Molecular insights from skin biopsies: Deciphering microvascular pathology in peripheral vascular diseases

Table 1 Characteristics of the Selected Studies

Ref.	Study design	Sample size	Biopsy type	Molecular markers assessed	Key findings
Sakaguchi and Watari[3]	Case-control	45	Punch biopsy	VEGF, ICAM-1	Identified increased VEGF expression in ischemic tissues
Hess et al[9]	RCT	120	Incisional biopsy	VEGF, eNOS	Demonstrated reduced eNOS levels in diabetic vasculopathy
Subherwal et al[12]	Cohort study	85	Punch biopsy	ICAM-1, VCAM-1	Found upregulation of ICAM-1 in inflammatory PVDs
Gibbons et al[13]	Observational	60	Shave biopsy	Endothelin-1, NO	Showed endothelial dysfunction in systemic sclerosis
Torrens Cid et al[5]	Cross-sectional	78	Punch biopsy	VEGF, MCP-1	Highlighted microvascular damage in diabetic patients
Becker et al[1]	Case series	30	Incisional biopsy	TNF-α, eNOS	Reported inflammatory changes in vasculitic neuropathy
Magro et al[8]	RCT	110	Punch biopsy	VEGF, CD31	Confirmed vascular remodeling in ischemic ulcers
Soor et al[7]	Cohort study	95	Incisional biopsy	ICAM-1, NO	Demonstrated endothelial activation in atherosclerosis
Gonzalez et al[4]	Observational	40	Punch biopsy	TNF-α, VEGF	Found significant inflammatory markers in early-stage PVD
Santos-Gόmez et al[10]	Cross-sectional	50	Shave biopsy	VCAM-1, NO	Linked endothelial dysfunction to vascular stiffening
Narula et al[21]	Case-control	55	Punch biopsy	MCP-1, CD31	Showed correlation between microvascular changes and disease severity
De Gottardi et al[6]	Cohort study	70	Punch biopsy	VEGF, TNF-α	Noted increased inflammatory cytokines in systemic vasculitis
Dinsdale et al[22]	RCT	105	Incisional biopsy	NO, eNOS	Demonstrated NO reduction in diabetic microangiopathy
Vital et al[15]	Observational	65	Punch biopsy	ICAM-1, CD31	Highlighted endothelial activation in diabetic foot ulcers
Shivaprasad et al[19]	Cross-sectional	85	Shave biopsy	TNF-α, MCP-1	Found persistent inflammation in non-healing ischemic wounds
Nebuchennykh et al[17]	Case series	30	Punch biopsy	VEGF, eNOS	Identified altered angiogenesis in peripheral ischemia
Yozgatli et al[20]	Observational	48	Punch biopsy	VEGF, NO	Showed evidence of impaired vasodilation in chronic ischemic conditions

eNOS: Endothelial nitric oxide synthase; ICAM-1: Intercellular adhesion molecule 1; MCP-1: Monocyte chemoattractant protein-1; NO: Nitric oxide; PVDs: Peripheral vascular diseases; RCT: Randomized controlled trial; TNF-α: Tumor necrosis factor alpha; VCAM-1: Vascular cellular adhesion molecule-1; VEGF: Vascular endothelial growth factor.

Table 2 Quality assessment for randomized controlled trials using the Cochrane risk of bias tool

Ref.	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Overall risk
Sakaguchi and Watari[3]	Low	Low	High	Low	Low	Low	Moderate
Hess et al[9]	Low	Low	Low	Low	Low	Low	Low
Subherwal et al[12]	High	High	High	Moderate	Low	Low	High
Gibbons et al[13]	Low	Moderate	Moderate	Low	High	Low	Moderate
Torrens Cid et al[5]	Low	Low	Low	Low	Low	Low	Low
Becker et al[1]	High	Moderate	High	Moderate	Low	Low	High
Magro et al[8]	Low	Low	Low	Low	Low	Low	Low
Soor et al[7]	Moderate	High	Moderate	Low	Low	Low	Moderate

Table 3 Quality assessment for observational and cross-sectional studies using the Newcastle-Ottawa Scale

Ref.	Selection (0-4)	Comparability (0-2)	Outcome assessment (0-3)	Total score (0-9)	Quality
Magro et al[8]	4	2	3	9	High
Gonzalez et al[4]	3	1	2	6	Moderate
Santos-Gόmez et al[10]	2	1	1	4	Low
Narula et al[21]	4	2	3	9	High
De Gottardi et al[6]	3	1	2	6	Moderate
Dinsdale et al[22]	4	2	3	9	High
Vital et al[15]	3	1	2	6	Moderate
Shivaprasad et al[19]	4	2	3	9	High
Nebuchennykh et al[17]	2	1	1	4	Low
Yozgatli et al[20]	4	2	3	9	High