Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing.

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood and adolescence. In more than 60% of cases of this heterogeneous disease, a genetic marker is identified via cytogenetic or molecular analyses. TCF3 gene fusions occur in 5%-11% of ALL patients. In < 1%, the TCF3 alteration in ALL leads to a TCF3-HLF fusion gene. Even though this is a very rare event, the detection of a TCF3-HLF fusion gene is associated with a very poor prognosis with incurable relapses in almost all patients. The frequent TCF3-PBX1 fusion gene, which is detectable in 5%-10% of childhood B-cell precursor ALLs and ~3.8% of adult B-cell precursor ALLs, is associated with a rather good prognosis, that is, an observed event-free 5-year survival of approximately 85%. Thus, the distinction of the different partner genes fused to TCF3 is essential for risk assessment. To verify RNA sequencing as a tool for detection of known and unknown fusion genes, we screened 200 cases of pediatric B-cell precursor ALL with "targeted" RNA sequencing in a pilot project in comparison to classical cytogenetic analyses (chromosome R-banding analysis), fluorescence in situ hybridization, and PCR. We observed a TCF3 fusion gene in 6.5% (13/200) of the patients. Ten (5%) patients displayed a TCF3-PBX1 fusion gene, two (1%) patients a TCF3-FLI1 fusion gene, and one (0.5%) patient a TCF3-HLF fusion gene. For the TCF3 fusions, we obtained discrepant results with the different methods, which are described in the article. Taken together, translocations leading to TCF3 fusion genes might appear cryptic and may remain undetected by a single method.

Short-term efficacy and adverse effects of collagenase clostridium histolyticum injections, percutaneous needle fasciotomy and limited fasciectomy in the treatment of Dupuytren's contracture: a network meta-analysis of randomized controlled trials.

AIMS: Dupuytren's contracture (DC) is a chronic debilitating fibroproliferative disorder. Common treatment options include collagenase clostridium histolyticum injections (CI), percutaneous needle fasciotomy (NF) and limited fasciectomy (LF). Superiority of one specific treatment remains controversial. This study aims to assess the short-term efficacy and safety of CI, NF, and LF for the treatment of DC. METHODS: We included randomized controlled trials of CI compared with placebo, NF and LF for patients with DC. PubMed, Embase and the Cochrane Library were searched from inception to August 2021. Contracture reduction rates in treated joints (within 0-5° of full extension within 30 days), relative reduction in total passive extension deficit (TPED), occurrence of one or more adverse events and number of treatment-related adverse events per patient were the outcomes of interest. The Cochrane risk-of-bias tool was employed for quality assessment of the studies. A network meta-analysis was performed using MetaXL. RESULTS: Nine studies met our inclusion criteria (n = 903). Overall, risk bias was mixed and mostly low. Short term TPED reduction achieved with LF was superior compared to CI and NF. Although CI achieved greater TPED reduction compared to NF, it was associated with the highest risk of overall adverse effects. The analyzed data was limited to a maximum three-year follow-up period and therefore insufficient for long-term outcome evaluation. CONCLUSIONS: In DC, LF may be able to provide patients with severe disease, superior flexion contracture release postoperatively. CI is a valid treatment alternative to NF, however the higher risk of overall adverse effects must be considered. The quality-of-evidence is limited due to short-term follow-up periods and a lack of standardized definitions of complications and adverse events.

Botulinum Toxin Versus Placebo: A Meta-Analysis of Treatment and Quality-of-life Outcomes for Hyperhidrosis.

AIMS: This study aims at assessing the treatment effect, disease severity and quality-of-life outcomes of botulinum toxin (BTX) injections for focal hyperhidrosis. METHODS: We included randomized controlled trials of BTX injections compared with placebo for patients with primary or secondary focal hyperhidrosis. PubMed, Embase and the Cochrane Library were searched to August 2020. Gravimetric sweat rate reduction, disease severity measured by Hyperhidrosis Disease Severity Scale and quality-of-life assessment measured by Dermatology Life Quality Index were the outcomes of interest. Cochrane risk-of-bias tools were employed for quality assessment of given randomized controlled trials. RESULTS: Eight studies met our inclusion criteria (n=937). Overall, risk bias was mixed and mostly moderate. BTX injections showed reduced risk in comparison with placebo for the gravimetric quantitative sweat reduction of > 50 % from baseline (risk difference: 0.63, 95% CI 0.51 to 0.74). Additionally, improvements were seen for disease severity and quality-of-life assessments evaluated by Hyperhidrosis Disease Severity Score reduction of ≥ 2 points (risk difference: 0.56, 95% CI 0.42 to 0.69) and mean change in Dermatology Life Quality Index (mean difference: - 5.55, 95% CI - 7.11 to - 3.98). The acquired data were insufficient to assess for long-term outcomes and limited to an eight-week follow-up period. CONCLUSIONS: In focal axillary hyperhidrosis, BTX significantly reduces sweat production and yields superior outcomes in assessments of disease severity and quality-of-life. However, the quality-of-evidence is overall moderate and included studies account for short-term trial periods only. Further studies assessing BTX in comparison with first-line treatments for hyperhidrosis are warranted. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Outcomes following burn injury in intensive care patients with major psychiatric disorders.

AIMS: Patients with psychiatric comorbidity have been shown to experience high rates of burn injury. Burn epidemiology, etiology, and outcomes have been sparsely documented for patients with major psychiatric disorders. The aim of this study was to analyze the epidemiologic characteristics and outcomes in intensive care burn patients with pre-existing and acute major psychiatric disorders . METHODS: A retrospective study was performed including intensive care burn patients admitted between March 2007 and December 2020. Demographic, clinical and epidemiological data were collected and analyzed. Major psychiatric co-morbidities were collected according to ICD-9 and ICD-10 classifications. Patients were stratified according to F-diagnoses. RESULTS: A total of 1325 patients were included. 16.6 % of all patients had one or more major psychiatric disorders- 9.3 % with anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders, 9.2 % with mood (affective) disorders, 3.5 % with schizophrenia and other non-mood psychotic disorders, and 1.8 % with disorders of adult personality and behavior. Patients with major psychiatric disorders presented with significantly higher burn severity, reflected by higher abbreviated burn severity index (ABSI) scores (5.9 vs. 5.3, p < 0.001) and larger total body surface area (TBSA) affected (15.9 vs. 12.5 %, p = 0.002). Burned TBSA ≥ 30 and inhalation injuries were observed more frequently in patients with MDP, however without statistical significance. They also experienced prolonged hospital length-of-stay (LOS) (25.5 vs. 16.3 days, p < 0.001), prolonged intensive care unit LOS (14.8 vs. 7.7 days, p < 0.001), underwent surgical interventions (3.5 vs. 2.3, p < 0.001) and mechanical ventilation more frequently (34.1 % vs. 16.5 %, p = 0.43) and had significantly longer ventilation durations (73.5 vs. 31.2 h, p = 0.002). Mortality rates were lower compared to patients without major psychiatric disorders (5.9 vs. 8.1, p < 0.001). CONCLUSIONS: The prevalence of major psychiatric disorders in burn patients is considerably high. Patients with psychiatric comorbidities were found to have greater burn severity, prolonged total hospital and ICU LOS, underwent surgical interventions and mechanical ventilation more frequently and had prolonged ventilation duration. Our results highlight the importance of identifying burn patients with major psychiatric disorders who may necessitate additional resources and require extensive inpatient psychiatric care and counseling.

Attempted Suicide by Burning: A Cross-sectional Analysis at a Regional Burn Center in Germany.

Attempted suicide by self-immolation or burning constitutes an uncommon form of attempted suicide in high income countries, presenting substantial challenges to burn units. The aim of this study was to analyze the epidemiologic characteristics and outcomes in intensive care burn patients treated for attempted suicide by burning. For this purpose, we examined intensive care burn patients admitted to a single major burn unit between March 2007 and December 2020. Demographic, clinical, epidemiological, and mortality data were collected and analyzed. Major psychiatric comorbidities were evaluated according to ICD-9 and ICD-10 classifications. A total of 1325 intensive care unit burn patients were included. Suicide by burning was attempted in 45 cases (3.4%). Attempted suicide victims presented with significantly higher burn severity, reflected by higher abbreviated burn severity index scores, and larger TBSA affected. Burned TBSA ≥30% and inhalation injuries were observed more frequently in suicidal patients. These patients also experienced prolonged hospital and intensive care unit length of stay, required surgical interventions and mechanical ventilation more frequently, and had significantly longer periods on ventilation, causing an overall higher mortality rate (24.4%). Psychiatric comorbidities were present in 75.6% of patients who attempted suicide. Despite the low prevalence, burn severity and mortality are considerably high in patients who attempted suicide by burning, presenting a significant challenge for healthcare providers. The majority of patients had a history of psychiatric disorder, highlighting the importance of identifying patients at high-risk who may profit from increased psychiatric intervention.

Epidemiology and outcome analysis of 1359 intensive care burn patients: A 14-year retrospective study in a major burn center.

AIMS: Globally, burn-related morbidity and mortality still remain high. In order to identify regional high-risk populations and to suggest appropriate prevention measure allocation, we aimed at analyzing epidemiological characteristics, etiology and outcomes of our 14-year experience with an intensive care unit (ICU) burn patient population. METHODS: A retrospective observational study was conducted including patients treated between March 2007 and December 2020 in our intensive care burn unit. Demographic, clinical and epidemiological data were collected and analyzed. RESULTS: A total of 1359 patients were included. 68% of the subjects were males and the largest age group affected entailed 45-64-year-old adults (34%). Regarding etiology, flame and contact burns were the most common in all age groups. Mean affected total body surface area (TBSA) was 13 ± 14.5% in all subjects. Most of the burns occurred domestically or during recreational activities. Mean hospital stay was 17.77 ± 19.7 days. The average mortality was 7.7%. The mortality rate showed an overall decreasing trend whilst burn severity remained consistent from 2007 to 2020. CONCLUSIONS: Despite consistent burn severity presentations of annual ICU admissions, burn injury mortality showed a decreasing trend, which was in part attributed to substantial progress in burn care and treatment and improved burn prevention awareness. Statistically significant age and gender differences could be detected with regard to burn etiology and seasonality, as well as outcomes, which highlight the importance of individualized primary prevention programs.

In-hospital Mortality Following Suicidal Burns: A Propensity Score-Matched Analysis.

We carried out a retrospective single-center study and analyzed all patients who have been admitted to our intensive care burn unit following suicide attempt and accidental burns within 14 years. Clinical and demographic parameters were collected and evaluated. Propensity score matching was performed in order to minimize the confounding effect of the parameters age, sex, total body surface area (TBSA), and the presence of full-thickness burns and inhalation injury. 45 burn patients following attempted suicide by burning and 1266 patients following accidental burn injury were admitted. Patients with suicidal burn injuries were significantly younger and showed significantly higher burn severity, reflected by larger TBSA affected, higher incidence of full-thickness burns and inhalation injury. They also experienced increased hospital length of stay (LOS) and longer ventilation durations. Their in-hospital mortality was significantly higher. Following propensity score matching in 42 case pairs, no differences were detected with regard to in-hospital mortality, hospital LOS, duration of mechanical ventilation, and frequency of surgical interventions. Attempted suicide by burning is associated with overall worse outcomes and higher mortality rates. Following propensity score matching, significant differences in outcomes were no longer detectable. Given the comparable survival probability compared to accidentally burned patients, life-sustaining treatment should not be withheld in burn patients following suicide attempt.

The modified 5-item frailty index as a predictor of complications in burn patients.

The modified 5-item frailty index (mFI-5), as a measure of frailty and biological age, has been shown to be a reliable predictor of complications and mortality in a variety of surgical specialties. However, its role in burn care remains to be fully elucidated. We, therefore, correlated frailty with in-hospital mortality and complications after burn injury. The medical charts of all burn patients admitted between 2007 and 2020 who had ≥ 10 % of their total body surface area affected were retrospectively reviewed. Data on clinical, demographic, and outcome parameters were collected and evaluated, and mFI-5 was calculated on the basis of the data obtained. Univariate and multivariate regression analyses were used to investigate the association between mFI-5 and medical complications and in-hospital mortality. A total of 617 burn patients were included in this study. Increasing mFI-5 scores were significantly associated with increased in-hospital mortality (p < 0.0001), myocardial infarction (p = 0.03), sepsis (p = 0.005), urinary tract infections (p = 0.006), and perioperative blood transfusions (p = 0.0004). They were also associated with an increase in the length of hospital stay and the number of surgical procedures, albeit without statistical significance. An mFI-5 score of ≥ 2 was a significant predictor of sepsis (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.03 to 3.95; p = 0.04), urinary tract infection (OR = 2.82; 95% CI: 1.47 to 5.19; p = 0.002), and perioperative blood transfusions (OR = 2.61; 95% CI: 1.61 to 4.25; p = 0.0001). Multivariate logistic regression analysis revealed that an mFI-5 score of ≥ 2 was not an independent risk factor for in-hospital mortality (OR = 1.44; 95% CI: 0.61 to 3.37; p = 0.40). mFI-5 is a significant risk factor for only a few select complications in the burn population. It is not a reliable predictor of in-hospital mortality. Therefore, its utility as a risk stratification tool in the burn unit may be limited.

Comparative Analysis of Composite Mortality Prediction Scores in Intensive Care Burn Patients.

Multiple outcome scoring models have been used in predicting mortality in burn patients. In this study, we compared the accuracy of five established models in predicting outcomes in burn patients admitted to the intensive care unit and assessed risk factors associated with mortality. Intensive care burn patients admitted between March 2007 and December 2020 with total body surface area (TBSA) affected ≥ 10% were analyzed. Multivariate analysis was conducted to examine variables associated with mortality. The ABSI, Ryan, BOBI, revised Baux and BUMP scores were analyzed by receiver operating characteristics. A total of 617 patients were included. Morality was 14.4%, with non-survivors being significantly older, male, and having experienced domestic burns. Multivariate analysis identified age, TBSA, full-thickness burns and renal insufficiency as independent mortality predictors. The BUMP score presented the highest mortality prognostication rate, followed by ABSI, revised Baux, BOBI and Ryan scores. BUMP, ABSI and revised Baux scores displayed AUC values exceeding 90%, indicating excellent prognostic capabilities. The BUMP score showed the highest accuracy of predicting mortality in intensive care burn patients and outperformed the most commonly used ABSI score in our cohort. The older models displayed adequate predictive performance and accuracy compared with the newest model.

The effect of the COVID-19 pandemic lockdown measures on plastic, reconstructive and hand surgery emergency presentations - A comparative retrospective study in a regional referral center in Germany.

Background: The global COVID-19 pandemic has led to social constraints and changes in injury patterns during the government-imposed restrictions. The aim of this study was to evaluate the effects of the lockdown period on the pattern of emergency presentations in a plastic, hand and reconstructive surgery department in a German referral center. Methods: A retrospective cohort study was conducted comparing patients presenting during the enforced lockdown period in 2020 and the same pre-pandemic period during the previous year 2019. All emergency presentations in the emergency unit requiring treatment by plastic, hand and reconstructive surgery were included. Patient demographics, reason for presentation, need for hospital admission, body region affected, location of injury and/or occurrence of first clinical symptoms and injuries of anatomical structures were considered. Results: Demographics were comparable among both groups. A 42.7% reduction in emergency cases was observed during the lockdown period. A significant elevation of domestic injuries and symptoms in the pandemic group (51.54% vs. 66.15%, p = 0.007) was registered. Concurrently, a decrease in recreational injuries (27.31% vs. 15.38%, p = 0.009) and workplace injuries (10.57% vs. 7.69%, p = 0.37) was noted. Hospital admission rates and length of stay were comparable. Similarly, no statistically significant differences could be detected regarding injuries of functional anatomical structures. The same holds true for crush injuries, animal bites, fall injuries, finger amputations, disc saw injuries, and distortion injuries. Fractures of the phalanges, the metacarpus/carpus and the forearm exhibited an increase. Conclusions: In spite of decreasing total emergency caseloads, there was an unchanged need for plastic, hand and reconstructive in-patient surgery and care during the lockdown period. Resource allocation has to be considered in future pandemic waves. Prevention strategies are warranted and should focus on finding measures to counteract domestic injuries.