Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

Supinator to Anterior Interosseous Nerve Transfer to Restore Digital Flexion in Spinal Cord and Peripheral Nerve Injury.

PURPOSE: Restoration of pinch and grasp is a chief concern of patients with cervical spinal cord injury or peripheral nerve injury involving the anterior interosseous nerve (AIN). We hypothesize that supinator nerve-to-AIN (Sup-AIN) nerve transfer is a viable option for AIN neurotization. METHODS: We performed a retrospective review of patients who received Sup-AIN. Reported outcomes included Medical Research Council strength of the flexor digitorum profundus and flexor pollicis longus and passive range of digit motion. Patients with <12 months of follow-up were excluded. RESULTS: Eleven patients underwent Sup-AIN, eight with peripheral nerve injury, and three with spinal cord injury. Three patients were excluded because of insufficient follow-up. Average follow-up was 17 months (range: 12-25 months). Six patients had M4 recovery (75%), one patient had M3 recovery (12.5%), and one did not recover function because of severe stiffness (12.5%). We observed no complications or donor site morbidity in our patients. CONCLUSIONS: The Sup-AIN nerve transfer is an effective option to restore digital flexion in patients with peripheral nerve injury or spinal cord injury involving the AIN motor distribution. In comparison to previously described extensor carpi radialis brevis to AIN and brachialis to AIN nerve transfers, Sup-AIN offers the benefits of a more expendable donor nerve and shorter regenerative distance, respectively. The one failed Sup-AIN in our series highlights the importance of patient selection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Upper-Extremity Nerve Transfers for Sensation: A Systematic Review.

PURPOSE: Sensory nerve transfers may be performed to restore protective sensation and tactile perception after peripheral nerve injury in the upper extremity. There is a paucity of literature on the available donor-recipient configurations for sensory nerve transfers. This article presents a systematic review of reported sensory nerve transfers in the upper extremity. METHODS: Original articles published between 1982 and 2022 were searched in MEDLINE and EMBASE. Articles describing a sensory nerve transfer were included if patient sensory outcomes were reported. Outcomes were categorized according to the modified British Medical Research Council scale, with an outcome of S3 or better defined as satisfactory. RESULTS: Of 1,049 articles, 39 met inclusion and quality criteria. Twenty-seven articles were primary research studies reporting on 197 patients who underwent 11 unique nondigital sensory donor nerve transfers and 24 unique digital donor nerve transfer procedures. The most reliable recipient nerve for restoring sensation to the ulnar border of the small finger was proper ulnar digital nerve of the small finger (38 patients, 89% satisfactory sensory outcome). The best available donors for transfer into the proper ulnar digital nerve of the small finger were proper ulnar digital nerve of the long finger (16 patients, 87.5% good sensory outcome) and palmar cutaneous branch of the median nerve (15 patients, 100% good sensory outcome). To restore sensation along the ulnar border of the thumb and radial aspect of the index finger, the best available donor was the superficial branch of the radial nerve, regardless of transfer into common digital nerve 1 (38 patients, success rate 63%) or directly to proper ulnar digital nerve of the thumb or proper radial digital nerve of the index finger (nine patients, success rates 67%). CONCLUSIONS: Outcomes after sensory nerve transfers are generally good. Surgeons should transfer into a digital nerve recipient when attempting to reconstruct sensation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Surgical Technique: Brachioradialis to Extensor Carpi Radialis Longus and Brevis Nerve Transfers for Tetraplegia.

Improving upper extremity function in high cervical spinal cord injury (SCI) patients with tetraplegia is a challenging task owing to the limited expendable donor muscles and nerves that are available. Restoring active wrist extension for these patients is critical because it allows for tenodesis grasp. This is classically achieved with brachioradialis (BR) to extensor carpi radialis brevis (ECRB) tendon transfer, but outcomes are suboptimal because BR excursion is insufficient and its origin proximal to the elbow further limits the functionality of the tendon transfer, particularly in the absence of elbow extension. As an alternative approach to restore wrist extension in patients with ICSHT group 1 SCI, we present the first clinical report of the BR to extensor carpi radialis longus (ECRL) and BR to ECRB nerve transfers.

Google Trends Analysis of Peripheral Nerve Disease and Surgery.

BACKGROUND: Despite advances in the surgical management of peripheral nerve pathologies over the past several decades, it is unknown how public awareness of these procedures has changed. We hypothesize that Google searches for peripheral nerve surgery have increased over time. METHODS: Google Trends was queried for search volumes of a list of 40 keywords related to the following topics in peripheral nerve surgery: spasticity, nerve injury, prosthetics, and nerve pain. Monthly relative search volume over the first 5 years of the study period (2010-2014) was compared with that of the last 5 years (2018-2022) of the study period. RESULTS: Search volumes for keywords "nerve injury," "nerve laceration," "peripheral nerve injury," "nerve repair," "nerve transfer", "neuroma," "neuroma pain," "nerve pain," "nerve pain surgery," and "neuroma pain surgery" all increased more than 10% points in relative search volume over the study period (P < 0.0001 for each keyword). In contrast, searches for "rhizotomy," "spasticity surgery," "targeted muscle reinnervation," "bionic arm," and "myoelectric prosthesis" either decreased or remained stable. Technical terms such as "selective neurectomy," "hyperselective neurectomy," "regenerative peripheral nerve interface," and "regenerative peripheral nerve interface surgery" did not have adequate search volume to be reported by Google Trends. CONCLUSIONS: The increase in Google searches related to nerve injury and pain between 2010 and 2022 may reflect increasing public recognition of these clinical entities and surgical techniques addressing them. Technical terms relating to nerve pain are infrequently searched, surgeons should use plain English terms for online discovery. Interest in spasticity and myoelectric prosthetics remains stable, indicating an opportunity for better public outreach.

Rare Mental Health Disorders Affecting Urologic Care: A Comprehensive Review.

Management of mental health illnesses and needs are important in fostering psychosocial support, interprofessional coordination, and greater adherence to treatment protocols in the field of urology. This can be especially true for mental health conditions that may greatly impact the presentation of a patient in the healthcare setting with urologic symptoms. This review describes the history, epidemiology, pathophysiology, clinical presentation, and treatment of somatic symptom disorder, illness anxiety disorder, compulsive sexual behavior/hypersexuality, factitious disorder, malingering symptoms, and conversion disorder in the realm of urology. Given the newly updated psychiatric diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, there has been a lack of studies reviewing how these illnesses may present in a urology patient encounter. Additionally, as these mental health illnesses may carry a rare incidence compared to other well-known mental health illness such as generalized depression or generalized anxiety disorder, we have found that the lack of provisions and recognition of the diseases can prolong the timeline for diagnosis and lead to an increased cost in both healthcare and quality of life of patients with these mental health illnesses. This review provides awareness on these mental health conditions which may greatly impact patient history and presentation within the field of urology. Additionally, urologic care providers may have an improved understanding of interdisciplinary management of such illnesses and the common symptoms patients may present with such diseases.

Pan-caspase inhibition as a potential host-directed immunotherapy against MRSA and other bacterial skin infections.

Staphylococcus aureus causes most skin infections in humans, and the emergence of methicillin-resistant S. aureus (MRSA) strains is a serious public health threat. There is an urgent clinical need for nonantibiotic immunotherapies to treat MRSA infections and prevent the spread of antibiotic resistance. Here, we investigated the pan-caspase inhibitor quinoline-valine-aspartic acid-difluorophenoxymethyl ketone (Q-VD-OPH) for efficacy against MRSA skin infection in mice. A single systemic dose of Q-VD-OPH decreased skin lesion sizes and reduced bacterial burden compared with vehicle-treated or untreated mice. Although Q-VD-OPH inhibited inflammasome-dependent apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC) speck formation and caspase-1-mediated interleukin-1ß (IL-1ß) production, Q-VD-OPH maintained efficacy in mice deficient in IL-1ß, ASC, caspase-1, caspase-11, or gasdermin D. Thus, Q-VD-OPH efficacy was independent of inflammasome-mediated pyroptosis. Rather, Q-VD-OPH reduced apoptosis of monocytes and neutrophils. Moreover, Q-VD-OPH enhanced necroptosis of macrophages with concomitant increases in serum TNF and TNF-producing neutrophils, monocytes/macrophages, and neutrophils in the infected skin. Consistent with this, Q-VD-OPH lacked efficacy in mice deficient in TNF (with associated reduced neutrophil influx and necroptosis), in mice deficient in TNF/IL-1R and anti-TNF antibody-treated WT mice. In vitro studies revealed that combined caspase-3, caspase-8, and caspase-9 inhibition reduced apoptosis, and combined caspase-1, caspase-8, and caspase-11 inhibition increased TNF, suggesting a mechanism for Q-VD-OPH efficacy in vivo. Last, Q-VD-OPH also had a therapeutic effect against Streptococcus pyogenes and Pseudomonas aeruginosa skin infections in mice. Collectively, pan-caspase inhibition represents a potential host-directed immunotherapy against MRSA and other bacterial skin infections.