Subclinical infection can be an initiator of inflammaging leading to degenerative disk disease: evidence from host-defense response mechanisms.

PURPOSE: There is considerable controversy on the role of genetics, mechanical and environmental factors, and, recently, on subclinical infection in triggering inflammaging leading to disk degeneration. The present study investigated sequential molecular events in the host, analyzing proteome level changes that will reveal triggering factors of inflammaging and degeneration. METHODS: Ten MRI normal disks (ND) from braindead organ donors and 17 degenerated disks (DD) from surgery were subjected to in-gel-based label-free ESI-LC-MS/MS analysis. Bacterial-responsive host-defense response proteins/pathways leading to Inflammaging were identified and compared between ND and DD. RESULTS: Out of the 263 well-established host-defense response proteins (HDRPs), 243 proteins were identified, and 64 abundantly expressed HDRPs were analyzed further. Among the 21 HDRPs common to both ND and DD, complement factor 3 (C3) and heparan sulfate proteoglycan 2 (HSPG2) were significantly upregulated, and lysozyme (LYZ), superoxide dismutase 3 (SOD3), phospholipase-A2 (PLA2G2A), and tissue inhibitor of metalloproteinases 3 (TIMP-3) were downregulated in DD. Forty-two specific HDRPs mainly, complement proteins, apolipoproteins, and antimicrobial proteins involved in the complement cascade, neutrophil degranulation, and oxidative-stress regulation pathways representing an ongoing host response to subclinical infection and uncontrolled inflammation were identified in DD. Protein-Protein interaction analysis revealed cross talk between most of the expressed HDRPs, adding evidence to bacterial presence and stimulation of these defense pathways. CONCLUSIONS: The predominance of HDRPs involved in complement cascades, neutrophil degranulation, and oxidative-stress regulation indicated an ongoing infection mediated inflammatory process in DD. Our study has documented increasing evidence for bacteria's role in triggering the innate immune system leading to chronic inflammation and degenerative disk disease.

Presence of preoperative Modic changes and severity of endplate damage score are independent risk factors for developing postoperative surgical site infection: a retrospective case-control study of 1124 patients.

PURPOSE: There is increasing evidence of an association between Modic changes (MC) and subclinical infection. However, the association of MC with postoperative surgical site infection (SSI) has not been adequately probed. This study primarily aimed to investigate a probable association between preoperative MC, total endplate damage score (TEPS), and SSI. METHODS: A retrospective analysis of 1124 patients who underwent surgery in a single institution (2016-2018) was performed, using both univariate and multiple logistic regression analyses to identify independent risk factors for SSI. RESULTS: The prevalence of SSI was 4% (44/1124 patients), with no association with age or sex. The prevalence of MC in the SSI group was significantly higher-79.54% (35/44) compared to 58.79% (635/1080) (p value = 0.006) in the control group with no specific relation to type or location of MC. A higher TEPS was associated with SSI (p value = 0.009). A receiver operating characteristic (ROC) curve for TEPS values to assess predictiveness of SSI showed TEPS ≥ 5.5 to have a better sensitivity of 84% than 72% for a TEPS ≥ 6.5. Univariate analysis showed TEPS > 6 (odds ratio 3.887) to have a stronger association with SSI than the presence of MC (odds ratio 2.725). Among various types of surgeries, discectomy had a higher association with SSI (p value = 0.03) when compared to fusion (p value = 0.071). However, multiple logistic regression analysis revealed only TEPS > 6, presence of MC and hypothyroidism as independent risk factors for SSI. CONCLUSION: Our data suggest that preoperative MC and TEPS > 6 are independent risk factors for developing surgical site infections. MC could be foci of chronic subclinical infection and not mere markers of degeneration, as initially described.

Bezold-Jarisch reflex causing bradycardia and hypotension in a case of severe dystrophic cervical kyphotic deformity: a case report and review of literature.

PURPOSE: A 17-year-old adolescent with neurofibromatosis and severe cervicothoracic deformity was identified to have thoracic inlet compression leading to bradycardia and hypotension, only during prone positioning, and we discuss its successful management. METHODS: Preoperative halo-gravity traction reduced the deformity from 126° to 91°. During prone positioning, sudden onset bradycardia was followed by asystole, which disappeared immediately on turning over to supine position. Surgery was called off after two additional failed attempts of prone positioning. RESULTS: A retrospective analysis of CT and MRI showed severe narrowing of the thoracic inlet. In this patient, the right thoracic inlet was severely narrow, and prone positioning caused a further dynamic compromise stimulating right vagal nerve. The right vagus supplies the sinoatrial node, which is the natural pacemaker of the heart, and its stimulation causes sympathetic inhibition. Bezold-Jarisch reflex is a cardio-inhibitory reflex occurring due to vagal stimulation resulting in sudden bradycardia, asystole, and hypotension. To facilitate prone positioning, the medial end of the clavicles, along with limited manubrium excision, was performed relieving the vagal compression. C2-T4 instrumented decompression followed by anterior reconstruction and cervical plating was performed. The postoperative period was uneventful, and the final deformity was 45°. CONCLUSION: Bezold-Jarisch Reflex as a result of narrow thoracic inlet caused by cervical kyphosis and compensatory hyperlordosis of the upper thoracic spine has never been reported. This case highlights the need to introspect into thoracic inlet morphology in severe cervicothoracic deformities. Thoracic inlet decompression is an efficient way of addressing this unique complication.