Differences In 60-day Mortality Research Articles

Mesenchymal Stem Cells on Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem cells (MSCs) on mortality in patients with COVID-19. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with MSCs, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Seventeen RCTs (enrolling 1019 participants) met the inclusion criteria. MSCs showed significant effect on 28-day mortality (RR 0.76, 95% CI 0.62 to 0.93; P = 0.008). There was no statistically significant difference in 60-day mortality (RR 0.87, 95% CI 0.70 to 1.09; P = 0.22), and 90-day mortality (RR 0.91, 95% CI 0.72 to 1.15; P = 0.44) between the two groups. MSCs significantly reduced 28-day mortality in patients with COVID-19. The long-term effect of MSCs on mortality require further study.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis

The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. ClinicalTrials.gov Identifier: NCT02281929.

Anastomotic Leak in Ovarian Cancer Cytoreduction Surgery: A Systematic Review and Meta-Analysis.

Anastomotic leaks (AL) following ovarian cytoreduction surgery could be detrimental, leading to significant delays in commencing adjuvant chemotherapy, prolonged hospital stays and increased morbidity. The aim of this study was to investigate risk factors associated with anastomotic leaks after ovarian cytoreduction surgery. The MEDLINE (via PubMed), Cochrane Library, EMBASE and Scopus bibliographical databases were searched. Original clinical studies investigating risk factors for AL in ovarian cytoreduction surgery were included. Eighteen studies with non-overlapping populations reporting on patients undergoing cytoreduction surgery for ovarian cancer (n = 4622, including 344 cases complicated by AL) were included in our analysis. Patients undergoing ovarian cytoreduction surgery complicated by AL had a significantly higher rate of 30-day mortality but no difference in 60-day mortality. Multiple bowel resections were associated with an increased risk of postoperative AL, while no association was observed with body mass index (BMI), American Society of Anesthesiologists (ASA) score, age, smoking, operative approach (primary versus interval cytoreductive, stapled versus hand-sewn anastomoses and formation of diverting stoma), neoadjuvant chemotherapy and use of hyperthermic intraperitoneal chemotherapy (HIPEC). Multiple bowel resections were the only clinical risk factor associated with increased risk for AL after bowel surgery in the ovarian cancer population. The increased 30-day mortality rate in patients undergoing ovarian cytoreduction complicated by AL highlights the need to minimize the number of bowel resections in this population. Further studies are required to clarify any association between neoadjuvant chemotherapy and decreased AL rates.

High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure

The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated. To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC). This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021. Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2. The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant. In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement. ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.

PurposeSevere community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.MethodsThis double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72–96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up.ResultsBetween January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57–1.40). There were no significant differences in secondary outcomes or complications.ConclusionsIn patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06684-3.

Hyperdynamic left ventricular ejection fraction is associated with higher mortality in COVID-19 patients

Study objectiveTo compare the characteristics and outcomes of COVID-19 patients with a hyperdynamic LVEF (HDLVEF) to those with a normal or reduced LVEF. DesignRetrospective study. SettingRush University Medical Center. ParticipantsOf the 1682 adult patients hospitalized with COVID-19, 419 had a transthoracic echocardiogram (TTE) during admission and met study inclusion criteria. InterventionsParticipants were divided into reduced (LVEF < 50%), normal (≥50% and <70%), and hyperdynamic (≥70%) LVEF groups. Main outcome measuresLVEF was assessed as a predictor of 60-day mortality. Logistic regression was used to adjust for age and BMI. ResultsThere was no difference in 60-day mortality between patients in the reduced LVEF and normal LVEF groups (adjusted odds ratio [aOR] 0.87, p = 0.68). However, patients with an HDLVEF were more likely to die by 60 days compared to patients in the normal LVEF group (aOR 2.63 [CI: 1.36–5.05]; p < 0.01). The HDLVEF group was also at higher risk for 60-day mortality than the reduced LVEF group (aOR 3.34 [CI: 1.39–8.42]; p < 0.01). ConclusionThe presence of hyperdynamic LVEF during a COVID-19 hospitalization was associated with an increased risk of 60-day mortality, the requirement for mechanical ventilation, vasopressors, and intensive care unit.

Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment

The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. ClinicalTrials.gov Identifier: NCT01606098.

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients. MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission. ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07−1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04−1.80; P = 0.026). ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.

Influenza A-associated severe pneumonia in hospitalized patients: Risk factors and NAI treatments

ObjectiveThe risk factors and the impact of NAI treatments in patients with severe influenza A-associated pneumonia remain unclear. MethodsA multicenter, retrospective, observational study was conducted in Zhejiang, China during a severe influenza epidemic in August 2017–May 2018. Clinical records of patients (>14 y) hospitalized with laboratory-confirmed influenza A virus infection and who developed severe pneumonia were compared to those with mild-to-moderate pneumonia. Risk factors related to pneumonia severity and effects of NAI treatments (monotherapy and combination of peramivir and oseltamivir) were analyzed. Results202 patients with influenza A-associated severe pneumonia were enrolled, of whom 84 (41.6%) had died. Male gender (OR = 1.782; 95% CI: 1.089–2.917; P = 0.022), chronic pulmonary disease (OR = 2.581; 95% CI: 1.447–4.603; P = 0.001) and diabetes mellitus (OR = 2.042; 95% CI: 1.135–3.673; P = 0.017) were risk factors related to influenza A pneumonia severity. In cox proportional hazards model, severe pneumonia patients treated with double dose oseltamivir (300mg/d) had a better survival rate compared to those receiving a single dose (150 mg/d) (HR = 0.475; 95%CI: 0.254–0.887; P = 0.019). However, different doses of peramivir (300 mg/d vs. 600 mg/d) and combination therapy (oseltamivir-peramivir vs. monotherapy) showed no differences in 60-day mortality (P = 0.392 and P = 0.658, respectively). ConclusionsPatients with male gender, chronic pulmonary disease, or diabetes mellitus were at high risk of developing severe pneumonia after influenza A infection. Double dose oseltamivir might be considered in treating influenza A-associated severe pneumonia.

Recent advances in venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.

To summarize results of the most recent trials on venovenous extracorporeal membrane oxygenation (VV-ECMO) in severe acute respiratory distress syndrome (ARDS) and to elaborate on the unmet needs regarding VV-ECMO management in this setting. Although it was terminated early for futility (i.e., failure to demonstrate a difference in 60-day mortality of 20%), the ECMO to Rescue Lung Injury in Severe ARDS trial of VV-ECMO for severe ARDS reported a nonsignificant, but clinically important, reduction in mortality (35 vs. 46%; relative risk 0.76; 95% confidence interval 0.55-1.04, P = 0.09). Refractory hypoxemia led to rescue ECMO in 28% of controls, who had more severe ARDS at inclusion, were extremely sick at the time of ECMO cannulation and for whom mortality was 57%. Beyond the rescue of patients dying of refractory hypoxemia, ECMO may now be used early in severe ARDS patients to reduce the intensity of mechanical ventilation and to minimize ventilator-induced lung injury. Future research in the field should focus on identification of patients who are more likely to benefit from this technique and the right timing for its initiation, optimization of daily management of patients under ECMO to further reduce complications, and selection of optimal ventilator management on ECMO. VV-ECMO is a reasonable therapeutic option for patients with severe ARDS and major hypoxemia or excessive pressures. Future trials should be designed to optimize patients' management while on VV-ECMO support.

Clinical differences between pulmonary and extrapulmonary acute respiratory distress syndrome: a retrospective cohort study of prospectively collected data in Japan.

Although acute respiratory distress syndrome (ARDS) reportedly shows various clinical phenotypes with different risk and prognostic factors, few studies have assessed the clinical features and prognosis of pulmonary and extrapulmonary ARDS. The aim of the present study was to investigate clinical differences between pulmonary and extrapulmonary ARDS. In total, 200 patients who met the Berlin criteria and were diagnosed with ARDS between October 2004 and September 2017 were included. We classified the patients into pulmonary and extrapulmonary ARDS groups. Both groups were assessed for 60-day mortality, duration of ventilation, and other clinical features. There were 150 and 50 patients in the pulmonary and extrapulmonary ARDS groups, respectively. The two groups showed no significant differences in any assessment parameters except the serum lactate dehydrogenase (LDH) level, which was higher in the extrapulmonary ARDS group (P=0.01). After adjustment for potentially confounding covariates, there were no significant differences in 60-day mortality (P=0.99) and the duration of ventilation (P=0.45) between the two groups. Mortality was significantly associated with the disseminated intravascular coagulation (DIC) score, high-resolution computed tomography (HRCT) score, and serum LDH level in the pulmonary ARDS group and the DIC score and HRCT score in the extrapulmonary ARDS group. Pulmonary and extrapulmonary ARDS may be comparable in terms of the prognosis and duration of ventilation. DIC and HRCT scores may be common clinical predictors of mortality with ARDS.

A Multi-Center, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury

ObjectiveAcute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU).Design, Setting, PatientsA randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy.ResultsNo significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol’s recommended range (≤ 0.4mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol’s recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86).ConclusionSCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit.Trial RegistrationClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893

An investigation of the efficacy of invasive-noninvasive sequential mechanical ventilation in senile patients with severe community-acquired pneumonia

To investigate the efficacy of invasive-noninvasive sequential mechanical ventilation (MV) in senile patients with severe community-acquired pneumonia (CAP). A prospective study was conducted. The patients with severe CAP aged ≥75 years admitted to Department of Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from November 2012 to July 2014, with refusal to have tracheostomy, were enrolled. All patients meeting the diagnostic criteria of CAP and severe CAP were first admitted into the Department of Emergency, and they were found to need MV without absolute contraindication for noninvasive ventilation (NIV) in RICU. The patients were mechanically ventilated via endotracheal intubation (ETI), and they were randomly divided into invasive-noninvasive sequential MV group (sequential MV group) and conventional MV group. NIV was initiated immediately when patients matched the conditions for early extubation in the sequential MV group. Oxygen therapy (5 L/min) via a Venturi mask was provided when the indications of conventional extubation were met. The baseline data and clinical characteristics were recorded, the risk factors of death were analyzed by logistic regression analysis, and 60-day survival rate was analyzed by Kaplan-Meier curve. Ninety-one senile patients with severe CAP were enrolled, among them 28 patients died within 60 days, with a mortality rate of 30.77%. No significant difference in 60-day mortality was found between sequential MV group (n=44) and conventional MV group [n=47, 25.0% (11/44) vs. 36.2% (17/47), χ2=1.331, P=0.249]. In the sequential MV group, the incidence of ventilator-associated pneumonia (VAP) was significantly decreased [27.3% (12/44) vs. 55.3% (26/47), χ2=7.350, P=0.007], and the rate of ETI≥2 times was increased [59.1% (26/44) vs. 29.8% (14/47), χ2=5.095, P=0.024] as compared with conventional MV group. Compared with survival group, the patients in non-survival group showed a higher incidence of cerebrovascular disease (60.7% vs. 25.4%, P=0.002), higher acute physiology and chronic health evaluation II (APACHEII) score (26.46±2.59 vs. 24.41±2.47, P=0.001), British Thoracic Society confusion, uremia, respiratory rate, blood pressure, ≥75 years (CURB-75 score, 4.00±0.47 vs. 3.68±0.53, P=0.013), a longer total duration of MV (days: 21.18±10.02 vs. 14.56±7.62, P=0.002), and a higher ratio of ETI≥2 times (53.6% vs. 33.3%, P<0.001). It was revealed by multivariate logistic regression analysis that ETI≥2 times and comorbidity of cerebrovascular infarction were independent predictors of a worse outcome in the senile patients [odds ratio (OR)=9.677, 95% confidence interval (95%CI)=3.075-30.457, P<0.001; OR=5.386, 95%CI=1.781-6.284, P=0.003]. It was showed by Kaplan-Meir survival analysis that ETI times and concurrent cerebrovascular infarction imparted significant effects on the 60-day survival rate (χ2=40.805, P=0.000; χ2=4.425, P=0.035). Invasive-noninvasive sequential MV may not improve the outcome of senile patients with severe CAP, and ETI≥2 times and concurrent cerebrovascular disorders drastically lowered the survival rate.

Does the Mean Arterial Pressure Influence Mortality Rate in Patients with Acute Hypoxemic Respiratory Failure under Mechanical Ventilation?

BackgroundIn sepsis patients, target mean arterial pressures (MAPs) greater than 65 mm Hg are recommended. However, there is no such recommendation for patients receiving mechanical ventilation. We aimed to evaluate the influence of MAP over the first 24 hours after intensive care unit (ICU) admission on the mortality rate at 60 days post-admission in patients showing acute hypoxemic respiratory failure under mechanical ventilation.MethodsThis prospective, multicenter study included 22 ICUs and compared the mortality and clinical outcomes in patients showing acute hypoxemic respiratory failure with high (75-90 mm Hg) and low (65-74.9 mm Hg) MAPs over the first 24 hours of admission to the ICU.ResultsOf the 844 patients with acute hypoxemic respiratory failure, 338 had a sustained MAP of 65-90 mm Hg over the first 24 hours of admission to the ICU. At 60 days, the mortality rates in the low (26.2%) and high (24.5%) MAP groups were not significantly different. The ICU days, hospital days, and 60-day mortality rate did not differ between the groups.ConclusionIn the first 24 hours of ICU admission, MAP range between 65 and 90 mm Hg in patients with acute hypoxemic respiratory failure under mechanical ventilation may not cause significantly differences in 60-day mortality.

Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance.

IntroductionSeveral guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.MethodsThis is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010.Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics.ResultsInitial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups.ConclusionsInitial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria.

A pooled safety and efficacy analysis of the FOLFOX4 regimen (bi-monthly oxaliplatin plus fluorouracil/leucovorin) in elderly compared to younger patients with colorectal cancer

3517 Background: The combination of oxaliplatin, fluorouracil, and leucovorin is effective in many patients with colon cancer treated in either the advanced or adjuvant disease setting. To better identify the risks &amp; benefits of this regimen for elderly patients we compared safety &amp; efficacy data for the FOLFOX4 regimen (oxaliplatin plus fluorouracil/leucovorin administered bimonthly) in patients over &amp; under 70 years of age. Methods: We conducted a retrospective analysis of 3742 patients (614 aged ≥ 70) with colorectal cancer enrolled in four clinical trials using the same FOLFOX4 regimen as adjuvant therapy, or as first- or second-line therapy in advanced disease. Endpoints included grade ≥ 3 adverse events, response rate (RR) (in studies of advanced disease), progression (metastatic)/relapse free (adjuvant) survival (P/RFS), overall survival (OS), and dose intensity. Results: Age ≥ 70 was associated with slightly higher rates of neutropenia and thrombocytopenia but no other grade ≥ 3 adverse events (see table). There was no difference in 60-day mortality (1.1% vs 2.3%, p=0.20). We observed no significant difference in any measure of therapeutic impact of FOLFOX based on age, including P/RFS, OS, response rate, or dose intensity (see table). Conclusions: The FOLFOX4 regimen maintains its efficacy/safety ratio in elderly patients with colorectal cancer, and was administered per protocol at similar drug doses compared to the younger patients enrolled on these trials. Age alone should not be a factor limiting the use of FOLFOX4 provided patients are carefully evaluated and monitored. This analysis was supported by Sanofi-Aventis [Table: see text] [Table: see text]