The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Indirect Comparison of Combined BRAF and MEK Inhibition in Melanoma Patients with Elevated Baseline Lactate Dehydrogenase.

The approval of BRAF and MEK inhibitors has significantly improved treatment outcomes for patients with BRAF-mutated metastatic melanoma. The 3 first-line targeted therapy trials have provided similar results, and thus the identification of predictive biomarkers may generate a more precise basis for clinical decision-making. Elevated baseline lactate dehydrogenase (LDH) has already been determined as a strong prognostic factor. Therefore, this indirect analysis compared subgroups with elevated baseline LDH across the pivotal targeted therapy trials co-BRIM, COMBI-v and COLUMBUS part 1. The Bucher method was used to compare progression-free survival, objective response rate and overall survival indirectly. The results show a non-significant risk reduction for progression in the subgroup with elevated baseline LDH receiving vemurafenib plus cobimetinib compared with dabrafenib plus trametinib and encorafenib plus binimetinib. Although an indirect comparison, these data might provide some guidance for treatment recommendations in melanoma patients with elevated LDH.

[Wounds and compression]. / Wunde und Kompression.

Chronic wounds of the lower extremities affect 1-2% of the western population and represent a significant impairment of the quality of life of the patients. In addition to the identification and treatment of the underlying causes, compression therapy represents a decisive and established therapeutic method. A targeted compression works by reducing edema and also by improving the hemodynamics. After the exclusion of contraindications, clinically different systems are used in the decongestion phase as well as for prophylaxis. Therapeutic options should be discussed together with the patient and family members in order to optimize the effect and increase the adherence to the chosen therapy.

Combination therapy of oral propranolol and combined Nd:YAG/pulsed dye laser therapy in infantile hemangiomas: a retrospective analysis of 48 treated hemangiomas in 30 children.

BACKGROUND AND AIMS: Infantile hemangiomas can be successfully treated by both systemic propranolol and neodymium:YAG (Nd:YAG)-dye laser combination therapy. In this retrospective study, the efficacy and safety of sequential and parallel therapy of complicated hemangiomas treated with both methods were evaluated. PATIENTS AND METHODS: 30 children with 48 complicated hemangiomas were treated with propranolol and Nd:YAG-dye laser combination therapy. Using photo comparison, the percentage remission rate was evaluated by three investigators on a four-step scale (I: 0-25 %, II: 26-50 %, III: 51-75 % and IV: 76-100 %). RESULTS: Eleven children received propranolol and laser therapy in parallel (A), twelve children received laser therapy after propranolol (B) and seven children received propranolol after laser therapy (C). Due to emigration abroad, one child was lost to follow-up. A strong improvement (IV) was observed in 23/29 (79.3 %) of all treated children (A: 90.9 %, B 75 %, C 66.7 %). The mean duration of propranolol therapy in all children was 8.6 months (A: 8.9 months, B: 8.2 months, C: 8.9 months). On average, 2.33 laser treatments were performed per hemangioma (A: 1.95, B: 3.2, C: 1.91). Serious side effects caused by propranolol and laser therapy were not observed. CONCLUSIONS: Propranolol and Nd:YAG-dye laser combination therapy can be used sequentially or in parallel safely and effectively. They complement each other in a meaningful manner.

Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma - an update.

CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforementioned immune-related adverse events. However, early diagnosis of rare neurological or cardiac side effects, which may be associated with increased mortality, frequently pose a challenge. The present update highlights our current understanding as well as new insights into the spectrum of side effects associated with checkpoint inhibitors and their management.

Deceptively bland cutaneous angiosarcoma on the nose mimicking hemangioma-A clinicopathologic and immunohistochemical analysis.

BACKGROUND: We investigated 2 cases of deceptively bland cutaneous angiosarcoma (AS), which showed a uniform clinical presentation with a rapidly growing tumor on the nose. It remains unclear whether this was a primary cutaneous manifestation or a metastasis. Both tumors initially presented a high histologic overlap with a benign vascular tumor. The diagnosis was primarily based on the rapidly progressing clinical course and on the results of the staging procedures. METHODS: Immunohistochemical stains were performed for cytokeratin (AE1/AE3 and MNF116), CD31, ERG, CD34 (HPCA1/my10), D2-40/podoplanin, LYVE-1, Ki67, PHH3, αSMA (1A4), MYC, FOS-B, CAMTA-1, TFE-3, WT1, nestin, VEGFR-2(KDR), VEGFR-3(FLT4), HHV8. MYC amplification was also investigated by fluorescence in situ hybridization. RESULTS: The tumor cells were negative for MYC and revealed no D2-40/podoplanin expression. SMA-positive pericytes formed rims around the vessel. The proliferative activity (Ki-67) was elevated, in one case only in a later stage. DISCUSSION: Cutaneous ASs can be rather bland and may easily be mistaken for benign vascular tumors. Both cases presented a uniform clinical picture, which implied a malignant vascular tumor. In contrast, the cytomorphology of the endothelial cells and the immunohistochemical profile were not suspicious. We worked out subtle histological criteria, which should allow an early detection of such tumors.

Testing Elevated Protease Activity: Prospective Analysis of 160 Wounds.

OBJECTIVE: Given that local elevated protease activity (EPA) has been implicated in impaired wound healing, a prospective single-center study was conducted to assess protease activity in various wound types. METHODS: Protease activity was determined using an easy-to-use test system (Woundchek Protease Status Test Kit; Systagenix, Gatwick, United Kingdom) in 160 wounds in 143 patients. The assay detects the combined activity of inflammatory proteases, mainly matrix metalloproteinases 8 and 9 and human neutrophil elastase. RESULTS: Local EPA was detected in 29 of 153 validly tested wounds (18.95%). No difference was detected between acute and chronic wounds, regardless of associated or causative conditions, with the sole exception of surgical wounds. Surgical wounds showed EPA significantly less frequently than nonsurgical wounds. Among nonsurgical wounds, EPA was detected more frequently in acute compared with chronic wounds. Wounds with signs of unimpeded healing (granulation or epithelialization) showed EPA less often than wounds covered with necrotic tissue or a fibrin layer. However, 14% of wounds with epithelialization or granulation exhibited EPA potentially impeding wound healing. Wounds treated with moisture-retentive wound dressings showed EPA significantly less frequently compared with wounds bandaged with dressings with less moisture-retentive properties. Remarkably, none of the wounds treated with collagen/oxidized regenerated cellulose/silver, which is a protease-modulating dressing, showed EPA. CONCLUSIONS: To the study authors' knowledge, this is the largest study assessing EPA in various wound types. The convenient applicability of the test system provides a basis for future studies assessing the pathophysiologic relevance of EPA. In some unsuspicious wounds, early detection of EPA might precede impaired healing and prompt protease-modulating treatment before failure to heal becomes apparent.

Pre-Existing Chronic Pain Influences the Severity of Acute Herpes Zoster Pain-A Prospective Observational Cohort Study.

OBJECTIVE: Pre-existing chronic pain has been associated with severe postoperative pain. To analyze the impact of chronic pain on non-surgical acute pain, a cohort of patients with acute herpes zoster was studied. METHODS: Consecutive patients, who needed hospitalization because of an acute zoster infection, were characterized and compared according to their pain history. Pain intensity, pain-related function, analgesic consumption, and psychological and physiological characteristics were assessed as baseline parameters on the day of hospitalization. Pain intensity and functional restrictions were evaluated on day 1, 4, 7, and on the day of discharge. The analgesic consumption was recorded and scored for each of these days. A multivariate analysis was performed for individual predictors. RESULTS: 59 patients were included; 25 patients (42.4%) had pre-existing chronic pain. These patients had more severe acute zoster pain on all assessment days and were more restricted in function, such as sleep quality and mobilization. There were, however, no differences in analgesic consumption. In patients without chronic pain, only the amount of analgesic consumption was associated with the severity of zoster pain. In contrast, in patients with chronic pain, the severity of the chronic pain, physical health, and the extent of neuropathic pain characteristics were associated with the intensity of zoster-related acute pain, while analgesic consumption was not. CONCLUSIONS: Patients with chronic pain had higher intensity of zoster-related acute pain. Furthermore, they showed more pain-related dysfunction and needed longer hospitalization than patients without chronic pain. These results go along with findings for acute postoperative pain.

The impact of nodal tumour burden on lymphoscintigraphic imaging in patients with melanomas.

PURPOSE: To retrospectively study the influence of nodal tumour burden on lymphoscintigraphic imaging in 509 consecutive patients with melanomas. METHODS: Bidirectional lymphatic drainage, the clear depiction of an afferent lymphatic vessel, time to depiction of the first sentinel lymph node (SLN) and number of depicted and excised nodes were recorded. Nodal tumour load was classified as SLN-negative, SLN micrometastases or macrometastases. RESULTS: In the overall population, using multivariate regression analysis, a short SLN depiction time was significantly associated with the depiction of a greater number of radioactive nodes, a short distance between the primary tumour site and the nodal basin, younger age and lower nodal tumour burden. The proportion of patients with clear depiction of an afferent lymphatic vessel depended on the nodal tumour load (46% in SLN-negative patients, 57% in SLN positive patients, and 69% in patients with macrometastases; P = 0.009). Macrometastasis was significantly associated with delayed depiction of the first radioactive node and a greater number of depicted hotspots. In patients with clinically nonsuspicious nodes, i.e. the classical target group for SLN biopsy, clear depiction of an afferent vessel was significantly associated with a higher number of SLNs during dynamic acquisition, SLN micrometastasis and a higher overall number of metastatic lymph nodes after SLN biopsy plus completion lymphadenectomy. The excision of more than two SLNs did not increase the metastasis detection rate. In patients with bidirectional or tridirectional lymphatic drainage, the SLN positivity rates for the first, second and third basin were 25.4%, 11.7% and 0.0 %, respectively (P = 0.002). CONCLUSION: In patients with clinically nonsuspicious lymph nodes, clear depiction of an afferent lymph vessel may be a sign of micrometastasis. Macrometastasis is associated with prominent afferent vessels, delayed depiction of the first radioactive node and a higher number of depicted hotspots.

Repetitive injections of botulinum toxin A continuously increase the duration of efficacy in primary axillary hyperhidrosis: a retrospective analysis in 101 patients.

BACKGROUND AND OBJECTIVES: Botulinum toxin type A is an effective, well-tolerated, albeit temporary treatment for primary axillary hyperhidrosis. However, little is known about the influence of repetitive injections on the duration of efficacy. PATIENTS AND METHODS: 139 patients with primary axillary hyperhidrosis were injected with 50 units of botulinum toxin per axilla. In 101 patients, who received at least three treatments, the duration of efficacy after the first, second, and last treatment was evaluated. RESULTS: The median duration of efficacy was 4.0 months, 4.5 months, and 5.0 months after the first, second, and last injection, respectively. Overall, the duration of efficacy was significantly longer after the last injection compared to the duration of efficacy after the first injection (p = 0.0055, Wilcoxon matched-pairs signed-rank test). Likewise, the difference between the first and second injection (p = 0.0302) as well as the difference between the second and the last injection (p = 0.0381) were significant. In 25.7 % of patients, the duration of efficacy remained unchanged over the entire treatment period. CONCLUSIONS: Repetitive botulinum toxin treatments led to a significantly increased duration of efficacy in axillary hyperhidrosis. While the average duration of efficacy continued to increase with each treatment, there were considerable interindividual differences.