Mental health is strongly associated with capability after lower extremity injury treated with free flap limb salvage or amputation

Background: Knowledge about factors associated with long-term outcomes, after severe traumatic injury to the lower extremity, can aid with the difficult decision whether to salvage or amputate the leg and improve outcome. We therefore studied factors independently associated with capability at a minimum of 1 year after amputation or free flap limb salvage. Methods: We included 135 subjects with a free flap lower extremity reconstruction and 41 subjects with amputation, between 1991 and 2021 at two urban-level 1 trauma centers with a mean follow-up of 11 ± 7 years. Long-term physical functioning was assessed using the Physical Component Score (PCS) of the Short-Form 36 (SF36) and the Lower Extremity Functional Scale (LEFS) questionnaires. Independent variables included demographics, injury characteristics, and the Mental Component Score (MCS) of the SF36. Results: Greater mental health was independently and strongly associated with greater capability, independent of amputation or limb reconstruction. Mental health explained 33% of the variation in PCS and 57% of the variation in LEFS. Injury location at the knee or leg was associated with greater capability, compared to the foot or ankle. Amputation or limb reconstruction was not associated with capability.Discussion: This study adds to the growing body of knowledge that physical health is best regarded through the lens of the bio-psycho-social model in which mental health is a strong determinant. This study supports making mental health an important aspect of rehabilitation after major lower extremity injury, regardless of amputation or limb salvage.</p

Mental health is strongly associated with capability after lower extremity injury treated with free flap limb salvage or amputation

Background: Knowledge about factors associated with long-term outcomes, after severe traumatic injury to the lower extremity, can aid with the difficult decision whether to salvage or amputate the leg and improve outcome. We therefore studied factors independently associated with capability at a minimum of 1 year after amputation or free flap limb salvage. Methods: We included 135 subjects with a free flap lower extremity reconstruction and 41 subjects with amputation, between 1991 and 2021 at two urban-level 1 trauma centers with a mean follow-up of 11 ± 7 years. Long-term physical functioning was assessed using the Physical Component Score (PCS) of the Short-Form 36 (SF36) and the Lower Extremity Functional Scale (LEFS) questionnaires. Independent variables included demographics, injury characteristics, and the Mental Component Score (MCS) of the SF36. Results: Greater mental health was independently and strongly associated with greater capability, independent of amputation or limb reconstruction. Mental health explained 33% of the variation in PCS and 57% of the variation in LEFS. Injury location at the knee or leg was associated with greater capability, compared to the foot or ankle. Amputation or limb reconstruction was not associated with capability.Discussion: This study adds to the growing body of knowledge that physical health is best regarded through the lens of the bio-psycho-social model in which mental health is a strong determinant. This study supports making mental health an important aspect of rehabilitation after major lower extremity injury, regardless of amputation or limb salvage.</p

Hydrogen sulfide attenuates intestinal ischemia-reperfusion injury when delivered in the post-ischemic period

Background and Aim:To investigate whether pharmacologic post-conditioning of intestinal tissue with hydrogen sulfide (HS) protects against ischemia reperfusion injury (IRI).Methods:In vitro, enterocytes were made hypoxic for 1, 2, or 3 h, treated with media containing between 0 and 100 mu M HS 20 min prior to the end of the hypoxic period, then returned to normoxia for 3 h. An apoptotic index (AI) was determined for each time point and (HS). In vivo, jejunal ischemia was induced in male Sprague-Dawley rats for 1, 2, or 3 h; 20 min prior to the end of the ischemic period animals were given an intravenous injection of NaHS sufficient to raise the bloodstream concentration to 0, 10 mu M, or 100 mu M HS. This was followed by jejunal reperfusion for 3 h, histologic processing, and measurement of villus height.Results:In vitro, there was a significant decrease in AI compared with non-HS-treated control at all time points after treatment with 10 mu M HS, and at the 2 h time point with 100 mu M HS (P < 0.017). In vivo, after 1 h ischemia, qualitative reduction of injury was noted with 10 mu M and 100 mu M; after 2 h ischemia, reduction was noted with 10 mu M but not 100 mu M; and after 3 h ischemia, there was no injury reduction. HS treatment resulted in significant quantitative preservation (P < 0.05) of villus height at all time points and doses, except for 3 h ischemia and delivery of 100 mu M (P = 0.129).Conclusions:Hydrogen sulfide provides significant protection to intestinal tissues in vitro and in vivo when delivered after the onset of ischemia

Therapeutic metabolic inhibition: hydrogen sulfide significantly mitigates skeletal muscle ischemia reperfusion injury in vitro and in vivo

BACKGROUND:: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury. The purpose of this study was to determine whether it is protective in skeletal muscle. METHODS:: This study used both in vitro (cultured myotubes subjected to sequential anoxia and normoxia) and in vivo (mouse hind-limb ischemia followed by reperfusion) models in which hydrogen sulfide (0 to 1000 μM) was delivered before the onset of oxygen deficiency. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. RESULTS:: In vitro, hydrogen sulfide reduced the apoptotic index by as much as 99 percent (p = 0.001), with optimal protection conferred by raising intravascular hydrogen sulfide to 10 μM. In vivo, 10 μM hydrogen sulfide delivered before 3 hours of hind-limb ischemia followed by 3 hours of reperfusion resulted in protection against ischemia-reperfusion injury-induced cellular changes, as evidenced by significant decreases in injury score and apoptotic index (by as much as 91 percent; p = 0.001). These findings were consistent at 4 weeks after injury and reperfusion. CONCLUSION:: These findings confirm that the preischemic delivery of hydrogen sulfide limits ischemia-reperfusion injury-induced cellular damage in myotubes and skeletal muscle and suggests that, when given in the appropriate dose, this molecule may have significant therapeutic applications in multiple clinical scenario

Development of an Acellular Bioengineered Matrix with a Dominant Vascular Pedicle

Background. This study assessed the feasibility of creating a tissue engineering platform by decellularization of fasciocutaneous tissue.Materials and Methods. A fasciocutaneous flap based upon the superficial inferior epigastric artery was harvested from the abdominal wall of 8-wk-old male Sprague-Dawley rats. All cellular components were removed by sequential treatment with sodium azide, DNAse, and sodium deoxycholate. The degree of decellularization was qualitatively assessed by histology and quantitatively assessed by spectrophotometry. Persistence of relevant extracellular matrix proteins was shown following staining with orcein and hematoxylin. The duration of circuit patency was determined by continuous perfusion with a peristaltic perfusion pump.Results. Gross and histologic examination demonstrated removal of cellular constituents with preservation of tissue matrix architecture, including macrochannels and microchannels. This was confirmed by the application of spectrophotometry to DNA isolates, which showed that the decellularized flap retained 4.04 ng/mu L, DNA, compared with the non-processed control, which retained 37.03 ng/mu L, DNA, and the acellular control, which was read as having 0.65 ng/mu L DNA. The extracellular matrix of vessel walls was shown to remain intact. Peristaltic perfusion of the cannulated pedicle inflow channel with phosphate buffered saline at a rate of 200 mu L/min confirmed circuit patency for 6 h.Conclusion. Fasciocutaneous flaps harvested with an intact vascular pedicle and associated tissue vascular network can be successfully decellularized and perfused ex vivo. This methodology, which is scalable to human size tissues, provides promise as a technique for the production of customizable engineered tissues. (C) 2010 Elsevier Inc. All rights reserved

Therapeutic delivery of hydrogen sulfide for salvage of ischemic skeletal muscle after the onset of critical ischemia

Background: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury (IRI).Methods: This study evaluated the potential utility of hydrogen sulfide in preventing IRI in skeletal muscle by using in vitro (cultured myotubes subjected to sequential hypoxia and normoxia) and in vivo (mouse hind limb ischemia, followed by reperfusion) models to determine whether intravenous hydrogen sulfide delivered after the ischemic event had occurred (pharmacologic postconditioning) conferred protection against IRI. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively.Results: In vitro; hydrogen sulfide reduced the apoptotic index after 1, 3, or 5 hours of hypoxia by as much as 75% (P = .002), 80% (P = .006), and 83% (P < .001), respectively. In vivo, hydrogen sulfide delivered after the onset of hind limb ischemia and before reperfusion resulted in protection against IRI-induced cellular changes, which was validated by significant decreases in the injury score and apoptotic index. The timing of hydrogen sulfide delivery was crucial: when delivered 20 minutes before reperfusion, hydrogen sulfide conferred significant cytoprotection (P < .001), but treatment 1 minute before reperfusion did not provide protection (P = NS).Conclusions: These findings confirm that hydrogen sulfide limits IRI-induced cellular damage in myotubes and skeletal muscle, even when delivered after the onset of ischemia in this murine model. These data suggest that when given in the appropriate dose and within the proper time frame, hydrogen sulfide may have significant therapeutic applications in multiple clinical scenarios. (J Vasc Surg 2011;53:785-91.

Is dangling of the lower leg after a free flap reconstruction necessary? Study protocol for a large multicenter randomized controlled study

textabstractBACKGROUND: Within the field of plastic surgery, free tissue transfer is common practice for knee and lower leg defects. Usually, after such free flap reconstruction, patients undergo a dangling protocol in the postoperative phase. A dangling protocol is designed to gradually subject the free flap to increased venous pressure resulting from gravitational forces. Worldwide there are multiple variations of dangling protocols. However, there is no evidence available in the literature that supports the use of a dangling protocol. METHODS: This is a multicenter randomized controlled trial that includes patients with a free flap lower leg reconstruction. The primary outcome is to assess whether a no-dangling protocol is not inferior to a dangling protocol, in terms of proportion of partial flap loss, 6 months after surgery. Secondary objectives are to identify differences in major and minor complications, length of stay, and costs, and to objectify blood gaseous changes during dangling. Furthermore, at 2 years we will assess difference in physical function, infection rates, and osseous union rates. DISCUSSION: The primary outcome of this study will give a more decisive answer to the question of whether a dangling protocol is necessary after a free flap reconstruction of the lower leg. The secondary outcomes of this study will provide a better insight into the physical functions, infection rates, and union rates in these patients. TRIAL REGISTRATION: Central Committee on Research Involving Human Subjects (CCMO), NL63146.041.17. Registered on 11 July 2018. Netherlands Trial Register, NTR7545 . Registered on 10 October 2018