Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation.

Background and Objectives: Burn surgery on the hands is a difficult procedure due to the complex anatomy and fragility of the area. Enzymatic debridement has been shown to effectively remove burn eschar while minimizing damage to the surrounding tissue and has therefore become a standard procedure in many burn centers worldwide over the past decade. However, surprisingly, our recent literature review showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Therefore, we decided to present our study on this topic to fill this gap. Materials and Methods: This study analyzed partial-thickness to deep dermal burns on the hands that had undergone enzymatic debridement at least 12 months prior. Objective measures, like flexibility, trans-epidermal water loss, erythema, pigmentation, and microcirculation, were recorded and compared intraindividually to the uninjured skin in the same area of the other hand to assess the regenerative potential of the skin after EDNX. The subjective scar quality was evaluated using the patient and observer scar assessment scale (POSAS), the Vancouver Scar Scale (VSS), and the "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire and compared interindividually to a control group of 15 patients who had received traditional surgical debridement for hand burns of the same depth. Results: Between January 2014 and December 2015, 31 hand burns in 28 male and 3 female patients were treated with enzymatic debridement. After 12 months, the treated wounds showed no significant differences compared to the untreated skin in terms of flexibility, trans-epidermal water loss, pigmentation, and skin surface. However, the treated wounds still exhibited significantly increased blood circulation and erythema compared to the untreated areas. In comparison to the control group who received traditional surgical debridement, scarring was rated as significantly superior. Conclusions: In summary, it can be concluded that the objective skin quality following enzymatic debridement is comparable to that of healthy skin after 12 months and subjectively fares better than that after tangential excision. This confirms the superiority of enzymatic debridement in the treatment of deep dermal burns of the hand and solidifies its position as the gold standard.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

Development of a risk-tailored approach and dashboard for efficient management and monitoring of investigator-initiated trials.

BACKGROUND: Most randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. Thoroughly identifying trial-specific risks to enable focussing of monitoring and management efforts on these critical areas during trial conduct may allow for the timely initiation of corrective action and to improve the efficiency of trial conduct. We developed a risk-tailored approach with an initial risk assessment of an individual trial that informs the compilation of monitoring and management procedures in a trial dashboard. METHODS: We performed a literature review to identify risk indicators and trial monitoring approaches followed by a contextual analysis involving local, national and international stakeholders. Based on this work we developed a risk-tailored management approach with integrated monitoring for RCTs and including a visualizing trial dashboard. We piloted the approach and refined it in an iterative process based on feedback from stakeholders and performed formal user testing with investigators and staff of two clinical trials. RESULTS: The developed risk assessment comprises four domains (patient safety and rights, overall trial management, intervention management, trial data). An accompanying manual provides rationales and detailed instructions for the risk assessment. We programmed two trial dashboards tailored to one medical and one surgical RCT to manage identified trial risks based on daily exports of accumulating trial data. We made the code for a generic dashboard available on GitHub that can be adapted to individual trials. CONCLUSIONS: The presented trial management approach with integrated monitoring enables user-friendly, continuous checking of critical elements of trial conduct to support trial teams in the academic setting. Further work is needed in order to show effectiveness of the dashboard in terms of safe trial conduct and successful completion of clinical trials.

Scoping review and characteristics of publicly available checklists for assessing clinical trial feasibility.

BACKGROUND: Whether there is sufficient capacity and capability for the successful conduct and delivery of a clinical trial should be assessed by several stakeholders according to transparent and evidence-based criteria during trial planning. For this openly shared, user-tested, and validated tools are necessary. Therefore, we systematically examined the public availability and content of checklists which assess the study-level feasibility in the planning phase of clinical trials. METHODS: In our scoping review we systematically searched Medline, EMBASE, and Google (last search, June 2021). We included all publicly available checklists or tools that assessed study level feasibility of clinical trials, examined their content, and checked whether they were user-tested or validated in any form. Data was analysed and synthesised using conventional content analysis. RESULTS: A total of 10 publicly available checklists from five countries were identified. The checklists included 48 distinct items that were classified according to the following seven different domains of clinical trial feasibility: regulation, review and oversight; participant recruitment; space, material and equipment; financial resources; trial team resources; trial management; and pilot or feasibility studies. None of the available checklists appeared to be user-tested or validated. CONCLUSIONS: Although a number of publicly available checklists to assess the feasibility of clinical trials exist, their reliability and usefulness remain unclear. Openly shared, user-tested, and validated feasibility assessment tools for a better planning of clinical trials are lacking.

A clinical comparison of pure knitted silk and a complex synthetic skin substitute for the treatment of partial thickness burns.

Currently, many dressings are commercially available for the treatment of burn wounds. Some of these wound dressings remain on the wound, prevent painful dressing changes, and reduce tissue scarring. Nevertheless, still a wound dressing that is cost-effective, produces good wound healing properties, and has a high patient satisfaction is needed. Standard care of superficial burn wounds differs between burn centres. This study aimed to determine a dressing with easy appliance, accurate pain control, favourable outcome, and cost-effectiveness. Therefore, we compared the widely used but expensive Suprathel with the rather new but much cheaper Dressilk in the clinical setting. In a prospective clinical study, the healing of partial thickness burn wounds after simultaneous treatment with Suprathel and Dressilk was examined in 20 patients intra-individually. During wound healing, pain, infection, exudation, and bleeding were evaluated. A subjective scar evaluation was performed using the Patient and Observer Scar Scale. Both dressings were easy to apply, remained on the wound in place, and were gradually cut back as reepithelisation proceeded and showed similar times to wound closure. Dressing changes were not necessary, and neither infections nor bleeding was detected. Overall exudation and pain were highest in the beginning but declined during the wound-healing phase without significant differences. In the follow-up scar evaluation after 12 months, patients reported overall high satisfaction. Overall, the modern dressings Suprathel and Dressilk (solely made out of pure silk) led to safe wound healing without infection and rapidly reduced pain. There was no need for dressing changes, and they had similar clinical outcomes in scar evaluation. Therefore, both dressings seem to be ideal for the treatment of superficial burns. Because acquisition costs remain one of the main factors in the treatment of burns, Dressilk, which is ~20 times cheaper than Suprathel, remains a good option for the treatment of partial thickness burns.

Comparison of wound healing and patient comfort in partial-thickness burn wounds treated with SUPRATHEL and epictehydro wound dressings.

Among the available dressings for partial-thickness burn wound treatment, SUPRATHEL has shown good usability and effectiveness for wound healing and patient comfort and has been used in many burn centres in the last decade. Recently, bacterial nanocellulose (BNC) has become popular for the treatment of wounds, and many studies have demonstrated its efficacy. epicitehydro , consisting of BNC and 95% water, is a promising product and has recently been introduced in numerous burn centres. To date, no studies including direct comparisons to existing products like SUPRATHEL have been conducted. Therefore, we aimed to compare epicitehydro to SUPRATHEL in the treatment of partial-thickness burns. Twenty patients with partial-thickness burns affecting more than 0.5% of their total body surface area (TBSA) were enrolled in this prospective, unicentric, open, comparative, intra-individual clinical study. After debridement, the wounds were divided into two areas: one was treated with SUPRATHEL and the other with epicitehydro . Wound healing, infection, bleeding, exudation, dressing changes, and pain were documented. The quality of the scar tissue was assessed subjectively using the Patient and Observer Scar Scale. Wound healing in patients with a mean TBSA of 9.2% took 15 to 16 days for both treatments without dressing changes. All wounds showed minimal exudation, and patients reported decreased pain with the only significant difference between the two dressings on day 1. No infection or bleeding occurred in any of the wounds. Regarding scar evaluation, SUPRATHEL and epicitehydro did not differ significantly. Both wound dressings were easy to use, were highly flexible, created a safe healing environment, had similar effects on pain reduction, and showed good cosmetic and functional results without necessary dressing changes. Therefore, epicitehydro can be used as an alternative to SUPRATHEL for the treatment of partial-thickness burn wounds.

Comparison of Long-Term Skin Quality and Scar Formation in Partial-Thickness Burn Wounds Treated with Suprathel® and epicitehydro® Wound Dressings.

Background and Objectives: Scar formation after burn trauma has a significant impact on the quality of life of burn patients. Hypertrophic scars or keloids can be very distressing to patients due to potential pain, functional limitations, or hyper- or hypopigmentation. In a previous study comparing Suprathel® and the new and cheaper dressing epicitehydro®, we were able to show that pain reduction, exudation, and time until wound-healing of partial-thickness burn wounds were similar, without any documented infections. No study exists that objectively measures and compares skin and scar quality after treatment with Suprathel® and epicitehydro® at present. Materials and Methods: In this study, the scar quality of 20 patients who had been treated with Suprathel® and epicitehydro® was objectively assessed using the Cutometer®, Mexameter®, and Tewameter®, as well as subjectively with the Patient and Observer Scar Assessment Scale, 3, 6, and 12 months after burn injury. Results: In all performed measurements, no significant differences were detected in scar formation after treatment of partial-thickness burn wounds with the two dressings. Conclusions: Both the newer and less expensive wound-dressing epicitehydro® and the well-known wound-dressing Suprathel® resulted in stable wound closure and showed good cosmetic results in the follow-up examinations.

Knowledge gaps in oncoplastic breast surgery.

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.

Rapid enzymatic burn debridement: A review of the paediatric clinical trial experience.

NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy-seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty-three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III-b follow-up study (9 NXB and 8 SOC). The average long-term modified Vancouver Scar Scale scores were 3.4 for NXB-treated wounds vs 4.4 for SOC-treated wounds (NS). There were no significant treatment-related adverse events. Additional studies are needed to strengthen these results.

Long-term Scar Quality after Treatment of Standardized Partial-Thickness Skin Graft Donor Sites.

BACKGROUND: The long-term aesthetic appearance of scars is of great importance to patients. Biobrane (Smith and Nephew, Fort Worth, Texas), a biosynthetic skin dressing, is a successfully established dressing for the treatment of superficial wounds. A new silk barrier dressing (Dressilk; Prevor, Moulin de Verville, France) has also shown good results in wound healing. This study evaluated the long-term scar quality of superficial wounds treated with these dressings. METHODS: From February 2012 to May 2013, 11 patients with burns in need of skin grafting received donor site treatment. Study authors dressed 2 adjacent, standardized, partial-thickness skin graft donor sites on each participant with Biobrane or Dressilk. Scar formation on both treated areas was compared 24 months after initial application using subjective and objective assessment methods. RESULTS: Independent of treatment, the majority of the patients described scar quality similar to normal skin using subjective and objective evaluation tools. However, for scar perfusion, significantly lower oxygen saturation was shown in both treated areas compared with untreated skin. CONCLUSIONS: Comparatively, the 2 wound dressings showed similar results, making silk dressings an interesting alternative to biosynthetic ones.

Treatment of Genital Burn Injuries: Traditional Procedures and New Techniques.

OBJECTIVE: Because genital burns are rare, only limited information on treatment guidelines is available in the literature. Vital tissue should be preserved to promote spontaneous healing because reconstruction does not always lead to satisfying results. The aim of this report is to present a general overview of current, prevailing treatment for genital burns and compare this to study authors' experiences. In addition, the article describes an entirely new approach of tissue-preserving bromelain-based enzymatic debridement of genital burn wounds. METHODS: This single-center study includes all patients who were treated for severe genital and perineal burn wounds at a burn intensive care unit between December 1995 and December 2016. A review of literature was performed in PubMed covering the years 1990 to 2016. RESULTS: A total of 149 patients were admitted with severe burns or scalding of the genitals or the perineum. As in the majority of cases reported in the current literature, most of these patients were treated conservatively. When there was demarcation of necrotic tissue, tangential excision and skin grafting were performed, and since 2015, 3 patients admitted to this facility have been treated with bromelain-based debridement followed by spontaneous healing. Certain small-scale studies in the literature describe a disproportionate number of surgical interventions. CONCLUSIONS: Based on this evidence, study authors support a conservative view of genital burn treatment. Enzymatic debridement allows earlier and more selective debridement, which can improve the aesthetic outcome.

Distribution of type I corticotropin-releasing factor (CRF1) receptors on GABAergic neurons within the basolateral amygdala.

The neuropeptide corticotropin-releasing factor (CRF) plays a critical role in mediating anxiety-like responses to stressors, and dysfunction of the CRF system has been linked to the etiology of several psychiatric disorders. Extra-hypothalamic CRF can also modulate learning and memory formation, including amygdala-dependent learning. The basolateral nucleus of the amygdala (BLA) contains dense concentrations of CRF receptors, yet the distribution of these receptors on specific neuronal subtypes within the BLA has not been characterized. Here, we quantified the expression of CRF receptors on three nonoverlapping classes of GABAergic interneurons: those containing the calcium-binding protein parvalbumin (PV), and those expressing the neuropeptides somatostatin (SOM) or cholecystokinin (CCK). While the majority of PV+ neurons and roughly half of CCK+ neurons expressed CRF receptors, they were expressed to a much lesser extent on SOM+ interneurons. Knowledge of the distribution of CRF receptors within the BLA can provide insight into how manipulations of the CRF system modulate fear and anxiety-like behaviors.

Psychological distress among individuals with a suicide attempt or suicidal ideation and suicide attempts patterns: first two years of the pandemic.

Background: The COVID-19 pandemic and related restrictions may have led to increased stress, particularly in people with mental health problems. Since stress factors play important role in the emergence of suicide attempts (SA) and suicidal ideation (SI), they may have been exacerbated by the pandemic, which could have led to an increased number of suicide attempts. Thus, we first investigated whether the pandemic affected personal stress experiences and appraisal of coping potential in individuals with and without SA and SI. In a second step, we analyzed the frequency and dynamics of SAs by patients admitted to a psychiatric university clinic over a period of four years. Methods: We examined stress experiences and appraisal of coping resources of inpatients recruited between March 2021 and February 2022 with SA (n=38), SI (n=27), and with mood disorder without SA or SI (n=45). In the second study, we investigated the time course of prospectively recorded patients with a suicide attempt (n=399) between January 1st 2018 and December 31st 2021 using interrupted time-series Poisson regression models. Results: There was a significant main effect of group (F[2,107]=6.58, p=0.002) regarding psychological stress levels, which was significantly higher in the SA and SI groups than in the psychiatric control group. No significant differences were found in the appraisal of coping resources or in the frequency of SAs before and during pandemic. However, the pandemic had a significant impact on the seasonal pattern of SAs. Conclusions: The pandemic increased psychological stress levels in individuals with SA and SI, which may be related to SI and do not necessarily result in SA. The pandemic did not affect the overall frequency of SA between March 2020 and December 2021, but interfered with the seasonal pattern of SA occurrence. Effective intervention strategies during a pandemic should include programs to strengthen the psychological resilience of people who are susceptible to mental health problems.

Monitoring of a simulated CO(2) leakage in a shallow aquifer using stable carbon isotopes.

Artificial carbon dioxide leakage into a shallow aquifer was monitored using stable carbon isotope measurements at a field site near the town of Wittstock, Brandenburg, Germany. Approximately 400 000 L of CO(2) were injected into a shallow aquifer at 18 m depth over 10 days. The (13)C/ (12)C ratios of the CO(2) were measured in both groundwater and soil gas samples to monitor the distribution of the injected CO(2) plume and to evaluate the feasibility and reliability of this approach to detect potential CO(2) leakage, for example from carbon capture and storage (CCS) sites. The isotopic composition of the injected CO(2) (δ(13)C -30.5 ‰) was differentiable from the background CO(2) (δ(13)C -21.9 ‰) and the artificial CO(2) plume was monitored over a period spanning more than 204 days. The results demonstrate that this stable isotope monitoring approach can be used to identify CO(2) sources and detect potential CO(2) migration from CCS sites into overlying shallow aquifers or even into the upper subsurface. A significant difference between the isotope ratios of the natural background and the injected CO(2) is required for this monitoring approach to be effective.

Sexual Health Screening for Gynecologic and Breast Cancer Survivors: A Review and Critical Analysis of Validated Screening Tools.

INTRODUCTION: Studies have shown that the sexual health concerns of gynecologic and breast cancer survivors are not adequately being addressed by clinicians. AIM: To provide a comprehensive narrative review of validated sexual health screening tools and aid clinicians in choosing a screening tool that will allow them to best address their patients' sexual health concerns METHODS: A review of PubMed and Google Scholar databases was conducted, using search terms "sexual health", "screening", "tools", "cancer", and "survivors" to identify sexual health screening tools meeting the following inclusion criteria: 1) published in a peer-reviewed journal, 2) were written in English, 3) included breast and/or gynecological cancer patient population, 4) included self-reported measure of sexual health and function, and 5) underwent psychometric validation. MAIN OUTCOME MEASURE: Criteria used to evaluate identified screening tools included ability to assess desire, arousal, satisfaction, orgasm, dyspareunia, solo sexual expression, relationship with partner, body image, distress over changes in sexual function, and support systems. Pre and post- treatment comparisons, differentiation between lack of sexual desire and inability, heterosexual bias, diversity in patient population, and ease of scoring were also evaluated. RESULTS: Based upon the inclusion criteria, the following 10 sexual health screening tools were identified and reviewed: Female Sexual Function Index, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for both Cervical and Endometrial Cancer, Sexual Adjustment and Body Image Scale, Sexual Adjustment and Body Image Scale- Gynecologic Cancer, Sexual Function and Vaginal Changes Questionnaire, Gynaecologic Leiden Questionnaire, Information on Sexual Health: Your Needs after Cancer, Sexual Satisfaction Questionnaire, and Sexual Activity Questionnaire. Most tools assessed satisfaction (n=10), desire (n=9), and dyspareunia (n=8). Fewer addressed objective arousal (n=7), body image/femininity (n=7), partner relationship (n=7), orgasm (n=5), pre/post treatment considerations (n=5), distress (n=4), and solo-sexual expression (n=2). Heterosexual bias (n=3) and failure to differentiate between lack of desire and inability (n=2) were encountered. CONCLUSION: Understanding the strengths and limitations of sexual health screening tools can help clinicians more effectively address cancer survivors' sexual health concerns, which is essential in providing comprehensive care and improving quality of life. Screening tools have room for improvement, such as eliminating heterosexual bias and including cancer and treatment-specific questions. Clinicians can use this guide to select the most appropriate screening tool for their patients and begin bridging the gap in sexual healthcare. Tounkel I, Nalubola S, Schulz A, et al. Sexual Health Screening for Gynecologic and Breast Cancer Survivors: A Review and Critical Analysis of Validated Screening Tools. Sex Med 2022;10:100498.

Evaluation of Scar Quality after Treatment of Superficial Burns with Dressilk® and Suprathel®-In an Intraindividual Clinical Setting.

BACKGROUND: Various synthetic and biological wound dressings are available for the treatment of superficial burns, and standard care differs among hospitals. Nevertheless, the search for an ideal wound dressing offering a safe healing environment as well as optimal scar quality while being economically attractive is a continuing process. In recent years, Dressilk®, which consists of pure silk, has become the standard of care for the treatment of superficial burns in our hospital. However, no long-term scar-evaluation studies have been performed to compare Dressilk® with the often-used and more expensive Suprathel® in the treatment of superficial burns. METHODS: Subjective and objective scar evaluations were performed three, six, and twelve months after treatment in patients who received simultaneous treatment of 20 superficial burn wounds with both Suprathel® and Dressilk®. The evaluations were performed using the Vancouver Scar Scale, the Cutometer®, Mexameter®, Tewameter®, and the O2C®. RESULTS: Both dressings showed mostly equivalent results in subjective scar evaluations. In the objective scar evaluations, the wounds treated with Dressilk® showed a faster return to the qualities of non-injured skin. Wound areas treated with the two dressings showed no significant differences in elasticity and transepidermal water loss after 12 months. Only oxygen saturation was significantly lower in wound areas treated with Suprathel® (p = 0.008). Subjectively, wound areas treated with Dressilk® showed significantly higher pigmentation after six months, which was not apparent after 12 months. CONCLUSION: Both wound dressings led to esthetically satisfying scar recovery without significant differences from normal uninjured skin after 12 months. Therefore, Dressilk® remains an economically and clinically interesting alternative to Suprathel® for the treatment of superficial burns.

Investigating the Clinical Profile of Suicide Attempters Who Used a Violent Suicidal Means.

In our study, we aimed to explore the profile of the high-risk subgroup of suicide attempters that used a violent means compared to suicide attempters that chose a non-violent suicide means. Therefore, we recruited a sample of inpatients with recent suicide attempts in three psychiatric hospitals in Thuringia, Germany. We used a structured clinical interview to assess the psychiatric diagnoses, sociodemographic data, and characteristics of the suicide attempt. Furthermore, we used several validated clinical questionnaires to measure suicidal ideations, suicide intent, depression severity, hopelessness, impulsivity, aggression, anger expression, and childhood trauma. We compared 41 individuals using violent means to 59 using non-violent means with univariate and multivariate statistical analyses. We found significantly (corrected for multiple comparisons) higher levels of impulsivity-related sensation-seeking in violent suicide attempters in univariate and multivariate analyses, and additionally in anger expression directed inward at an uncorrected statistical threshold. Besides that, there were no significant differences between the two groups. We assume that underlying neurocognitive mechanisms, such as impaired decision-making processes and/or differences in risk/loss assessment, could explain the higher levels of questionnaire-based sensation-seeking in subjects who use violent suicide means. Further research is needed, including neuroimaging and biochemical techniques, to gain more insight into the mechanisms underlying the choice of a suicidal means.

Novel X-linked inhibitor of apoptosis inhibiting compound as sensitizer for TRAIL-mediated apoptosis in chronic lymphocytic leukaemia with poor prognosis.

Given that aggressive DNA damaging chemotherapy shows suboptimal efficacy in chronic lymphocytic leukaemia (CLL), alternative therapeutic approaches are needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce tumour-specific apoptosis. However, apoptosis might be inhibited by elevated levels of X-linked inhibitor of apoptosis (XIAP). Use of XIAP-inhibiting compounds might sensitize primary CLL cells towards TRAIL-mediated apoptosis. A novel small molecule, compound A (CA), an inhibitor of XIAP, was used in combination with TRAIL to induce apoptosis in primary CLL cells (n = 48). XIAP was significantly more highly expressed in primary CLL cells (n = 28) compared to healthy B cells (n = 16) (P = 0·02). Our data obtained by specific knock-down of XIAP by siRNA identified XIAP as the key factor conferring resistance to TRAIL in CLL. Combined treatment with CA/TRAIL significantly increased apoptosis compared to untreated (P = 8·5 × 10⁻¹°), solely CA (P = 4·1 × 10⁻¹²) or TRAIL treated (P = 4·8 × 10⁻¹°) CLL cells. CA rendered 40 of 48 (83·3%) primary CLL samples susceptible to TRAIL-mediated apoptosis. In particular, cells derived from patients with poor prognosis CLL (ZAP-70(+) , IGHV unmutated, 17p-) were highly responsive to this drug combination. Our highly-effective XIAP inhibitor CA, in concert with TRAIL, shows potential for the treatment of CLL cases with poor prognosis and therefore warrants further clinical investigation.