The prognostic impact of abdominal surgery in cancer patients with neutropenic enterocolitis: a systematic review and meta-analysis, on behalf the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH).

Neutropenic enterocolitis (NE) is a diagnostic and therapeutic challenge associated with high mortality rates, with controversial opinions on its optimal management. Physicians are usually reluctant to select surgery as the first-choice treatment, concerns being raised regarding the potential risks associated with abdominal surgery during neutropenia. Nevertheless, no published studies comforted this idea, literature is scarce and surgery has never been compared to medical treatment. This review and meta-analysis aimed to determine the prognostic impact of abdominal surgery on outcome of neutropenic cancer patients presenting with NE, versus medical conservative treatment. This meta-analysis included studies analyzing cancer patients presenting with NE, treated with surgical or medical treatment, searched by PubMed and Cochrane databases (1983-2016), according to PRISMA recommendations. The endpoint was hospital mortality. Fixed-effects models were used. The meta-analysis included 20 studies (385 patients). Overall estimated mortality was 42.2% (95% CI = 40.2-44.2). Abdominal surgery was associated with a favorable outcome with an OR of 0.41 (95% CI = 0.23-0.74; p = 0.003). Pre-defined subgroups analysis showed that neither period of admission, underlying malignancy nor neutropenia during the surgical procedure, influenced this result. Surgery was not associated with an excess risk of mortality compared to medical treatment. Defining the optimal indications of surgical treatment is needed.Trial registration PROSPERO CRD42016048952.

Protective effect of early low-dose hydrocortisone on ventilator-associated pneumonia in the cancer patients: a propensity score analysis.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a care-related event that could be promoted by immune suppression caused by critical diseases, malignancies and cancer treatments. Low dose of hydrocortisone was proposed for modulation of immune response in the critically ill population. METHODS: In this monocentric observational study, all cancer patients mechanically ventilated for more than 48 h were included. Effect of low-dose hydrocortisone administered during the first 48 h of mechanical ventilation was evaluated applying inverse probability weighting analysis after propensity score assessment. VAP impact on 1-year mortality, ICU length of stay and mechanical ventilation duration was secondarily determined. RESULTS: Within this cohort, 190 cancer patients were followed. VAP was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12-0.44; P < 0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10-2.34; P = 0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95% CI 0.6-7.8). CONCLUSIONS: Immune modulation with low-dose hydrocortisone administered in the first days of mechanical ventilation could protect from VAP occurrence in cancer patients.

Respiratory events in ward are associated with later intensive care unit (ICU) admission and hospital mortality in onco-hematology patients not admitted to ICU after a first request.

INTRODUCTION: Prognostic impact of delayed intensive care unit(ICU) admission in critically ill cancer patients remains debatable. We determined predictive factors for later ICU admission and mortality in cancer patients initially not admitted after their first ICU request. METHODS: All cancer patients referred for an emergency ICU admission between 1 January 2012 and 31 August 2013 were included. RESULTS: Totally, 246(54.8%) patients were immediately admitted. Among 203(45.2%) patients denied at the first request, 54(26.6%) were admitted later. A former ICU stay [OR: 2.75(1.12-6.75)], a request based on a clinical respiratory event[OR: 2.6(1.35-5.02)] and neutropenia[OR: 2.25(1.06-4.8)] were independently associated with later ICU admission. Survival of patients admitted immediately and later did not differ at ICU(78.5% and 70.4%, respectively; p = 0.2) or hospital(74% and 66%, respectively; p = 0.24) discharge. Hospital mortality of patients initially not admitted was 29.7% and independently associated with malignancy progression[OR: 3.15(1.6-6.19)], allogeneic hematopoietic stem cell transplantation[OR: 2.5(1.06-5.89)], a request based on a clinical respiratory event[OR: 2.36(1.22-4.56)] and severe sepsis[OR: 0.27(0.08-0.99)]. CONCLUSION: Compared with immediate ICU admission, later ICU admission was not associated with hospital mortality. Clinical respiratory events were independently associated with both later ICU admission and hospital mortality.

Surgical treatment of acute abdominal complications in hematology patients: outcomes and prognostic factors.

The decision to operate on hematology patients with abdominal emergencies can be difficult, as neutropenia and thrombocytopenia are common and the usual causes of abdominal pain are broad. We conducted a retrospective observational study including all hematology patients undergoing emergency abdominal surgery between January 1998 and January 2013. Of the fifty-eight consecutive patients included in the study, nineteen (33%) underwent an operation during the neutropenia period. In the multivariate analysis, a laparotomy after 2002 was protective (HR: 0.05; 95%CI: 0.001-0.24), whereas preoperative septic shock (HR: 8.58; 95%CI: 2.25-32.63) and use of dialysis (HR: 6.67; 95%CI: 2.11-21.07) were independently associated with hospital mortality. Surgery during neutropenia or thrombocytopenia was not associated with prognosis. In hematology patients, emergency abdominal surgery is associated with encouraging hospital survival rates. Surgery should be performed prior to septic shock, regardless of whether neutropenia or thrombocytopenia is present.

Postoperative sepsis in cancer patients undergoing major elective digestive surgery is associated with increased long-term mortality.

BACKGROUND: Major postoperative events (acute respiratory failure, sepsis, and surgical complications) are frequent early after elective gastroesophageal and pancreatic surgery. It is unclear whether these complications impact equally on long-term outcome. METHODS: Prospective observational study including the patients admitted to the surgical intensive care unit between January 2009 and October 2011 after elective gastroesophageal and pancreatic surgery. Risk factors for 30-day major postoperative events and long-term outcome were evaluated. RESULTS: During the study period, 259 patients were consecutively included. Among them, 166 (64%), 54 (21%), and 39 (15%) patients underwent pancreatic surgery, gastric surgery, and esophageal surgery, respectively. Using the Clavien-Dindo classification, 117 patients (45%) developed at least 1 postoperative complication, including 60 (23%) patients with acute respiratory failure, 77 (30%) with sepsis, and 89 (34%) with surgical complications. The median follow-up from the time of intensive care unit admission was 34 months (95% confidence interval, 30-37 months). The 1-year survival was 95% (95% confidence interval, 92-98). Among the perioperative variables, postoperative sepsis and an American Society of Anesthesiologists score higher than 2 were independently associated with long-term mortality. In septic patients, death (n = 16) was significantly associated with cancer recurrence (n = 10; P < .0001). Independent factors associated with postoperative sepsis were a Sequential Organ Failure Assessment score on day 1, a systemic inflammatory response syndrome on day 3, positive intraoperative microbiological samples, Simplified Acute Physiology Score II and an American Society of Anesthesiologists score higher than 2 (P < .005). CONCLUSIONS: Postoperative sepsis was the only major postoperative event associated with long-term mortality. Postoperative sepsis may reflect a deep impairment of immune response, which is potentially associated with cancer recurrence and mortality.

Allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning regimen: Outcomes of patients admitted to intensive care unit.

PURPOSE: The prognosis of allogeneic hematopoietic stem cell transplantation (HSCT) patients admitted to the intensive care unit (ICU) is still poor. Overall, when these patients receive reduced intensity conditioning (RIC) regimens, the survival is better. To date, no study has specifically evaluated the outcome of RIC allogeneic HSCT admitted to the ICU. METHODS: We realized a retrospective study of 102 patients admitted to the ICU among a cohort of 601 consecutive patients receiving RIC regimens. The primary objective of the study was to assess in-ICU and inhospital mortality rates. RESULTS: The ICU mortality was 39.2%, and the hospital mortality was 59.8%. The median overall survival of ICU patients was 8.2 months (95% confidence interval [CI], 5.7-10.6) vs 75 (95% CI, 63-87) in non-ICU patients (P < .0001). During hospital stay, an ICU admission for neurologic dysfunction was independently associated with hospital survival (P = .012). The use of invasive mechanical ventilation (IMV; P = .011), Simplified Acute Physiology Score II (P = .003), and longer time between diagnosis of malignancy and HSCT (P = .012) were associated with hospital mortality. The overall survival of the ICU survivors was significantly lower than that of non-ICU patients (hazard ratio, 3.61 [95% CI, 2.18-4.59]; P < .001). The median survival of ICU survivors was 9 months (95% CI, 4-14) vs 75 (95% CI, 63-87) in non-ICU patients (P < .0001). Noninvasive ventilation (NIV) was successful (not followed by IMV in 61% of cases [25/41 NIV patients]), and failure of NIV was not associated with hospital mortality in patients treated with subsequent IMV. CONCLUSION: From our study, short-term survival rates of ICU patients receiving RIC regimens justify a broad ICU admission policy. The use of IMV is associated with hospital mortality, whereas the use of NIV is frequently successful. Long-term outcome remains poor after ICU discharge.

[Febrile neutropenia in onco-hematology patients hospitalized in Intensive Care Unit]. / Prise en charge de la neutropénie fébrile chez le patient d'onco-hématologie admis en réanimation.

Febrile neutropenia in cancer patients is associated with a high mortality. Patients are frequently admitted to Intensive Care Unit (ICU) for severe sepsis or septic shock. Empirical antibiotic treatment, including monotherapy ß-lactam covering Pseudomonas aeruginosa, must be prompt. The ICU management is slightly different, due to a particular microbial ecology. A standardized approach to obtain a microbiological documentation is the cornerstone in these patients, leading to an adapted antimicrobial treatment. Systematic reassessment of initial antibiotic regimen should be realised. Neutropenic patients with severe sepsis or septic shock should receive promptly a ß-lactam-aminoglycoside combination, as well as glycopeptides in case of severity or absence of documented infection. Early catheter removal should be considered widely. In the actual context of growing resistance, antibiotics saving became a major concern. According to context and microbial documentation, an escalade or de-escalade approach is recommended, to take into account multi-resistant pathogens. The addition of antifugal treatment is also a major issue in these patients and has well-defined indications. In neutropenic patients admitted in the ICU for severe sepsis or septic shock, controlling local microbial epidemiology and the emergence of multi-resistant bacteria are the key issues.

De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study.

BACKGROUND: In severe sepsis, guidelines recommend de-escalating the empirical antimicrobial treatment as soon as the microbiological results are available. We aimed to determine the rate of de-escalation of the empirical antimicrobial treatment in neutropenic patients with severe sepsis. The characteristics of antimicrobial treatment associated with de-escalation and its impact on short- and long-term survival were also determined. METHODS: In the intensive care unit (ICU) of a cancer referral center, we prospectively collected observational data related to the antimicrobial management in neutropenic patients who developed severe sepsis and were admitted to ICU for at least 48 h. De-escalation of antimicrobial therapy consisted either of deleting one of the empirical antibiotics of a combined treatment, or, whenever possible, to use a betalactam antibiotic with a narrower spectrum of activity. Multivariate logistic regression was conducted to determine the factors associated with de-escalation, while a Cox proportional hazards model with a time-dependent covariate was fitted to assess the effect of de-escalation on 30-day survival. Finally 1-year survival after ICU discharge was compared across de-escalation groups. RESULTS: Cumulative incidence of de-escalation of the empirical antimicrobial treatment among the 101 patients of the cohort was 44%, [95% confidence interval (CI) 38-53%], including 30 (68%) patients with ongoing neutropenia. A microbiological documentation was available in 63 (63%) patients. Factors associated with de-escalation were the adequation of the empirical antimicrobial treatment in ICU [OR = 10.8 (95% CI 1.20-96)] for adequate documented treatment versus appropriate empirical treatment, the compliance with guidelines regarding the empirical choice of the anti-pseudomonal betalactam [OR = 10.8 (95% CI 1.3-89.5)]. De-escalation did not significantly modify the hazard of death within the first 30 days [HR = 0.51 (95% CI 0.20-1.33)], nor within 1 year after ICU discharge [HR = 1.06 (95% CI 0.54-2.08)]. CONCLUSION: Our data suggest that, in ICU, de-escalation of the empirical antimicrobial treatment is frequently applied in neutropenic cancer patients with severe sepsis. No evidence of any prognostic impact of this de-escalation was found.

Cluster analysis application identifies muscle characteristics of importance for beef tenderness.

BACKGROUND: An important controversy in the relationship between beef tenderness and muscle characteristics including biochemical traits exists among meat researchers. The aim of this study is to explain variability in meat tenderness using muscle characteristics and biochemical traits available in the Integrated and Functional Biology of Beef (BIF-Beef) database. The BIF-Beef data warehouse contains characteristic measurements from animal, muscle, carcass, and meat quality derived from numerous experiments. We created three classes for tenderness (high, medium, and low) based on trained taste panel tenderness scores of all meat samples consumed (4,366 observations from 40 different experiments). For each tenderness class, the corresponding means for the mechanical characteristics, muscle fibre type, collagen content, and biochemical traits which may influence tenderness of the muscles were calculated. RESULTS: Our results indicated that lower shear force values were associated with more tender meat. In addition, muscles in the highest tenderness cluster had the lowest total and insoluble collagen contents, the highest mitochondrial enzyme activity (isocitrate dehydrogenase), the highest proportion of slow oxidative muscle fibres, the lowest proportion of fast-glycolytic muscle fibres, and the lowest average muscle fibre cross-sectional area. Results were confirmed by correlation analyses, and differences between muscle types in terms of biochemical characteristics and tenderness score were evidenced by Principal Component Analysis (PCA). When the cluster analysis was repeated using only muscle samples from m. Longissimus thoracis (LT), the results were similar; only contrasting previous results by maintaining a relatively constant fibre-type composition between all three tenderness classes. CONCLUSION: Our results show that increased meat tenderness is related to lower shear forces, lower insoluble collagen and total collagen content, lower cross-sectional area of fibres, and an overall fibre type composition displaying more oxidative fibres than glycolytic fibres.

Meta-analysis of the comparison of the metabolic and contractile characteristics of two bovine muscles: longissimus thoracis and semitendinosus.

This study used the BIF-Beef data warehouse to determine whether semitendinosus (ST) was a muscle with a faster contraction speed and more glycolytic than longissimus thoracis (LT), regardless of the sex and breed of animals. With more than 500 animals from 7 breeds, we confirmed that LT was more oxidative than ST in males and females, but not in steers, and in all the breeds studied except Montbéliard. The LT had more slow oxidative (SO) and fewer fast oxido-glycolytic (FOG) and fast-glycolytic (FG) muscle fibres than the ST muscle, regardless of sex, in all breeds except Montbéliard and Holstein. SO proportion and the oxidative activity were negatively correlated to FG proportion and to the glycolytic activity. Similarly, FOG proportion was positively correlated to the glycolytic activity and negatively to FG proportion. However, these relationships are not consistent across sexes and breeds. In conclusion, differences in muscle types may be affected by sex or breed but to a moderate extent only.

Association of mechanical chest compression and prehospital thrombolysis.

Pulmonary embolism (PE) is a common cause of sudden death; the use of prehospital thrombolysis is currently a last-resort option and requires a prolonged cardiopulmonary resuscitation (CPR). Novel mechanical devices have recently been introduced that provides automatic mechanical chest compression (AMCC) according to the guidelines and continually without decrease efficiency throughout prolonged resuscitation. A 54 year-old woman with a history of breast cancer experienced sudden chest pain and severe dyspnea. A mobile intensive care unit was dispatched to her home. During physical examination, she suddenly collapsed with pulseless electrical activity as the initial rhythm. Prehospital thrombolysis during CPR combined with use of AMCC was performed based on a strongly suspected diagnosis of massive PE. After 75 minutes of effective CPR, return of spontaneous circulation was attained. After admission to an intensive care unit, computed tomographic scan confirmed bilateral PE. The patient was discharged 3 weeks after CPR in good neurologic condition. To our knowledge, this is the first case describing combined use of thrombolysis and AMCC in out-ofhospital cardiac arrest. However, for the time being, prehospital thrombolysis in CPR continues to be a measure that should only be performed on a case-by-case basis based on informed decision. Further studies are needed to evaluate the efficacy and safety of AMCC with thrombolysis and thus prolonged CPR.

Prognosis of acute respiratory distress syndrome in neutropenic cancer patients.

To date, no study has been specifically designed to identify determinants of death in neutropenic cancer patients presenting with acute respiratory distress syndrome (ARDS). The aim of this study was to identify early predictive factors of 28-day mortality in these patients. Factors associated with 28-day mortality during intensive care unit (ICU) stay were also described. 70 consecutive cancer patients with ARDS and neutropenia were prospectively analysed over a 6-yr period. Mortality at 28 days was 63%. Factors independently associated with good prognosis were: lobar ARDS (OR 0.10, 95% CI 0.02-0.48), use of initial antibiotic treatment active on difficult to treat bacteria (ticarcillin-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia or extended-spectrum ß-lactamase-producing strains) (OR 0.08, 95% CI 0.02-0.33) and first-line chemotherapy (OR 0.08, 95% CI 0.02-0.37). During the ICU stay, mortality was associated with the markers of organ dysfunctions, the absence of neutropenia recovery and the use of vasopressors. During the first 3 weeks, the conditional probability of discharge alive from ICU did not decrease. At ICU admission, first-line chemotherapy, lobar ARDS and antibiotic treatment active on difficult-to-treat bacteria were associated with survival. During ICU stay, mortality was associated with organ dysfunctions and use of vasopressors. Most survivors have an ICU stay of >3 weeks.

Monocyte deactivation in neutropenic acute respiratory distress syndrome patients treated with granulocyte colony-stimulating factor.

INTRODUCTION: In severely neutropenic septic acute respiratory distress syndrome (ARDS) patients, macrophages and monocytes are the last potentially remaining innate immune cells. We have previously shown, however, a deactivation of the alveolar macrophage in neutropenic septic ARDS patients. In the present study, we tried to characterize in vitro monocyte baseline cytokine production and responsiveness to lipopolysaccharide exposure. METHODS: Twenty-two consecutive patients with cancer were prospectively enrolled into a prospective observational study in an intensive care unit. All patients developed septic ARDS and were divided into two groups: neutropenic patients (n = 12) and non-neutropenic patients (n = 10). All of the neutropenic patients received granulocyte colony-stimulating factor whereas no patient in the non-neutropenic group received granulocyte colony-stimulating factor. We compared monocytes from neutropenic patients with septic ARDS with monocytes from non-neutropenic patients and healthy control individuals (n = 10). Peripheral blood monocytes were cultured, and cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10, and IL-1 receptor antagonist) were assayed with and without lipopolysaccharide stimulation. RESULTS: TNFalpha, IL-6, IL-10 and IL-1 receptor antagonist levels in unstimulated monocytes were lower in neutropenic patients compared with non-neutropenic patients. Values obtained in the healthy individuals were low as expected, comparable with neutropenic patients. In lipopolysaccharide-stimulated monocytes, both inflammatory and anti-inflammatory cytokine production were significantly lower in neutropenic patients compared with non-neutropenic patients and control individuals. CONCLUSION: Consistent with previous results concerning alveolar macrophage deactivation, we observed a systemic deactivation of monocytes in septic neutropenic ARDS. This deactivation participates in the overall immunodeficiency and could be linked to sepsis, chemotherapy and/or the use of granulocyte colony-stimulating factor.

N-terminal pro-brain natriuretic peptide as an early prognostic factor in cancer patients developing septic shock.

INTRODUCTION: The overall prognosis of critically ill patients with cancer has improved during the past decade. The aim of this study was to identify early prognostic factors of intensive care unit (ICU) mortality in patients with cancer. METHODS: We designed a prospective, consecutive, observational study over a one-year period. Fifty-one cancer patients with septic shock were enrolled. RESULTS: The ICU mortality rate was 51% (26 deaths). Among the 45 patients who benefited from transthoracic echocardiography evaluation, 17 showed right ventricular dysfunction, 18 showed left ventricular diastolic dysfunction, 18 showed left ventricular systolic dysfunction, and 11 did not show any cardiac dysfunction. During the first three days of ICU course, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly higher in patients presenting cardiac dysfunctions compared to patients without any cardiac dysfunction. Multivariate analysis discriminated early prognostic factors (within the first 24 hours after the septic shock diagnosis). ICU mortality was independently associated with NT-proBNP levels at day 2 (odds ratio, 1.2; 95% confidence interval, 1.004 to 1.32; p = 0.022). An NT-proBNP level of more than 6,624 pg/ml predicted ICU mortality with a sensitivity of 86%, a specificity of 77%, a positive predictive value of 79%, a negative predictive value of 85%, and an accuracy of 81%. CONCLUSION: We observed that critically ill cancer patients with septic shock have an approximately 50% chance of survival to ICU discharge. NT-proBNP was independently associated with ICU mortality within the first 24 hours. NT-proBNP could be a useful tool for detecting high-risk cancer patients within the first 24 hours after septic shock diagnosis.