Digital Volumetric Measurements Based on 3D Scans of the Lower Limb: A Valid and Reproducible Method for Evaluation in Lymphedema Therapy.

BACKGROUND: Exact quantification of volumetric changes of the extremities is difficult and often error-prone. The aim of this study was to establish a standardized method based on 3-dimensional (3D) scans. Furthermore, this study tests the method in terms of reproducibility and evaluates volume changes after surgical therapy in patients suffering from lymphedema on the lower extremity. METHODS: 3D scans of the lower limb were performed with a mobile 3D scanner; "repeatability" and "interobserver reliability" of digital volumetry were tested. Furthermore, the method was applied on 31 patients suffering from chronic lymphedema. RESULTS: Calculations of repeatability of the volume based on 20 3D scans of the same lower leg showed a mean volume of 2.488 ± 0.011 liters (range: 2.470-2.510). The mean volume of the different examiners did not differ significantly (F(2,18) = 1.579, P = 0.233). The paired t-test showed a significant mean volume decrease of 375 mL (95% confidence interval = 245/505 mL) between pretreatment and post-treatment (t (30) = 5.892, P < 0.001). CONCLUSIONS: 3D volumetry is a noninvasive, easy, and quick method to assess volume changes of the lower leg. Other than the low costs, it is reproducible and precise and therefore ideal for evolution of therapy in lymphedema.

Breast Lipofilling: Is the Bra Really Full? Clinical Bra Pressure Measurement and In Vitro Testing of Processed and Unprocessed Fat Cells.

BACKGROUND: Breast lipofilling, a popular cosmetic and reconstructive procedure, involves the transplantation of autologous fat to enhance breast volume and contour. Despite its widespread use, cell processing and the aftertreatment remain controversial. This study investigates the pressure applied by a compression bra and reports in vitro stress tests of processed and unprocessed fat cells. METHODS: Clinical bra pressure measurements were conducted on a cohort of 45 patients following lipofilling, reduction mammoplasties and DIEP flaps. Laboratory analysis included cell vitality testing using Resazurin assays of processed and unprocessed fat cells after exposure to mechanical or hyperbaric pressure. RESULTS: Our findings show a mean overall pressure value of the compression bra for all patients of 6.7 ± 5.7 mmHg (range 0-35). Cell processing is superior to sedimentation only regarding fat cell vitality. However, neither mechanical pressure within the specified range nor hyperbaric oxygen exposure significantly affected fat graft survival as measured by Resazurin assays. CONCLUSION: The in vitro measurements showed that it was impossible to harm fat cells with external pressure during lipofilling procedures, regardless of their processing. In the clinical context, the compression bra applied pressure values deceeding the perfusion pressure and may therefore not diminish oxygen supply nor harm the transplanted cells. Therefore, we recommend the use of a compression bra for all lipofilling procedures around the breast. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

The influence of negative pressure wound therapy on bacterial and fungal growth.

BACKGROUND: The use of negative pressure wound therapy (NPWT) in superinfected wounds is controversial. The mechanism of action is unclear, but recent studies have shown lower atmospheric oxygen levels within the dressing. Therefore, different oxygen-favoring bacteria and fungi might benefit or face impaired thriving conditions. The aim of this in vitro study is to investigate the influence of NPWT on bacterial and fungal growth. METHODS: Salmonella enterica subsp. enterica serovar Typhimurium, Pseudomonas aeruginosa and Candida albicans strains were cultured on concentrated agars and attached to a standard NPWT-device. After 48 hours, colonies were separately harvested from the agar and foam. Optical density (OD) was obtained in order to estimate bacterial loads. RESULTS: For all tested microorganisms, no overall significant differences were found compared to controls. Subanalysis showed lower OD levels from the agar beneath the foam in the NPWT-group. CONCLUSION: NPWT removed bacteria and fungi from the wound surface but accumulation is found within the foam. The use of NPWT showed no influence on bacterial or fungal growth selection. With superinfected wounds, the use of NPWT should thoroughly be evaluated as toxins and virulence factors may not fully be evacuated.

Technical Aspects of High-Resolution Color-Coded Duplex Sonography for the Design of Perforator Flaps.

BACKGROUND: Technical aspects are of utmost significance for an efficient execution in designing perforator flaps with high-resolution color-coded Duplex sonography (CCDS). The following study evaluates decisive factors for a successful microvessel examination conducted by the microsurgeon. METHODS: Technical knowledge presented in this study was based on a series of more than 200 perforator flaps planned with CCDS. Flap reconstructions were performed at the University Hospital Regensburg, Germany, from July 2013 to January 2021. Standard high-resolution ultrasound (US) devices with linear multifrequency transducers of 4 to 18 MHz were used. Modes and device settings were evaluated regarding applicability by microsurgeons. Key steps for safe perforator identification and further optional steps for additional assessment should be discriminated. RESULTS: Different US modes including brightness mode (B-mode), color flow (CF), power Doppler (PD), pulse wave (PW), and blood flow (B-Flow) were used. Transducers from 15 MHz and up were favorable to detect microvessels. Knobology of a standard US device regarding buttons, switches, and specific onscreen options with relevance for perforator mapping was subcategorized in four different groups. For qualitative and quantitative evaluation of microvessels, different US modes were tested with respect to their usefulness.Vital elements of the CCDS exam are disaggregated into three key steps for safe perforator identification and three optional steps for further perforator characterization. A standardized protocol for the CCDS exams was applied. Downregulation of pulse-repetition frequency/scale to adapt device sensitivity to slow-flow velocities represented the most important criterion to visualize microvessels.Qualitative microvessel evaluation was performed in B-mode, CCDS, PD mode, and B-Flow mode. Quantitative assessment was executed using PW-mode and CCDS measuring the microvessels' diameter (mm) and flow characteristics. Quantitative information may be obtained using PW-mode and the distance-measuring tool in CF-mode. CONCLUSION: Technical aspects with respect to proper device trimming and application decisively impact CCDS-guided perforator vessel identification and evaluation.

Glenohumeral joint lavage does not affect clinical outcomes in open reduction and internal fixation of displaced intracapsular proximal humeral fractures: a prospective, randomized, double-blinded trial.

BACKGROUND: This prospective, randomized, and double-blinded trial evaluates the effect of intraoperative glenohumeral joint lavage in open reduction and internal fixation of displaced intracapsular proximal humeral fractures. METHODS: Between January 2016 and April 2018, 86 patients (mean age: 65.2 ± 16.3 years) with a displaced intracapsular proximal humeral fracture were treated by open reduction and internal fixation using locking plates. Patients were randomized to either locked plating followed by intraoperatively performed glenohumeral joint lavage (group L, n = 36) or locked plating without the lavage (group NL, n = 36). Functional outcome assessment included range of shoulder motion, strength, and the Constant score, obtained 6 weeks, 3 months, 6 months, and 12 months postoperatively. A total of 62 shoulders could be reviewed for final investigation (86% follow-up). RESULTS: One year after open reduction and internal fixation, the mean Constant score was 70 ± 14 (group L, n = 31) compared with 73 ± 14 (group NL, n = 31, P = .272). The mean forward flexion and abduction in group L was 134 ± 33 and 128 ± 33 as compared with 139 ± 32 and 135 ± 32 in group NL, respectively (P = .538, P = .427). The mean external rotation was 40 ± 16 (group L) compared with 44 ± 16 (group NL) (P = .210). The overall complication rate was 9.6% and did not differ significantly between the groups (P = .321). In group L, there were 2 cases of avascular necrosis (6.5%) and 1 case of secondary displacement (3.2%). In group NL, 1 case of avascular necrosis (3.2%) and 1 case of secondary displacement were noted (3.2%, P = .742). CONCLUSION: The results of this study do not demonstrate a need for glenohumeral joint lavage in open reduction and internal fixation of displaced intracapsular proximal humeral fractures with regard to shoulder function at 1-year follow-up.

Adipose Tissue in Multiple Symmetric Lipomatosis Shows Features of Brown/Beige Fat.

INTRODUCTION: Multiple symmetric lipomatosis (MSL) (syn.: Launois-Bensaude Syndrome, benign symmetric lipomatosis) is a rare disease of fatty tissue. The pathophysiology of MSL still remains unclear, although several approaches have been described in order to understand it. Beside morphological characteristics and some molecular cell biological approaches, little is known about the histological and immunohistochemical characterization of adipose tissue from patients with MSL. METHODS: From the 45 patients with MSL in our database, 10 were included in the study. Fat tissue samples were collected from affected and unaffected areas. The forearm served as a control area as this area is not affected in MSL. The specimens were analyzed after selected stainings were taken (hematoxylin-eosin = HE, Elastica van Gieson, Ladewig, CD200, CIDEA, myf5, p107, Prdm16, Sca-1, syndecan, UCP1, MAC387, Glut4). RESULTS: In patients suffering from MSL, no macroscopic or microscopic morphological difference could be found between affected and unaffected adipose tissue in HE stainings. The majority of samples showed positivity for UCP1 (9/10 clinically affected tissues, 7/10 clinically unaffected tissues) and CD200. CONCLUSION: Marker profiles support the hypothesis that affected adipose tissue derives from brown or beige adipose tissue rather than from white fat. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Pressure distribution and flow characteristics during negative pressure wound therapy.

AIM OF THE STUDY: Negative pressure wound therapy is thought to improve wound healing by altering capillary perfusion. However, despite many theories, the underlying mechanism of action remains controversial. Recent evidence suggests an increased tissue pressure and a temporary decreased microvascular blood flow as the main reasons for the good clinical results [1]. In an attempt to further explain the mechanism of action, we investigated the pressure distribution on the foam interface, and the influence on perfusion in a pre-experimental design. MATERIALS AND METHODS: Pressure distribution was measured using a sensor based on a capacitive dielectric elastomer with flexible electrodes. In vitro flow measurements were done with vessel imitations in a block of 300 bloom ballistic gel to simulate soft tissue. RESULTS: A peak pressure of up to 187 mmHg (255 g/cm2) within the foam interface, as well as decreased perfusion, were found using a standard negative pressure wound therapy setup. In conclusion, negative pressure wound therapy applies positive pressure to adjacent tissue and decreases local flow. The amount of suction applied is proportional to the pressure on the foam interface and reduction in flow. CONCLUSION: In line with previous studies investigating the underlying mechanism of action, these findings may contribute to possible alterations in the use of negative pressure wound therapy, e.g. lowering suction pressure in patients with diminished peripheral blood flow.

Screw-tip augmentation versus standard locked plating of displaced proximal humeral fractures: a retrospective comparative cohort study.

BACKGROUND: This study compared the clinical and radiologic outcomes of screw tip-augmented locking plate osteosynthesis vs. standard locked plating in elderly patients with displaced proximal humeral fractures. METHODS: Of the 94 patients older than 65 years with displaced proximal humeral fractures, 55 underwent fixation with a locking plate only whereas 39 underwent fixation using a locking plate with fluoroscopy-controlled polymethyl methacrylate augmentation of screw tips. RESULTS: At 2 years' follow-up, the locking plate-only group showed a mean Constant score (CS) of 62.6 ± 17.4 points, mean CS as a percentage of the uninjured side of 78.2% ± 18.9%, and mean age- and sex-adjusted CS of 72.4 ± 20.5 points. Among the 39 patients who underwent locked plating with polymethyl methacrylate augmentation of screw tips, the mean CS was 63.7 ± 18.5 points (P = .28), the mean CS as a percentage of the uninjured side was 79.5% ± 20.4% (P = .36), and the mean age- and sex-adjusted CS was 76.8 ± 26.2 points (P = .11). The mean Disabilities of the Arm, Shoulder and Hand score was 26.4 ± 21.3 in the locking plate-only group compared with 23.6 ± 19.2 in the group with screw tip-augmented locking plate osteosynthesis (P = .41). The overall complication rate was 16.3% in the locking plate-only group compared with 12.8% in the group with screw tip-augmented osteosynthesis (P = .86); loss of fixation occurred in 10.9% vs. 5.1% (P = .74). The follow-up rate was 81%. CONCLUSIONS: Loss of fixation was less frequent when augmentation of screw tips was performed; however, at the 2-year follow-up, the clinical and radiologic outcomes were not significantly different compared with standard locked plating without augmentation.

Augmentation of plate osteosynthesis for proximal humeral fractures: a systematic review of current biomechanical and clinical studies.

INTRODUCTION: Secondary dislocation due to loss of fixation is the most common complication after plate fixation of proximal humeral fractures. A wide range of different techniques for augmentation has been described to improve the primary and secondary stability. Nevertheless, comparative analyses on the specific advantages and limitations are missing. Therefore, the aim of the present article was to systematically review and evaluate the current biomechanical and clinical studies. MATERIALS AND METHODS: The databases of PubMed and EMBASE were comprehensively searched for studies on augmentation techniques for proximal humeral fractures using defined search terms. Subsequently, all articles identified were screened for eligibility and subdivided in either clinical or biomechanical studies. Furthermore, the level of evidence and study quality were assessed according the Oxford Centre for Evidence-Based Medicine and the Coleman Methodology Score, respectively. RESULTS: Out of 2788, 15 biomechanical and 30 clinical studies were included. The most common techniques were structural allogenic or autologous bone grafting to enhance the medial support, metaphyseal void filling utilizing synthetic bone substitutes or bone grafts, and screw-tip augmentation with bone cement. Biomechanical data were available for structural bone grafting to enhance the medial support, void filling with synthetic bone substitutes, as well as for screw-tip augmentation. Clinical evidence ranged from level II-IV and study quality was 26-70/100 points. Only one clinical study was found investigating screw-tip augmentation. All studies included revealed that any kind of augmentation positively enhances mechanical stability, reduces the rate of secondary dislocation, and improves patients' clinical outcome. None of the studies showed relevant augmentation-associated complication rates. CONCLUSIONS: Augmentation of plate fixation for proximal humeral fractures seems to be a reliable and safe procedure. All common techniques mechanically increase the constructs' stability. Clinically evaluated procedures show reduced complication rates and improved patient outcomes. Augmentation techniques seem to have the highest significance in situations of reduced bone mineral density and in high-risk fractures, such as 4-part fractures. However, more high-quality and comparative clinical trials are needed to give evidence-based treatment recommendations.

Oxygen levels during negative pressure wound therapy.

AIM OF THE STUDY: Negative pressure wound therapy (NPWT) has become an established treatment modality when dealing with chronic and infected wounds. The underlying mechanism of action is still under discussion and remains controversial. Evidence exists showing rather hypoxic conditions as the main reason for the positive results and bacterial clearance. In an attempt to further explain the mechanism of action, we investigated oxygen levels within the foam interface of a NPWT device. MATERIALS AND METHODS: We used an optical sensor based on the principle of dynamic fluorescence quenching and tested five different commonly available NPWT systems used during our daily clinical routine. All measurements were done in an in vitro experimental design for at least 24 h and multiple vacuum intensities were investigated. RESULTS: Oxygen levels decreased as much as 22.8% and the amount of vacuum applied inversely correlated with the oxygen reduction. A stepwise increase in vacuum of 25 mmHg showed a linear mean drop of 2.75% per setting. All devices were able to maintain a constant level of negative pressure, and no significant difference between the various dressings was found (p > 0.05). CONCLUSION: Therefore, oxygen levels are decreased within the foam of NPWT dressings, likely leading to oxygen deprivation effects in the underlying wound tissue.

Negative Pressure Wound Therapy-A Vacuum-Mediated Positive Pressure Wound Therapy and a Closer Look at the Role of the Laser Doppler.

Background: Negative pressure wound therapy (NPWT) is an intensely investigated topic, but its mechanism of action accounts for one of the least understood ones in the area of wound healing. Apart from a misleading nomenclature, by far the most used diagnostic tool to investigate NPWT, the laser Doppler, also has its weaknesses regarding the detection of changes in blood flow and velocity. The aim of the present study is to explain laser Doppler readings within the context of NPWT influence. Methods: The cutaneous microcirculation beneath an NPWT system of 10 healthy volunteers was assessed using two different laser Dopplers (O2C/Rad-97®). This was combined with an in vitro experiment simulating the compressing and displacing forces of NPWT on the arterial and venous system. Results: Using the O2C, a baseline value of 194 and 70 arbitrary units was measured for the flow and relative hemoglobin, respectively. There was an increase in flow to 230 arbitrary units (p = 0.09) when the NPWT device was switched on. No change was seen in the relative hemoglobin (p = 0.77). With the Rad-97®, a baseline of 92.91% and 0.17% was measured for the saturation and perfusion index, respectively. No significant change in saturation was noted during the NPWT treatment phase, but the perfusion index increased to 0.32% (p = 0.04). Applying NPWT compared to the arteriovenous-vessel model resulted in a 28 mm and 10 mm increase in the venous and arterial water column, respectively. Conclusions: We suspect the vacuum-mediated positive pressure of the NPWT results in a differential displacement of the venous and arterial blood column, with stronger displacement of the venous side. This ratio may explain the increased perfusion index of the laser Doppler. Our in vitro setup supports this finding as compressive forces on the bottom of two water columns within a manometer with different resistances results in unequal displacement.

Patient characteristics may affect the lymphatic staining ability of Indocyanine green and Patent blue during lymphaticovenous anastomosis.

BACKGROUND: The use of dyes like Indocyanine green (ICG) and Patent blue facilitates the identification of lymphatic vessels during lymphaticovenous anastomosis (LVA) surgery. However, some patients experience "staining failure". In these cases, no stained lymphatic vessels can be detected, making supermicrosurgical LVA even more complex. OBJECTIVE: This study aims to investigate patient-related factors that may interfere with lymphatic vessel staining during LVA. METHODS: A retrospective study was conducted on 30 patient charts, focusing on patient characteristics and the staining quality of ICG and Patent blue dye. Statistical analyses were performed to identify correlations between variables. RESULTS: Significant correlations were found between higher age and secondary lymphedema, longer duration of lymphedema in male patients until surgery and reoccurring cellulitis and Patent blue staining. Notably, recurrent infections to the lymphatic system resulted in inferior staining ability during LVA surgery. CONCLUSIONS: Due to staining failure the detection of functional lymphatic vessels remains challenging in LVA surgery. A more extensive preoperative workup is recommended for patients with recurrent cellulitis to optimize surgical feasibility and procedure quality in LVA treatment for lymphedema.

Therapist versus Machine-Immediate Effects of Manual versus Mechanical Lymphatic Drainage in Patients with Secondary Lymphedema.

Background: Complex decongestive therapy (CDT) is the standard and basic therapy for lymphedema. The central component of CDT is manual lymphatic drainage (MLD). In addition to CDT, other measures such as intermittent pneumatic compression therapy (IPCT) (active compression machine therapy) are available. In this prospective research study, the objective and subjective effects of MLD and IPCT on lymphedema of the lower extremity were investigated and both therapies were directly compared. Furthermore, the patients' body mass index (BMI) and stage of lymphedema were tested for their effect on the respective therapy. Methods: Patients participating in the study received both therapies (MLD and IPCT) on the same lymphedema-affected limb at an interval of two days. The objective volumetric therapy effect was measured by the digital volume measurement of the affected limb. The subjective effects of the therapies were measured using two specially designed questionnaires. Results: A total of 40 patients were included in the study. There was no significant difference in the volume differences between the interventions, BMI categories, lymphedema, or treatment order regarding the immediate and two-day effect. Conclusions: No significant difference was found in the subjective or objective therapy efficacy of the two methods. Intermittent pneumatic compression therapy is considered a comparable therapeutic procedure when properly indicated.

Evidence-Based Approaches to Anticoagulation in Reconstructive Microsurgery-A Systematic Literature Review.

This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The objective was to balance the prevention of thrombotic complications commonly leading to flap failure, with the risk of increased bleeding complications associated with anticoagulant use. A meticulous PubMed literature search following Evidence-Based-Practice principles yielded 79 relevant articles, including both clinical and animal studies. The full-texts were carefully reviewed and evaluated by the modified Coleman methodology score. Clinical studies revealed diverse perioperative regimens, primarily based on aspirin, heparin, and dextran. Meta-analyses demonstrated similar flap loss rates with heparin or aspirin. High doses of dalteparin or heparin, however, correlated with higher flap loss rates than low dose administration. Use of dextran is not recommended due to severe systemic complications. In animal studies, systemic heparin administration showed predominantly favorable results, while topical application and intraluminal irrigation consistently exhibited significant benefits in flap survival. The insights from this conducted systematic review serve as a foundational pillar towards the establishment of evidence-based guidelines for anticoagulation in microsurgery. An average Coleman score of 55 (maximum 103), indicating low overall study quality, however, emphasizes the need for large multi-institutional, randomized-clinical trials as the next vital step.

Negative Pressure Wound Therapy with Instillation: Analysis of the Rinsing Fluid as a Monitoring Tool and Approach to the Inflammatory Process: A Pilot Study.

BACKGROUND: Negative pressure wound therapy with instillation (NPWTi) is an established wound conditioning tool. Previous investigations discovered that the rinsing fluid is a suitable monitoring tool containing various cells and cytokines. METHODS: The aim of this pilot study was to analyze rinsing fluid samples from patients treated with NPWTi and link them to the clinical course, including microbiological contamination. In 31 consecutive patients with acute and chronic wounds, laboratory analysis was performed to evaluate IL-6, IL-8, bFGF, Tnf-a, and VEGF. RESULTS: IL-6 showed a significant increase to 1540 pg/mL on day two and 860 pg/mL on day four (p = 0.01 and p = 0.04, resp.). IL-8 steadily increased from a median of 2370 pg/mL to a maximum of 19,400 pg/mL on day three (p = 0.01). The median bFGF showed a steady decline from 22 pg/mL to 10 pg/m (p = 0.35) on day three. The median Tnf-a increased from 11 pg/mL to 44 pg/mL (p = 001). The median VEGF values fluctuated but showed an overall increase from 35 pg/mL to 250 pg/mL (p = 0.07). Regarding IL-8, diabetic and non-diabetic patients both showed a gradual increase with non-significant higher median values for the diabetics. The subgroup analysis of IL-6 showed increasing and higher values in cases with bacterial superinfections (p = 0.07). CONCLUSION: We were able to use an established wound conditioning tool to gather important information about the inflammatory response during NPWTi treatment. Cytokine and cell courses were mostly consistent with the literature, especially in diabetic patients, and should be further investigated.

Statin Use Ameliorates Survival in Oral Squamous Cell Carcinoma-Data from a Population-Based Cohort Study Applying Propensity Score Matching.

The anti-cancer properties of statins have attracted much attention recently, but little is known about the prognostic role of statins in oral squamous cell carcinoma (OSCC). In a retrospective approach, we analyzed a population-based cohort of 602 OSCC patients with primary curative tumor resection to negative margins and concomitant neck dissection between 2005-2017. Long-term medication with statins was correlated with overall survival (OAS) as well as recurrence-free survival (RFS) using uni- and multivariable Cox regression. Additionally, propensity score matching was applied to adjust for confounders. Statin use was present in 96 patients (15.9%) at a median age of 65.7 years. Statin treatment correlated with ameliorated survival in multivariable Cox regression in the complete cohort (OAS: HR 0.664; 95% CI 0.467-0.945, p = 0.023; RFS: HR 0.662; 95% CI 0.476-0.920, p = 0.014) as well as matched-pair cohort of OSCC patients (OAS: HR 0.691; 95% CI 0.479-0.997, p = 0.048; RFS: HR 0.694; 95% CI 0.493-0.976, p = 0.036) when compared to patients not taking statins at time of diagnosis. These findings were even more pronounced by sub-group analysis in the matched-pair cohort (age < 70 years). These data indicate that statin use might ameliorate the oncological outcome in primarily resected OSCC patients, but prospective clinical trials are highly recommended.

A20 as a Potential New Tool in Predicting Recurrence and Patient's Survival in Oral Squamous Cell Carcinoma.

A20, known as a potent inhibitor of NF-κB signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003-2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan-Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388-0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411-0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC.

Quality of life evaluation and lack of correlation with volumetric results after lymphovenous anastomoses in lymphedema therapy of the lower extremity.

OBJECTIVE: Chronic primary or secondary lymphedema has huge effects on patients' quality of life (QOL) because of the associated swelling and pain, decreased range of motion, and depression and anxiety and generally requires numerous adaptations. Many studies have shown a positive objective effect of lymphovenous anastomoses (LVAs) on chronic lymphedema. In the present study, we assessed the effect of LVAs on QOL in patients with primary or secondary lymphedema of the lower extremity at 6 months after surgery and examined the correlation between changes in the QOL and volumetric measurements. METHODS: Only patients with either primary or secondary lymphedema of the lower extremity who had undergone LVAs were included in the present study. To assess QOL, a specially designed questionnaire based on the Lymphedema Quality of Life Inventory was used to evaluate the subjective therapeutic results from the patients' perspective. Objective therapy success was assessed using three-dimensional volumetric measurements of the lower leg. The measuring points, for both the subjective and the objective measurements, were the day before and 6 months after therapy. RESULTS: The mean change in volume at 6 months after LVA was -6.5% ± 5.6% (P < .001). Significantly better QOL in terms of physical (37.6% ± 25.2%) and psychosocial (27.0% ± 43.0%) domains and practical restrictions (22.3% ± 24.8%) was found (P < .001 for all). No correlation was found between QOL improvement and volume decrease (P > .05). CONCLUSIONS: For patients with lymphedema of the lower extremity, LVAs can lead to a significant volumetric decrease and QOL improvement at 6 months after treatment with no demonstrable relationship between QOL improvement and volume reduction.

Analysis of Rinsing Fluid during Negative Pressure Wound Therapy with Instillation: A Potential Monitoring Tool in Acute and Chronic Wound Treatment. A Pilot Study.

BACKGROUND: During negative pressure wound therapy (NPWT), open wounds are draped with a nontransparent sponge, making daily wound evaluation impossible. Sometimes, late or undetected bacterial infections and postoperative bleeding result in repetitive surgery, thus prolonging inpatient time. With the introduction of additional fluid instillation (NPWTi), the wound surface is rinsed, and bacteria, proteins and biomarkers are flushed into a collecting canister, which is later discarded. METHODS: The aim of this pilot study was to analyze rinsing fluid samples (0.9% sodium chloride) from the NPWTi device in patients with acute and chronic wounds. In 31 consecutive patients a standardized laboratory analysis was performed to evaluate cellular composition and potassium, phosphate, lactate dehydrooxygenase, pH and total protein levels. RESULTS: While there was an increase in the total cellular amount and the number of polymorphonuclear cells, the number of red blood cells (RBC) decreased after surgery. Potassium and pH showed no significant changes in the first three postoperative days, whereas total protein showed an undulant and partially significant course. CONCLUSION: We were able to quantify cellular metabolites by analyzing the rinsing fluid of NPWTi. We propose the analysis of this material as a novel and potentially promising tool to monitor wound status without removal of the dressing. The establishment of reference values might help to improve the NPWTi therapy.

Lipedema-Pathogenesis, Diagnosis, and Treatment Options.

BACKGROUND: Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. METHODS: This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library databases. RESULTS: The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diagnosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory healthinsurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. CONCLUSION: The diagnosis of lipedema remains a challenge because of the hetero - geneous presentation of the condition and the current lack of objective measuring instruments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.