Advances in cancer immunotherapies.

Therapeutic modalities that engage the immune system to recognize and eliminate cancer, known as cancer immunotherapy, has emerged as a distinct pillar of cancer therapy. Among the most promising treatment approaches are therapeutic vaccines, immune checkpoint blockade, bispecific T-cell engagers (BiTEs) and adoptive cell therapies. These approaches share a common mechanism of action, which is elicitation of a T-cell-based immune response, either endogenous or engineered, against tumor antigens, but interactions between the innate immune system, particularly antigen-presenting cells, and immune effectors also underlie the efficacy of cancer immunotherapies and approaches engaging these cells are also under development. To view this SnapShot, open or download the PDF.

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma.

Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.

Which Second-Line Tyrosine Kinase Inhibitor(s) for Chronic Myeloid Leukemia?

OPINION STATEMENT: In patients with chronic myeloid leukemia who require second-line tyrosine kinase inhibitor therapy, many options exist. These treatments include alternate generation tyrosine kinase inhibitors and in some cases consideration of allogeneic transplant. Although efficacious, each tyrosine kinase inhibitor possesses distinct side effects and pharmacological profiles that prevent a generalizable treatment approach. Furthermore, there is limited head-to-head trial data that would suggest the superiority of one tyrosine kinase inhibitor over another to help guide treatment decisions in specific clinical settings. Therefore, we treat each patient independently. A patient's treatment plan must be personalized by a variety of clinical factors to optimize response and tolerability. Our general approach is to first examine the reason for treatment failure, which may be due to either intolerance or relapse. Second, we consider the age and patient's comorbidities such as lung disease, diabetes, or cardiovascular disease. In patients who have inadequate responses, we analyze the patient's BCR-ABL1 mutational profile, which is beneficial if that patient harbors a specific tyrosine kinase inhibitor responsive mutation, such as T315I. Using these steps, we can provide a generalizable approach to choosing the appropriate second-line tyrosine inhibitor for chronic myeloid leukemia.

[Physical Strain after Abdominal Surgery - Results of a Patient Survey]. / Belastbarkeit nach abdominellen Eingriffen ­ Ergebnisse einer Patientenbefragung.

INTRODUCTION: Incision hernias are common complications after abdominal surgery and affect the recommendations on postoperative physical strain, as it is thought that excessively early strain causes incisional hernias. However, there is no evidence to justify this. This study evaluates the effect of postoperative strain on the risk of incisional hernia. MATERIALS AND METHODS: Patients with a laparoscopy (LS) or laparotomy (LT) were asked to complete a questionnaire on postoperative strain, complaints and quality of life. Patients with hernia surgery, or open abdomen therapy for complicated courses (Clavien-Dindo > III) were excluded. RESULTS: 393 patients completed the questionnaire (43.6%). 274 were LS and 128 LT. The incidence of incisional hernias was 5.2% (LS) and 18.0% (LT, p = 0.001). Incisional hernia patients were younger and more commonly males. 30.5% of incisional hernia patients did not return to normal physical strain postoperatively. Abdominal binders did not affect the hernia rate. The incisional hernia patients showed decreased quality of life scores in both mental and physical domains. CONCLUSION: Early postoperative physical strain was not a risk factor for incisional hernia development in this study. However, prospective studies are needed to create necessary evidence to recommend earlier postoperative return to normal physical strain.

Traumatic diaphragmatic rupture: epidemiology, associated injuries, and outcome-an analysis based on the TraumaRegister DGU®.

INTRODUCTION: Traumatic diaphragmatic rupture is a rare injury in the severely injured patient and is most commonly caused by blunt mechanisms. However, penetrating mechanisms can also dominate depending on regional and local factors. Traumatic diaphragmatic rupture is difficult to diagnose and can be missed by primary diagnostic procedures in the resuscitation room. Initially not life-threatening, diaphragmatic ruptures can cause severe sequelae in the patient's long-term course if untreated. The objective of this study was to assess the epidemiology, associated injuries, and outcome of traumatic diaphragmatic ruptures based on a multicenter registry-based analysis. MATERIAL AND METHODS: Data from all patients enrolled in the TraumaRegister DGU® between 2009 and 2018 were retrospectively analyzed. That multicenter database collects data on prehospital, intra-hospital emergency, intensive care therapy, and discharge. Included were all patients with a Maximum Abbreviated Injury Scale (MAIS) score of 3 or above and patients with a MAIS score of 2 who died or were treated in the intensive care unit, for whom standard documentation forms had been completed and who had sustained a diaphragmatic rupture (AIS score of 3 or 4). The data has been analyzed using descriptive statistics and chi-square test or Mann-Whitney U test. RESULTS: Of the 199,933 patients included in the study population, 687 patients (0.3%) had a diaphragmatic rupture. Of these, 71.9% were male. The mean patient age was 46.1 years. Blunt trauma accounted for 73.5% of the injuries. Primary diagnosis was established in the resuscitation room in 93.1% of the patients. Multislice helical computed tomography (MSCT) was performed in 82.7% of the cases. Rib fractures were detected in 60.7% of the patients with a diaphragmatic injury. Patients with diaphragmatic rupture had a higher mean Injury Severity Score (ISS) than patients without a diaphragmatic injury (32.9 vs. 18.6) and a higher mortality rate (13.2% vs. 9.0%). CONCLUSIONS: In contrast to the literature, primary diagnostic procedures in the resuscitation room detected relevant diaphragmatic ruptures (AIS ≥ 3) in more than 90% of the patients in our study population. In addition, complex associated serial rib fractures are an important diagnostic indicator.

Status quo of the use of DCS concepts and outcome with focus on blunt abdominal trauma : A registry-based analysis from the TraumaRegister DGU®.

INTRODUCTION: Damage control surgery (DCS) is a standardized treatment concept in severe abdominal injury. Despite its evident advantages, DCS bears the risk of substantial morbidity and mortality, due to open abdomen therapy (OAT). Thus, identifying the suitable patients for that approach is of utmost importance. Furthermore, little is known about the use of DCS and the related outcome, especially in blunt abdominal trauma. METHODS: Patients recorded in the TraumaRegister DGU® from 2008 to 2017, and with an Injury Severity Score (ISS) ≥ 9 and an abdominal injury with an Abbreviated Injury Scale (AIS) score ≥ 3 were included in that registry-based analysis. Patients with DCS and temporary abdominal closure (TAC) were compared with patients who were treated with a laparotomy and primary closure (non-DCS) and those who did receive non-operative management (NOM). Following descriptive analysis, a matched-pairs study was conducted to evaluate differences and outcomes between DCS and non-DCS group. Matching criteria were age, abdominal trauma severity, and hemodynamical instability at the scene. RESULTS: The injury mechanism was predominantly blunt (87.1%). Of the 8226 patients included, 2351 received NOM, 5011 underwent laparotomy and primary abdominal closure (non-DCS), and 864 were managed with DCS. Thus, 785 patient pairs were analysed. The rate of hepatic injuries AIS > 3 differed between the groups (DCS 50.3% vs. non-DCS 18.1%). DCS patients had a higher ISS (p = 0.023), required more significant volumes of fluids, more catecholamines, and transfusions (p < 0.001). More DCS patients were in shock at the accident scene (p = 0.022). DCS patients had a higher number of severe hepatic (AIS score ≥ 3) and gastrointestinal injuries and more vascular injuries. Most severe abdominal injuries in non-DCS patients were splenic injuries (AIS, 4 and 5) (52.1% versus 37.9%, p = 0.004). CONCLUSION: DCS is a strategy used in unstable trauma patients, severe hepatic, gastrointestinal, multiple abdominal injuries, and mass transfusions. The expected survival rates were achieved in such extreme trauma situations.

Protamine loops DNA in multiple steps.

Protamine proteins dramatically condense DNA in sperm to almost crystalline packing levels. Here, we measure the first step in the in vitro pathway, the folding of DNA into a single loop. Current models for DNA loop formation are one-step, all-or-nothing models with a looped state and an unlooped state. However, when we use a Tethered Particle Motion (TPM) assay to measure the dynamic, real-time looping of DNA by protamine, we observe the presence of multiple folded states that are long-lived (∼100 s) and reversible. In addition, we measure folding on DNA molecules that are too short to form loops. This suggests that protamine is using a multi-step process to loop the DNA rather than a one-step process. To visualize the DNA structures, we used an Atomic Force Microscopy (AFM) assay. We see that some folded DNA molecules are loops with a ∼10-nm radius and some of the folded molecules are partial loops-c-shapes or s-shapes-that have a radius of curvature of ∼10 nm. Further analysis of these structures suggest that protamine is bending the DNA to achieve this curvature rather than increasing the flexibility of the DNA. We therefore conclude that protamine loops DNA in multiple steps, bending it into a loop.

[Diagnosis and Treatment of Severe Fournier's Gangrene: Introduction of a Surgical Approach, Evaluation of Risk Factors, Microbiological Characteristics and Review of the Literature]. / Diagnose und zielgerichtete Therapie der Fournier-Gangrän mit septischem Verlauf: Vorstellung eines Behandlungsalgorithmus, Identifikation von Risikofaktoren, Betrachtung des Mikrobioms und Abgleich mit der Literatur.

BACKGROUND: Fournier's gangrene is a necrotising fasciitis type I occurring in the perineal and genital region. The disease expands progressively and still has poor outcome, especially in critical ill patients. This study's focus was placed on the evaluation of risk factors and comorbidities, on the bacteriological spectrum, laboratory analyses, mortality and the course according to the algorithmic approach. METHOD: The medical records were reviewed of 10 patients with severe Fournier's gangrene from 2010 to 2019 who underwent intensive care therapy for at least 48 hours. Ten patients with Fournier's gangrene and sepsis and intensive therapy lasting at least 48 hours were recorded and analysed descriptively. RESULTS: The patient cohort consisted of six men and four women with a median age of 62 years (range 42 - 78 years). The median time between the onset of symptoms and hospitalisation was four days (range 3 - 5 days). The commonest aetiological event was a minor trauma. Predisposing factors included diabetes mellitus (30%) and overweight (80% BMI > 25). 90% of patients exhibited polymicrobial infection. All patients had systemic sepsis with SOFA-Score between 3 and 17 points. The mortality rate was 40%. Significant differences between surviving and deceased patients were shown by PCT, INR and aPTT (p < 0.05). CONCLUSION: Severe Fournier's gangrene continues to be a major challenge with a high mortality rate. Only rapid diagnosis, urgent extensive surgical debridement and intensive care therapy can lead to a favourable outcome in these critically ill patients. Vacuum-assisted closure can be successfully used in the management of soft-tissue defects.

The Significance of Visceral Protection in Preventing Enteroatmospheric Fistulae During Open Abdomen Treatment in Patients With Secondary Peritonitis: A Propensity Score-matched Case-control Analysis.

OBJECTIVE: To evaluate the influence of a visceral protective layer (VPL) on the formation of enteroatmospheric fistulae (EAF) in open abdomen treatment (OAT) for peritonitis. BACKGROUND: EAF formation is a severe complication of OAT. Despite the widespread use of OAT, there are no robust evidence-based recommendations for preventing EAF. METHODS: A total of 120 peritonitis patients with secondary peritonitis as a result of a perforation of a hollow viscus or anastomotic insufficiency who had undergone OAT were included, and 14 clinical parameters were recorded in prospective OAT databases at 2 tertiary referral centers. For this analysis, patients with a VPL were assigned to the treatment group and those without a VPL to the control group. Propensity Score (PS) matching was performed. Known risk factors in OAT such as malignant disease, mortality, emergency operation, OAT duration, and fascial closure were matching variables. The influence of VPL on EAF formation was statistically evaluated using logistic regression analysis. RESULTS: With 34 patients in each group, no notable differences were identified with regard to age, sex, underlying disease, mortality, emergency operation, fascial closure, and OAT duration. Overall, a mortality rate of 22.1% for OAT due to peritonitis was observed. Mean OAT duration was approximately 9 days, and secondary fascial closure was achieved in more than two-thirds of all patients. Fascial traction was used in more than 75% of cases. EAF formation was significantly more frequent in the control group (EAF formation: VPL group 2.9% vs control 26.5%; P = 0.00). In the final regression analysis, the use of VPL resulted in a significant reduction in the risk of EAF formation (odds ratio 0.08; 95% confidence interval 0.01-0.71, P = 0.02), which translates to a relative risk reduction of 89.1%. CONCLUSION: VPL effectively prevents EAF formation during OAT in patients with peritonitis. We recommend the consistent use of VPL as part of a standardized OAT treatment algorithm.

[The Impact of Lockdown during the COVID-19 Pandemic on Care for Elective Patients (C-elective Study) - Results of a Multicenter Survey]. / Die Auswirkung des Lockdowns während der COVID-19-Pandemie auf die Versorgung von elektiven Patienten (C-elective-Studie).

BACKGROUND: Due to the COVID-19-related lockdown regulations, surgical clinics had to cut down elective procedures. The impact of the cancellation and postponing surgery on patients is unclear. METHODS: All patients from six hospitals with canceled surgery during the first lockdown (03/16-04/24/2020) were asked to answer a questionnaire. RESULTS: In total, 225 patients took part. In 88 (39.1%) patients, the disease-related complaints changed, mainly towards an increase in severity (82.6%). That was especially true for hernia patients (44.4%). In 4% of the cases, there was a complication requiring surgery in the time interval between the original date of the operation and the interview. For about a third, the cancelation of scheduled surgery caused major administrative difficulties. Most of the patients (76.3%) understood the measures taken, though 40.4% of them considered that their indication was very urgent. DISCUSSION AND CONCLUSION: The overall complication rate was low, and patients agreed to the measures taken; however, especially hernia patients showed increasing symptoms and some acute incarcerations. It seems reasonable to monitor symptomatic patients closely, in order to prioritise them when surgical capacity is restricted.

Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

BACKGROUND: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. METHODS: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. RESULTS: Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. CONCLUSIONS: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

Association Between Weight Loss and Glycemic Outcomes: A Post Hoc Analysis of a Remote Patient Monitoring Program for Diabetes Management.

Background: Evidence-based guidelines for the management of type 2 diabetes (T2D) consist of blood glucose monitoring, medication adherence, and lifestyle modifications that may particularly benefit from reminders, consultation, education, and behavioral reinforcements through remote patient monitoring (RPM). Objectives: To identify predictors of weight loss and to examine the association between weight loss and hemoglobin A1C (HbA1C) outcomes for T2D patients who were enrolled in an RPM program for diabetes management. Materials and Methods: The study applied logistic and ordinary least-squares regression models to examine the relationship between baseline characteristics and the likelihood of weight loss during the RPM, and how the magnitude of weight loss was related to changes in HbA1C outcomes for 1,103 T2D patients who went through 3 months of RPM from 2014 to 2017. Results: Older patients were 3% more likely to have weight loss (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.05), whereas patients with higher baseline HbA1C had 9% reduced odds (OR, 0.91; 95% CI, 0.85-0.97) of experiencing weight loss. For every pound of weight lost, there was a 0.02-point (95% CI, 0.01-0.03) reduction on the HbA1C measured at the end of the RPM. Moreover, compared with those who had weight loss of ≤3%, participants who had lost 5-7%, or >7% of their baseline weight had a 0.37- and 0.58-point reduction in HbA1C, respectively. Conclusions: This study revealed a notable relationship between weight loss and positive HbA1C outcomes for T2D patients in an RPM-facilitated diabetes management program, which pointed to the potential of integrating evidence-based lifestyle modification programs into future telemedicine programs to improve diabetes management outcomes.

Histopathologic quantification of viable tumor versus treatment effect in surgically resected recurrent glioblastoma.

PURPOSE: The prognostic impact of the histopathologic features of recurrent glioblastoma surgical specimens is unknown. We sought to determine whether key histopathologic characteristics in glioblastoma tumors resected after chemoradiotherapy are associated with overall survival (OS). METHODS: The following characteristics were quantified in recurrent glioblastoma specimens at our institution: extent of viable tumor (accounting for % of specimen comprised of tumor and tumor cellularity), mitoses per 10 high-power fields (0, 1-10, > 10), Ki-67 proliferative index (0-100%), hyalinization (0-6; none to extensive), rarefaction (0-6), hemosiderin (0-6), and % of specimen comprised of geographic necrosis (0-100%; converted to 0-6 scale). Variables associated with OS in univariate analysis, as well as age, eastern cooperative oncology group performance status (ECOG PS), extent of repeat resection, time from initial diagnosis to repeat surgery, and O6-methylguanine-DNA methyltransferase promoter methylation, were included in a multivariable Cox proportional hazards model. RESULTS: 37 specimens were assessed. In a multivariate model, high Ki-67 proliferative index was the only histopathologic characteristic associated with worse OS following repeat surgery for glioblastoma (hazard ratio (HR) 1.3, 95% CI 1.1-1.5, p = 0.003). Shorter time interval from initial diagnosis to repeat surgery (HR 1.11, 95% CI 1.02-1.21, p = 0.016) and ECOG PS ≥ 2 (HR 4.19, 95% CI 1.72-10.21, p = 0.002) were also independently associated with inferior OS. CONCLUSION: In patients with glioblastoma undergoing repeat resection following chemoradiotherapy, high Ki-67 index in the recurrent specimen, short time to recurrence, and poor PS are independently associated with worse OS. Histopathologic quantification of viable tumor versus therapy-related changes has limited prognostic influence.

Diabetes Management Through Remote Patient Monitoring: The Importance of Patient Activation and Engagement with the Technology.

Background: The documented efficacy and promise of telemedicine in diabetes management does not necessarily mean that it can be easily translated into clinical practice. An important barrier concerns patient activation and engagement with telemedicine technology. Objective: To assess the importance of patient activation and engagement with remote patient monitoring technology in diabetes management among patients with type 2 diabetes. Methods: Ordinary least squares and logistic regression analyses were used to examine how patient activation and engagement with remote patient monitoring technology were related to changes in hemoglobin A1c (HbA1c) for 1,354 patients with type 2 diabetes monitored remotely for 3 months between 2015 and 2017. Results: Patients with more frequent and regular participation in remote monitoring had lower HbA1c levels at the end of the program. Compared to patients who uploaded their biometric data every 2 days or less frequently, patients who maintained an average frequency of one upload per day were less likely to have a postmonitoring HbA1c > 9% after adjusting for selected covariates on baseline demographics and health conditions. Conclusions: Higher levels of patient activation and engagement with remote patient monitoring technology were associated with better glycemic control outcomes. Developing targeted interventions for different groups of patients to promote their activation and engagement levels would be important to improve the effectiveness of remote patient monitoring in diabetes management.

Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma.

BACKGROUND & AIMS: Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, the aim of this study was to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC. METHODS: Fluorescence-activated cell scanning (FACS) was applied to detect various taMP populations in patients' sera that were associated with the presence of a tumour (AnnexinV+ EpCAM+ CD147+ taMPs) or could discriminate between cirrhosis (due to HCV or HBV) and liver cancers (AnnexinV+ EpCAM+ ASGPR1+ taMPs). In total 172 patients with liver cancer (HCC or CCA), 54 with cirrhosis and no liver neoplasia, and 202 control subjects were enrolled. RESULTS: The results indicate that AnnexinV+ EpCAM+ CD147+ taMPs were elevated in HCC and CCA. Furthermore, AnnexinV+ EpCAM+ ASGPR1+ CD133+ taMPs allowed the distinction of liver malignancies (HCC or CCA) and cirrhosis from tumour-free individuals and, more importantly, from patients carrying other non-liver cancers. In addition, AnnexinV+ EpCAM+ ASGPR1+ taMPs were increased in liver cancer-bearing patients compared to patients with cirrhosis that lacked any detectable liver malignancy. The smallest sizes of successfully detected cancers were ranging between 11-15mm. AnnexinV+ EpCAM+ ASGPR1+ taMPs decreased at 7days after curative R0 tumour resection suggesting close correlations with tumour presence. ROC values, sensitivity/specificity scores and positive/negative predictive values (>78%) indicated a potent diagnostic accuracy of AnnexinV+ EpCAM+ ASGPR1+ taMPs. CONCLUSION: These data provide strong evidence that AnnexinV+ EpCAM+ ASGPR1+ taMPs are a novel biomarker of HCC and CCA liquid biopsy that permit a non-invasive assessment of the presence and possible extent of these cancers in patients with advanced liver diseases. LAY SUMMARY: Microparticles (MPs) are small vesicles that bleb from the membrane of every cell, including cancer cells, and are released to circulate in the bloodstream. Since their surface composition is similar to the surface of their underlying parental cell, MPs from the bloodstream can be isolated and by screening their surface components, the presence of their parental cells can be identified. This way, it was possible to detect and discriminate between patients bearing liver cancer and chronic liver cirrhosis.

[Characteristics and Treatment Strategies for Penetrating Injuries on the Example of Gunshot and Blast Victims without Ballistic Body Armour in Afghanistan (2009 - 2013)]. / Besonderheiten und Versorgung penetrierender Verletzungen am Beispiel von Schuss- und Explosionsopfern ohne ballistischen Körperschutz in Afghanistan (2009 ­â€Š2013).

Much like other countries, Germany has recently seen terrorist attacks being planned, executed or prevented at the last minute. This highlights the need for expertise in the treatment of penetrating torso traumas by bullets or explosions. Data on the treatment of firearm injuries and, even more so, blast injuries often stems from crises or war regions. However, it is difficult to compare injuries from such regions with injuries from civilian terrorist attacks due to the ballistic body protection (protective vests, body armour) worn by soldiers. Methods An analysis was performed based on data from patients who were treated in the German Military Hospital Mazar-e Sharif for gunshots or injuries from explosions in the years 2009 to 2013. The data selection was based on patients with penetrating injuries to the thorax and/or abdomen. For better comparability with civilian attack scenarios, this study only included civilian patients without ballistic body protection (body armour, protective vests). Results Out of 117 analysed patients, 58 were affected by firearms and 59 by explosive injuries of the thorax or abdomen. 60% of patients had a thoracic injury, 69% had an abdominal injury, and 25.6% had combined thoracic-abdominal injuries. Blast injury patients were significantly more affected by thoracic trauma. As regards abdominal injuries, liver, intestinal, and colonic lesions were leading in number. Patients with blast injuries had significantly more injured organs and a significantly higher ISS averaging 29. 26% of the shot patients and 41% of the blast wounded patients received Damage Control Surgery (DCS). Despite a lower ISS, gunshot victims did not have a lower total number of operations per patient. Overall mortality was 13.7% (10.3% gunshot wounds, 16.7% blast injury). The highest mortality rate (25.7%) was recorded for patients with combined thoracoabdominal injuries (vs. 8.3% for thoracic and 8.7% for abdominal injuries). The ISS of deceased patients was significantly higher at 32.9%. Conclusion Patients without ballistic protection of the torso have high mortality rates, especially when suffering thoracoabdominal blast injuries. Blast injuries frequently lead to the DCS indication. The care of firearm and blast injury patients requires knowledge and competence in the damage control procedures for thorax and abdomen.

Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC.

Analysis of surgical quality indicators after certification as a Hernia Center.

Certifications are an increasingly used tool of quality management in the health care system. The primary goal is to improve the quality of treatment due to implemented measures based on a defined catalog of criteria and standardization of the treatment processes. However, the extent to which this affects medical and health-economic indicators is unknown. Therefore, the study aims to examine the possible effects of the certification as a Reference Center for Hernia Surgery on the treatment quality and reimbursement dimensions. The observation and recording periods were defined as 3 years before (2013-2015) and 3 years after certification as a "Reference Center for Hernia Surgery" (2016-2018). Possible changes due to the certification were examined based on multidimensional data collection and analysis. In addition, the aspects of structure, process and result quality, and the reimbursement situation were reported. One thousand three hundred and nineteen cases before and one thousand four hundred and three cases after certification were included. After the certification, the patients were older (58.1 ± 16.1 vs. 64.0 ± 16.1 years, p < 0.01), had a higher CMI (1.01 vs. 1.06), and a higher ASA score (< III 86.9 vs. 85.5%, p < 0.01). The interventions became more complex (e.g., recurrent incisional hernias 0.5% vs. 1.9%, p < 0.01). The mean length of hospital stay was significantly reduced for incisional hernias (8.8 ± 5.8 vs. 6.7 ± 4.1 days, p < 0.001). The reoperation rate for incisional hernias also decreased significantly from 8.24 to 3.66% (p = 0.04). The postoperative complication rate for inguinal hernias was significantly reduced (3.1 vs. 1.1%, p = 0.002). The reimbursement of the hernia center increased by 27.6%. There were positive changes in process and outcome quality and reimbursement after the certification, which supports the effectivity of certifications in hernia surgery.

[The use of botulinum toxin in hernia surgery: results of a survey in certified hernia centers]. / Die Anwendung von Botulinumtoxin in der Hernienchirurgie: Ergebnisse einer Umfrage an zertifizierten Hernienzentren.

BACKGROUND: Botulinum toxin application into the abdominal wall prior to major hernia repair can reduce the complexity of surgery and has been increasingly used in recent years, even if it is an off-label use. OBJECTIVE: To what extent is botulinum toxin used in hernia surgery in German-speaking countries and what is the current evidence in the literature? MATERIAL AND METHODS: In a voluntary online survey of German Society for General and Visceral Surgery (DGAV)-certified competence centers and reference centers for hernia surgery, aspects of botulinum toxin application were surveyed and the results analyzed. RESULTS: A total of 57 centers took part in the survey, of which 27 (47%) use botulinum toxin. The main reasons for not using it were lack of experience and reimbursement. Of the centers 85% have treated less than 50 patients with botulinum toxin. The main indications were midline hernias (M2-4 according to the EHS classification) with a hernia gap > 10 cm (W3 according to EHS classification) and loss of domain situations. The application was predominantly ultrasound-guided by designated hernia surgeons with 100-200 Allergan or 500 Speywood units 4-6 weeks preoperatively and without complications related to the botulinum toxin application. CONCLUSION: Botulinum toxin injections in hernia surgery appear to be safe and effective. Ultrasound-guided preoperative bilateral administration is supported by the available data. Specific course and information formats should be offered by the hernia surgery institutions.