Clinical phenotyping of spondylodiscitis and isolated spinal epidural empyema: a 20-year experience and cohort study.

Background: The incidence of spondylodiscitis (SD) and isolated spinal epidural empyema (ISEE) has been increasing in the last decades, but the distinct differences between both entities are poorly understood. We aimed to evaluate the clinical phenotypes and long-term outcomes of SD and ISEE in depth. Methods: We performed a chart review and analyzed data from our cohorts of consecutive SD and ISEE patients who were treated and assessed in detail for demographic, clinical, imaging, laboratory, and microbiologic characteristics at a university neurosurgical center in Germany from 2002 to 2021. Between-group comparisons were performed to identify meaningful differences in both entities. Results: We included 208 patients (72 females: age 75 [75 32-90] y vs. 136 males: 65 [23-87] y, median [interquartile range], p < 0.001), of which 142 (68.3%) had SD and 66 (31.7%) had ISEE. Patients with SD were older than ISEE (ISEE: 62 y vs. SD: 70 y, p = 0.001). While SD was more common in males than females (males: n = 101, 71.1% vs. females: n = 41, 28.9%, p < 0.001), there was no sex-related difference in ISEE (males: n = 35, 53.0% vs. females: n = 31, 47.0%, p = 0.71). Obesity was more frequent in ISEE than in SD (ISEE: n = 29, 43.9% vs. SD: n = 37, 26.1%, p = 0.016). However, there were no between-group differences in rates of diabetes and immunodeficiency. In the entire study population, a causative pathogen was identified in 192 (92.3%) patients, with methicillin-susceptible staphylococcus aureus being most frequent (n = 100, 52.1%) and being more frequent in ISEE than SD (ISEE: n = 43, 65.2% vs. SD: n = 57, 40.1%, p = 0.003). SD and ISEE occurred most frequently in the lumbar spine, with no between-group differences (ISEE: n = 25, 37.9% vs. SD: n = 65, 45.8%, p = 0.297). Primary infectious sources were identified in 145 patients (69.7%) and among this skin infection was most common in both entities (ISEE: n = 14, 31.8% vs. SD: n = 25, 24.8%, p = 0.418). Furthermore, epidural administration was more frequent the primary cause of infection in ISEE than SD (ISEE: n = 12, 27.3% vs. SD: n = 5, 4.9%, p < 0.001). The most common surgical procedure in SD was instrumentation (n = 87, 61%) and in ISEE abscess evacuation (n = 63, 95%). Patients with ISEE displayed lower in-hospital complication rates compared to SD for sepsis (ISEE: n = 12, 18.2% vs. SD: n = 94, 66.2%, p < 0.001), septic embolism (ISEE: n = 4/48 cases, 8.3% vs. SD: n = 52/117 cases, 44.4%, p < 0.001), endocarditis (ISEE: n = 1/52 cases, 1.9% vs. SD: n = 23/125 cases, 18.4%, p = 0.003), relapse rate (ISEE: n = 4/46, 8.7% vs. SD: n = 27/92, 29.3%, p = 0.004), and disease-related mortality (ISEE: n = 1, 1.5% vs. SD: n = 11, 7.7%, p = 0.108). Patients with SD showed prolonged length of hospital stay (ISEE: 22 [15, 30] d vs. SD: 38 [29, 53] d, p < 0.001) and extended intensive care unit stay (ISEE: 0 [0, 4] d vs. SD: 3 [0, 12] d, p < 0.002). Conclusions: Our 20-year experience and cohort analysis on the clinical management of SD and ISEE unveiled distinct clinical phenotypes and outcomes in both entities, with ISEE displaying a more favorable disease course with respect to complications and relapse rates as well as disease-related mortality.

Distribution of RET proto-oncogene variants in children with appendicitis.

BACKGROUND: In addition to patient-related systemic factors directing the immune response, the pathomechanisms of appendicitis (AP) might also include insufficient drainage leading to inflammation caused by decreased peristalsis. Genetic predisposition accounts for 30%-50% of AP. M. Hirschsprung (HSCR), also characterized by disturbed peristalsis, is associated with variants in the RET proto-oncogene. We thus hypothesized that RET variants contribute to the etiology of AP. METHODS: DNA from paraffin-embedded appendices and clinical data of 264 children were analyzed for the RET c.135A>G variant (rs1800858, NC_000010.11:g.43100520A>G). In 46 patients with gangrenous or perforated AP (GAP), peripheral blood DNA was used for RET sequencing. RESULTS: Germline mutations were found in 13% of GAP, whereas no RET mutations were found in controls besides the benign variant p.Tyr791Phe (NC_000010.11:g.43118460A>T). In GAP, the polymorphic G-allele in rs2435352 (NC_000010.11:g.43105241A>G) in intron 4 was underrepresented (p = 0.0317). CONCLUSION: Our results suggest an impact of the RET proto-oncogene in the etiology of AP. Mutations were similar to patients with HSCR but no clinical features of HSCR were observed. The pathological phenotypes in both populations might thus represent a multigenic etiology including RET germline mutations with phenotypic heterogeneity and incomplete penetrance.

Architecture of the Cutaneous Autonomic Nervous System.

The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Sensory fibers can be assessed using quantitative sensory test. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity.