Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature

Table 1 Risk of bias assessment

Manuscript type	Ref.	Related questions													Total	Risk of bias
Randomized control trial		Was true randomization used for assignment of participants to treatment groups?	Was allocation to treatment groups concealed?	Were treatment groups similar at the baseline?	Were participants blind to treatment assignment?	Were those delivering the treatment blind to treatment assignment?	Were treatment groups treated identically other than the intervention of interest?	Were outcome assessors blind to treatment assignment?	Were outcomes measured in the same way for treatment groups?	Were outcomes measured in a reliable way?	Was follow-up complete and if not, were differences between groups in terms of their follow-up adequately described and analyzed?	Were participants analyzed in the groups to which they were randomized?	Was appropriate statistical analysis used?	Was the trial design appropriate and any deviations from the standard randomized control trial design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial?
	Godek et al[13]	Y	Y	Y	Y	N	Y	N	Y	Y	Y	Y	Y	Y	85%	Low
Cohort studies		Were the two groups similar and recruited from the same population?	Were the exposures measured similarly to assign people to both exposed and unexposed groups?	Was the exposure measured in a valid and reliable way?	Were confounding factors identified?	Were strategies to deal with confounding factors stated?	Were the groups/participants free of the outcome at the start of the study (or at the moment of exposure)?	Were the outcomes measured in a valid and reliable way?	Was the follow-up time reported and sufficient to be long enough for outcomes to occur?	Was follow-up complete, and if not, were the reasons for loss to follow-up described and explored?	Were strategies to address incomplete follow-up utilized?	Was appropriate statistical analysis used?	N/A	N/A
	Becker et al[15]	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	N/A	N/A	100%	Low
	Goni et al[16]	Y	Y	Y	N	N	Y	Y	Y	Y	Y	N	N/A	N/A	73%	Low
	HS et al[17]	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	N/A	N/A	100%	Low
	Godek et al[19]	Y	Y	Y	N	N	Y	Y	Y	Y	Y	Y	N/A	N/A	82%	Low
	Godek et al[18]	Y	Y	Y	N	N	N	Y	Y	Y	Y	Y	N/A	N/A	73%	Low

Table 2 Designs and conclusions of included studies

Ref.	Study design	Sample size	Age (mean)	BMI (mean)	Female	Pathology	Intervention (s)	Latest follow-up	Outcomes measured	Conclusion
Becker et al[15]	Randomized prospective cohort study	ACS: n = 32, 5 mg Triamcinolone: n = 27, 10 mg Triamcinolone: n = 25	53.9 (range: 29-81)	Not reported	38.10%	Lumbar radiculopathy	3 weekly transforaminal injections of ACS, 5 mg triamcinolone, or 10 mg triamcinolone	20 weeks post-final injection	VAS, ODI	Epidural ACS injection for unilateral lumbar radiculopathy significantly improved patient pain and disability compared to baseline to an extent potentially superior to ESI. No statistically significant difference in symptom improvement was observed between 5 mg and 10 mg epidural injection of triamcinolone
Goni et al[16]	Pilot study	ACS: n = 20; MPS: n = 20	ACS: 42.25; MPS: 46.80	Not reported	ACS: 40%; MPS: 45%	Cervical radiculopathy	A single 2-3 mL transforaminal injection of ACS or MPS	6 months post-injection	VAS, NDI, NPDS, PCS, MCS	Patients with cervical radiculopathy treated with epidural ACS injection experienced sustained improvement of pain, disability and quality of life. ACS produced as good or better improvement of symptoms with longer duration of relief compared to epidural methylprednisolone
HS et al[17]	Prospective study	ACS: n = 20	37.15	24.92 kg/m2	Not reported	Lumbar radiculopathy	A single 2 mL transforaminal injection of ACS	6 months post-injection	VAS, SLRT, ODI, PCS, MCS	Epidural ACS injection can modify the disease course of unilateral lumbar radiculopathy by significantly improving pain, disability, and quality of life
Godek et al[19]	Pilot study	ACS: n = 15	38.8	Not reported	40%	Lumbar radiculopathy	1-2 weekly transforaminal injections of 3-4 mL ACS	6 months post-injection	VAS, ODI, SLRT, OLST, Analgesic use	ACS is a promising option for significantly improving pain and disability in patients with single-level lumbar radiculopathy. No radicular damage or sever adverse events were reported
Godek et al[18]	Retrospective study	ACS: n = 497	57.1 ± 16.5 (range: 17-93)	Not reported	57.70%	Cervical DDD (transforaminal injection): n = 89. Thoracic Spine DDD (transforaminal injection): n = 8. Lumbar Spine DDD (transforaminal injection): n = 271. Lumbar Spine DDD (interlaminar injection): n = 1. Lumbar Spine Stenosis (transforaminal injection): n = 118. Lumbar Spine Stenosis (interlaminar injection): n = 10	Cervical: 4 doses of 3-4 mL transforaminal ACS injections. Thoracic: 6 doses of 3-4 mL transforaminal ACS injections. Lumbar: 4-6 doses of 4 mL ACS injected transforaminally or interlaminarly	6 months post-final injection	Modified McNabb scale	ACS injection was well tolerated with very few and limited cases of adverse events. ACS injection produced satisfactory improvement in Modified McNabb Scale scores for patients with cervical or lumbar discopathy. Unsatisfactory results predominated in cases of lumbar spinal stenosis
Godek et al[13]	Randomized control trial	ACS: n = 100	46.29 + 13.61	26.67 ± 4.49	51%	Lumbar Radiculopathy due to DDD (interlaminar injection): n = 50. Lumbar Radiculopathy due to DDD (transforaminal injection): n = 50	2 weekly interlaminar or transforaminal injections of 8 mL ACS	24 weeks post-final injection	NRS, ODI, RMQ, EQ-5D-5 L mobility, EQ-5D-5 L self-care, EQ-5D-5 L usual activities, EQ-5D-5 L pain/discomfort, EQ-5D-5 L anxiety/depression, EQ-5D-5 L-based LSS, EQ-5D-5 L VAS, EQ-5D-5 L Index	Epidural and transforaminal ACS injections both significantly improve patient outcomes compared to baseline. Treatment with transforaminal ACS injection produced statistically superior improvement in EQ-5D-5 L scores compared to epidural ACS injection

BMI: Body mass index; ACS: Autologous conditioned serum; VAS: Visual acuity scale; ODI: Oswestry disability index; ESI: Epidural steroid injection; MPS: Methylprednisolone; NDI: Neck disability index; NPDS: Neck pain disability scale; PCS: Physical component score; MCS: Mental component score; SLRT: Straight leg raise test; OLST: One leg standing test; DDD: Degenerative disk disease; RMQ: Roland Morris questionnaire; EQ-5D-5 L: Euro quality of life-five dimensions-five levels; LSS: Level sum score.