Pharmakokinetik von Mycophenolatmofetil nach primärer orthotoper Herztransplantation – Entwicklung von Kurzalgorithmen zur therapeutischen Arzneimittelüberwachung–

Pharmacokinetics of mycophenolate mofetil (MMF) show large interindividual variability. Concentration-controlled dosing of MMF based on routine therapeutic drug monitoring, which requires area under the concentration-time curve (mycophenolic acid [MPA]-AUC0-12h) determinations, is uncommon. Dose adjustments are based on predose concentrations (C0h) or side effects. The aim of this study was to compare C0h with postdose concentrations (C0.5h-C12h) and to develop practical methods for estimation of MPA-AUCs on the basis of a limited sampling strategy (LSS) in heart transplant recipients under MMF and tacrolimus maintenance immunosuppression. Full MPA-AUC0-12h profiles were generated by high-performance liquid chromatography in 28 patients. Statistical analysis for MPA-AUC0-12h was performed by a case resampling bootstrap method. Bland and Altmann analysis was performed to test agreement between "predicted AUC" and "measured AUC." C1h provided the highest coefficient of determination (r2 = 0.57) among the concentrations determined during the 12-hour interval, which were correlated with AUC. All other MPA levels were better surrogates of the MPA-AUC0-12h when compared with C0h (r2 = 0.14). The best estimation of MPA-AUC0-12h was achieved with four sampling points with the algorithm AUC = 1.25*C1h + 5.29*C4h + 2.90*C8h + 3.61*C10h (r2 = 0.95). Since LSS with four time points appeared unpractical, the authors prefer models with three or two points. To optimize practicability, LSS with sample points within the first 2 hours were evaluated resulting in the algorithms: AUC = 1.09*C0.5h + 1.19*C1h + 3.60*C2h (r2 = 0.84) and AUC = 1.65*C0.5h + 4.74*C2h (r2 = 0.75) for three and two sample points, respectively. The results provide strong evidence for the use of either LSS or the use of time points other than C0h for therapeutic drug monitoring of MMF. Using the algorithms for the estimation of MPA-AUC0-12h based on LSS within the first 2 hours after MMF dosing may help to optimize treatment with MMF by individualization of dosing

A meta-analysis evaluating risk factors for compound free flaps for upper extremity defect reconstruction comparing complications and functional outcomes of compound free flaps with and without bone components

Background: Compound flaps offer the advantage of one stage defect reconstruction respecting all relevant tissues and early functional recovery by optimal vascularity of all components. Due to its specific vascular anatomy and the three-dimensional donor site, compound flaps with bone components may result in higher complication rates compared to soft tissue compound flaps. The meta-analysis summarizes the available evidence and evaluates whether bone components are a risk factor for periprocedural complications in upper extremity multidimensional defect reconstruction. Method: PubMed and Embase were searched for all publications addressing compound free flaps for upper extremity defect reconstruction with bone or soft tissue components published between January 1988 and May 2018. The methodological quality was assessed with the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies. Flap loss, thrombosis rate, early infection, hematoma, seroma, as well as donor site complications were extracted and analyzed. Results: Twelve out of 1157 potentially eligible studies (evidence-III) comprising 159 patients were finally included with publication bias for all summarized complication rates. Complication rates for flaps with/ without bone components were: total flap loss 5%, 95% CI = 3%–10% (6%/5%); partial flap loss 8%, 95% CI = 5%–15%, (9%/8%); arterial/venous thrombosis 7%, 95% CI = 4%–12%, (8%/5%)/14%, 95% CI = 9%–21% (16%/6%, P < .05) with higher risk for flaps with bone components; infection 6%, 95% CI = 3%–12% (6%/6%); hematoma 6%, 95% CI = 3%–11% (6%/5%); seroma 5%, 95% CI = 3%–10% (5%/5%); dehiscence 10%, 95% CI = 6%–17% (11%/9%). Conclusion: Compound flaps for upper extremity defect reconstruction including bone components have a higher venous thrombosis rate compared to compound soft-tissue flaps

The Use of Closed Incision Negative Pressure Therapy on the Medial Thigh Donor Site in Transverse Musculocutaneous Gracilis Flap Breast Reconstruction

The objective of this study was to examine the impact of closed incision negative pressure therapy (CINPT) on donor site complications and patient perceptions in transverse musculocutaneous gracilis (TMG) flap breast reconstruction. Our institution conducted a retrospective cohort study, including all patients with TMG flap breast reconstruction from 1 January 2010 to 31 December 2021. Patients were grouped according to conventional wound management or CINPT. Outcomes were surgical site complications, fluid drainage, time to drain removal, and in-hospital stay length. A patient survey was created. A total of 56 patients with 83 TMG flaps were included (control group: 35 patients with 53 TMG flaps; CINPT group: 21 patients with 30 TMG flaps). Patient characteristics were similar in both groups. The flap width was significantly larger in the CINPT group (8.0 cm vs. 7.0 cm, p = 0.013). Surgical site complications were reduced in the CINPT group without statistical difference (30.0% vs. 50.9%, p = 0.064). Fluid drainage and time to drain removal were similar in both groups. The average in-hospital stay was significantly shortened in the CINPT group (10.0 days vs. 13.0 days, p = 0.030). The survey excluded pain, skin irritations, and discomfort during sleep and movement in the CINPT group and showed that the patients felt well protected. This study fails to provide compelling evidence for CINPT to enhance incision healing on the donor site in TMG flap breast reconstruction. There was a trend toward reduced surgical site complications on the donor thigh and the in-hospital stay was shortened. Prophylactic CINPT increases patient comfort and provides a feeling of additional wound protection

The Free Myocutaneous Tensor Fasciae Latae Flap&mdash;A Workhorse Flap for Sternal Defect Reconstruction: A Single-Center Experience

Introduction: Deep sternal wound infections (DSWI) after cardiac surgery pose a significant challenge in reconstructive surgery. In this context, free flaps represent well-established options. The objective of this study was to investigate the clinical outcome after free myocutaneous tensor fasciae latae (TFL) flap reconstruction of sternal defects, with a special focus on surgical complications and donor-site morbidity. Methods: A retrospective chart review focused on patient demographics, operative details, and postoperative complications. Follow-up reexaminations included assessments of the range of motion and muscle strength at the donor-site. Patients completed the Quality of Life 36-item Short Form Health Survey (SF-36) as well as the Lower Extremity Functional Scale (LEFS) questionnaire and evaluated aesthetic and functional outcomes on a 6-point Likert scale. The Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scales (POSAS) were used to rate scar appearance. Results: A total of 46 patients (mean age: 67 &plusmn; 11 years) underwent sternal defect reconstruction with free TFL flaps between January 2010 and March 2021. The mean defect size was 194 &plusmn; 43 cm2. The mean operation time was 387 &plusmn; 120 min with a flap ischemia time of 63 &plusmn; 16 min. Acute microvascular complications due to flap pedicle thromboses occurred in three patients (7%). All flaps could be salvaged without complete flap loss. Partial flap loss of the distal TFL portion was observed in three patients (7%). All three patients required additional reconstruction with pedicled or local flaps. Upon follow-up, the range of motion (hip joint extension/flexion (p = 0.73), abduction/adduction (p = 0.29), and internal/external rotation (p = 0.07)) and muscle strength at the donor-sites did not differ from the contralateral sides (p = 0.25). Patient assessments of aesthetic and functional outcomes, as well as the median SF-36 (physical component summary (44, range of 33 to 57)) and LEFS (54, range if 35 to 65), showed good results with respect to patient comorbidities. The median VSS (3, range of 2 to 7) and POSAS (24, range of 18 to 34) showed satisfactory scar quality and scar appearance. Conclusion: The free TFL flap is a reliable, effective, and, therefore, valuable option for the reconstruction of extensive sternal defects in critically ill patients suffering from DSWIs. In addition, the TFL flap shows satisfactory functional and aesthetic results at the donor-site