Reconstructive surgery for treating pressure ulcers.

BACKGROUND: There are several possible interventions for managing pressure ulcers (sometimes referred to as pressure injuries), ranging from pressure-relieving measures, such as repositioning, to reconstructive surgery. The surgical approach is usually reserved for recalcitrant wounds (where the healing process has stalled, or the wound is not responding to treatment) or wounds with full-thickness skin loss and exposure of deeper structures such as muscle fascia or bone. Reconstructive surgery commonly involves wound debridement followed by filling the wound with new tissue. Whilst this is an accepted means of ulcer management, the benefits and harms of different surgical approaches, compared with each other or with non-surgical treatments, are unclear. This is an update of a Cochrane Review published in 2016. OBJECTIVES: To assess the effects of different types of reconstructive surgery for treating pressure ulcers (category/stage II or above), compared with no surgery or alternative reconstructive surgical approaches, in any care setting. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was January 2022. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) that assessed reconstructive surgery in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted study data, assessed the risk of bias and undertook GRADE assessments. We would have involved a third review author in case of disagreement. MAIN RESULTS: We identified one RCT conducted in a hospital setting in the USA. It enrolled 20 participants aged between 20 and 70 years with stage IV ischial or sacral pressure ulcers (involving full-thickness skin and tissue loss). The study compared two reconstructive techniques for stage IV pressure ulcers: conventional flap surgery and cone of pressure flap surgery, in which a large portion of the flap tip is de-epithelialised and deeply inset to obliterate dead space. There were no clear data for any of our outcomes, although we extracted some information on complete wound healing, wound dehiscence, pressure ulcer recurrence and wound infection. We graded the evidence for these outcomes as very low-certainty. The study provided no data for any other outcomes. AUTHORS' CONCLUSIONS: Currently there is very little randomised evidence on the role of reconstructive surgery in pressure ulcer management, although it is considered a priority area. More rigorous and robust research is needed to explore this intervention.

Protease activity as a prognostic factor for wound healing in venous leg ulcers.

BACKGROUND: Venous leg ulcers (VLUs) are a common type of complex wound that have a negative impact on people's lives and incur high costs for health services and society. It has been suggested that prolonged high levels of protease activity in the later stages of the healing of chronic wounds may be associated with delayed healing. Protease modulating treatments have been developed which seek to modulate protease activity and thereby promote healing in chronic wounds. OBJECTIVES: To determine whether protease activity is an independent prognostic factor for the healing of venous leg ulcers. SEARCH METHODS: In February 2018, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase and CINAHL. SELECTION CRITERIA: We included prospective and retrospective longitudinal studies with any follow-up period that recruited people with VLUs and investigated whether protease activity in wound fluid was associated with future healing of VLUs. We included randomised controlled trials (RCTs) analysed as cohort studies, provided interventions were taken into account in the analysis, and case-control studies if there were no available cohort studies. We also included prediction model studies provided they reported separately associations of individual prognostic factors (protease activity) with healing. Studies of any type of protease or combination of proteases were eligible, including proteases from bacteria, and the prognostic factor could be examined as a continuous or categorical variable; any cut-off point was permitted. The primary outcomes were time to healing (survival analysis) and the proportion of people with ulcers completely healed; the secondary outcome was change in ulcer size/rate of wound closure. We extracted unadjusted (simple) and adjusted (multivariable) associations between the prognostic factor and healing. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion at each stage, and undertook data extraction, assessment of risk of bias and GRADE assessment. We collected association statistics where available. No study reported adjusted analyses: instead we collected unadjusted results or calculated association measures from raw data. We calculated risk ratios when both outcome and prognostic factor were dichotomous variables. When the prognostic factor was reported as continuous data and healing outcomes were dichotomous, we either performed regression analysis or analysed the impact of healing on protease levels, analysing as the standardised mean difference. When both prognostic factor and outcome were continuous data, we reported correlation coefficients or calculated them from individual participant data.We displayed all results on forest plots to give an overall visual representation. We planned to conduct meta-analyses where this was appropriate, otherwise we summarised narratively. MAIN RESULTS: We included 19 studies comprising 21 cohorts involving 646 participants. Only 11 studies (13 cohorts, 522 participants) had data available for analysis. Of these, five were prospective cohort studies, four were RCTs and two had a type of case-control design. Follow-up time ranged from four to 36 weeks. Studies covered 10 different matrix metalloproteases (MMPs) and two serine proteases (human neutrophil elastase and urokinase-type plasminogen activators). Two studies recorded complete healing as an outcome; other studies recorded partial healing measures. There was clinical and methodological heterogeneity across studies; for example, in the definition of healing, the type of protease and its measurement, the distribution of active and bound protease species, the types of treatment and the reporting of results. Therefore, meta-analysis was not performed. No study had conducted multivariable analyses and all included evidence was of very low certainty because of the lack of adjustment for confounders, the high risk of bias for all studies except one, imprecision around the measures of association and inconsistency in the direction of association. Collectively the research indicated complete uncertainty as to the association between protease activity and VLU healing. AUTHORS' CONCLUSIONS: This review identified very low validity evidence regarding any association between protease activity and VLU healing and there is complete uncertainty regarding the relationship. The review offers information for both future research and systematic review methodology.

Arterial smooth muscle dynamics in development and repair.

Arterial vasculature distributes blood from early embryonic development and provides a nutrient highway to maintain tissue viability. Atherosclerosis, peripheral artery diseases, stroke and aortic aneurysm represent the most frequent causes of death and are all directly related to abnormalities in the function of arteries. Vascular intervention techniques have been established for the treatment of all of these pathologies, yet arterial surgery can itself lead to biological changes in which uncontrolled arterial wall cell proliferation leads to restricted blood flow. In this review we describe the intricate cellular composition of arteries, demonstrating how a variety of distinct cell types in the vascular walls regulate the function of arteries. We provide an overview of the developmental origin of arteries and perivascular cells and focus on cellular dynamics in arterial repair. We summarize the current knowledge of the molecular signaling pathways that regulate vascular smooth muscle differentiation in the embryo and in arterial injury response. Our review aims to highlight the similarities as well as differences between cellular and molecular mechanisms that control arterial development and repair.

Nasal decontamination for the prevention of surgical site infection in Staphylococcus aureus carriers.

BACKGROUND: Surgical site infection rates in the month following surgery vary from 1% to 5%. Due to the large number of surgical procedures conducted annually, the costs of these surgical site infections (SSIs) can be considerable in financial and social terms. Nasal decontamination using antibiotics or antiseptics is performed to reduce the risk of SSIs by preventing organisms from the nasal cavity being transferred to the skin where a surgical incision will be made. Staphylococcus aureus (S aureus) colonises the nasal cavity and skin of carriers and can cause infection in open or unhealed surgical wounds. S aureus is the leading nosocomial (hospital-acquired) pathogen in hospitals worldwide. The potential effectiveness of nasal decontamination of S aureus is thought to be dependent on both the antibiotic/antiseptic used and the dose of application; however, it is unclear whether nasal decontamination actually reduces postoperative wound infection in S aureus carriers. OBJECTIVES: To assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are S aureus carriers undergoing surgery. SEARCH METHODS: In September 2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched three clinical trial registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) which enrolled S aureus carriers with any type of surgery and assessed the use of nasal decontamination with antiseptic/antibiotic properties were included in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment. MAIN RESULTS: We located two studies (291 participants) for inclusion in this review. The trials were clinically heterogeneous with differences in duration of follow-up, and nasal decontamination regimens. One study compared mupirocin (2% contained in a base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45% to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment also in cardiac surgery patients. The trials reported limited outcome data on SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality). Mupirocin compared with placeboThis study found no clear difference in SSI risk following use of mupirocin compared with placebo (1 trial, 257 participants); risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130 events in the mupirocin group and 11/127 in the control group; low-certainty evidence (downgraded twice due to imprecision). Anerdian compared with no treatmentIt is uncertain whether there is a difference in SSI risk following treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR 0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in the control group; very low certainty evidence (downgraded twice due to imprecision and once due to risk of bias). AUTHORS' CONCLUSIONS: There is currently limited rigorous RCT evidence available regarding the clinical effectiveness of nasal decontamination in the prevention of SSI. This limitation is specific to the focused question our review addresses, looking at nasal decontamination as a single intervention in participants undergoing surgery who are known S aureus carriers. We were only able to identify two studies that met the inclusion criteria for this review and one of these was very small and poorly reported. The potential benefits and harms of using decontamination for the prevention of SSI in this group of people remain uncertain.

Reconstructive surgery for treating pressure ulcers.

BACKGROUND: The management of pressure ulcers involves several interventions ranging from pressure-relieving measures such as repositioning, to treatments that can include reconstructive surgery. Such surgery may be considered for recalcitrant wounds when full thickness skin loss arises and deeper structures such as muscle fascia and even bone are exposed. The surgery commonly involves wound debridement followed by the addition of new tissue into the wound. Whilst reconstructive surgery is an accepted means of ulcer management, the benefits and harms of surgery compared with non-surgical treatments, or alternative surgical approaches are not clear. OBJECTIVES: To assess the effects of reconstructive surgery for healing pressure ulcers (stage II or above), comparing surgery with no surgery or comparing alternative forms of surgery in any care setting. SEARCH METHODS: We searched the following electronic databases to identify reports of relevant randomised clinical trials (searched 26 September 2016): the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL. We also searched three clinical trials registers and reference lists of relevant systematic reviews, meta-analyses and health technology assessment reports. SELECTION CRITERIA: Published or unpublished randomised controlled trials that assessed reconstructive surgery in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection. We planned that two review authors would also assess the risk of bias and extract study data. MAIN RESULTS: We did not identify any studies that met the review eligibility criteria nor any registered studies investigating the role of reconstructive surgery in the management of pressure ulcers. AUTHORS' CONCLUSIONS: Currently there is no randomised evidence that supports or refutes the role of reconstructive surgery in pressure ulcer management. This is a priority area and there is a need to explore this intervention with more rigorous and robust research.