Laminin ß4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid.

BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies. OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance. METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed. RESULTS: Laminin ß4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes. LIMITATIONS: A higher number of sera needs to be tested to verify that laminin ß4 is the diagnostically relevant antigen of anti-p200 pemphigoid. CONCLUSION: The identification of laminin ß4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.

Acute Microcirculatory Effects of Remote Ischemic Conditioning in Superficial Partial Thickness Burn Wounds.

Microcirculation is a critical factor in burn wound healing. Remote ischemic conditioning (RIC) has been shown to improve microcirculation in healthy skin and demonstrated ischemic protective effects on heart, kidney, and liver cells. Therefore, we examined microcirculatory effects of RIC in partial thickness burn wounds. The hypothesis of this study is that RIC improves cutaneous microcirculation in partial thickness burn wounds. Twenty patients with partial thickness burn wounds within 48 hours after trauma were included in this study. RIC was performed with an upper arm blood pressure cuff on a healthy upper arm using three ischemia cycles (5 min inflation to 200 mm Hg) followed by 10-minute reperfusion phases. The third and final reperfusion phase lasted 20 minutes. Microcirculation of the remote (lower/upper extremities or torso) burn wound was continuously quantified, using a combined Laser Doppler and white light spectrometry. The capillary blood flow in the burn wounds increased by a maximum of 9.6% after RIC (percentage change from baseline; P < .01). Relative hemoglobin was increased by a maximum of 2.8% (vs. baseline; P < .01), while cutaneous tissue oxygen saturation remained constant (P > .05). RIC improves microcirculation in partial thickness burn wounds by improving blood flow and elevating relative hemoglobin.

A single application of cold atmospheric plasma (CAP) improves blood flow parameters in chronic wounds.

OBJECTIVE: To find out whether application of cold atmospheric plasma (CAP) affects microcirculation in chronic wounds. METHODS: We treated 20 patients with chronic wounds on the lower extremity with CAP. Blood flow parameters of wounds were assessed with combined Laser-Doppler-Flowmetry and spectrophotometry in tissue depth of 2 and 6-8 mm. Parameters were assessed under standardized conditions before and over the course of 30 min after application of CAP. RESULTS: Deep capillary blood flow increased significantly by up to 24.33% (percentage change) after treatment with CAP and remained significantly elevated until the end of measuring period at 30 min. Superficial oxygen tissue saturation was significantly elevated by 14.05% for the first 5 min after treatment. Postcapillary venous filling pressure was significantly elevated by 10.23% 19 min after CAP and stayed significantly elevated starting from minute 24 until the end of measuring. CONCLUSION: Cold atmospheric plasma increases microcirculation parameters in chronic wounds significantly. As CAP is known for its benefits in wound healing, the effects observed may explain the improved healing of chronic wounds after its use. Whether CAP-application can increase blood flow in chronic wounds for longer periods of time or boosts blood flow when applied more than once should be subject to further research.

Smart Scar Care-Industry 4.0 in Individualized Compression Garments: A Randomized Controlled Crossover Feasibility Study.

BACKGROUND: We tested the workflow and comparability of compression garments (CG) automatically knitted from 3D-body-scan data (3DBSD) versus manually measured data for scar treatment. Industry 4.0 has found its way into surgery, enhancing the trend toward personalized medicine, which plays an increasingly important role in CG scar therapy. Therefore, we conducted a study to evaluate the workflow from 3DBSD to fast and precisely knitted CG and compared it with standard of care. METHODS: A randomized controlled crossover feasibility study was conducted as part of the individual medical technology research project "Smart Scar Care." Objective and patient-reported outcome measures were documented for 10 patients with hypertrophic burn scars at baseline and after wearing CG automatically knitted from 3DBSD versus CG from manually measured data for one month. RESULTS: The "scan-to-knit" workflow and the study design were feasible in 10 of 10 patients. No adverse effects were found. 3DBSD showed a bias of half a centimeter compared with manually measured data and wider limits of agreement. With respect to fit, comfort, suitability, Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, stiffness and microcirculation, this was a promising pilot study. Stiffness and blood flow were increased in scars compared with normal skin. The highest rank correlations were found between pain and itch, stiffness and Patient and Observer Scar Assessment Scale, Vancouver Scar Scale, and pain. CONCLUSIONS: These results indicate that automatically knitted CG using 3DBSD could become an alternative to the standard of care, especially with regard to economical and faster patient care. The produced scan data opens the door for objective scar science.

The repetitive application of cold atmospheric plasma (CAP) improves microcirculation parameters in chronic wounds.

BACKGROUND: Chronic wounds, such as venous leg ulcers, diabetic foot ulcers, and pressure ulcers, impose a significant burden on patients and health care systems worldwide. Cold atmospheric plasma (CAP) accelerates wound healing and decreases bacterial load in chronic wounds in both in vitro and in vivo experiments. For the first time, we examined the effects of a repetitive application of CAP on the microcirculation in chronic wounds. HYPOTHESIS: The repetitive application of cold atmospheric plasma application further improves microcirculation in chronic wounds. METHODS: Twenty patients with chronic wounds were treated repetitively with CAP. The repetitive application consisted of three CAP sessions, each lasting 90 s and separated by a 10-minute microcirculation measuring period. Microcirculation parameters were assessed with combined Laser-Doppler-Flowmetry and spectrophotometry in a tissue depth of 2 mm. RESULTS: Tissue oxygen saturation was significantly increased after the first CAP application. The effect amplitude and duration were further increased after the second and third CAP application with a maximum increase by 16,7% (percent change; p = 0,004 vs. baseline) after the third application. There was no significant increase in capillary blood flow until the third CAP application. After the third CAP application, an increase by 22,6% (p = 0,014) was observed. Postcapillary filling pressure was not significantly increased over the measuring period. The repetitive application of CAP further enhances the microcirculation in chronic wounds compared to a single application. CONCLUSION: The repetitive application of CAP boosts and prolongs tissue oxygen saturation and capillary blood flow in chronic wounds compared to a single application. This insight could provide an impetus for new treatment protocols.

A Rare Manifestation of Primary Bone Lymphoma: Solitary Diffuse Large B-Cell Lymphoma of the Little Finger.

Solitary primary non-Hodgkin bone lymphoma of the hand is a rare entity with only 3 cases reported in the literature. We report the case of a 77-year-old patient with isolated large B-cell bone lymphoma of the proximal phalanx of the little finger without rheumatoid arthritis or methotrexate treatment. The patient was treated with digital amputation and at 6 months' follow-up showed no relapse or dissemination of the disease.

Repetitive shock wave therapy improves muscular microcirculation.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is mainly applied in tendon as well as bone problems based on stem-cell activation and healing acceleration. The effect of ESWT on muscle tissue is much less understood to date. However, from a clinical perspective, muscle injuries are of distinct interest especially in elite athletes such as soccer players. MATERIAL AND METHODS: A total of 26 rats were randomized into two groups. Group A received a single application of high-energetic focused ESWT (0.3 mJ/mm(2), 4 Hz, 1000 impulses, 10 J), whereas group B underwent the same procedure every 10 min for three sessions (3 × 0.3 mJ/mm(2), 4 Hz, 3 × 1000 impulses, totaling 30 J). Blood flow at a depth of 8 mm was measured continuously and noninvasively by a combined Laser-Doppler-Imaging and photospectrometric technique (Oxygen-to-see, O2C, LEA Medizintechnik, Germany). RESULTS: One minute after the application of high-energy ESWT blood flow in group A increased by 16.5% (P = 0.007). Thereafter, it decreased from minute 2 after application and remained significantly unchanged to baseline value until the end of the measuring period at 50 min (P = 0.550). Group B showed a similar significant increase in blood flow of 16.4% (P = 0.049) and a decrease afterward, too. After the second focused ESWT blood flow was boosted to 26.6% (P = 0.004), remaining significantly elevated until the third application was initiated. Muscular blood flow was increased to 29.8% after the third focused ESWT (P < 0.001), remaining significantly increased for another 10 min. CONCLUSIONS: Focused ESWT enhances blood flow in the muscle of rats. Moreover, repetitive ESWT extended this beneficial effect.

LPS-Stimulated Human Skin-Derived Stem Cells Enhance Neo-Vascularization during Dermal Regeneration.

High numbers of adult stem cells are still required to improve the formation of new vessels in scaffolds to accelerate dermal regeneration. Recent data indicate a benefit for vascularization capacity by stimulating stem cells with lipopolysaccharide (LPS). In this study, stem cells derived from human skin (SDSC) were activated with LPS and seeded in a commercially available dermal substitute to examine vascularization in vivo. Besides, in vitro assays were performed to evaluate angiogenic factor release and tube formation ability. Results showed that LPS-activated SDSC significantly enhanced vascularization of the scaffolds, compared to unstimulated stem cells in vivo. Further, in vitro assays confirmed higher secretion rates of proangiogenic as well as proinflammatoric factors in the presence of LPS-activated SDSC. Our results suggest that combining activated stem cells and a dermal substitute is a promising option to enhance vascularization in scaffold-mediated dermal regeneration.

Electrocautery Devices With Feedback Mode and Teflon-Coated Blades Create Less Surgical Smoke for a Quality Improvement in the Operating Theater.

Monopolar electrocautery is a fast and elegant cutting option. However, as it creates surgical smoke containing polycyclic aromatic hydrocarbons (PAHs), it may be hazardous to the health of the surgical team. Although new technologies, such as feedback mode (FM) and Teflon-coated blades (TBs), reduce tissue damage, their impact on surgical smoke creation has not yet been elucidated. Therefore, we analyzed the plume at its source.The aim of this study was to evaluate if electrocautery FM and TBs create less surgical smoke.Porcine tissue containing skin was cut in a standardized manner using sharp-edged Teflon-coated blades (SETBs), normal-shaped TBs, or stainless steel blades (SSBs). Experiments were performed using FM and pure-cut mode. Surgical smoke was sucked through filters or adsorption tubes. Subsequently, filters were scanned and analyzed using a spectrophotometer. A high-performance liquid chromatography (HPLC-UV) was performed to detect benzo[a]pyrene (BaP) and phenanthrene as 2 of the most critical PAHs. Temperature changes at the cutting site were measured by an infrared thermometer.In FM, more surgical smoke was created using SSB compared with TBs (P < 0.001). Furthermore, differences between FM and pure-cut mode were found for SSB and TB (P < 0.001), but not for SETB (P = 0.911). Photometric analysis revealed differences in the peak heights of the PAH spectrum. In HLPC-UV, the amount of BaP and phenanthrene detected was lower for TB compared with SSB. Tissue temperature variations increased when SSB was used in FM and pure-cut mode. Furthermore, different modes revealed higher temperature variations with the use of SETB (P = 0.004) and TB (P = 0.005) during cutting, but not SSB (P = 0.789).We found that the use of both TBs and FM was associated with reduced amounts of surgical smoke created during cutting. Thus, the surgical team may benefit from the adoption of such new technologies, which could contribute to the primary prevention of smoke-related diseases.

Reduced Amputation Rate by Circular TNP Application on Split-Skin Grafts After Deep Dermal Foot Scalds in Insulin-Dependent Diabetic Patients.

The incidence of insulin-dependent diabetes mellitus (IDDM) is expected to increase significantly. Due to peripheral neuropathy and angiopathy in IDDM patients, feet scalding results in deep burn injuries. Regularly amputations are needed with tremendous consequences. In relatively healthy patients, split-skin graft (SSG) take is better when topical negative pressure (TNP) is applied. We compared the outcome of circular TNP dressing with that of antiseptic dressing on freshly laid SSG after tangential excision in IDDM patients with deep dermal foot scalds. Seventy patients admitted to a burn center with isolated foot burns were identified (2008-2013). Ten of them suffered from IDDM and presented with a deep dermal foot scald. After tangential excision and split-skin grafting, five of them were treated with TNP. The others received an antiseptic dressing regime. Differences were analyzed using either Chi-square or Student's t-test. Group comparison regarding age, gender, body mass index, HbA1c on arrival, glucose in serum, IDDM disease duration, and TBSA revealed no significant differences. But percentage of graft take was at a significantly higher rate in the TNP group (90.2 ± 4.017 vs 39 ± 15.362) and fewer operations had to be performed compared to the control group (2.0 ± 0.447 vs 4.6 ± 0.927). Due to reduced occurrence of necrosis, the number of amputations required was significantly lower in the TNP group. TNP application on freshly laid SSG following tangential excision in IDDM patients after deep dermal foot scalds minimized amputation rates and therefore is of great benefit for such patients.

Are Multimorbidities Underestimated in Scoring Systems of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Like in SCORTEN?

OBJECTIVE: Toxic epidermal necrolysis and Stevens-Johnson syndrome have related high morbidity and mortality. We predict that preexisting multimorbidity is a major prognostic factor of both these diseases. METHODS: A retrospective analysis in toxic epidermal necrolysis and Stevens-Johnson syndrome patients over the past 10 years. Three severity categories (minor, moderate, and severe multimorbidity) were defined according to a point-rating system. RESULTS: Twenty-seven inpatients, with a median age of 63 years, diagnosed with toxic epidermal necrolysis (n = 13) or Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 14) were assessed in this study. Of these, 14 patients died during the course of the study. Nonsurvivors showed significantly higher multimorbidity (P = .038), with higher scoring on the points system for disease severity (P = .003), than survivors and CART (Classification and Regression Trees) cross-validation (P < .05). LIMITATIONS: Restricted number of patients due to low prevalence rate. CONCLUSION: The complexity of associated multimorbidity appears to have a large influence on toxic epidermal necrolysis and Stevens-Johnson syndrome prognosis, which has not been considered in any of the established scoring systems.

Impact of hypernatremia on burn wound healing: results of an exploratory, retrospective study.

Severely burned patients need extensive initial fluid resuscitation. Formulas to calculate fluid needs during burn shock are well established. However, protocols for normalizing circulating fluid volume after cellular integrity has recovered do not exist. Resultant electrolyte shifts can cause hypernatremia, a possible sign of hypovolemia, which may in turn result in decreased tissue perfusion, subsequently affecting burn wound healing. The purpose of this retrospective chart review was to explore the hypothesis that hypernatremia in burn patients is a possible sign of systemic dehydration and that dehydration may affect burn wound skin graft take. Medical chart data from otherwise healthy burn victims with deep partial-thickness burns (total burn surface area [TBSA] >10%) who underwent skin grafting 7 days post injury were reviewed. Thirty (11 female; 19 male) patients with an average TBSA of 30% (± 11%) and an Abbreviated Burn Severity Index (ABSI) score of 7.9 (± 1.8) were included. Of those, 17 had normal average serum levels between day 2 and 6 following injury and 13 developed hypernatremia (serum sodium ≥146 mmol/L) an average of 5.5 days (± 1.5) after injury. Patients in this group underwent an average of 1.3 (± 0.8) re-grafting procedures compared to 0.35 (± 0.5) for patients without hypernatremia (P = 0.001). There was good correlation (r = 0.525) between daily infusion-diuresis ratios (IDR) and serum sodium levels, as well as between serum sodium levels and re-skin grafting occurrences (r = 0.62). The results indicate that research to confirm that hypernatremia is an indicator of dehydration and affects skin graft take is warranted and that protocols to optimize fluid volume following burn shock treatment are needed.

A rare desmoid tumor of the shoulder--excision, implantation of brachytherapy applicators and wound closure by pedicle musculus latissimus dorsi flap.

Desmoid tumors are non-metastatic mesenchymal tumors with an aggressive local growth. Depending on the anatomic location, morbidity varies. We report of a patient with a desmoid tumor of the right shoulder which was treated in our department by surgical excision, plastic-surgical wound closure and postoperative adjuvant radiation.

Rhabdomyolysis and acute renal failure in severely burned patients.

Rhabdomyolysis (RML) is a precarious complication in severely burned patients and the principal treatment goal is prevention of acute renal failure (ARF). This 10-year retrospective study analyses the causes for RML in severely burned patients and evaluates treatment algorithms. Eight of 714 patients (1%) were diagnosed with RML. Percentage TBSA burn was 25 ± 13%. The mean abbreviated burn severity index score (ABSI) was 9 ± 2. ARF was found in 75% (6/8) of the patients. Serum myoglobin (MB) was reduced by 41 ± 16% after 24-h treatment by solitary volume repletion (VR) and by 44 ± 20% through VR+continuous veno-venous hemodiafiltration (CVVHDF). Mortality was 50% (4/8). Peak mean CPK-levels were more than two and MB-levels more than four times higher in non-survivors than in survivors. Burns associated with RML result in poor survival. VR and CVVHDF are effective measures in treating RML. CVVHDF is effective in removing MB when using high flux filter membranes. Early CVVHDF (within 24h of diagnosis) with high-cut off membranes could reduce the risk of ARF and mortality.

Transdermal fluid loss in severely burned patients.

INTRODUCTION: The skin protects against fluid and electrolyte loss. Burn injury does affect skin integrity and protection against fluid loss is lost. Thus, a systemic dehydration can be provoked by underestimation of fluid loss through burn wounds. PURPOSE: We wanted to quantify transdermal fluid loss in burn wounds. METHOD: Retrospective study. 40 patients admitted to a specialized burn unit were analyzed and separated in two groups without (Group A) or with (Group B) hypernatremia. Means of daily infusion-diuresis-ratio (IDR) and the relationship to totally burned surface area (TBSA) were analyzed. RESULTS: In Group A 25 patients with a mean age of 47 ± 18 years, a mean TBSA of 23 ± 11%, and a mean abbreviated burned severity index (ABSI) score of 6.9 ± 2.1 were summarized. In Group B 15 patients with a mean age of 47 ± 22 years, a mean TBSA of 30 ± 13%, and a mean ABSI score of 8.1 ± 1.7 were included. Statistical analysis of the period from day 3 to day 6 showed a significant higher daily IDR-amount in Group A (Group A vs. Group B: 786 ± 1029 ml vs. -181 ± 1021 ml; p<0.001) and for daily IDR-TBSA-ratio (Group A vs. Group B: 40 ± 41 ml/% vs. -4 ± 36 ml/%; p<0.001). CONCLUSIONS: There is a systemic relevant transdermal fluid loss in burn wounds after severe burn injury. Serum sodium concentration can be used to calculate need of fluid resuscitation for fluid maintenance. There is a need of an established fluid removal strategy to avoid water and electrolyte imbalances.

Does hypernatremia impact mortality in Toxic Epidermal Necrolysis?

INTRODUCTION: In-hospital hypernatremia is associated with increased mortality rates. We want to elucidate the impact of in-hospital acquired hypernatremia in mortality of Toxic Epidermal Necrolysis (TEN). PURPOSE: Is there an association between hypernatremia and mortality in patients with TEN? METHOD: Retrospective study of 25 patients with TEN. Laboratory electrolyte results, diuresis and survival were analyzed. Patients were separated in two groups without (Group A) or with (Group B) hypernatremia. RESULTS: In Group A 10 patients with a TBSA of 74 ± 25% (mean ± standard deviation), and a SCORTEN-Score of 2.7 ± 0.9 were summarized. Diuresis within the first 10 days after admission was 1 ± 0.3 ml/kg/hour. In Group B 15 patients with a TBSA of 76 ± 19%, and a SCORTEN-Score of 3.5 ± 1 were included. Diuresis within the first 10 days after admission was 1.4 ± 0.4 ml/kg/hour. Hypernatremia occurred on day 3.3 ± 2.4 after admission and persisted for 5.3 ± 2.9 days. Statistical analysis showed a significantly higher diuresis (p=0.007) and SCORTEN-Score (p=0.04) in the hypernatremic patients. One normonatremic and 8 hypernatremic patients died during ICU-stay (overall mortality rate 36%). A significantly higher mortality rate was found in Group B (odds ratio: 13,5; 95% confidence interval: 1.34-135.98; p=0.01) during ICU-stay. CONCLUSION: TEN patients with an in-hospital acquired hypernatremia have an increased mortality risk. Close electrolyte monitoring is advisable in these patients.

Latissimus dorsi muscle flap for lower extremity reconstruction in children.

UNLABELLED: Complete loss of free latissimus dorsi muscle flaps to the leg is frequently reported. The purpose of this study is to analyze the outcome of latissimus dorsi muscle flaps to the lower extremity in children. PATIENTS AND METHODS: This retrospective analysis includes 11 children treated with a free latissimus dorsi muscle flap after severe trauma to the lower leg and foot. RESULTS: Fourteen free latissimus dorsi muscle flaps were performed in 11 children with a mean age of 13 ± 4 years. The injuries were caused by traffic accidents, lawnmower accidents, and a crush trauma. Thirteen (92.8%) flaps needed surgical revision. Three complete flap losses and 1 partial flap loss were registered. CONCLUSIONS: Free latissimus dorsi muscle flaps seem to be a useful technique for lower extremity salvage after severe injury, but there is a relevant flap failure risk in children.

Increased mortality in hypernatremic burned patients.

INTRODUCTION: In-hospital hypernatremia develops usually iatrogenically from inadequate or inappropriate fluid prescription. In severely burned patient an extensive initial fluid resuscitation is necessary for burn shock survival. After recovering of cellular integrity the circulating volume has to be normalized. Hereby extensive water and electrolyte shifts can provoke hypernatremia. PURPOSE: Is a hypernatremic state associated with increased mortality? METHOD: Retrospective study for the incidence of hypernatremia and survival in 40 patients with a totally burned surface area (TBSA) >10%. Age, sex, TBSA, ABSI-Score and fluid resuscitation within the first 24 hours were analyzed. Patients were separated in two groups without (Group A) or with (Group B) hypernatremia. RESULTS: Hypernatremia occurred on day 5+/-1.4. No significant difference for age, sex, TBSA, ABSI-Score and fluid resuscitation within the first 24 hours were calculated. In Group A all patients survived, while 3 of the hypernatremic patient in Group B died during ICU-stay (Odds-ratio = 1.25; 95% CI 0.971-1.61; p=0.046). CONCLUSION: Burned patients with an in-hospital acquired hypernatremia have an increased mortality risk. In case of a hypernatremic state early intervention is obligatory. There is a need of a fluid removal strategy in severely burned patient to avoid water imbalance.