Tissue-Engineered Soft-Tissue Reconstruction Using Noninvasive Mechanical Preconditioning and a Shelf-Ready Allograft Adipose Matrix.

BACKGROUND: Adipose tissue defects leading to severe functional (disability) and morphologic (disfigurement) morbidity are often treated in plastic surgery with fat grafting, which can be limited by resorption, necrosis, and cyst formation. This study aimed to assess whether adipose scaffolds could provide an environment for in situ autologous fat grafting, and to study whether adipose cell migration and proliferation (adipogenesis) within scaffolds could be enhanced by preliminarily increasing the vascularity (preconditioning) of the surrounding tissue receiving the scaffolds. METHODS: Using an established rodent model of subcutaneous tissue/scaffold grafting, the authors tested the potential of a human-derived, shelf-ready, injectable, decellularized allograft adipose matrix to reconstruct soft-tissue defects when used in combination with noninvasive mechanical (suction-induced) skin preconditioning. RESULTS: Combined use of the allograft adipose matrix and noninvasive skin preconditioning significantly improved long-term volume retention (50 to 80 percent higher at a 12-week follow-up) and histologic quality of reconstructed tissues compared with standard of care (autologous adipose grafts). The components of the allograft adipose matrix supported adipogenesis and angiogenesis. Combining the allograft adipose matrix with living adipose grafts mitigated negative outcomes (lower long-term volume retention, higher presence of cystic-like areas). CONCLUSIONS: This study suggests that the synergistic use of the allograft adipose matrix and noninvasive tissue preconditioning provides an effective solution for improving fat grafting. These strategies can easily be tested in clinical trials and could establish the basis for a novel therapeutic paradigm in reconstructive surgery.

Mouse Mast Cell Protease-4 Recruits Leukocytes in the Inflammatory Phase of Surgically Wounded Skin.

Objective: Mouse mast cell protease-4 (mMCP-4, also known as chymase) has both pro- and anti-inflammatory roles depending on the disease model. However, its effects have not been studied in surgically wounded skin. Given the significant clinical applications of modulating the inflammatory response in wound healing, we examined the role of mMCP-4 and the effect of its inhibitor chymostatin on leukocyte and polymorphonuclear cell (PMN) recruitment in our skin model. Approach: Recruitment was assessed on day-1 postwounding of three groups of mice (n = 10 each): mMCP-4 null mice, wild-type (WT) mice treated with the mMCP-4 inhibitor chymostatin, and WT with no other intervention. Leukocytes were stained with CD-45 cell marker, and PMN cells were stained with chloroacetate esterase. Results: The WT mice had 27 ± 9 leukocytes per field compared with 11 ± 6 for the mMCP-4 nulls, a decrease of 60% (p = 0.03), whereas the chymostatin-injected group had a count comparable with the uninjected WT controls at 24 ± 9. The WT group had a PMN count of 96 ± 12 cells, compared with just 24 ± 8 in the mMCP-4 null group, a decrease of 75% (p = 0.001), whereas the chymostatin-treated group had 60 ± 18 cells, a decrease of 38% compared with the WT group (p = 0.03). Innovation: We showed that the inflammatory process can be influenced by impeding the arrival of PMNs into the surgically injured site using the mMCP-4 inhibitor chymostatin. Conclusion: Chymase contributes to the recruitment of white blood cells in surgically wounded skin.

Preclinical Optimization of a Shelf-Ready, Injectable, Human-Derived, Decellularized Allograft Adipose Matrix.

IMPACT STATEMENT: Trauma, disease, surgery, or congentital defects can cause soft tissue losses in patients, leading to disfigurement, functional impairment, and a low quality of life. In the lack of available effective methods to reconstruct these defects, acellular adipose matrices could provide a novel therapeutic solution to such challenge.

The role of mouse mast cell proteases in the proliferative phase of wound healing in microdeformational wound therapy.

BACKGROUND: Stored in the secretory granules of cutaneous mouse mast cells are mouse mast cell proteases (mMCP-4, -5, and -6). Using transgenic mouse lines that lacked these enzymes, it was shown that mMCP-4 and mMCP-5 modulate the outcome of burn-induced skin injury. Whether or not these proteases also play a role in the repair of surgically damaged skin, with or without microdeformational wound therapy, remains to be determined. METHODS: Wild-type C57BL/6 mice and transgenic C57BL/6 mouse lines lacking mMCP-4, -5, or -6 were subjected to surgical wounding of their skin. Wounds were splinted with a stabilizing patch, and the mice received either microdeformational wound therapy (n = 5) or occlusive dressing (n = 5) for 7 days. Wound healing parameters were assessed in the proliferative phase. RESULTS: Cell proliferation in the wounded wild-type mice receiving microdeformational wound therapy was 60 ± 3 percent. Cell proliferation was only 35 ± 5 percent, 25 ± 5 percent, and 45 ± 4 percent for the treated mMCP-4-, mMCP-5-, and mMCP-6-null mice, respectively (p = 0.005). Blood vessel sprouting was higher in the control mice with microdeformational wound therapy (170 ± 40 vessels/high-power field) compared with mouse mast cell protease 6-null mice with microdeformational wound therapy (70 ± 20 vessels/high-power field; p = 0.005), and higher in the control mice with occlusive dressing (110 ± 30 vessels/high-power field) compared with mMCP-4-null mice with occlusive dressing (50 ± 20 vessels/high-power field; p = 0.01). Qualitatively, the granulation tissue of all the protease-deficient groups receiving microdeformational wound therapy was disrupted. CONCLUSION: Results suggest that mouse mast cell proteases 4, 5, and 6 are mediators of the critical role mast cells play in microdeformational wound therapy in the proliferative phase of healing.

Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing.

Mast cells (MCs) are active participants in blood coagulation and innate and acquired immunity. This review focuses on the development of mouse and human MCs, as well as the involvement of their granule serine proteases in inflammation and the connective tissue remodeling that occurs during the different phases of the healing process of wounded skin and other organs. The accumulated data suggest that MCs, their tryptases, and their chymases play important roles in tissue repair. While MCs initially promote healing, they can be detrimental if they are chronically stimulated or if too many MCs become activated at the same time. The possibility that MCs and their granule serine proteases contribute to the formation of keloid and hypertrophic scars makes them potential targets for therapeutic intervention in the repair of damaged skin.

Transversus abdominis-plane block versus local anesthetic wound infiltration in lower abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative pain management is of great importance in perioperative anesthetic care. Transversus abdominis plane (TAP) block has been described as an effective technique to reduce postoperative pain and morphine consumption after open lower abdominal operations. Meanwhile, local anesthetic infiltration (LAI) is also commonly used as a traditional method. However, the effectiveness of these two methods has not been compared before. METHODS: A meta-analysis of all relevant randomized controlled trials (RCTs) was conducted to compare the efficacy of single shot TAP block with that of single shot LAI for postoperative analgesia in adults. Major medical databases and trial registries were searched for published and unpublished RCTs. The endpoints include postoperative visual analog scale (VAS) pain score, morphine requirement, and rate of postoperative nausea and vomiting (PONV). For continuous data, weighted mean differences (WMDs) were formulated; for dichotomous data, risk ratios (RR) were calculated. Results were derived using a random-/fixed-effects model with 95% confidence interval (CI). RESULTS: Four RCTs, encompassing 96 TAP-block and 100 LAI patients, were included in the final analysis. Patients in the TAP-block group had lower VAS pain scores 24 hours postoperatively compared with the LAI group, both at rest (WMD [95% CI] = -0.67 [p < 0.01] and with movement (WMD = -0.89, p < 0.01). There were no significant between-group differences in 24-hour postoperative morphine requirements, the rates if PONV or VAS pain scores at 2 and 4 h postoperatively. CONCLUSION: TAP block and LAI provide comparable short-term postoperative analgesia, but TAP block has better long-lasting effect.

Prevalence of depression and anxiety in adult patients with ß-thalassemia major and intermedia.

OBJECTIVE: To evaluate and compare the prevalence and risk factors for anxiety and depression in adults with beta-thalassemia major (TM) and intermedia (TI). METHOD: A cross-sectional study of TI and TM patients at a Chronic Care Center in Lebanon. A total of 80 patients agreed to participate (32 TI (median age 24 years) and 48 TM (median age 23 years)). The Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) questionnaires were used to assess the depression and anxiety levels of patients, respectively. Data on patient demographics, clinical complications, and socioeconomic status were also collected. RESULTS: Patients with TM had a significantly longer median duration with a known thalassemia diagnosis than patients with TI (p < 0.001). A considerable proportion of patients had depression (35.0%), State (S)-anxiety (22.5%) or Trait (T)-anxiety (36.2%). Patients with TI had a higher median S-anxiety score compared with TM (p = 0.035), although the median T-anxiety and depression scores were similar. On linear regression analysis, the significant association between the thalassemia diagnosis (TM versus TI) and S-anxiety score (beta: 5.740; 95% CI: 0.201 to 11.278; p = 0.042) was no longer observed upon adjustment for the co-variate duration with a known thalassemia diagnosis (beta: 3.162; 95% CI: -2.949 to 9.274; p = 0.306). CONCLUSIONS: A considerable proportion of adult patients with TM and TI show evidence of depression and anxiety. Patients with TI are more liable to state anxiety than TM patients of a similar age, which is attributed to a shorter duration of living with a thalassemia diagnosis.

Antithrombotic prophylaxis in the middle East.

Several factors have been proposed to explain the persistence of a high incidence of venous thromboembolism worldwide with its associated morbidity and mortality. Underutilization of anticoagulants and failure of adherence to thromboprophylaxis guidelines are emerging global health concerns. We herein review this alarming observation with special emphasis on the Middle East region. We also discuss strategies that could help control this increasingly reported problem.

Thalassemia and venous thromboembolism.

Although the life expectancy of thalassemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Clinical experience and available clues on optimal management are also discussed.

Health-related quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: new insights.

BACKGROUND: In patients with ß thalassaemia intermedia (TI), the milder anaemia and transfusion independence imply better health-related quality of life (HR-QoL). However, the unbalanced pathophysiology of the disease allows for several serious clinical complications to manifest, which may have a negative impact on HR-QoL. METHODS: This was a cross-sectional study on adult patients with transfusion- and iron chelation-independent TI and ß thalassaemia major (TM) attending the Chronic Care Center, Hazmieh, Lebanon. A total of 80 patients agreed to participate in the study [32 TI (median age 24 yr) and 48 TM (median age 23 yr)]. The RAND SF-36 survey was used to assess HR-QoL. Data on patient demographics, clinical complications and socioeconomic status were collected. RESULTS: Patients with TI and TM were comparable with age and gender, but patients with TM had a significantly longer median duration with a known thalassaemia diagnosis. Patients with TI had a higher proportion of multiple complications. Socioeconomic parameters were comparable, except for patients with TI being more commonly married. The mean Total, Physical Health and Mental Health Scores were significantly lower in patients with TI compared to TM, indicating poorer HR-QoL. There was a statistically significant positive correlation between the duration with a known thalassaemia diagnosis and a higher Mental Health Score (r(s) = 0.73, P = 0.020). The mean Physical Health Score was significantly lower in patients with multiple clinical complications compared to patients with single or no complications (P = 0.012). Associations remained independently significant at multivariate analysis. CONCLUSION: Patients with transfusion-independent TI have lower HR-QoL compared to TM patients. At a comparable age, the shorter duration since diagnosis and the multiplicity of complications may explain these findings.