cutaneous nerve fiber loss in experimental diabetic neuropathy.

Diabetes is by far, the most common cause of neuropathy, inducing neurodegeneration of terminal sensory nerve fibers associated with loss of sensation, paresthesia, and persistent pain. Foretinib prevents die-back degeneration in cultured sensory and sympathetic neurons by rescuing mitochondrial activity and has been proven safe in prospective clinical trials. Here we aimed at investigating a potential neuroprotective effect of Foretinib in experimental diabetic neuropathy. A mouse model of streptozotocin induced diabetes was used that expresses yellow fluorescent protein (YFP) in peripheral nerve fibers under the thy-1 promoter. Streptozotocin-injected mice developed a stable diabetic state (blood glucose > 270 mg/dl), with a significant reduction of intraepidermal nerve fiber density by 25% at 5 weeks compared to the non-diabetic controls. When diabetic mice were treated with Foretinib, a significantly greater volume of the cutaneous nerve fibers (67.3%) in the plantar skin was preserved compared to vehicle treated (37.8%) and non-treated (44.9%) diabetic mice while proximal nerve fiber morphology was not affected. Our results indicate a neuroprotective effect of Foretinib on cutaneous nerve fibers in experimental diabetic neuropathy. As Foretinib treated mice showed greater weight loss compared to vehicle treated controls, future studies may define more sustainable treatment regimen and thereby may allow patients to take advantage of this neuroprotective drug in chronic neurodegenerative diseases like diabetic neuropathy.

Optical tissue clearing enables rapid, precise and comprehensive assessment of three-dimensional morphology in experimental nerve regeneration research.

Morphological analyses are key outcome assessments for nerve regeneration studies but are historically limited to tissue sections. Novel optical tissue clearing techniques enabling three-dimensional imaging of entire organs at a subcellular resolution have revolutionized morphological studies of the brain. To extend their applicability to experimental nerve repair studies we adapted these techniques to nerves and their motor and sensory targets in rats. The solvent-based protocols rendered harvested peripheral nerves and their target organs transparent within 24 hours while preserving tissue architecture and fluorescence. The optical clearing was compatible with conventional laboratory techniques, including retrograde labeling studies, and computational image segmentation, providing fast and precise cell quantitation. Further, optically cleared organs enabled three-dimensional morphometry at an unprecedented scale including dermatome-wide innervation studies, tracing of intramuscular nerve branches or mapping of neurovascular networks. Given their wide-ranging applicability, rapid processing times, and low costs, tissue clearing techniques are likely to be a key technology for next-generation nerve repair studies. All procedures were approved by the Hospital for Sick Children's Laboratory Animal Services Committee (49871/9) on November 9, 2019.

Strategies to Improve Cross-Face Nerve Grafting in Facial Paralysis.

Cross-face nerve grafting enables the reanimation of the contralateral hemiface in unilateral facial palsy and may recover a spontaneous smile. This chapter discusses various clinically applicable strategies to increase the chances for good functional outcomes by maintaining the viability of the neural pathway and target muscle, increasing the number of reinnervating nerve fibers and selecting functionally compatible donor nerve branches. Adopting those strategies may help to further improve patient outcomes in facial reanimation surgery.

Désinfection à la chaleur humide des respirateurs N95, inactivation du SRAS-CoV-2 et effets sur les propriétés des respirateurs.

CONTEXTE: La demande sans précédent de respirateurs N95 durant la pandémie de maladie à coronavirus 2019 (COVID-19) a entraîné une pénurie mondiale. Nous avons validé un protocole de décontamination rapide et économique répondant aux normes réglementaires afin de permettre la réutilisation sûre de ce type de masque. MÉTHODES: Nous avons contaminé 4 modèles courants de respirateurs N95 avec le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) et avons évalué l'inactivation virale après une désinfection de 60 minutes à 70 °C et à une humidité relative de 0 %. De même, nous avons étudié l'efficacité de la désinfection thermique, à une humidité relative allant de 0 % à 70 %, de masques contaminés à Escherichia coli. Enfin, nous avons examiné des masques soumis à de multiples cycles de désinfection thermique: nous avons évalué leur intégrité structurelle à l'aide d'un microscope à balayage, et leurs propriétés protectrices au moyen des normes du National Institute for Occupational Safety and Health des États-Unis relatives à la filtration particulaire, à la résistance respiratoire et à l'ajustement. RÉSULTATS: Une seule désinfection thermique a suffi pour que le SRAS-CoV-2 ne soit plus décelable sur les masques étudiés. En ce qui concerne les masques contaminés à E. coli, une culture de 24 heures a révélé que la bactérie n'était pratiquement plus décelable sur les masques désinfectés à 70 °C et à une humidité relative de 50 %, contrairement aux masques non désinfectés (densité optique à une longueur d'onde de 600 nm : 0,02 ± 0,02 contre 2,77 ± 0,09; p < 0,001), mais qu'elle persistait sur les masques traités à une humidité relative moindre. Les masques ayant subi 10 cycles de désinfection avaient toujours des fibres de diamètre semblable à celui des fibres des masques non traités, et ils répondaient encore aux normes d'ajustement, de filtration et de résistance respiratoire. INTERPRÉTATION: La désinfection thermique a réussi à décontaminer les respirateurs N95 sans compromettre leur intégrité structurelle ni modifier leurs propriétés. Elle pourrait se faire dans les hôpitaux et les établissements de soins de longue durée avec de l'équipement facilement accessible, ce qui réduirait la pénurie de N95.

Simulating Surgical Skills in Animals: Systematic Review, Costs & Acceptance Analyses.

Background: Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods: Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results: 915 articles were analyzed, thereof 91 studies described in-vivo animal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307€ and 5,861€ depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26; 1-low, 10 high). Conclusion: Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow's surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools.

Effect of moist heat reprocessing of N95 respirators on SARS-CoV-2 inactivation and respirator function.

BACKGROUND: Unprecedented demand for N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of these masks. We validated a rapidly applicable, low-cost decontamination protocol in compliance with regulatory standards to enable the safe reuse of N95 respirators. METHODS: We inoculated 4 common models of N95 respirators with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and evaluated viral inactivation after disinfection for 60 minutes at 70°C and 0% relative humidity. Similarly, we evaluated thermal disinfection at 0% to 70% relative humidity for masks inoculated with Escherichia coli. We assessed masks subjected to multiple cycles of thermal disinfection for structural integrity using scanning electron microscopy and for protective functions using standards of the United States National Institute for Occupational Safety and Health for particle filtration efficiency, breathing resistance and respirator fit. RESULTS: A single heat treatment rendered SARS-CoV-2 undetectable in all mask samples. Compared with untreated inoculated control masks, E. coli cultures at 24 hours were virtually undetectable from masks treated at 70°C and 50% relative humidity (optical density at 600 nm wavelength, 0.02 ± 0.02 v. 2.77 ± 0.09, p < 0.001), but contamination persisted for masks treated at lower relative humidity. After 10 disinfection cycles, masks maintained fibre diameters similar to untreated masks and continued to meet standards for fit, filtration efficiency and breathing resistance. INTERPRETATION: Thermal disinfection successfully decontaminated N95 respirators without impairing structural integrity or function. This process could be used in hospitals and long-term care facilities with commonly available equipment to mitigate the depletion of N95 masks.

Acute and long-term costs of 268 peripheral nerve injuries in the upper extremity.

BACKGROUND: Peripheral nerve injury in the upper extremity is linked to high socioeconomic burden, yet cost-analyses are rare and from small cohorts. The objective of this study was to determine the costs and long-term socioeconomic effects of peripheral nerve injuries in the upper extremity in Germany. METHODS: We analyzed data of 250 patients with 268 work-related upper extremity nerve injuries from acute treatment to long-term follow-up on rehabilitation, sick-leave and disability-pension. RESULTS: Patients were on average 39.9±14.2 years old, male (85%) and mean inpatient treatment was 7±6 days. Location of nerve was 8% (N = 19) proximal to the wrist, 26% (N = 65) at the wrist and metacarpus, and 66% (N = 166) at phalangeal level. Acute in-patient treatment for (single) median nerve injury accounted for 66% with hospital reimbursement of 3.570€, ulnar nerve injury for 24% and 2.650€ and radial nerve injury for 10% and 3.166€, all including finger nerve injuries. The remaining were combined nerve injuries, with significantly higher costs, especially if combined with tendon 5.086€ or vascular injury 4.886€. Based on location, nerve injuries proximal to the wrist averaged 5.360±6.429€, at the wrist and metacarpus 3.534±2.710€ and at the phalangeal level 3.418±3.330€. 16% required rehabilitation with average costs of 5.842€ and stay of 41±21 days. Sick leave was between 11-1109 days with an average of 147 days with socioeconomic costs of 197€/day, equaling on average 17.640€. 30% received a mean yearly disability pension of 3.187€, that would account to 102.167€ per lifetime. CONCLUSION: This large German patient sample indicates that nerve injury has a major impact on function and employment, resulting in significant health care costs. Both proximal and distal nerve injuries led to long-term disability, subsequent sick-leave and in 30% to permanent disability pension. These data are determined to support future studies and health economical work on prevention, treatment and rehabilitation of these often small injuries with great consequences.