Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

Randomized Controlled Trial of Surgical Rib Fixation to Nonoperative Management in Severe Chest Wall Injury.

OBJECTIVE: To compare the effectiveness of surgical stabilization of rib fractures (SSRFs) to nonoperative management in severe chest wall injury. BACKGROUND: SSRF has been shown to improve outcomes in patients with clinical flail chest and respiratory failure. However, the effect of SSRF outcomes in severe chest wall injuries without clinical flail chest is unknown. METHODS: Randomized controlled trial comparing SSRF to nonoperative management in severe chest wall injury, defined as: (1) a radiographic flail segment without clinical flail or (2) ≥5 consecutive rib fractures or (3) any rib fracture with bicortical displacement. Randomization was stratified by the unit of admission as a proxy for injury severity. Primary outcome was hospital length of stay (LOS). Secondary outcomes included intensive care unit (ICU) LOS, ventilator days, opioid exposure, mortality, and incidences of pneumonia and tracheostomy. Quality of life at 1, 3, and 6 months was measured using the EQ-5D-5L survey. RESULTS: Eighty-four patients were randomized in an intention-to-treat analysis (usual care = 42, SSRF = 42). Baseline characteristics were similar between groups. The numbers of total fractures, displaced fractures, and segmental fractures per patient were also similar, as were the incidences of displaced fractures and radiographic flail segments. Hospital LOS was greater in the SSRF group. ICU LOS and ventilator days were similar. After adjusting for the stratification variable, hospital LOS remained greater in the SSRF group (RR: 1.48, 95% CI: 1.17-1.88). ICU LOS (RR: 1.65, 95% CI: 0.94-2.92) and ventilator days (RR: 1.49, 95% CI: 0.61--3.69) remained similar. Subgroup analysis showed that patients with displaced fractures were more likely to have LOS outcomes similar to their usual care counterparts. At 1 month, SSRF patients had greater impairment in mobility [3 (2-3) vs 2 (1-2), P = 0.012] and self-care [2 (1-2) vs 2 (2-3), P = 0.034] dimensions of the EQ-5D-5L. CONCLUSIONS: In severe chest wall injury, even in the absence of clinical flail chest, the majority of patients still reported moderate to extreme pain and impairment of usual physical activity at one month. SSRF increased hospital LOS and did not provide any quality of life benefit for up to 6 months.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

Impact of Social Media on Community Consultation in Exception From Informed Consent Clinical Trials.

BACKGROUND: Exception from informed consent (EFIC) allows clinician scientists to perform much needed emergency research. Obtaining this exception, however, requires many meetings with community groups for consultation, which can make the process time-consuming and expensive. We aim to determine the impact of using social media in lieu of some community meetings in an effort to obtain an EFIC. MATERIALS AND METHODS: An economic analysis of four randomized clinical trials was performed. Costs were conservatively estimated using personnel costs, social media costs, and adjusted to 2016 US dollars. People were considered reached if they attended a community meeting or were directed to the study website by social media and spent ≥1 min. RESULTS: The Early Whole Blood study required 14 meetings, reached 272 people, and cost $8260 ($30/person reached). The Pragmatic, Randomized Optimal Platelet and Plasma Ratios study required 14 meetings, reached 260 people, and cost $7479 overall ($29/person reached). The Prehospital Tranexamic Acid Use for Traumatic Brain Injury study required 12 meetings, reached 198 people, and cost $6340 ($32/person reached). Only the damage control laparotomy trial utilized social media in lieu of some community meetings. The damage control laparotomy trial required six meetings at which 137 people were reached. The $1000 social media campaign reached 229 people. The cost was $3977 overall and $11/person reached. CONCLUSIONS: Including a social media campaign during the EFIC process increased the number of potential patients reached and reduced total and per person costs reached costs. Obtaining an EFIC for future emergency clinical trials may be facilitated by the inclusion of a social media campaign.

The Effects of Missed Doses of Antibiotics on Hospitalized Patient Outcomes.

BACKGROUND: Missing doses of antibiotics in hospitalized patients is a well-described but inadequately recognized issue. We hypothesized that missing doses of antibiotics decreases quality of care. METHODS: Retrospective study on patients admitted to the Shock Trauma ICU from February to June 2015. Patients prescribed a multidose course of antibiotics were evaluated. A missed antibiotic dose was one ordered but never given (a completely missed dose) or a dose that was not given within an hour before or after the planned time (an off-schedule missed dose). Patient outcomes included a positive culture, ventilator, ICU and hospital length of stay (LOS), and mortality. Multiple statistical methods were used as appropriate; significance was set as P < 0.05. RESULTS: For the 5-mo study period, 280 patients were admitted and 200 met inclusion criteria. Eight percent of patients (16/200) did not miss any antibiotic doses, 39% (77/200) had only off-schedule doses, 2% (4/200) had only completely missed doses, and 51% (103/200) had both off-schedule and completely missed doses. For the 200 patients, 8167 doses were ordered and 2096 (26%) were missed. Adjusting for age, gender, BMI, injury severity score, and doses of antibiotics showed that those who miss doses off-schedule had longer LOS than those who do not miss doses of antibiotics. There was a significant nonlinear relationship between LOS and frequency of early (P-value = 0.02) and late (P-value = 0.01) doses. CONCLUSIONS: To reduce length of hospital stay and optimize quality, methods to improve compliance with antibiotic dosing schedules should be investigated.

Outcome of routine cerebrospinal fluid screening for enterovirus and human parechovirus infection among infants with sepsis-like illness or meningitis in Cornwall, UK.

Enteroviruses (EV) and human parechoviruses (HPeV) are known and emerging cause of sepsis-like illnesses in infants; however, testing is not yet routine. We retrospectively evaluated the number of diagnosed EV/HPeV infections in children under the age of 5 years who presented with sepsis-like illness or meningitis in Cornwall, UK, before and after routine implementation of viral screening of cerebrospinal fluid samples. During the 4-year period prior to routine testing, we identified 20 cases of EV meningitis and no cases of HPeV. In the year after introduction of routine screening, 27 cases of EV and 14 cases of HPeV were identified in 1 year. The majority of EV/HPeV infections occurred among children under 3 months old between May and August. Clinical and laboratory characteristics of EV and HPeV infections were mostly indistinguishable. We found that CSF pleocytosis and biochemistry-based testing strategy could miss 48.1 and 78.5% of EV and HPeV cases, respectively. With routine viral screening, the mean length of hospital stay (3.8 vs 5.9 days, P < 0.001) and antibiotic days (2.8 vs 4.7 days, P < 0.001) were significantly reduced in EV/HPeV-positive cases compared to a similar cohort without any detectable microbial aetiology. CONCLUSION: Routine EV and HPeV testing of CSF samples in children has the potential to reduce length of stay and antibiotic use. What is Known: • EV and HPeV are frequent cause of meningitis and sepsis-like illness among young children. • There is increasing evidence supporting routine EV and HPeV testing of paediatric CSF. What is New: • Outcome of routine EV and HPeV testing in Cornwall, UK. • The value of testing all paediatric CSF without any screening criteria. • A rapid diagnosis of EV/HPeV can significantly reduce length of hospital stay and unnecessary antibiotics.

Impact of the withdrawal of macrotextured implant on reconstruction practices.

INTRODUCTION: On 22 November 2018, the French Society for Plastic, Reconstructive and Aesthetic Surgery recommended that Allergan® macrotextured breast implants be recalled, a decision endorsed by the French national health products safety agency (ANSM) on 2nd April 2019. At the Georges-François Leclerc Cancer Center (CGFL) in Dijon, we decided to stop using macrotextured implants as of November 2018 in favor of smooth implants. The purpose of this study is to evaluate the impact of the recall of macrotextured implants on breast reconstruction surgical practices and their complications. METHODS: This is a single-centre, retrospective study performed at the CGFL in Dijon, France. Reconstruction techniques and complications were compared between two periods, i.e. before the recall of macrotextured breast implants (period 1: 1st September 2017-November 22, 2018) and after the recall (period 2: 23 November 2018-31st March 2020). All patients who underwent breast reconstruction for the first time were included. RESULTS: Data were collected from 168 reconstructions in period 2, and 159 in period 2. The rate of use of breast implants during reconstructions decreased significantly in period 2 (53.6% vs. 23.9%; P<0.001). The rate of autologous reconstructions increased significantly for muscle sparing latissimus dorsi (2.4% vs. 12.6%; P<0.001) and exclusive fat grafting (9.5% vs. 21.5%; P<0.01). Clavien-Dindo Stage IIIb complications decreased in period 2 (10% vs. 18.4%; P=0.04). CONCLUSION: Since the recall of macrotextured breast implants, the reconstruction rate has decreased in our centre in favor of autologous techniques with lower complication rates.

Evaluation of post-operative complications and adjuvant treatments following immediate prepectoral versus subpectoral direct-to-implant breast reconstruction without acellular dermal matrix.

BACKGROUND: In immediate breast reconstruction (IBR), it is unclear whether there is any difference in the complication rates between prepectoral versus subpectoral implant placement without acellular dermal matrix (ADM). AIM: To compare the rates of early post-operative complications and time to initiation of adjuvant treatment in patients undergoing IBR between prepectoral and subpectoral implant placement without ADM for the two surgical procedure. METHODS: We retrospectively retrieved data of patients who underwent IBR with prepectoral versus subpectoral implant placement between January 1, 2020 and December 31, 2022 in a large cancer center in France. RESULTS: We included 192 patients: 119 in the prepectoral and 73 in the subpectoral group. Their clinical characteristics were similar. Thirty patients (15.6%) received adjuvant chemotherapy, among them 27 (14.1%) received it within 12 weeks, and there was no difference between the groups (p = 0.12). In the prepectoral group, 39 patients (32.8%) received adjuvant radiotherapy versus 5 (6.8%) in the subpectoral group (p < 0.001), but there was no significant difference in time to treatment commencement. Overall, 35 patients (29.4%) in the prepectoral group and 17 (23.3%) in the subpectoral group experienced post-operative complications (p = 0.44). Using multivariable analysis, the only factor associated with post-operative complications was determined to be mastectomy weight (odds ratio 1.98 (1.10-3.59) for weight ≥500 g; p = 0.02). CONCLUSION: Prepectoral implant placement without ADM can be proposed to patients undergoing IBR with an indication for adjuvant treatment. However, in our study, the reoperation rate with this technique was slightly higher (p = 0.008). This is partly due to the learning curve for surgeons using this new technique.

[Updated indications and techniques for immediate breast reconstruction, particularly in the case of adjuvant radiotherapy]. / Actualisation des indications et techniques de reconstruction mammaire immédiate, notamment en cas de radiothérapie adjuvante.

In 2023, 62,000 patients were diagnosed with breast cancer in France. Every year, 22,000 mastectomies are performed. Breast reconstruction (BR) should be an integral part of breast cancer management. Yet the MR rate in France is only 28% within 3 years of mastectomy, of which 14% are immediate breast reconstruction (IBR). The number of contraindications to RMI has steadily declined over the last few decades, although some of them remain definitive, such as inflammatory cancer (T4d). Today, many specialists involved in the management of breast cancer consider that IBR can be proposed in cases where adjuvant chemotherapy and/or radiotherapy is indicated, if it is not expected to delay carcinological management. The surgical team must then inform the patient of all available BR techniques. If a team does not offer a particular technique, the patient should be referred to a center that does. In all cases, the proposal for curative and reparative treatment should be the subject of a multidisciplinary discussion involving, in particular, a surgeon, a radiotherapist and a medical oncologist. When adjuvant radiotherapy is indicated, the patient must be informed of the increased risk of complications and deterioration of the aesthetic result. In this indication, RMI by prosthesis is a validated technique. However, if the patient has a history of radiotherapy, autologous techniques should be preferred. In a context of shared decision-making, the choice of whether or not to undergo MR and the type of technique must ultimately be made by the patient, in agreement with the multidisciplinary team.

Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: Mastectomy versus conservative treatment.

INTRODUCTION: Patients with BRCA1/2 mutations have a higher risk of developing breast cancer compared to the wild-type population. For patients with a BRCA mutation, there are no specific recommendations for surgical management. The aim of this study was therefore to retrospectively investigate overall survival (OS) and recurrence-free survival (RFS) of BRCA mutated patients with localized invasive breast cancer, by comparing conservative surgery versus mastectomy. METHODS: This study was based on data from the Côte d'Or breast and gynecological cancer registry. Data from patients with a constitutional BRCA1/2 mutation who presented with invasive breast cancer were collected retrospectively from 1998 to 2018. The Kaplan-Meier method was used to describe RFS and OS. RESULTS: A total of 104 patients were included in the analysis, of whom 69 had conservative surgery and 35 underwent mastectomy. Regarding survival, there was no significant difference in OS (HR =1.49; 95 % confidence interval (CI) [0.76-2.93], p = 0.25). Similarly, there was no significant difference in RFS (HR =1.40; 95 % CI [0.81-2.40], p = 0.22), survival without homolateral recurrence (HR =0.88; 95 % CI [0.30-2.61], p = 0.89), without contralateral recurrence (HR =1.50; 95 % CI [0.55-4.09], p = 0.42), or without distant metastatic recurrence (HR =1.42, 95 % CI [0.69-2.90], p = 0.33). CONCLUSION: In invasive breast cancer in a patient with a germline BRCA1/2 mutation, conservative surgery, when possible, appears to be a feasible option over total mastectomy, with no difference in overall survival. However, the patient should be informed of the aggressive nature of recurrence in this population requiring chemotherapy in most cases.

Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock.

OBJECTIVE: Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. METHODS: The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores. RESULTS: Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. CONCLUSIONS: Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

Evaluation of the management of intracystic papillary carcinoma.

INTRODUCTION: Intracystic papillary carcinoma is defined as papillary carcinoma located in a dilated or cystic duct. There is no consensus regarding the management of this lesion. The aim of our study is to evaluate the frequency of associated invasive lesions and the need to perform an axillary staging during surgery. MATERIAL AND METHODS: This is a retrospective study concerning intracystic papillary carcinomas diagnosed at the Georges-François Leclerc Cancer Center between January 2010 and December 2021. Inclusion criteria were an age superior to 18 years and a histologic diagnosis confirmed at biopsy. RESULTS: Fifty-nine patients were included in this study. All but one patient underwent surgery: 39 patients (67.2%) underwent lumpectomy, and 18 patients (31.1%) underwent total mastectomy. An axillary staging was performed in 51 patients (86.4%). On final histologic analysis, 31 patients (52.5%) had pure intracystic papillary carcinoma and/or associated with in situ and 27 patients (45.8%) had invasive and/or microinvasive lesions. After univariate analysis, the only variable significantly associated with the presence of invasive lesions on final histologic analysis was the palpation of the lesion with a P-value of 0.09. DISCUSSION: Through this study, it appears necessary to discuss the realization of an axillary staging by conducting an axillary sentinel node procedure because of the high frequency of invasive lesions associated with intracystic papillary carcinoma.

Axillary pathologic response after neoadjuvant chemotherapy and surgery according to breast cancers subtypes and survival impact.

PURPOSE: To retrospectively assess the rate of pathologic complete response in the axilla according to breast cancer biologic subtypes, and to study the impact of nodal response on survival. METHODS: Inclusion criteria were all T-stage breast cancers with initial lymph node involvement, non-metastatic, treated with neoadjuvant chemotherapy followed by surgery with axillary lymph node dissection, managed at the George-François Leclerc Cancer Center in Dijon, France, between 2000 and 2018. RESULTS: Among 437 patients included, the rate of complete nodal response rate varied according to tumor subtypes: 69.4% in Hormone Receptors (HR)-/HER2-positive, 47.4% in HR-/HER2-negative, 46.7% in HR+/HER2-positive, 8.5% in HR+/HER2-negative. By multivariate analysis, the factors significantly associated with complete nodal response were HER2-positive profile (OR 4.48 [2.14-9.65], P<0.001 if HR+; OR 8.02 [3.54-18.74], P<0.001 if HR-), triple negative tumors (OR 3.01 [1.40-6.58], P=0.005), SBRIII grade (OR 6.85 [2.28-29.58], P=0.002) and breast complete response (OR 18.69 [9.67-38.53], P<0.001). Five-year recurrence rates were 15.7% in ypN0, 23% in ypN1, 41.2% in ypN2, 50% in ypN3 patients (P<0.001). Five-year overall survival rates were 92.2% in ypN0, 85.7% in ypN1, 72.2% in ypN2, 65.4% in ypN3 patients (P<0.001). CONCLUSION: The impact of nodal response on survival was significant. Pathologic complete response in the axilla appears to be a good surrogate marker of long-term outcome in patients treated for these cancers.

Reduction in transfer of micro-organisms between patients and staff using short-sleeved gowns and hand/arm hygiene in intensive care during the COVID-19 pandemic: A simulation-based randomised trial.

Background: Current personal protective equipment (PPE) practices in UK intensive care units involve "sessional" use of long-sleeved gowns, risking nosocomial infection transmitted via gown sleeves. Data from the first wave of the COVID19 pandemic demonstrated that these changes in infection prevention and control protocols were associated with an increase in healthcare associated bloodstream infections. We therefore explored the use of a protocol using short-sleeved gowns with hand and arm hygiene to reduce this risk. Methods: ICU staff were trained in wearing short-sleeved gowns and using a specific hand and arm washing technique between patients (experimental protocol). They then underwent simulation training, performing COVID-19 intubation and proning tasks using either experimental protocol or the standard (long-sleeved) control protocol. Fluorescent powder was used to simulate microbial contamination, detected using photographs under ultraviolet light. Teams were randomised to use control or experimental PPE first. During the simulation, staff were questioned on their feelings about personal safety, comfort and patient safety. Results: Sixty-eight staff and 17 proning volunteers were studied. Experimental PPE completely prevented staff contamination during COVID-19 intubation, whereas this occurred in 30/67 staff wearing control PPE (p = .003, McNemar). Proning volunteers were contaminated by staff in 15/17 control sessions and in 1/17 with experimental PPE (p = .023 McNemar). Staff comfort was superior with experimental PPE (p< .001, Wilcoxon). Their personal safety perception was initially higher with control PPE, but changed towards neutrality during sessions (p < .001 start, 0.068 end). Their impressions of patient safety were initially similar (p = .87), but finished strongly in favour of experimental PPE (p < .001). Conclusions: Short-sleeved gowns with hand and forearm cleansing appear superior to sessional long-sleeved gowns in preventing cross-contamination between staff and patients.

Impact of therapeutic strategy on disease-free and overall survival of early-stage cervical cancer: Surgery alone versus preoperative radiation.

BACKGROUND AND OBJECTIVES: There is no international consensus for management of early-stage cervical cancer (ESCC). This study aimed to retrospectively investigate disease-free survival (DFS) and overall survival (OS) in patients with ESCC according to the therapeutic strategy used, surgery alone versus preoperative radiation following by surgery. METHODS: Data were retrospectively collected from 1998 to 2015 using the Gynecological Cancer Registry of the Côte d'Or. The inclusion criteria were FIGO 2018 ≤ IB2; squamous cell carcinoma, adenocarcinoma or adenosquamous type. Survival curves were compared using the log-rank test. RESULTS: One hundred twenty-six patients were included. Median survival was 90 months. There was no significant difference in DFS (HR = 0.91, 95%CI [0.32-2.53], p = 0.858) or in OS between surgery alone versus preoperative radiation following by surgery (HR = 0.97, 95%CI [0.31-2.99], p = 0.961). In the subgroup of patients with stage ≥IB1, there was no significant difference in DFS (HR = 3.26, p = 0.2) or in OS (HR = 3.87, p = 0.2). CONCLUSION: Our study did not identify any difference in survival according to the treatment strategy. Preoperative radiation following by surgery can be an alternative to surgery alone for ESCC.

Building a Covid-19 secure intensive care unit: A human-centred design approach.

Background: The Covid-19 pandemic has highlighted weaknesses in the National Health Service critical care provision including both capacity and infrastructure. Traditionally, healthcare workspaces have failed to fully incorporate Human-Centred Design principles resulting in environments that negatively affect the efficacy of task completion, patient safety and staff wellbeing. In the summer of 2020, we received funds for the urgent construction of a Covid-19 secure critical care facility. The aim of this project was to design a pandemic resilient facility centred around both staff and patient requirements and safety, within the available footprint. Methods: We developed a simulation exercise, underpinned by Human-Centred Design principles, to evaluate intensive care designs through Build Mapping, Tasks Analysis and Qualitative data. Build Mapping involved taping out sections of the design and mocking up with equipment. Task Analysis and qualitative data were collected following task completion. Results: 56 participants completed the build simulation exercise generating 141 design suggestions (69 task related, 56 patient and relative related, 16 staff related). Suggestions translated to 18 multilevel design improvements; five significant structural changes (Macro level) including wall moves and lift size change. Minor improvements were made at a Meso and Micro design level. Critical care design drivers identified included functional drivers (visibility, Covid-19 secure environment, workflow, and task efficiency) and behavioural drivers (learning and development, light, humanising intensive care and design consistency). Conclusion: Success of clinical tasks, infection control, patient safety and staff/patient wellbeing are highly dependent on clinical environments. Primarily, we have improved clinical design by focusing on user requirements. Secondly, we developed a replicable approach to exploring healthcare build plans revealing significant design changes, that may have only been identified once built.

Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort.

PURPOSE: In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. METHODS: Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. RESULTS: Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. CONCLUSION: Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Association of Changes in Antithrombin Activity Over Time With Responsiveness to Enoxaparin Prophylaxis and Risk of Trauma-Related Venous Thromboembolism.

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity <80%). Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis. Design, Setting, and Participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January 7, 2019, and February 28, 2020. Adult trauma patients admitted to the trauma service at high risk for VTE, based on injury pattern and severity, were screened and enrolled. Patients who were older than 70 years, were pregnant, had a known immunologic or coagulation disorder, or were receiving prehospital anticoagulants were excluded. Exposures: Blood samples were collected on emergency department arrival and daily for the first 8 days of hospitalization. Main Outcomes and Measures: Patients' antithrombin activity and anti-FXa levels were measured by a coagulation analyzer, and thrombin generation was measured by calibrated automated thrombography. Responsiveness to enoxaparin was assessed by measuring anti-FXa levels 4 to 6 hours after the first daily enoxaparin dose and compared between patients who developed VTE and who did not. In addition, the associations of ex vivo supplementation of antithrombin with plasma anti-FXa levels were assessed. Results: Among 150 patients enrolled (median [IQR] age, 35 [27-53] years; 37 [24.7%] female and 113 [75.3%] male; 5 [3.3%] Asian, 32 [21.3%] Black, and 113 [75.3%] White; and 51 [34.0%] of Hispanic ethnicity), 28 (18.7%) developed VTE. Patients with VTE had significantly lower antithrombin activity on admission compared with patients without VTE (median [IQR], 91% [79%-104%] vs 100% [88%-112%]; P = .04), as well as lower antithrombin activity on hospital days 5 (median (IQR), 90% [83%-99%] vs 114% [99%-130%]; P = .011), 6 (median [IQR], 97% [81%-109%] vs 123% [104%-134%]; P = .003), 7 (median [IQR], 82% [74%-89%] vs 123% [110%-140%]; P < .001), and 8 (median [IQR], 99% [85%-100%] vs 123% [109%-146%]; P = .011). Anti-FXa levels were significantly lower in patients with VTE vs those without VTE at hospital day 4 (median [IQR], 0.10 [0.05-0.14] IU/mL vs 0.18 [0.13-0.23] IU/mL; P = .006), day 6 (median [IQR], 0.12 [0.08-0.14] IU/mL vs 0.22 [0.13-0.28] IU/mL; P = .02), and day 7 (median [IQR], 0.11 [0.08-0.12] IU/mL vs 0.21 [0.13, 0.28] IU/mL; P = .002). Multivariable analyses found that for every 10% decrease in antithrombin activity during the first 3 days, the risk of VTE increased 1.5-fold. Conclusions and Relevance: The results of this cohort study suggest that after severe trauma, antithrombin deficiency is common and contributes to enoxaparin resistance and VTE. Interventional studies are necessary to determine the efficacy of antithrombin supplementation in the reduction of VTE incidence.

Role of COX-2 in tumorospheres derived from a breast cancer cell line.

BACKGROUND: Cyclooxygenase-2 (COX-2) expression in primary breast cancer predicts tumor cell dissemination to bone marrow, which is a risk factor for recurrence and distant metastasis. "Stem-like" phenotype may be important in cancer metastasis. METHODS: To investigate the role of COX-2 protein in breast cancer stem-like cells, we analyzed it by co-immunofluorescence in tumorospheres derived from the MCF7 estrogen receptor-positive breast cancer cell line. To evaluate COX-2 function we utilized a COX-2 inhibitor in a clonogenicity assay performed with tumorospheres-derived cells. RESULTS: We detected rare cells in tumorospheres (one cell per tumorosphere) with very high COX-2 expression (COX-2(high)). COX-2 transfected MCF7 cells were able to generate long-term tumorospheres culture, even though transfection efficiency was only one in a million cells. We detected expression of OCT4 in some COX-2(high) cells, supporting the hypothesis that these cells could be cancer stem-like cells. It is important that COX-2(high) cells showed less expression of Ki-67 than did neighboring cells, indicating that COX-2(high) cells may be progenitors of tumorospheres. Celecoxib inhibited the growth of tumorosphere cultures and the ability of tumorosphere-derived cells to form colonies in vitro, indicating an active role of COX-2 in these processes. However, 2 µM celecoxib failed to eradicate tumorosphere-initiating cells. Finally, we detected rare COX-2(high) cells among SUM149 inflammatory breast cancer cells growing on plastic in serum-containing medium; the SUM149 cell line produces a very high level of COX-2 protein. CONCLUSION: Our results support a role for COX-2 in stem-like breast cancer cells and suggest a mechanism behind a role for COX-2 in disseminated tumor cells, which are known to exhibit characteristic biomarkers and functional properties of stem-like cells.