Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass

Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non‐invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid‐PBMC co‐incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.     

Childhood trauma and distress experiences associate with psychotic symptoms in patients attending primary and psychiatric outpatient care. Results of the RADEP study

GoalWe studied the prevalence of and association between psychotic symptoms and childhood trauma experiences in primary care patients compared with psychiatric care patients.Patients and methodsWe note 911 primary care and psychiatric care patients over 16 years of age filled in a questionnaire including a list of lifetime psychotic symptoms of the Composite International Diagnostic Interview (CIDI) and the childhood Trauma and Distress Scale (TADS). Prevalence of and correlations between psychotic symptoms and childhood trauma and stressful experiences were calculated. Association between the sum of CIDI symptoms and the TADS sum score was analysed by Anova.ResultsIn primary care, more than half of the patients had had at least one psychotic symptom during their lifetime, and nearly 70% of patients had experienced a childhood trauma at some time or more often. In psychiatric care patients, CIDI symptoms were more prevalent and TADS scores were higher than in primary care patients. In the whole sample, CIDI symptoms correlated with TADS scores. The association remained even when the effects of age, service, and patient's functioning were taken into account. There was a dose-response between TADS scores and CIDI symptoms.ConclusionChildhood trauma experiences associate with psychotic symptoms. In clinical work, it is important to acknowledge that psychotic symptoms and childhood trauma experiences are common not only in psychiatric care but also in primary care patients, and thus require adequate attention.     

Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial

Purpose

We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO₂) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury.

Methods

Using a 2³ factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5–4.7 kPa) or high-normal (5.8–6.0 kPa) PaCO₂ and to normoxia (arterial oxygen tension [PaO₂] 10–15 kPa) or moderate hyperoxia (PaO₂ 20–25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO₂ and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months.

Results

In total 120 patients were included in the analyses. There was a clear separation in PaCO₂ (p?<?0.001) and PaO₂ (p?<?0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9–28.3 µg/l) in the low-normal PaCO₂ group and 22.5 µg/l (14.2–34.9 µg/l) in the high-normal PaCO₂ group, p?=?0.400; and 22.3 µg/l (14.8–27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2–34.9 µg/l) in the moderate hyperoxia group, p?=?0.594). High-normal PaCO₂ and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes.

Conclusions

Both high-normal PaCO₂ and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected.

Registration

ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.

     

In vitro interactions of antimicrobial combinations with fosfomycin against KPC-2-producing Klebsiella pneumoniae and protection of resistance development

Using time-kill methodology, we investigated the interactions of fosfomycin with meropenem or colistin or gentamicin against 17 genetically distinct Klebsiella pneumoniae clinical isolates carrying blaKPC-2. Synergy was observed with meropenem or colistin against 64.7 and 11.8% of tested isolates, while the combination with gentamicin resulted in indifference. All studied combinations showed improved bactericidal activity, compared to fosfomycin alone and prevented the development of fosfomycin resistance in 69.2, 53.8, and 81.8% of susceptible isolates, respectively.     

Evaluation of CHROMagar™ KPC for the detection of carbapenemase-producing Enterobacteriaceae in rectal surveillance cultures

In this study, the performance of the chromogenic medium CHROMagar? KPC was evaluated and was compared with in-house-daily prepared McConkey agar plates supplemented with imipenem (1 mg/L) for the detection of carbapenemase-producing Enterobacteriaceae. In this surveillance study, rectal swabs were cultured on both media and polymerase chain reaction (PCR) for bla_KPC and bla_VIM was used to confirm the genotype of growing colonies of Enterobacteriaceae. CHROMagar KPC was also tested with 17 genotypically characterised carbapenemase-producing and non-producing Gram-negative bacteria. It was shown that CHROMagar allows rapid detection of carbapenemase-producing Enterobacteriaceae, although bla_KPC- and bla_VIM-harbouring isolates could not be differentiated by colour or colony morphology. The positive and negative predictive values of the tested methods for the detection of carbapenemase-producing Enterobacteriaceae were, respectively, 100% and 98.8% for CHROMagar KPC and 94.7% and 88.6% for imipenem-supplemented McConkey agar. CHROMagar KPC medium is a useful screening medium for carbapenemase-producing Enterobacteriaceae in stools in settings with a high proportion of patients colonised with a variety of carbapenemase-producers.