Multicenter Prospective Observational Study Research Articles

Predicting early diagnosis of intensive care unit-acquired weakness in septic patients using critical ultrasound and biological markers

ObjectiveEarly diagnosis of intensive care unit-acquired weakness (ICUAW) is crucial for improving the outcomes of critically ill patients. Hence, this study was designed to identify predisposing factors for ICUAW and establish a predictive model for the early diagnosis of ICUAW.MethodsThis prospective observational multicenter study included septic patients from the comprehensive ICUs of West China Hospital of Sichuan University and 10 other hospitals between September and November 2023. Inclusion criteria were as follows: age over 18 years; expected ICU stay longer than 3 days; and voluntary informed consent. Patients were classified into ICUAW (MRC score < 48) and non-ICUAW (MRC score ≥ 48) groups based on muscle strength assessments. The analyzed key predictive factors encompassed demographic data, SOFA and APACHE II scores, inflammatory markers (PCT, IL-6, and CRP), and ultrasound measurements of muscle thickness and cross-sectional area. Logistic regression analysis was conducted for variable selection and nomogram model construction.ResultsA total of 116 septic patients were included, comprising 77 males and 39 females (mean age: 56.94 ± 19.90 years). A nomogram model predicting ICUAW probability was developed, which involved vastus intermedius diameter, rectus femoris cross-sectional area, IL-6, and CRP. The AUC of the composite diagnostic ROC curve was 0.966 (95%CI: 0.936 − 0.996), with a sensitivity of 88% and a specificity of 95.8%.ConclusionsConclusively, a nomogram model is constructed for diagnosing ICUAW in septic patients, which is simple and rapid and allows for visual representation, with excellent diagnostic capability.

D-dimer cutoff values for predicting functional prognosis in patients with severe head trauma: a multi-centre prospective observational study.

D-dimer, a fibrinolysis indicator, may predict functional and life outcomes in traumatic brain injury (TBI) patients. We aimed to identify optimal D-dimer cutoff values for poor functional outcomes in severe TBI. We used data from a multi-centre prospective observational cohort study that included patients with TBI with a Glasgow Coma Scale (GCS) score ≤ 8 within 48h after injury or required neurosurgical procedures. We selected patients admitted ≤ 1h after injury. Neurological function at discharge was assessed using the modified Rankin Scale (mRS). The association between D-dimer levels at admission and neurological function (mRS ≥ 4 or < 4), adjusted for age, GCS, systolic blood pressure, and head abbreviated injury scale (AIS) score, was determined by logistic regression analysis. The predictive utility of D-dimer levels was assessed using the area under the receiver operating characteristic curve (AUC), with the cutoff value being determined using Youden's index. Among the 336 patients, most were male; approximately half had experienced motor vehicle accidents. The median (interquartile range) of age, GCS scores, and head AIS scores were 65 (40.25 - 78.75) years, 7 (4 - 9), and 5 (4 - 5), respectively. Overall, 214 (63.7%) patients had poor neurological function (mRS ≥ 4). D-dimer levels > 28µg/mL predicted poor functional prognosis (odds ratio = 3.84 [95% confidence interval 1.62 - 9.11]); the AUC and cutoff values were 0.73 and 27.2µg/mL, respectively. A cutoff value of 27.2µg/mL for early-stage D-dimer levels could predict the functional prognosis of patients with severe isolated TBI.

P0893 Angiopoietin-like Protein 8 (ANGPTL8) in Inflammatory Bowel Disease and Its Response to Anti-TNFα Therapy; A Prospective Multi Center Study

Abstract Background Crohn’s disease (CD) is a chronic condition characterized by persistent inflammation of the gastrointestinal tract. Tumour necrosis factor-alpha (TNFα), a key pro-inflammatory cytokine, plays a crucial role in the disease process. Anti-TNF therapies have significantly improved CD treatment by reducing inflammation. Emerging evidence show that Angiopoietin-like protein 8 (ANGPTL8) is a novel protein and may also be involved in regulating inflammation. This study aimed to investigate the changes in ANGPTL8 level in patients with IBD compared to healthy individuals and evaluates the impact of Anti-TNF therapies on this protein. Methods This is a prospective multi-center observational study. Patients were recruited from January 2022 to June 2024. Patients were divided into 3 groups; patients with CD in clinical remission receiving infliximab for at least 24 weeks (IFX-experienced group), healthy controls (control group), and patients with CD scheduled to start infliximab (IFX-naïve group). ANGPTL8 levels were measured 24 hours before next maintenance infliximab dose in IFX-experienced group, randomly in control group, and at week 0 and week 24 in IFX-naïve group. ANGPTL8 levels were measured using enzyme-linked immunosorbent assays (ELISA). A normality test was conducted for continuous variables, accordingly variables with normal distribution a parametric t-test was applied, otherwise Mann–Whitney U test was applied to compare between treated and untreated groups for skewed variables. Results A total of 166 patients were included in this study. The number of patients with CD and IFX-experienced and IFX-naive were 82 and 13, respectively. Seventy-one were healthy controls. Mean age ranged from 27 to 33 years of age across the three groups (table 1). Eighty-four (51%) were females. ANGPTL8 levels were significantly higher in patients with CD (138.26 ± 8.47 pmol) compared to the healthy control group (102.52 ± 5.99 pmol, p = 0.001). Among the 13 IFX-naive patients receiving anti-TNFα treatment, ANGPTL8 levels decreased significantly from 145.06 ± 17.93 pmol pre-treatment (week 0) to 81.78 ± 10.61 pmol post-treatment (week 24), p = 0.007. Conclusion Our findings suggest that ANGPTL8 is elevated in CD and may be involved in the inflammatory processes. The marked reduction in ANGPTL8 levels following anti-TNFα treatment indicates its potential as a biomarker for treatment response. Further research is needed to understand the exact mechanisms through which ANGPTL8 influences CD progression and its utility in clinical practice.

P1235 COlombian PrevaLence of Extraintestinal Manifestations in Inflammatory bowel disease in an adult and pediatric cohort after evaluation by a multidisciplinary group COLEMI – study

Abstract Background Inflammatory Bowel Disease (IBD) is increasingly recognized as a systemic disorder, given its high prevalence of extra-intestinal manifestations (EIM) affecting various organs. The frequency of these manifestations varies depending on factors such as geographical region, IBD subtype, disease location, disease duration, and the timeliness of diagnosis, yet data on this topic remain limited in Latin America. This study aimed to assess the prevalence of the primary EIMs in IBD patients in Colombia, as well as to examine differences between Crohn's disease (CD) and ulcerative colitis (UC). Methods Prospective observational descriptive multicenter study in adult and pediatric patients with IBD of the Colombian IBD Foundation, with suspicious of EIM and after confirmed with by a multidisciplinary group in Colombia. Results A total of 266 out of 482 (55.1%) patients with inflammatory bowel disease (IBD) were suspected of having extra-intestinal manifestations (EIM) by their gastroenterologists, of which 197 (74.1%) were confirmed upon evaluation by a multidisciplinary team, resulting in an EIM prevalence of 40.9%, with a predominance of female patients (67.5%). Of the cohort, 95% were adults and 5% were pediatric patients, with 134/197 (68%) diagnosed with ulcerative colitis (UC) and 63/197 (32%) with Crohn's disease (CD), 49.2% of whom required biologic therapy. In UC patients, extensive colitis (E3) was the most common disease extension, while ileo-colonic (L3) involvement predominated in CD. The most frequent types of EIM were articular (36%), followed by cutaneous (34.5%) and ocular (24.9%) manifestations. The hospitalization rate due to IBD was 72.5%, with EIM present in 37.5% of UC patients and 52.5% of CD patients (Figure 1). Hepatobiliary manifestations (odds ratio [OR] = 1.931; 95% confidence interval [CI] 0.4311-13.66, p=0.44) were more common in UC compared to CD, whereas articular (OR=2.277; 95% CI 1.228-4.22), cutaneous (OR=1.027; 95% CI 0.5474-1.925), oral (OR=2.017; 95% CI 0.8727-4.661), and ocular (OR=2.683; 95% CI 1.374-5.23) manifestations were more frequent in CD (Figure 1). In terms of the number of EIMs, 71.5% of UC patients had one, 16% had two, and 12.5% had three or more, while in CD, 50.7% had one, 27% had two, and 22.2% had three or more. A higher prevalence of EIM was observed in the central region of the country (Figure 2). Conclusion The prevalence of EIM in this Colombian cohort was high (40,9%), predominating the CD, female, extensive disease and higher requirement for biologicals.

Association between nutritional status, daily nutrition delivery and clinical outcomes of critically ill adult patients admitted to the intensive care unit: a protocol for Isfahan multicentre prospective observational cohort ICU study (the Isfahan-ICU study)

IntroductionThere is currently limited information regarding the association between the modified Nutrition Risk in Critically Ill (mNUTRIC) score, nutrition delivery and clinical outcomes in critically ill patients admitted to the...

P0592 Safety of the Adjuvant Recombinant Herpes Zoster Vaccine in Crohn’s Disease and Ulcerative Colitis: A Real-World Study

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing, and herpes zoster (HZ) occurrence in IBD patients, particularly those on immunosuppressive drugs, is a growing concern. The herpes zoster adjuvant recombinant vaccine (Shingrix) may provide a safer alternative to live vaccines, but real-world data on its safety in IBD patients is limited. Methods This multicenter prospective observational study is being conducted from August 2023 to July 2025. Patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) who receive the herpes zoster subunit vaccine will be followed for 30 days post-vaccination to assess adverse events (AE) and vaccine safety. Results A total of 244 patients were enrolled in the study, consisting of 141 with ulcerative colitis (UC) and 103 with Crohn’s disease (CD). The mean age of the cohort was 45.3 years, with UC patients being older on average (49.7 years) than CD patients (39.3 years, p&amp;lt;0.01). After the first dose, injection site pain was the most commonly reported local adverse event, occurring in 51.2% of patients (UC: 49.6%, CD: 53.4%; p=0.56). Other local adverse events, such as redness (2.0%) and swelling (1.2%), showed no significant differences between UC and CD groups (p&amp;gt;0.05). Systemic adverse events following the first dose included fatigue (19.3%), myalgia (34.0%), headache (16.0%), shivering (11.5%), fever (11.5%), and gastrointestinal symptoms (6.6%). There were no significant differences between UC and CD patients for these events (p&amp;gt;0.05). Rare severe adverse events were noted, including one case of a disease flare requiring hospitalization in a CD patient post-vaccination (0.4%). Additional events classified as 'others' included itching, Bell’s palsy, and dizziness, with no significant group differences. For the second dose, 132 patients (UC: 78, CD: 54) were followed. Local adverse events included injection site pain reported by 53.8% of patients (UC: 48.7%, CD: 61.1%; p=0.16). Systemic adverse events, such as fatigue (25.8%), myalgia (35.6%), and headache (15.9%), were similarly reported without significant differences between UC and CD groups (p&amp;gt;0.05). Severe adverse events were not observed after the second dose. Other non-severe adverse events reported included sore throat, nausea, and rash, with no group-specific statistical significance. Conclusion The herpes zoster adjuvant recombinant vaccine appears to be safe for use in IBD patients, with no significant differences in adverse events between UC and CD groups. This study suggests that the adjuvant vaccine is a viable alternative to live attenuated vaccines, especially in patients receiving immunosuppressive therapy. Further studies are warranted to confirm its long-term safety and efficacy in this population.

P0741 Adherence to mesalazine suppositories maintenance treatment in patients with ulcerative proctitis: MESUPO multicenter prospective observational study from GETECCU

Abstract Background Mesalazine suppositories are recommended in guidelines for the induction and maintenance of remission in patients with ulcerative proctitis (UP). Nevertheless, nonadherence can be frequent and the recommended dose of mesalazine suppositories in maintenance treatment remains unknown. The aim of this study was to determine the frequency of non-adherence to mesalazine suppositories, evaluate potential factors for nonadherence and the impact on quality of life and number of relapses in patients with UP. Methods A multicenter, prospective observational study was designed in patients ≥18 years old with UP under maintenance treatment with mesalazine suppositories (Claversal© 500 mg, Pentasa© 1g or Salofalk©1g). We evaluated adherence, sociodemographic data and complications associated with poor adherence at 6 and 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio, MPR). We defined good adherence as MPR ≥80% over 12 months. Health-Related Quality of Life (HRQoL) was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9). Relapse was defined as partial Mayo ≥2. Quantitative data were analyzed using Rstudio software (version 2023.12.1 + 402) Results A total of 188 patients with mean age 51 were consecutively included across 14 Spanish hospitals (Table 1). Of these, mean MPR was 76% and 56% presented MPR ≥80%. Mean age was higher among patients with MPR ≥80% (p=0.045). A total of 31 patients (16%) had a relapse and 3 (1.6%) patients were hospitalized during the follow-up. Unemployment(OR=5.08, p=0.025), concomitant anal pathology (OR=5.08, p =0.025) and use of corticosteroids during the follow-up (OR=4.25, p=0.041) were associated with better adherence. There were no differences between the different brands and doses of suppositories analyzed. Low adherence was not related with increased number of flares (p=0.927), hospitalizations (p=0.225) or decreased quality of life (p = 0.353) over the 12 months of follow-up. Conclusion Almost half of patients with UP on maintenance treatment with mesalazine suppositories have low adherence. Older age, unemployment, use of corticosteroids during the follow-up or the presence of concomitant anal pathology may increase adherence, but poor adherence to mesalazine suppositories was not related with risk of relapse, hospitalizations or worst quality of life.

Andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage: the prospective observational multicenter ASTRO-DE study.

Hematoma expansion after intracranial hemorrhage (ICH) in anticoagulated patients signifi-cantly influences clinical outcomes and mortality, emphasizing the need for effective reversal agents. Andexanet alfa is a specific reversal agent for factor Xa associated major bleeding. The ASTRO-DE study collected real-world evidence on the effect of andexanet alfa on mitigat-ing hematoma expansion and altering prognosis in rivaroxaban- or apixaban-treated patients with ICH. ASTRO-DE was a prospective non-interventional cohort study conducted at 25 certified stroke centers in Germany. The primary outcome was the hematoma volume change and the propor-tion of patients with hematoma growth ≤33% within 12-72 h or until first control imaging. Sec-ondary endpoints included in-hospital thromboembolic events and mortality up to 90 days. A total of 137 patients (47.4% male, mean age 80.0 years) with ICH (92.6% spontaneous, 87.4% intracerebral), mean NIHSS on admission of 11.2 points, and mean initial hematoma volume of 26.5 mL (median: 14.1 mL) were analyzed. Ninety patients (65.7%) suffered ICH while treated with apixaban and 47 (34.3%) with rivaroxaban. The median time between symptom onset and application of andexanet alfa was 3.3 h, door-to-needle time was 1.3 h. The mean change in hematoma volume until the first control imaging, conducted after a median of 15.6 h, was 2.3 mL (95% CI: 0.4 to 4.2), while the change within 12-72 h was 1.8 mL (95% CI: 0.4 to 3.2). Hema-toma growth ≤33% was achieved in 90.3% of the 93 evaluable patients based on first control imaging and in 90.5% of the 63 evaluable patients, considering only imaging performed within the 12-72 h window. During hospitalization, death occurred in 30/137 patients (21.9%) and 17 thromboembolic events in 11/137 (8.0%) patients. The 90-day-mortality was 47/128 (36.7%). ASTRO-DE is the first prospective observational study systematically collecting standardized clinical routine data with andexanet alfa treatment. The study demonstrated favorable hemo-stasis and minimal mean hematoma volume growth in patients with ICH associated with apixa-ban or rivaroxaban treatment.

Translated article] Prospective observational follow-up study of psychoactive drug treatment initiated in the intensive care unit.

The treatment and prevention of delirium in the intensive care unit (ICU) have gained significant importance in patient care in recent years. Some studies have linked delirium with increased risks of mortality, prolonged hospital stay, and more days of mechanical ventilation. This study aims to analyse the use of psychotropic drugs initiated in the ICU and their continuation upon hospital discharge, as well as to evaluate their contribution to polypharmacy and associated adverse clinical effects. A multicentre prospective observational case study was designed, focusing on patients over 18 years old admitted to the ICU and treated with psychotropic drugs. Data on demographics, variables related to admission and psychotropic drug treatment, as well as clinical outcomes and adverse effects, will be collected. Among other variables, the frequency of psychotropic treatments initiated in the ICU and continued upon discharge from the ICU and the hospital will be measured. Data collection will be performed through review of electronic medical records and prescription programmes, and IBM SPSS 20.0 statistical package will be used for analysis. Delirium is common in ICU patients and is associated with long-term negative consequences. Although antipsychotics are used to treat delirium, their prolonged use can have adverse effects, and their continuation after ICU discharge contributes to polypharmacy. This study aims to provide information on the use of psychotropic drugs initiated in the ICU and their continuation upon discharge, with the goal of identifying opportunities for intervention and reducing unnecessary use of these medications.

Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry

BackgroundGrowth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its...

Sex Differences in Sudden Cardiac Death During Long-Term Follow-up in Patients With Chronic Heart Failure - A Report From the CHART-2 Study.

Although sudden cardiac death (SCD) generally occurs more frequently in men than in women, there are limited data on sex differences in SCD in patients with chronic heart failure (HF) across a range of left ventricular ejection fraction (LVEF). We examined sex differences in SCD incidence, timing, and risk factors in 4,683 patients with chronic HF (3,186 men, 1,497 women) from a multicenter prospective observational cohort study (CHART-2). Over a median follow-up of 8.8 years after study enrollment, there were 215 SCDs (160 in men, 55 in women). The SCD incidence rates in men and women were 6.1 and 4.6 per 1,000 person-years, respectively (P=0.088). Among women, more than half the SCDs occurred in the first 5 years of follow-up. Beyond 5 years, the SCD incidence rate was significantly lower in women than in men (3.6 vs. 5.9 per 1,000 person-years, respectively; P=0.044). After adjusting for confounders, age, increased B-type natriuretic peptide, and LVEF <50% were common prognostic factors. After 5 years of follow-up, left ventricular (LV) enlargement was a risk factor for SCD in both sexes. These results indicate that there are sex differences in SCD, especially beyond 5 years of follow-up, with a lower prevalence in women. LV enlargement is a common long-term prognostic factor in both sexes, suggesting the importance of preventing LV remodeling in HF management.

Long-Term Clinical Impact of Paravalvular Leak Following Transcatheter Aortic Valve Implantation.

Background: Paravalvular leak (PVL) was initially recognized as one of the most common complications after transcatheter aortic valve implantation (TAVI) and has been linked to adverse clinical outcomes, including mortality. This study aims to assess the long-term clinical effects of PVL in patients undergoing TAVI with the latest generation of transcatheter aortic valves, as part of the national observational prospective multicenter study OBSERVANT II. Methods: OBSERVANT II included all consecutive patients with severe aortic stenosis who underwent TAVI across 28 Italian centers from December 2016 to September 2018. A total of 2125 patients were included in this analysis and stratified according to the presence of moderate-to-severe PVL (significant PVL, n = 155) versus no/trace-to-mild PVL (no significant PVL, n = 1970). The primary endpoint was 5-year major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, stroke, myocardial infarction, and coronary revascularization. Five-year all cause death and re-hospitalization for heart failure (HF) were the secondary endpoints. Results: In our cohort, the incidence of moderate-to-severe PVL was 7%. Age, aortic anulus perimeter, and self-expandable valves were determinants of PVL. The risk of MACCE, all-cause death, and re-hospitalization for HF at the 5-year follow-up were not different between the study groups [HR = 1.07 (95% CI: 0.85-1.34) p = 0.571; HR = 1.10 (95% CI: 0.87-1.39) p = 0.435; HR = 1.20 (95% CI: 0.88-1.62) p = 0.245, respectively]. Conclusions: In this analysis of the OBSERVANT II study, moderate/severe PVL was not associated with a higher incidence of MACCE and re-hospitalization for heart failure at the 5-year follow-up.

Clinical presentation, acute care management and discharge information of patients with thoracic trauma in South Africa and Sweden: a prospective multicenter observational study

PurposeThoracic trauma causes pain and hospitalisation. Middle- and high-income countries have different trauma contexts and populations. To report patients’ clinical presentation (pain and shortness of breath) and its influence on hospital length of stay (LOS), acute care management, and discharge destinations in South Africa (SA) and Sweden.MethodsProspective observational multicenter study by means of clinical record review. Two centers in SA and four centers in Sweden participated. One thousand nine hundred and eighteen adults with thoracic trauma were screened over the 20 months period. Study objectives guided information retrieved from clinical records. Statistical analysis was done with significance at p-value < 0.05.ResultsThree-hundred-sixty-four participants were recruited with most being male (n = 170/179 (95%) SA; n = 125/185 (68%) Sweden). Type and mechanism of injury differed (SA penetrating (82%) versus Sweden blunt (95%); SA assaults (90%) versus Sweden falls (44%)). Unilateral haemopneumothorax was common (SA 68%, Sweden 35%) and managed with intercostal drainage. Rib cage injuries were common in the Swedish cohort with rib fixation surgery for 17%. Physiotherapy treatment frequency was mostly daily. Blunt injury resulted in higher pain levels during deep breathing (day 1: p = 0.014; day 2: p < 0.001; day 3: p < 0.001) and shortness of breath during activity (day 1: p = 0.036; day 2: p = 0.003; day 3: p < 0.001). LOS was shorter for SA cohort (5 (± 4) versus 7 (± 5) days; p = 0.024). Age influenced LOS in the blunt injury group. Discharge destination was mostly home (99% SA, 56% Sweden).ConclusionPriority care is indicated for those who are older and have blunt thoracic injury to prevent pulmonary complications and prolonged hospitalisation.

Adherence to Recommendations and Yield of Critical Care EEG Monitoring: A Prospective Multicentric Study.

The American Clinical Neurophysiology Society has provided a set of recommendations on the use of critical care EEG monitoring (CEEG). However, these recommendations have not been prospectively validated. We aimed to assess the adherence to the American Clinical Neurophysiology Society recommendations for obtaining CEEG for different indications and the yield of obtained CEEG according to these different indications. This was a multicenter prospective observational study of critically ill adult patients between April 01, 2022, and June 22, 2022, in two academic medical centers and a large teaching hospital. Indications for CEEG, according to the American Clinical Neurophysiology Society recommendations, were determined based on clinical data at the time of discharge from the intensive care unit. The use of CEEG and detection of electrographic seizures were retrieved from the EEG databases. A total of 600 patients were enrolled in this study. The primary admission diagnoses were medical (49%), surgical (30%), or neurologic/neurosurgical (21%). Approximately 60% of patients had an altered mental status. A few (6%) patients had a preceding clinical seizure, and 1% had generalized convulsive status epilepticus. Indications were identified in 226 admissions. Of these patients, 88 (39%) underwent CEEG. In addition, 12 patients underwent CEEG without clear indications. Of the 100 patients, 33 (33%) had electrographic seizures. Adherence to recommendations and yields was highest for refractory status epilepticus, altered mental status after any clinical seizure, and acute brain injury. Adherence and yield varied the most and were inversely correlated in the group of patients without acute brain injury, suggesting that additional clinical factors may have contributed to patient selection. Patients meeting American Clinical Neurophysiology Society indications and receiving CEEG had a high seizure risk. Emerging CEEG programs should focus on epilepsy-related and neurologic diagnosis. Although recommendations effectively identify groups of patients with a high seizure risk, additional clinical factors might further help select candidates in the low-risk group.

What is the Surgical Burden of Treatment for High-Energy Lower Extremity Trauma? A Secondary Analysis of the OUTLET Study.

To describe and enumerate surgeries for patients who underwent reconstruction or amputation after severe distal tibia, ankle, and mid to hindfoot injuries. Design: Secondary analysis of a multicenter prospective observational study. 31 U.S. level-I trauma centers and 3 military treatment facilities. Participants aged 18 to 60 with Gustilo type-III pilon (OTA 43B or 43C), IIIB or C ankle fracture (OTA 44A, 44B, or 44C), type-III talar or calcaneal fracture (OTA 81B, 82B, or 82C), or open or closed crush or blast injuries to the hindfoot or midfoot who underwent limb reconstruction or amputation from 2012 to 2017. Number of temporizing, definitive, and complication surgeries were compared by treatment and injury. 574 participants with 221 ankle and pilon, 140 talus and calcaneal, and 213 other foot injuries were followed for 18 months. The mean age was 38 (range 8-64) and 33% were female. Participants underwent reconstruction (n=472), primary amputation (n=76), and failed reconstruction followed by amputation (n=26). 841 temporizing, 958 definitive, and 501 complication surgeries were performed. The number of surgeries was highest for those who underwent failed reconstruction (mean 5.8, 95% CI: 4.9-6.8, range 3-13) compared to reconstruction (mean 3.8, 95% CI: 3.5-4.0, range 1-21), and primary amputation (mean 4.9, 95% CI: 4.3-5.5, range 2-14) (p<0.01). Those with ankle and pilon injuries required more surgeries (4.7, 95% CI: 4.3-5.1, range 1-21) than hindfoot (3.4, 95% CI: 3.0-3.7, range 1-10), and other foot injuries (3.7, 95% CI: 3.4-4.0, range 1-14) (p<0.01). The average participant would complete definitive treatment 23 days after their injury, and those who required surgery for a complication spent 41 days in the complication phase of treatment. Patients with high-energy lower extremity trauma underwent nearly 4 surgeries over 3 weeks until completion of definitive treatment, regardless of whether they underwent limb reconstruction or amputation. Those with ankle or pilon injuries and failed reconstruction attempts experienced the most operations, and those with complications required over an additional month of surgical care. These data may inform a shared decision-making process around limb optimization. Therapeutic Level II.

Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA.

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations. We compared the progression-free survival (PFS), overall survival (OS), and pretreatment co-occurring genetic alterations detected in plasma between patients with stages IVA (n = 83) and IVB disease (n = 84). Multivariate analysis of PFS and OS revealed that stage IVB was associated with a poor prognosis (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.04, p < 0.001, HR: 2.35, 95% CI: 1.45-3.90, p < 0.001, respectively). Pre-osimertinib treatment, significantly more TP53- (52.4% vs. 27.7%, p = 0.002), EGFR amplification- (58.3% vs. 23.2%, p < 0.001), and MET amplification-positive cases (22.6% vs. 7.2%, p = 0.008) were found among stage IVB than among stage IVA or lower cases. Patients with EGFR-positive NSCLC in stage IVB exhibited significantly shorter PFS and OS than those in earlier stages when treated with first-line osimertinib. The prevalence of baseline TP53 mutations, EGFR amplification, and MET amplification in plasma were significantly higher in stage IVB cases, implicating them in the worse outcomes of this group.

Satisfaction of young women with estradiol valerate/dienogest in real clinical practice in Russia: results of prospective multicenter observational study Q-SWAN

Satisfaction of young women with estradiol valerate/dienogest in real clinical practice in Russia: results of prospective multicenter observational study Q-SWAN

Emergency and postoperative access to critical and enhanced care: a multicentre prospective observational study.

The ability to admit patients to enhanced or critical care may be limited by bed availability. In a network with low provision of critical and enhanced care beds, we aimed to assess the proportion of patients having surgery with moderate (1%-< 5%) or high (≥ 5%) predicted risk of 30-day postoperative mortality and their postoperative care location. We also aimed to study referral and admission outcomes to critical care. This prospective, 7-day observational study was conducted across 19 acute hospital sites within the South West Critical Care Network. All adult inpatients having a procedure under the care of an anaesthetist (excluding cardiac and obstetric procedures) had a surgical outcome risk tool score calculated retrospectively, and their postoperative destination captured. Synchronously, all critical care referrals, admissions and refusal decisions were captured, along with critical care bed capacity. Of 2222 eligible patients, 1728 (78%) were captured. Retrospective surgical outcome risk tool score calculation revealed 1060 (61%) patients had a low, 418 (24%) a moderate and 250 (15%) a high risk of postoperative mortality. In patients with a moderate predicted risk of postoperative morbidity, 72/418 (17%) received enhanced or critical care and 64/249 (26%) patients with a high predicted risk received critical care. All critical care referral and admission activity was captured; in total, 263/680 (39%) of patients referred were admitted to critical care. Referrals to critical care exceeded the available level 3-equivalent beds on 79% of occasions. These data describe constraints in access to postoperative and emergency enhanced/critical care in the south-west of England. There is poor compliance with national guidance regarding the postoperative care location of patients with a moderate or high risk of postoperative mortality.

A machine learning model to predict neurological deterioration after mild traumatic brain injury in older adults.

Neurological deterioration after mild traumatic brain injury (TBI) has been recognized as a poor prognostic factor. Early detection of neurological deterioration would allow appropriate monitoring and timely therapeutic interventions to improve patient outcomes. In this study, we developed a machine learning model to predict the occurrence of neurological deterioration after mild TBI using information obtained on admission. This was a retrospective cohort study of data from the Think FAST registry, a multicenter prospective observational study of elderly TBI patients in Japan. Patients with an admission Glasgow Coma Scale (GCS) score of 12 or below or who underwent surgical treatment immediately upon admission were excluded. Neurological deterioration was defined as a decrease of 2 or more points from a GCS score of 13 or more within 24 h of hospital admission. The model predictive accuracy was judged with the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and the Youden index was used to determine the cutoff value. A total of 421 of 721 patients registered in the Think FAST registry between December 2019 and May 2021 were included in our study, among whom 25 demonstrated neurological deterioration. Among several machine learning algorithms, eXtreme Gradient Boosting (XGBoost) demonstrated the highest predictive accuracy in cross-validation, with an AUROC of 0.81 (±0.07) and an AUPRC of 0.33 (±0.08). Through SHapley Additive exPlanations (SHAP) analysis, five important features (D-dimer, fibrinogen, acute subdural hematoma thickness, cerebral contusion size, and systolic blood pressure) were identified and used to construct a better performing model (cross-validation AUROC of 0.84 and AUPRC of 0.34; testing data AUROC of 0.77 and AUPRC of 0.19). At the cutoff value from the Youden index, the model showed a sensitivity, specificity, and positive predictive value of 60, 96, and 38%, respectively. When neurosurgeons attempted to predict neurological deterioration using the same testing data, their values were 20, 94, and 19%, respectively. In this study, our predictive model showed an acceptable performance in detecting neurological deterioration after mild TBI. Further validation through prospective studies is necessary to confirm these results.

Hypothermia-associated acute pancreatitis: A multicenter prospective observational study.

Hypothermia-associated pancreatitis lacks comprehensive understanding owing to limited studies exploring its mechanism, epidemiology, risk factors, and outcomes. We aimed to investigate the frequency, characteristics, and predictive factors associated with the development of acute pancreatitis in patients with accidental hypothermia. This study comprised a post hoc analysis of data from a multicenter prospective observational study (ICE-CRASH study) conducted in 36 tertiary emergency hospitals in Japan. Patients aged ≥18 years with core body temperatures ≤32°C admitted to emergency departments between 2019 and 2022 were enrolled. We identified patients who developed acute pancreatitis within 1 week of admission and described their characteristics. Age, vital signs, and blood gas analysis data were analyzed as potential predictors of acute pancreatitis using receiver operating characteristic (ROC) curve analysis. Of 421 eligible patients with accidental hypothermia, 16 (3.8%) developed acute pancreatitis within 1 week. The age distribution of patients with acute pancreatitis showed bimodal peaks around 50-80 years. Patients with acute pancreatitis had a higher proportion of alcohol consumption than those without acute pancreatitis. ROC curve analysis showed age and pH as significant factors; however, their predictive power was not high. The incidence of acute pancreatitis was 3.8% in patients with accidental hypothermia with core body temperatures ≤32°C. An association was found between the development of acute pancreatitis and alcohol consumption. No strong predictors of acute pancreatitis were identified.