QoL during KTd or KRd induction followed by K maintenance or observation in transplant noneligible patients with newly diagnosed multiple myeloma: Longitudinal and cross-sectional analysis of the randomized AGMT 02 study.

Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Randomized comparison between KTd and KRd induction therapy followed by maintenance therapy with K or observation in transplant-ineligible patients with newly diagnosed multiple myeloma.

Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.

Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT.

The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.

Attrition Rates in Multiple Myeloma Treatment under Real World Conditions-An Analysis from the Austrian Myeloma Registry (AMR).

Multiple myeloma (MM) is characterized by serial relapses, necessitating the application of sequential lines of therapy (LoT). Reports on attrition rates (ARs) vary widely. The present study analysed ARs from the Austrian Myeloma Registry. Attrition was defined as being either deceased, progressive without having received another LoT, or lack of follow-up for ≥5 years. A total of 571 patients diagnosed between January 2009 and August 2021 were included (median age: 72 years; median follow-up: 50.8 months). Some 507 patients received at least one LoT. Of the total, 43.6% underwent autologous stem cell transplantation (SCT, transplant eligible = TE)) with primarily VRd (Bortezomib/Lenalidomide/Dexamethasone) given as induction (26.5%), followed by lenalidomide maintenance in 55.7% of cases. Transplant-ineligible (NTE) patients were predominantly treated with Vd (Bortezomib/Dexamethasone, 21.6%), receiving maintenance in 27.1%. A total of 37.5% received a second LoT. ARs across one to five LoTs were 16.7-27%. Frontline induction/ SCT followed by maintenance reduced ARs associated with age and achievement of deep remission in the frontline. Deep remission prolongs follow-up and time-to-next-treatment (TTNT), while high-risk-cyctogenetics negatively affected these outcomes. Our results demonstrate considerably lower ARs for MM patients within the AMR data versus other healthcare systems. Young age and the achievement of significant remissions after optimal frontline therapy resulted in particularly low ARs. These promising results support a key role for the ease of drug access and reimbursement policies in governing long-term MM patient outcomes.

Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents-A Prospective Cohort Study of the AGMT Study-Group.

Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3-4 anemia 43.4%, grade 3-4 thrombopenia 36.8%, grade 3-4 neutropenia 36.1%). Grade 3-4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.

Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response.

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.

Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients.

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.

Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer-Results from the AGMT GASTRIC-5 Registry.

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870-24,530) vs. 6.9 months (95% CI: 3.980-9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.

Early hypothermia as risk factor in severely burned patients: A retrospective outcome study.

INTRODUCTION: Burn trauma-related hypothermia is a frequent observation but risk factors and impact on patient related outcome are ambiguously reported. It is expected that hypothermia is associated with increased mortality and reduced overall outcome in severely burned patients, but available evidence is limited. METHODS: This retrospective single-center-study reviewed preclinical service protocols and medical records of patients sustaining a burn with a total body surface area (TBSA) ≥15% from 2008 to 2012. General patient and burn specific characteristics, outcome parameters as well as body temperature at admission measured via urine catheter or nasal temperature probe were recorded and statistically analyzed comparing normothermic (≥36 °C), mild hypothermic (<36 °C) and severely hypothermic (<34.5 °C) patients. Chi-square test was performed to demonstrate impact of hypothermia on primary outcome parameters and to reveal risk factors for developing hypothermia. To assess independent influences on mortality, a multivariate logistic regression analysis was performed. RESULTS: Out of 300 patients matching inclusion criteria, a sufficient record of temperature was found in 144 patients (48%). Out of 141 eligible patients with an average burn extent (SD) of 33.38% (24.5%) TBSA, 31.9% (n = 45) suffered from severe hypothermia (<34.5 °C) and 28.4% (n = 40) showed mild hypothermia. Total burn extent, presence of full thickness burns, presence of inhalation injury, preclinical mechanical ventilation and administration of sedative drugs were risk factors for developing hypothermia. Patients' age, total burn extent and presence of full thickness burns could be identified as independent factor for mortality. Although a trend towards an independent positive influence of normothermia at admission on mortality was seen, it was not statistically significant. CONCLUSION: Incidental hypothermia of burned patients is associated with an increased mortality and needs to be addressed by emergency health care providers and immediately at the burn center. Especially patients with extensive burns, full-thickness burns, inhalation injury or patients undergoing preclinical intubation are at risk for hypothermia and benefit from any measures for temperature preserving.

Health-related quality of life and patient burden in patients with split-thickness skin graft donor site wounds.

Split-thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross-sectional study of adult patients with split-thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split-thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ-5D) averaged 77.4 ± 30.0. Wound-QoL (range: 0-4) was rated 0.8 ± 0.8 post-surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound-QoL scores of chronic wounds donor site-related QoL impairments in split-thickness skin-graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient-reported outcomes.

Ischaemic Preconditioning Suppresses Necrosis of Adipocutaneous Flaps in a Diabetic Rat Model Regardless of the Manner of Preischaemia Induction.

Ischaemic insult in the skin flaps is a major problem in reconstructive surgery particularly in patients with diabetes mellitus. Here, we sought to investigate the effectiveness of ischaemic preconditioning (IP) on diabetic skin flaps in rat animal model. Hundred Wistar rats (90 streptozotocin treated animals and 10 nondiabetic controls) were used. Diabetes mellitus was confirmed by measuring glucose level in blood, HbA1c, and ketonuria. We used blood vessel clamping, hind limb tourniquet, and NO donors (Spermine/NO complex) to induce short-term ischaemia of tissues that will be excised for skin flaps. Animals were followed for 5 days. Flaps were photographed at day 5 and percent of necrosis was determined using planimetry. Significant decrease in percent of necrotic tissue in all groups that received preconditioning was observed. Results show that ischaemic preconditioning suppresses flap necrosis in diabetic rats irrespective of direct or remote tissue IP and irrespective of chemically or physically induced preischaemia. Spermine/NO complex treatment 10 minutes after the flap ischaemia suppressed tissue necrosis. Treatment with NO synthase inhibitor L-NAME reversed effects of IP showing importance of NO for this process. We show that IP is a promising approach for suppression of tissue necrosis in diabetic flaps and potential of NO pathway as therapeutic target in diabetic flaps.

Risk factors for cartilage damage and osteoarthritis of the elbow joint: case-control study and systematic literature review.

INTRODUCTION: This case-control study compares patients with healthy elbows to a group of symptomatic patients with cartilage damage/osteoarthritis. MATERIALS AND METHODS: The control group (n = 126) was recruited during routine medical examinations of patients (general medical offices). Included in the case group were a total of 92 patients who were undergoing arthroscopy as a result of chronic elbow discomfort. All patients were questioned with regard to occupational stress and athletic stress. RESULTS: A significantly increased risk of cartilage damage/osteoarthritis was found with subjectively perceived increased stress in occupational settings: OR = 3.8 (95% CI 2.1-6.7); p < 0.001; for the individual stresses of the elbow joint in occupational settings, the following severities in effects were found: Exposure to heavy work OR = 3.9 (95% CI 2.2-6.8); Force OR = 3.7 (95% CI 2.1-6.5); Vibration OR = 4.6 (95% CI 2.5-8.5); Repetition OR = 9.2 (95% CI 3.6-23.3); p < 0.001. Elbow-stressing sport types represent a potential risk factor for the development of cartilage damage/osteoarthritis of the elbow joint: OR = 2.5 (95% CI 1.3-4.7); p = 0.003. CONCLUSIONS: Cartilage damage/radiographic osteoarthritis of the elbow joint are rare with respect to the overall prevalence of osteoarthritis. In the large number of patients with cartilage damage/radiographic osteoarthritis of the elbow joint, occupational or athletic stress factors and injuries sustained, in addition to other causes (rheumatism, gout), can prove as possible causes of these as secondary to symptomatic forms of osteoarthritis.

Primary Cardiac Tumors in Infants and Children: Surgical Strategy and Long-Term Outcome.

BACKGROUND: Primary cardiac tumors in infants and children are extremely rare; hence, there is very little literature available, and most knowledge is based on collections of case reports. This report is a comprehensive review of our 26-year experience with primary cardiac tumors in children with emphasis on surgical indications, strategies, and long-term outcome. METHODS: Between 1986 and 2012, 47 children (mean age 5.9 ± 2.4 months; range, 1 day to 17 years) underwent either subtotal or total resection of cardiac tumors (rhabdomyoma, 13; fibroma, 12; teratoma, 9; myxoma, 8; hemangioma, 2; rhabdomyosarcoma, 1; non-Hodgkin's lymphoma, 1; lymphangioma, 1). The majority were diagnosed by echocardiography (n = 33). Clinical patterns were varied: 40 had an atypical heart murmur and 6 were asymptomatic. Outflow tract obstruction of more than 30 mm Hg was present in 11 children. Three patients had abnormal coronary arteries secondary to pressure from tumor bulk. Indications of resection were hemodynamic/respiratory compromise, severe arrhythmia, and a significant embolization risk. Strategy of resection varied according to location and hemodynamic status without damage to adjacent structures. RESULTS: Morbidity included bleeding in a patient and a transient low output state in another. A 5-month-old infant with left ventricular fibroma underwent left ventricular assist device implantation secondary to failure from weaning off cardiopulmonary bypass, and she eventually underwent heart transplantation 17 days later. Early mortality (n = 2, 4.2%) included a 5-month-old infant who underwent complete resection of rhabdomyoma located in the left ventricle, with concomitant pulmonary valve replacement; unfortunately, he underwent left ventricular assist device implantation for postoperative heart failure and died on the 13th postoperative day. An 8-month-old child with 3 cm × 4 cm fibroma obstructing the right ventricular outflow tract compressing the right coronary artery died of severe right-side heart failure on the 13th postoperative day. One late death (2.1%) occurred; a 16-year-old with non-Hodgkin's lymphoma died 7 months after the surgery. Mean duration of follow-up is 11.6 ± 3.5 years. All survivors (93.4%) are well, free of tumor-related symptoms and tumor recurrence/progression, even when resection was incomplete. CONCLUSIONS: This study illustrates that although primary cardiac tumors in infants and children have a wide and unusual spectrum of clinical presentation, an individualized approach to tumor resection allows restoration of an adequate hemodynamic function and satisfactory long-term, tumor-free outcome.

A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients.

BACKGROUND: The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients. METHODS: The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays. RESULTS: Over a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05). CONCLUSIONS: For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.

Prospective randomized phase II Trial of accelerated reepithelialization of superficial second-degree burn wounds using extracorporeal shock wave therapy.

BACKGROUND: As extracorporeal shock wave therapy (ESWT) can enhance healing of skin graft donor sites, this study focused on shock wave effects in burn wounds. METHODS: A predefined cohort of 50 patients (6 with incomplete data or lost to follow-up) with acute second-degree burns from a larger study of 100 patients were randomly assigned between December 2006 and December 2007 to receive standard therapy (burn wound debridement/topical antiseptic therapy) with (n = 22) or without (n = 22) defocused ESWT (100 impulses/cm at 0.1 mJ/mm) applied once to the study burn, after debridement. Randomization sequence was computer-generated, and patients were blinded to treatment allocation. The primary endpoint, time to complete burn wound epithelialization, was determined by independent, blinded-observer. A worst case scenario was applied to the missing cases to rule out the impact of withdrawal bias. RESULTS: Patient characteristics across the 2 study groups were balanced (P > 0.05) except for older age (53 ± 17 vs. 38 ± 13 years, P = 0.002) in the ESWT group. Mean time to complete (≥95%) epithelialization (CE) for patients that did and did not undergo ESWT was 9.6 ± 1.7 and 12.5 ± 2.2 days, respectively (P < 0.0005). When age (continuous variable) and treatment group (binary) were examined in a linear regression model to control the baseline age imbalance, time to CE, age was not significant (P = 0.33) and treatment group retained significance (P < 0.0005). Statistical significance (P = 0.001) was retained when ESWT cases with missing follow-up were assigned the longest time to CE and when controls with missing follow-up were assigned the shortest time to CE. CONCLUSIONS: In this randomized phase II study, application of a single defocused shock wave treatment to the superficial second-degree burn wound after debridement/topical antiseptic therapy significantly accelerated epithelialization. This finding warrants confirmation in a larger phase III trial (ClinicalTrials.gov identifier: NCT01242423).

Method for autologous single skin cell isolation for regenerative cell spray transplantation with non-cultured cells.

BACKGROUND: There is a therapeutic gap for patients with deep partial thickness wounds (Grade IIb) of moderate size that were initially not treated with split- or mesh grafting to avoid overgrafting, but developed delayed wound healing around two weeks after injury--at which time grafting is typically not indicated anymore. Delayed wound healing is often associated with esthetically unsatisfactory results and sometimes functional problems. An innovative cell isolation method for cell spray transplantation at the point of care, which eliminates cell culture prior to treatment, was implemented for this population of burn patients in our center. METHODS: Autologous skin cell spray transplantation was initiated by taking healthy skin. The dermal/epidermal layers were separated using enzymatic digestion with 40 min dispase application, followed by 15 min trypsin application for basal kerationcyte isolation, 7 min cell washing by centrifugation, followed by transferring the cells for spraying into Ringer lactate solution. The procedure was performed on site in a single session immediately following the biopsy. After sharp wound debridement, cells were immediately transplanted by deposition with a cell sprayer for even distribution of the cell suspension. RESULTS AND CONCLUSIONS: Eight patients were treated (mean age 30.3 years, mean burn total body surface area 14%, mean Abbreviated Burn Severity Index (5 points). The mean time to complete re-epithelialization was 12.6 days. All patients exhibited wound healing with improved esthetic and functional quality. Our initial experience for the use of non-cultured cells using a two-enzyme approach with cell washing suggests shortened time for wound closure, suggesting that the method may potentially avoid longer-term complications.

Risk assessment of the application of a plasma jet in dermatology.

Regardless of the fact that several highly efficient antiseptics are commercially available, the antiseptic treatment of chronic wounds remains a problem. In the past, electrical plasma discharges have been frequently used in biometrical science for disinfection and sterilization of material surfaces. Plasma systems usually have a temperature of several hundred degrees. Recently, it was reported that "cold" plasma can be applied onto living tissue. In in vitro studies on cell culture, it could be demonstrated that this new plasma possesses excellent antiseptic properties. We perform a risk assessment concerning the in vivo application of a "cold" plasma jet on patients and volunteers. Two potential risk factors, UV radiation and temperature, are evaluated. We show that the UV radiation of the plasma in the used system is an order of magnitude lower than the minimal erythema dose, necessary to produce sunburn on the skin in vivo. Additionally, thermal damage of the tissue by the plasma can be excluded. The results of the risk assessment stimulate the in vivo application of the investigated plasma jet in the treatment of chronic wounds.

Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.

A glycine to valine substitution at codon 12 (G12V) in Kirsten-Ras (K-Ras) gene has been associated with reduced overall survival in colorectal cancer patients; however, the effect of other K-Ras mutations than G12V still remains unclear. Therefore, we investigated the role of different K-Ras mutations on overall survival in a homogeneous, large patient cohort with standardized therapy and uniform analysis of K-Ras mutation status. The study included 342 patients with histopathologically proven colorectal cancer. Survival data were provided by the federal agency for statistics in Austria. Occurrence of K-Ras mutations at codons 12, 13 and 61 were determined by capillary sequencing. The overall K-Ras mutation frequency in carcinoma tissue was 28%. Carriers of the G12V mutation at the K-Ras gene showed a significantly decreased overall survival compared to carriers of the wild-type [HR=2.56 (1.15-5.69)]. Other mutations than G12V were associated with better overall survival compared to wild-type [HR=0.44 (0.2-0.99)]. In conclusion, for the first time, our study showed clearly that different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.