Severe drug-induced liver injury associated with prolonged use of Linezolid

This study aims to describe a patient developing concomitant severe liver failure and lactic acidosis after long-term treatment with linezolid. A 55-year-old Caucasian woman developed concomitant severe liver failure and lactic acidosis after a treatment with linezolid for 50 days because of infected hip prosthesis. Other causes of liver failure and lactic acidosis were excluded by extensive diagnostic workup. A liver biopsy showed microvesicular steatosis. As linezolid toxicity was considered to be the cause of the lactic acidosis and the severe hepatic failure, the antibiotic was withdrawn. After 4 days of supportive therapy and hemodialysis, the serum lactate level returned within normal limits. The prothrombin time ratio and thrombocytes recovered within 2 weeks. Bilirubin levels normalized within 14 weeks. Since no other cause could be identified, liver injury was considered to be drug-related. Resolution of the hepatotoxicity occurred after discontinuation of linezolid, supportive treatment measures, and hemodialysis. Both lactic acidosis and microvesicular steatosis after the use of linezolid are related to mitochondrial dysfunction. The Council for International Organizations of Medical Sciences/Roussel Ucalf Causality Assessment Method scale revealed that the adverse drug event was probable. Prolonged exposure to linezolid may induce severe hepatotoxicity. Clinicians should be aware of this possible adverse effect especially in case of long-term treatment

Management and outcomes in critically ill nonagenarian versus octogenarian patients.

BACKGROUND: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. METHODS: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. RESULTS: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). CONCLUSION: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. TRIAL REGISTRATION: NCT03134807 and NCT03370692

Fatal acute pulmonary injury associated with everolimus

OBJECTIVE: To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. CASE SUMMARY: In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. DISCUSSION: Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. CONCLUSIONS: This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity

Trombotische microangiopathie als eerste teken van gemetastaseerd borstcarcinoom

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Outcome in critically ill patients with allogeneic BM or peripheral haematopoietic SCT : a single-centre experience

Outcome in haematological patients who develop critical illness has significantly improved over the last two decades, but less so in allogeneic BMT recipients. We prospectively investigated the outcome of 44 haematological patients with allogeneic BM or haematopoietic SCT (ABMT/AHSCT) requiring admission to the intensive care unit (ICU) of Ghent University Hospital between January 2000 and December 2007. We related outcome to the cause of critical illness, which was categorized as documented or clinically suspected bacterial infection, non-bacterial infection and non-infectious disease. Mechanical ventilation was required in 32 patients, and 12 patients received renal replacement therapy. Overall ICU-mortality, in-hospital mortality and 6-month mortality rates were 61, 75 and 80%, respectively. Hospital mortality rates in patients with bacterial infection (n = 14), non-bacterial infection (n = 13) and non-infectious disease (n = 17) were 43, 85 and 94% (P = 0.003). After adjustment for severity of illness sequential organ failure assessment (SOFA) score, bacterial infection (odds ratio 0.06, 0.01-0.36, P = 0.002) was associated with significantly lower odds for hospital mortality. On the basis of our experience, ICU referral of ABMT/AHSCT patients is justifiable, as an acceptable fraction of these patients have longer-term survival. Documented or clinically suspected bacterial infection as the cause of critical illness is associated with better prognosis in comparison with other causes

Assessing independency in daily activities in very preterm children at preschool age

This study investigates whether very low birth weight (VLBW) preschoolers experience disability in daily activities and what the risk factors for disability in daily activities are. The Dutch Pediatric Evaluation of Disability Inventory (PEDI-NL) was used to detect disability in daily activities in 143 VLBW children without cerebral palsy (CP) at 44 months of corrected age (CA). Data from the psychomotor-developmental index (PDI) and the mental developmental index (MDI) of the Bayley Scales of Infant Development II (BSID II) at 24 months CA, and data relating to perinatal and socio-economic status were available. Disability in daily activities was found in 27 (19%) VLBW children without CP. High frequencies of disability were found in 19 (13%) children on the mobility domain and in 12 (8%) children on the social functioning domain. The multiple logistic regression analyses showed that low BSID II outcomes ( <2 SD) were risk factors for disability in the mobility domain, but not for disability in the social functioning domain. The predictive value of the BSID II outcomes is moderate, 46% of the VLBW children with a low PDI and 44% with a low MDI developed a disability in the mobility domain. This study showed a higher frequency of disability in daily activities in VLBW preschoolers compared to term born peers. Therefore, it is suggested to assess VLBW children's performance of daily activities before they start schoo

Aspiration pneumonia : an underestimated cause of severe respiratory failure in patients with haematological malignancies and severe oral mucositis?

Aspiration pneumonia is rarely considered in the differential diagnosis of respiratory failure in patients suffering from haematologic malignancies in daily practice. We describe four patients who were admitted with severe respiratory failure in the ICU over a one-year-period prospective survey (a total of 72 patients with haematological malignancies of which 34 presented with respiratory failure). All of these patients had chemotherapy-induced severe oral mucositis (WHO grade III-IV) for which three of them received opioids. All had a history of cough after oral rinsing and two of them experienced sudden brief desaturation in the days before ICU referral. Two of these patients, both in allogeneic bone marrow transplant setting, died. With this data, we want to draw the attention to the diagnosis of aspiration pneumonia in this group of patients

The infant behavioral assessment and intervention program in very low birth weight infants; Outcome on executive functioning, behaviour and cognition at preschool age

Background: The Infant Behavioral Assessment and Intervention Program (IBAIP (c)) improved motor function at 24 months, and mental and behavioural development in high risk subgroups of very low birth weight (VLBW) infants. Aim: To determine IBAIP's effects on executive functioning, behaviour and cognition at preschool age. Study design: Follow-up of a randomised controlled trial (RCT). Subjects: At 44 months corrected age, all 176 VLBW infants were invited for follow-up. Forty-one term born children were assessed for comparison. Outcome measures: Visual Attention Task (VAT), Gift delay, Peabody Picture Vocabulary Test III-NL (PPVT), Visual motor integration tests and Miller assessment for preschoolers. Parents completed Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and Child Behavior Checklist (CBCL). Results: At preschool age, 76 (88%) children of the intervention group and 75 (83%) children of the control group participated. There were no significant differences between the intervention and the control group. However, positive interaction effects between intervention and infants with bronchopulmonary dysplasia, infants born at gestational age <28 weeks, and infants of low educated mothers were found on CBCL, CBCL and BRIEF-P, and PPVT respectively. Most interaction effects exceeded 1 standard deviation in favour of the intervention children. The 151 VLBW children performed significantly worse than the term born children on the VAT, BRIEF-P and CBCL. Conclusion: IBAIP effects in VLBW children did not sustain until preschool age on executive functioning, behaviour and cognition. However, the most vulnerable children had a clinical relevant profit from IBAIP. VLBW children performed worse than the term born children. This study is a follow-up at preschool age of the multi-centre RCT of IBAIP versus usual care in VLBW infants. The RCT was performed in Amsterdam, The Netherlands (IBAIP RCT registered on http://www.controlled-trials.com number ISRCTN65503576). (c) 2012 Elsevier Ireland Ltd. All rights reserve

Attention in 3-Year-Old Children with VLBW and Relationships with Early School Outcomes

To compare attention skills of children with a very low birth weight (VLBW) with children with a normal birth weight (NBW) when entering primary school, and explore the association of attention skills with school career 2 years later. Participants were 151 children with VLBW and 41 with NBW. Attention was assessed at 3 years and 8 months of corrected age (CA) and school career at 5½ years of CA. Children performed two tests, parents completed three questionnaires, and an assessor systematically observed children's attention. Children with VLBW had significantly lower mean scores on five of the six measures. Significantly more children with VLBW had scores in the clinical range on the Child Behavior Checklist completed by the parents (13% versus 0%) and scores representing dysfunction on assessor observations (19% versus 2%). At 5½ years of age, 36% of the children with VLBW followed special education or had grade retention. Dysfunctional attention as observed by the assessor was most strongly associated with need for learning support at 5½ years of age. At preschool age, children with VLBW have attention difficulties. Attentive behavior at preschool age is a predictor of school career 2 years late