Purpose
To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of
Clostridioides difficile
infection (CDI) and to compare this cohort with patients ...with similar characteristics who did not receive the monoclonal antibody.
Methods
A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment).
Results
Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-
Clostridioides
antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 0.20–1.65). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure.
Conclusion
We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.
Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening ...condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation.
We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates.
We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings.
Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.
PROSPERO (CRD42019128790).
5610 Background: Human epidermal growth factor receptor 2 (HER2)-low is a new category defined by HER2 1+ or 2+ by immunohistochemistry (IHC) and lack of HER2 amplification by in situ hybridization ...(ISH). Trastuzumab deruxtecan demonstrated antitumor activity in HER2-expressing gynecologic tumors. Little is known about HER2-low frequency in EC subtypes, the heterogeneity of the expression, the best scoring criteria or the prognostic value. Methods: This is a single center, retrospective study including patients diagnosed with EC amenable to curative treatment from 2003 to 2019. Two tissue cores of each sample were selected for the creation of 5 tissue microarrays (TMA). Molecular subrogated (MS) classification (WHO 5ed) was performed: polymerase epsilonmutated (POLEmut), mismatch repair deficient (dMMR), TP53 abnormal (p53abn) or non-specific molecular profile (NSMP). HER2 was assessed by IHC (4B5) and ISH on TMAs. HER2 scoring was done according to ASCO/CAP guidelines for breast and the proposed endometrial criteria. HER2 heterogeneity was defined as a difference in HER2 IHC ≥2+ or discrepancy in HER2 ISH between cores. Primary objective was to describe the frequency of HER2-low in MS. Secondary objectives included to assess heterogeneity, concordance between breast and endometrial criteria and the impact of HER2-low on recurrence-free (RFS) and overall survival (OS). Results: 193 patients were analyzed. Median age was 66.4 years (31-90). According to FIGO 2009 classification, stage I, II and III-IV corresponded to 71.5%, 14% and 14.5% of patients. Most cases (57.5%) were low-grade endometrioid followed by 14% serous, 11.9% high-grade endometrioid, 5.2% clear cell, 2.6% carcinosarcoma and 8.7% other histology. Regarding MS, 3.1% were POLEmut, 25.4% dMMR, 28% p53abn, 40.9% NSMP and 2.6% unclassifiable. Considering the entire cohort, 69.9% were HER2-negative (0+), 25.8% HER2-low and 4.3% HER2-positive (3+ or ISH+). The frequency of HER2-low was highest for POLEmut (66.7%) followed by p53abn (42.6%) (Table). Low heterogeneity in HER2 expression was demonstrated, with an agreement between cores in 84.5% of cases. Breast and endometrial criteria showed concordance in 85.5% of patients, with a kappa of 0,624 (p<0,05). HER2-low nor HER2-positive versus HER2-negative had an impact on RFS or OS. Conclusions: This is the first study showing the spectrum of HER2 expression in a MS cohort of EC. HER2-low is more frequent in POLEmut and p53abn subtypes. HER2-low had no prognostic significance. Table: see text
Abstract
Introduction
The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with ...vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing.
Methods
To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk.
Results
In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22–1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27–2.04) by propensity score analysis.
Conclusions
Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.
Background
Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and ...extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons.
Methods
We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28.
Results
Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio OR 1.35, confidence interval for 95% CI 95% 1.19–1.54;
p
< 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 CI 95% 1.01–1.30;
p
= 0.03), and a higher odds for reintubation (OR 1.41 CI 95% 1.20–1.66;
p
< 0.001) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 CI 95% 1.22–1.77;
p
< 0.001), of failed extubation after the first attempt of weaning (OR 1.28 CI 95% 1.06–1.55;
p
= 0.009), and for reintubation (OR 1.49 CI 95% 1.17–1.88;
p
< 0.001). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV.
Conclusions
Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.
To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge.
An observational, prospective and multicenter, ...nation-wide study.
Eight adult ICU across eight academic acute care hospitals in Mexico.
All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge.
None.
The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty.
196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio OR 3.70, 95% confidence interval 1.40-9.81, P = .008).
Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.
In recent years, video-assisted thoracoscopic lung resections (VATS) have been associated with lower morbidity than open surgery. The aim of our study is to compare postoperative morbidity among ...patients from the national database of the Spanish Group of Video-assisted Thoracic Surgery (GE-VATS) after open and video-assisted anatomic lung resections using a propensity score analysis.
From December 2016 to March 2018, a total of 3533 patients underwent anatomical lung resection at 33 centers. Pneumonectomies and extended resections were excluded. A propensity score analysis was performed to compare the morbidity of the thoracotomy group (TG) vs the VATS group (VATSG). Treatment and intention-to-treat (ITT) analyses were conducted.
In total, 2981 patients were finally included in the study: 1092 (37%) in the TG and 1889 (63%) in the VATSG for the treatment analysis; and 816 (27.4%) in the TG and 2165 patients (72.6%) in the VATSG for the ITT analysis. After propensity score matching, in the treatment analysis, the VATSG was significantly associated with fewer overall complications than the TG OR 0.680 95%CI 0.616, 0.750), fewer respiratory (OR 0.571 0.529, 0.616) cardiovascular (OR 0.529 0.478, 0.609) and surgical (OR 0.875 0.802, 0.955) complications, lower readmission rate (OR 0.669 0.578, 0.775) and a reduction of hospital length of stay (-1.741 (-2.073, -1.410). Intention-to-treat analysis showed only statistically significant differences in overall complications (OR 0.76 0.54-0.99) in favor of the VATSG.
In this multicenter population, VATS anatomical lung resections have been associated with lower morbidity than those performed by thoracotomy. However, when an intention-to-treat analysis was performed, the benefits of the VATS approach were less prominent.
OBJECTIVESIn recent years, video-assisted thoracoscopic lung resections (VATS) have been associated with lower morbidity than open surgery. The aim of our study is to compare postoperative morbidity ...among patients from the national database of the Spanish Group of Video-Assisted Thoracic Surgery (GE-VATS) after open and video-assisted anatomic lung resections using a propensity score analysis.METHODSFrom December 2016 to March 2018, a total of 3533 patients underwent anatomical lung resection at 33 centers. Pneumonectomies and extended resections were excluded. A propensity score analysis was performed to compare the morbidity of the thoracotomy group (TG) vs the VATS group (VATSG). Treatment and intention-to-treat (ITT) analyses were conducted.RESULTSIn total, 2981 patients were finally included in the study: 1092 (37%) in the TG and 1889 (63%) in the VATSG for the treatment analysis; and 816 (27.4%) in the TG and 2165 patients (72.6%) in the VATSG for the ITT analysis. After propensity score matching, in the treatment analysis, the VATSG was significantly associated with fewer overall complications than the TG OR 0.680 95%CI 0.616, 0.750), fewer respiratory (OR 0.571 0.529, 0.616) cardiovascular (OR 0.529 0.478, 0.609) and surgical (OR 0.875 0.802, 0.955) complications, lower readmission rate (OR 0.669 0.578, 0.775) and a reduction of hospital length of stay (-1.741 (-2.073, -1.410). Intention-to-treat analysis showed only statistically significant differences in overall complications (OR 0.76 0.54-0.99) in favor of the VATSG.CONCLUSIONIn this multicenter population, VATS anatomical lung resections have been associated with lower morbidity than those performed by thoracotomy. However, when an intention-to-treat analysis was performed, the benefits of the VATS approach were less prominent.
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To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge.
An observational, prospective and ...multicenter, nation-wide study.
Eight adult ICU across eight academic acute care hospitals in Mexico.
All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge.
None.
The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty.
196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio OR 3.70, 95% confidence interval 1.40–9.81, P = .008).
Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.
Analizar el deterioro de fragilidad en sobrevivientes de COVID-19 grave ingresados en la Unidad de Cuidados Intensivos (UCI) a los seis meses después del alta.
Estudio observacional, prospectivo y multicéntrico, de ámbito nacional.
Ocho UCI en ocho hospitales académicos en México.
Se incluyeron todos los pacientes adultos consecutivos con COVID-19 ingresados en la UCI con insuficiencia respiratoria aguda entre el 8 de marzo de 2020 y el 28 de febrero de 2021. La fragilidad se definió según la escala FRAIL y se obtuvo al ingreso en la UCI y 6 meses después del alta hospitalaria.
Ninguna.
El objetivo principal fue la fragilidad a los 6 meses después del alta. Se utilizó un modelo de regresión logística para evaluar los predictores durante la estancia en UCI asociados con la fragilidad.
196 supervivientes de la UCI se incluyeron en el análisis. A los 6 meses desde el alta, 164 pacientes fueron evaluados: 40 pacientes (20,4%) fueron clasificados como no frágiles, 67 (34,2%) como prefrágiles y 57 pacientes (29,1%) como frágiles. La necesidad de ventilación mecánica invasiva fue el único factor asociado independientemente con la fragilidad a los 6 meses de seguimiento (Odds Ratio OR 3,70; intervalo de confianza del 95%: 1,40 a 9,81, P = ,008).
El deterioro de la fragilidad aparece globalmente en más de la mitad de los supervivientes de la UCI con COVID-19 grave a los 6 meses. La necesidad de ventilación mecánica invasiva en los supervivientes de la UCI fue el único predictor asociado independientemente con la fragilidad.
