Delineating genotype and parent-of-origin effect on the phenotype in MSH6-associated Lynch syndrome.

BACKGROUND: This study investigates the potential influence of genotype and parent-of-origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease-causing MSH6 germline variants. PATIENTS AND METHODS: A cohort of 1615 MSH6 variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant. Hazard ratios (HRs) were calculated using weighted Cox regression, considering external information to address ascertainment bias. The findings were cross-validated using the Prospective Lynch Syndrome Database (PLSD) for endometrial cancer (EC). RESULTS: No significant association was observed between genotype and colorectal cancer (CRC) risk (HR = 1.06, 95% confidence interval [CI]: 0.77-1.46). Patients lacking expected RNA expression exhibited a reduced risk of EC (Reference Cohort 1: HR = 0.68, 95% CI: 0.43-1.03; Reference Cohort 2: HR = 0.63, 95% CI: 0.46-0.87). However, these results could not be confirmed in the PLSD. Moreover, no association was found between POE and CRC risk (HR = 0.78, 95% CI: 0.52-1.17) or EC risk (Reference Cohort 1: HR = 0.93, 95% CI: 0.65-1.33; Reference Cohort 2: HR = 0.8, 95% CI: 0.64-1.19). DISCUSSION AND CONCLUSION: No evidence of POE was detected in MSH6 families. While RNA expression may be linked to varying risks of EC, further investigation is required to explore this observation.

Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS).

Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020-March 2023) and genetic diagnoses from medical files. Associations between lifestyle and breast cancer were calculated using logistic regression corrected for age. Index patients with breast cancer before PHTS diagnosis (breast cancer index) were excluded for ascertainment bias correction. In total, 125 patients were included who completed the questionnaire at a mean age of 44 years (SD = 13). This included 21 breast cancer indexes (17%) and 39 females who developed breast cancer at 43 years (SD = 9). Breast cancer patients performed about 1.1 times less often 0-1 times/week physical activity than ≥2 times (ORtotal-adj = 0.9 (95%CI 0.3-2.6); consumed daily about 1.2-1.8 times more often ≥1 than 0-1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4-4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4-6.9); were about 1.04-1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4-2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4-4.2)); and overweight or obesity (72%) was about 1.02-1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4-2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3-2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients' breast cancer risk is important.

The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2.

PURPOSE: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies. METHODS: Exome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291). RESULTS: In total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T>C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins. CONCLUSION: Our study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.

Nonoperative treatment of multiple rib fractures, the results to beat: International multicenter prospective cohort study among 845 patients.

BACKGROUND: Optimal treatment (i.e. nonoperative or operative) for patients with multiple rib fractures remains debated. Studies that compare treatments are rationalized by the alleged poor outcomes of nonoperative treatment. METHODS: The aim of this prospective international multicenter cohort study (between January 2018 and March 2021) with one-year follow-up, was to report contemporary outcomes of nonoperatively treated patients with multiple rib fractures. Including 845 patients with three or more rib fractures. Primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (HLOS), (pulmonary) complications, and quality of life. RESULTS: Mean age was 57.7 ± 17.0 years, median Injury Severity Score was 17 (13-22) and the median number of rib fractures was 6 (4-8). In-hospital mortality rate was 1.5% (n = 13), 112 (13.3%) patients had pneumonia and four (0.5%) patients developed a symptomatic non-union. The median HLOS was 7 (4-13) days, and median intensive care unit length of stay was 2 (1-5) days. Mean EQ-5D-5L index value was 0.83 ± 0.18 one year after trauma. Polytrauma patients had a median HLOS of 10 (6-18) days, a pneumonia rate of 17.6% (n = 77) and mortality rate of 1.7% (n = 7). Elderly patients (≥65 years) had a median HLOS of 9 (5-15) days, a pneumonia rate of 19.7% (n = 57) and mortality rate of 4.1% (n = 12). CONCLUSIONS: Overall, nonoperative treatment of patients with multiple rib fractures shows low mortality and morbidity rate and good quality of life after one year. Future studies evaluating the benefit of operative stabilisation should use contemporary outcomes to establish the therapeutic margin of rib fixation. LEVEL OF EVIDENCE: Level III, Therapeutic/Care Management.

Outcome of severely injured patients in a unique trauma system with 24/7 double trauma surgeon on-call service.

BACKGROUND: The presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system. METHODS: From 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed. RESULTS: Three hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%). CONCLUSION: In this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes.

Discordant Staining Patterns and Microsatellite Results in Tumors of MSH6 Pathogenic Variant Carriers.

Diagnosis of Lynch syndrome (LS) caused by a pathogenic germline MSH6 variant may be complicated by discordant immunohistochemistry (IHC) and/or by a microsatellite stable (MSS) phenotype. This study aimed to identify the various causes of the discordant phenotypes of colorectal cancer (CRC) and endometrial cancer (EC) in MSH6-associated LS. Data were collected from Dutch family cancer clinics. Carriers of a (likely) pathogenic MSH6 variant diagnosed with CRC or EC were categorized based on an microsatellite instability (MSI)/IHC test outcome that might fail to result in a diagnosis of LS (eg, retained staining of all 4 mismatch repair proteins, with or without an MSS phenotype, and other staining patterns). When tumor tissue was available, MSI and/or IHC were repeated. Next-generation sequencing (NGS) was performed in cases with discordant staining patterns. Data were obtained from 360 families with 1763 (obligate) carriers. MSH6 variant carriers with CRC or EC (n = 590) were included, consisting of 418 CRCs and 232 ECs. Discordant staining was reported in 77 cases (36% of MSI/IHC results). Twelve patients gave informed consent for further analysis of tumor material. Upon revision, 2 out of 3 MSI/IHC cases were found to be concordant with the MSH6 variant, and NGS showed that 4 discordant IHC results were sporadic rather than LS-associated tumors. In 1 case, somatic events explained the discordant phenotype. The use of reflex IHC mismatch repair testing, the current standard in most Western countries, may lead to the misdiagnosis of germline MSH6 variant carriers. The pathologist should point out that further diagnostics for inheritable colon cancer, including LS, should be considered in case of a strong positive family history. Germline DNA analysis of the mismatch repair genes, preferably as part of a larger gene panel, should therefore be considered in potential LS patients.

In patients with combined clavicle and multiple rib fractures, does fracture fixation of the clavicle improve clinical outcomes? A multicenter prospective cohort study of 232 patients.

BACKGROUND: Clavicle and rib fractures are often sustained concomitantly. The combination of injuries may result in decreased stability of the chest wall, making these patients prone to (respiratory) complications and prolonged hospitalization. This study aimed to assess whether adding chest wall stability by performing clavicle fixation improves clinical outcomes in patients with concurrent clavicle and rib fractures. METHODS: A prospective multicenter study was performed including all adult patients admitted between January 2018 and March 2021 with concurrent ipsilateral clavicle and rib fractures. Patients treated operatively versus nonoperatively for their clavicle fracture were matched using propensity score matching. The primary outcome was hospital length of stay (HLOS). Secondary outcomes were intensive care unit length of stay, duration of mechanical ventilation, pain, complications, and quality of life at 6 weeks and 12 months of follow-up. RESULTS: In total, 232 patients with concomitant ipsilateral clavicle and rib fractures were included. Fifty-two patients (22%) underwent operative treatment of which 39 could be adequately matched to 39 nonoperatively treated patients. No association was observed between clavicle plate fixation and HLOS (mean difference, 2.3 days; 95% confidence interval, -2.1 to 6.8; p = 0.301) or any secondary endpoint. Eight of the 180 nonoperatively treated patients (4%) had a symptomatic nonunion, for which 5 underwent secondary clavicle fixation. CONCLUSION: We found no evidence that, in patients with combined clavicle and multiple rib fractures, plate fixation of the clavicle reduces HLOS, pain, or (pulmonary) complications, nor that it improves quality of life. STUDY TYPE: Therapeutic/Care Management; Level III.

Non-operative vs. operative treatment for multiple rib fractures after blunt thoracic trauma: a multicenter prospective cohort study.

BACKGROUND: Patients with multiple rib fractures without a clinical flail chest are increasingly being treated with rib fixation; however, high-quality evidence to support this development is lacking. METHODS: We conducted a prospective multicenter observational study comparing rib fixation to non-operative treatment in all patients aged 18 years and older with computed tomography confirmed multiple rib fractures without a clinical flail chest. Three centers performed rib fixation as standard of care. For adequate comparison, the other three centers performed only non-operative treatment. As such clinical equipoise formed the basis for the comparison in this study. Patients were matched using propensity score matching. RESULTS: In total 927 patients with multiple rib fractures were included. In the three hospitals that performed rib fixation, 80 (14%) out of 591 patients underwent rib fixation. From the nonoperative centers, on average 71 patients were adequately matched to 71 rib fixation patients after propensity score matching. Rib fixation was associated with an increase in hospital length of stay (HLOS) of 4.9 days (95%CI 0.8-9.1, p = 0.02) and a decrease in quality of life (QoL) measured by the EQ5D questionnaire at 1 year of 0.1 (95% CI - 0.2-0.0, p = 0.035) compared to non-operative treatment. A subgroup analysis of patients who received operative care within 72 h showed a similar decrease in QoL. Up to 22 patients (28%) who underwent surgery experienced implant-related irritation. CONCLUSIONS: We found no benefits and only detrimental effects associated with rib fixation. Based on these results, we do not recommend rib fixation as the standard of care for patients with multiple rib fractures. TRIAL REGISTRATION: Registered in the Netherlands Trial Register NTR6833 on 13/11/2017.

Epidemiology of combined clavicle and rib fractures: a systematic review.

PURPOSE: The aim of this systematic review was to provide an overview of the incidence of combined clavicle and rib fractures and the association between these two injuries. METHODS: A systematic literature search was performed in the MEDLINE, EMBASE, and CENTRAL databases on the 14th of August 2020. Outcome measures were incidence, hospital length of stay (HLOS), intensive care unit admission and length of stay (ILOS), duration of mechanical ventilation (DMV), mortality, chest tube duration, Constant-Murley score, union and complications. RESULTS: Seven studies with a total of 71,572 patients were included, comprising five studies on epidemiology and two studies on treatment. Among blunt chest trauma patients, 18.6% had concomitant clavicle and rib fractures. The incidence of rib fractures in polytrauma patients with clavicle fractures was 56-60.6% versus 29% in patients without clavicle fractures. Vice versa, 14-18.8% of patients with multiple rib fractures had concomitant clavicle fractures compared to 7.1% in patients without multiple rib fractures. One study reported no complications after fixation of both injuries. Another study on treatment, reported shorter ILOS and less complications among operatively versus conservatively treated patients (5.4 ± 1.5 versus 21 ± 13.6 days). CONCLUSION: Clavicle fractures and rib fractures are closely related in polytrauma patients and almost a fifth of all blunt chest trauma patients sustain both injuries. Definitive conclusions could not be drawn on treatment of the combined injury. Future research should further investigate indications and benefits of operative treatment of this injury.

Epidemiology and outcome of rib fractures: a nationwide study in the Netherlands.

PURPOSE: Rib fractures following thoracic trauma are frequently encountered injuries and associated with a significant morbidity and mortality. The aim of this study was to provide current data on the epidemiology, in-hospital outcomes and 30-day mortality of rib fractures, and to evaluate these results for different subgroups. METHODS: A nationwide retrospective cohort study was performed with the use of the Dutch Trauma Registry which covers 99% of the acutely admitted Dutch trauma population. All patients aged 18 years and older admitted to the hospital between January 2015 and December 2017 with one or more rib fractures were included. Incidence rates were calculated using demographic data from the Dutch Population Register. Subgroup analyses were performed for flail chest, polytrauma, primary thoracic trauma, and elderly patients. RESULTS: A total of 14,850 patients were admitted between 2015 and 2017 with one or more rib fractures, which was 6.0% of all trauma patients. Of these, 573 (3.9%) patients had a flail chest, 4438 (29.9%) were polytrauma patients, 9273 (63.4%) were patients with primary thoracic trauma, and 6663 (44.9%) were elderly patients. The incidence rate of patients with rib fractures for the entire cohort was 29 per 100.000 person-years. The overall 30-day mortality was 6.9% (n = 1208) with higher rates observed in flail chest (11.9%), polytrauma (14.8%), and elderly patients (11.7%). The median hospital length of stay was 6 days (IQR, 3-11) and 37.3% were admitted to the intensive care unit (ICU). CONCLUSIONS: Rib fractures are a relevant and frequently occurring problem among the trauma population. Subgroup analyses showed that there is a substantial heterogeneity among patients with rib fractures with considerable differences regarding the epidemiology, in-hospital outcomes, and 30-day mortality.

Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma.

Multiple myeloma (MM) is a plasma cell malignancy whereby a single clone of plasma cells over-propagates in the bone marrow, resulting in the increased production of monoclonal immunoglobulin. While the complex genetic architecture of MM is well characterized, much less is known about germline variants predisposing to MM. Genome-wide sequencing approaches in MM families have started to identify rare high-penetrance coding risk alleles. In addition, genome-wide association studies have discovered several common low-penetrance risk alleles, which are mainly located in the non-coding genome. Here, we further explored the genetic basis in familial MM within the non-coding genome in whole-genome sequencing data. We prioritized and characterized 150 upstream, 5' untranslated region (UTR) and 3' UTR variants from 14 MM families, including 20 top-scoring variants. These variants confirmed previously implicated biological pathways in MM development. Most importantly, protein network and pathway enrichment analyses also identified 10 genes involved in mitogen-activated protein kinase (MAPK) signaling pathways, which have previously been established as important MM pathways.

Is a chest radiograph indicated after chest tube removal in trauma patients? A systematic review.

PURPOSE: The aim of this systematic review was to assess the necessity of routine chest radiographs after chest tube removal in ventilated and nonventilated trauma patients. METHODS: A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, and CINAHL on May 15, 2020. Quality assessment was performed using the Methodological Index for Nonrandomized Studies criteria. Primary outcome measures were abnormalities on postremoval chest radiograph (e.g., recurrence of a pneumothorax, hemothorax, pleural effusion) and reintervention after chest tube removal. Secondary outcome measures were emergence of new clinical symptoms or vital signs after chest tube removal. RESULTS: Fourteen studies were included, consisting of seven studies on nonventilated patients and seven studies on combined cohorts of ventilated and nonventilated patients, all together containing 1,855 patients. Nonventilated patients had abnormalities on postremoval chest radiograph in 10% (range across studies, 0-38%) of all chest tubes and 24% (range, 0-78%) of those underwent reintervention. In the studies that reported on clinical symptoms after chest tube removal, all patients who underwent reintervention also had symptoms of recurrent pathology. Combined cohorts of ventilated and nonventilated patients had abnormalities on postremoval chest radiograph in 20% (range, 6-49%) of all chest tubes and 45% (range, 8-63%) of those underwent reintervention. CONCLUSION: In nonventilated patients, one in ten developed recurrent pathology after chest tube removal and almost a quarter of them underwent reintervention. In two studies that reported on clinical symptoms, all reinterventions were performed in patients with symptoms of recurrent pathology. In these two studies, omission of routine postremoval chest radiograph seemed safe. However, current literature remains insufficient to draw definitive conclusions on this matter, and future studies are needed. LEVEL OF EVIDENCE: Systematic review study, level IV.

The Development of Swedish Military Healthcare System: Part II-Re-evaluating the Military and Civilian Healthcare Systems in Crises Through a Dialogue and Study Among Practitioners.

INTRODUCTION: Historical changes have transformed Sweden from being an offensive to a defensive and collaborative nation with national and international engagement, allowing it to finally achieve the ground for the civilian-military collaboration and the concept of a total defense healthcare. At the same time, with the decreasing number of international and interstate conflicts, and the military's involvement in national emergencies and humanitarian disaster relief, both the need and the role of the military healthcare system within the civilian society have been challenged. The recent impact of the COVID-19 in the USA and the necessity of military involvement have led health practitioners to anticipate and re-evaluate conditions that might exceed the civilian capacity of their own countries and the need to have collaboration with the military healthcare. This study investigated both these challenges and views from practitioners regarding the benefits of such collaboration and the manner in which it would be initiated. MATERIAL AND METHOD: A primary study was conducted among responsive countries using a questionnaire created using the Nominal Group Technique. Relevant search subjects and keywords were extracted for a systematic review of the literature, according to the PRISMA model. RESULTS: The 14 countries responding to the questionnaire had either a well-developed military healthcare system or units created in collaboration with the civilian healthcare. The results from the questionnaire and the literature review indicated a need for transfer of military medical knowledge and resources in emergencies to the civilian health components, which in return, facilitated training opportunities for the military staff to maintain their skills and competencies. CONCLUSIONS: As the world witnesses a rapid change in the etiology of disasters and various crises, neither the military nor the civilian healthcare systems can address or manage the outcomes independently. There is an opportunity for both systems to develop future healthcare in collaboration. Rethinking education and training in war and conflict is indisputable. Collaborative educational initiatives in disaster medicine, public health and complex humanitarian emergencies, international humanitarian law, and the Geneva Convention, along with advanced training in competency-based skill sets, should be included in the undergraduate education of health professionals for the benefit of humanity.

Complications and outcome after rib fracture fixation: A systematic review.

BACKGROUND: In recent years, there has been a growing interest in operative treatment for multiple rib fractures and flail chest. However, to date, there is no comprehensive study that extensively focused on the incidence of complications associated with rib fracture fixation. Furthermore, there is insufficient knowledge about the short- and long-term outcomes after rib fracture fixation. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The MEDLINE, EMBASE, and Cochrane databases were searched to identify studies reporting on complications and/or outcome of surgical treatment after rib fractures. Complications were subdivided into (1) surgery- and implant-related complications, (2) bone-healing complications, (3) pulmonary complications, and (4) mortality. RESULTS: Forty-eight studies were included, with information about 1,952 patients who received rib fracture fixation because of flail chest or multiple rib fractures. The overall risk of surgery- and implant-related complications was 10.3%, with wound infection in 2.2% and fracture-related infection in 1.3% of patients. Symptomatic nonunion was a relatively uncommon complication after rib fixation (1.3%). Pulmonary complications were found in 30.9% of patients, and the overall mortality was 2.9%, of which one third appeared to be the result of the thoracic injuries and none directly related to the surgical procedure. The most frequently used questionnaire to assess patient quality of life was the EuroQol-5D (EQ-5D) (n = 4). Four studies reporting on the EQ-5D had a weighted mean EQ-5D index of 0.80 indicating good quality of life after rib fracture fixation. CONCLUSION: Surgical fixation can be considered as a safe procedure with a considerably low complication risk and satisfactory long-term outcomes, with surgery- and implant-related complications in approximately 10% of the patients. However, the clinically most relevant complications such as infections occur infrequently, and the number of complications requiring immediate (surgical) treatment is low. LEVEL OF EVIDENCE: Systematic Review, level III.

Exome sequencing identifies the first genetic determinants of sirenomelia in humans.

Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.

The evolution of trauma care in the Netherlands over 20 years.

INTRODUCTION: In 1999 an inclusive trauma system was initiated in the Netherlands and a nationwide trauma registry, including all admitted trauma patients to every hospital, was started. The Dutch trauma system is run by trauma surgeons who treat both the truncal (visceral) and extremity injuries (fractures). MATERIALS AND METHODS: In this comprehensive review based on previous published studies, data over the past 20 years from the central region of the Netherlands (Utrecht) was evaluated. RESULTS: It is demonstrated that the initiation of the trauma systems and the governance by the trauma surgeons led to a region-wide mortality reduction of 50% and a mortality reduction for the most severely injured of 75% in the level 1 trauma centre. Furthermore, major improvements were found in terms of efficiency, demonstrating the quality of the current system and its constructs such as the type of surgeon. Due to the major reduction in mortality over the past few years, the emphasis of trauma care evaluation shifts towards functional outcome of severely injured patients. For the upcoming years, centralisation of severely injured patients should also aim at the balance between skills in primary resuscitation and surgical stabilization versus longitudinal surgical involvement. CONCLUSION: Further centralisation to a limited number of level 1 trauma centres in the Netherlands is necessary to consolidate experience and knowledge for the trauma surgeon. The future trauma surgeon, as specialist for injured patients, should be able to provide the vast majority of trauma care in this system. For the remaining part, intramural, regional and national collaboration is essential.

Multicentre prospective cohort study of nonoperative versus operative treatment for flail chest and multiple rib fractures after blunt thoracic trauma: study protocol.

INTRODUCTION: A trend has evolved towards rib fixation for flail chest although evidence is limited. Little is known about rib fixation for multiple rib fractures without flail chest. The aim of this study is to compare rib fixation with nonoperative treatment for both patients with flail chest and patients with multiple rib fractures. METHODS AND ANALYSIS: In this study protocol for a multicentre prospective cohort study, all patients with three or more rib fractures admitted to one of the five participating centres will be included. In two centres, rib fixation is performed and in three centres nonoperative treatment is the standard-of-care for flail chest or multiple rib fractures. The primary outcome measures are intensive care unit length of stay and hospital length of stay for patients with a flail chest and patients with multiple rib fractures, respectively. Propensity score matching will be used to control for potential confounding of the relation between treatment modality and length of stay. All analyses will be performed separately for patients with flail chest and patients with multiple rib fractures without flail chest. ETHICS AND DISSEMINATION: The regional Medical Research Ethics Committee UMC Utrecht approved a waiver of consent (reference number WAG/mb/17/024787 and METC protocol number 17-544/C). Patients will be fully informed of the purpose and procedures of the study, and signed informed consent will be obtained in agreement with the General Data Protection Regulation. Study results will be submitted for peer review publication. TRIAL REGISTRATION NUMBER: NTR6833.

A 5-Year Evaluation of the Implementation of Triple Diagnostics for Early Detection of Severe Necrotizing Soft Tissue Disease: A Single-Center Cohort Study.

BACKGROUND: The standardized approach with triple diagnostics (surgical exploration with visual inspection, microbiological and histological examination) has been proposed as the golden standard for early diagnosis of severe necrotizing soft tissue disease (SNSTD, or necrotizing fasciitis) in ambivalent cases. This study's primary aim was to evaluate the protocolized approach after implementation for diagnosing (early) SNSTD and relate this to clinical outcome. METHODS: A cohort study analyzing a 5-year period was performed. All patients undergoing surgical exploration (with triple diagnostics) for suspected SNSTD since implementation were prospectively identified. Demographics, laboratory results and clinical outcomes were collected and analyzed. RESULT: Thirty-six patients underwent surgical exploration with eight (22%) negative explorations. The overall 30-day mortality rate was 25%, with an early, SNSTD-related mortality rate of 11% (n = 3). Of these, one patient (4%) underwent primary amputation, but died during surgery. No significant differences between baseline characteristics were found between patients diagnosed with SNSTD in early/indistinctive or late/obvious stage. Patient diagnosed at an early stage had a significantly shorter ICU stay (2 vs. 6 days, p = 0.031). Mortality did not differ between groups; patients who died were all ASA IV patients. CONCLUSION: Diagnosing SNSTD using the approach with triple diagnostics resulted in a low mortality rate and only a single amputation in a pre-terminal patient in the first 5 years after implementation. All deceased patients had multiple preexisting comorbidities consisting of severe systemic diseases, such as end-stage heart failure. Early detection proved to facilitate faster recovery with shorter ICU stay.

Epidural Analgesia for Severe Chest Trauma: An Analysis of Current Practice on the Efficacy and Safety.

BACKGROUND: Adequate pain control is essential in the treatment of patients with traumatic rib fractures. Although epidural analgesia is recommended in international guidelines, the use remains debatable and is not undisputed. The aim of this study was to describe the efficacy and safety of epidural analgesia in patients with multiple traumatic rib fractures. METHODS: A retrospective cohort study was performed. Patients with ≥3 rib fractures following blunt chest trauma who received epidural analgesia between January 2015 and January 2018 were included. The main outcome parameters were the success rate of epidural analgesia and the incidence of medication-related side effects and catheter-related complications. RESULTS: A total of 76 patients were included. Epidural analgesia was successful in a total of 45 patients (59%), including 22 patients without and in 23 patients with an additional analgesic intervention. In 14 patients (18%), epidural analgesia was terminated early without intervention due to insufficient sensory blockade (n=4), medication-related side effects (n=4), and catheter-related complications (n=6). In 17 patients (22%), the epidural catheter was removed after one or multiple additional interventions due to insufficient pain control. Minor epidural-related complications or side effects were encountered in 36 patients (47%). One patient had a major complication (opioid intoxication). CONCLUSION: Epidural analgesia was successful in 59% of patients; however, 30% needed additional analgesic interventions. As about half of the patients had epidural-related complications, it remains debatable whether epidural analgesia is a sufficient treatment modality in patients with multiple rib fractures.