Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

The Use and Efficacy of FFR-CT: Real-World Multicenter Audit of Clinical Data With Cost Analysis.

BACKGROUND: Fractional flow reserve-computed tomography (FFR-CT) is endorsed by UK and U.S. chest pain guidelines, but its clinical effectiveness and cost benefit in real-world practice are unknown. OBJECTIVES: The purpose of this study was to audit the use of FFR-CT in clinical practice against England's National Institute for Health and Care Excellence guidance and assess its diagnostic accuracy and cost. METHODS: A multicenter audit was undertaken covering the 3 years when FFR-CT was centrally funded in England. For coronary computed tomographic angiograms (CCTAs) submitted for FFR-CT analysis, centers provided data on symptoms, CCTA and FFR-CT findings, and subsequent management. Audit standards included using FFR-CT only in patients with stable chest pain and equivocal stenosis (50%-69%). Diagnostic accuracy was evaluated against invasive FFR, when performed. Follow-up for nonfatal myocardial infarction and all-cause mortality was undertaken. The cost of an FFR-CT strategy was compared to alternative stress imaging pathways using cost analysis modeling. RESULTS: A total of 2,298 CCTAs from 12 centers underwent FFR-CT analysis. Stable chest pain was the main symptom in 77%, and 40% had equivocal stenosis. Positive and negative predictive values of FFR-CT were 49% and 76%, respectively. A total of 46 events (2%) occurred over a mean follow-up period of 17 months; FFR-CT (cutoff: 0.80) was not predictive. The FFR-CT strategy costs £2,102 per patient compared with an average of £1,411 for stress imaging. CONCLUSIONS: In clinical practice, the National Institute for Health and Care Excellence criteria for using FFR-CT were met in three-fourths of patients for symptoms and 40% for stenosis. FFR-CT had a low positive predictive value, making its use potentially more expensive than conventional stress imaging strategies.

Impact of New UNOS Allocation Criteria on Heart Transplant Practices and Outcomes.

BACKGROUND: In October 2018, a new heart allocation policy was implemented with intent of prioritizing the sickest patients and decreasing waitlist time. We examined the effects of the new policy on transplant practices and outcomes 1 year before and 1 year after the change. METHODS: Transplant recipients from October 2017 to September 2019 at our institution were identified and divided into 2 cohorts, a preallocation and postallocation criteria change. Patient demographics, clinical data, and bridging strategy were assessed. Early outcomes including ischemic time, severe primary graft dysfunction, need for renal replacement therapy, and duration of hospital stay were investigated. RESULTS: In the 12 months before the change, 38 patients were transplanted as compared to 33 patients in the 12 months after the change. The average wait-time to transplant decreased after the allocation change (49 versus 313 d, P = 0.02). Patients were more likely to be bridged with an intra-aortic balloon pump (45% versus 3%) and less likely to be supported with a durable left ventricular assist device (LVAD) after the change (24% versus 82%). There was an increase in total ischemic time after the change (177 versus 117 min, P ≤ 0.01). There were no significant differences in other early posttransplant outcomes. CONCLUSIONS: Implementation of the new allocation system for heart transplantation resulted in dramatic changes in the bridging strategy utilized at our institution. Temporary mechanical support usage increased following the change and the number of recipients supported with durable LVADs decreased. Early posttransplant outcomes appear similar.

Inhibition of Enterococcus faecalis biofilm formation by highly active lactones and lactams analogues of rubrolides.

Seven ß-aryl substituted γ-alkylidene-γ-lactones analogues of rubrolides were synthesized from mucobromic acid and converted through a lactamization with isobutylamine into their corresponding γ-hydroxy-γ-lactams (76-85%). These lactams were converted into (Z)- and (E)-γ-alkylidene-γ-lactams (23-45%). All compounds were fully characterized by IR, NMR ((1)H and (13)C), COSY and HETCOR bidimensional experiments, and NOE difference spectroscopy experiments when necessary. Evaluation of these three different classes of compounds against Enterococcus faecalis biofilm formation showed that all classes are active and the highest biofilm inhibition activity was caused by lactam 13f (IC50 = 0.76 µg/mL). Moreover, in almost all cases at least one of the lactams is more active than its correspondent γ-alkylidene-γ-lactone. The use of rubrolides as a lead structure has proven successful for the identification of new compounds displaying novel antibacterial activities, namely biofilm inhibition, which have the potential for the development of antimicrobial drugs targeted to inhibition of the initial stages of bacterial infections, rather than bacterial viability. Such drugs are less prompt to induce bacterial resistance, being therefore a more cost-effective investment for pharmaceutical research.

γ-Alkylidene-γ-lactones and isobutylpyrrol-2(5H)-ones analogues to rubrolides as inhibitors of biofilm formation by gram-positive and gram-negative bacteria.

Several molecules have been discovered that interfere with formation of bacterial biofilms, opening a new strategy for the development of more efficient treatments in case of antibiotic resistant bacteria. Amongst the most active compounds are some natural brominated furanones from marine algae Delisea pulchra that have proven to be able to control pathogenic biofilms. We have recently reported that some rubrolide analogues are able to inhibit biofilm formation of Enterococcus faecalis. In the present Letter we describe results of the biological evaluation of a small library of 28 compounds including brominated furanones and the corresponding lactams against biofilm formation of Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus mutans. Our results showed that in general these compounds were more active against biofilms of S. epidermidis and P. aeruginosa, with little or no inhibition of planktonic bacterial growth. In some cases they were able to prevent biofilm formation of P. aeruginosa at concentrations as low as 0.6 µg/mL (1.3 µM, compound 3d) and 0.7 µg/mL (1.3 µM, 3f). Results also indicate that, in general, lactams are more active against biofilms than their precursors, thus designating this class of molecules as good candidates for the development of a new generation of antimicrobial drugs targeted to biofilm inhibition.

Survival of bronchiectatic patients with respiratory failure in ICU.

BACKGROUND: The outcome of patients with bronchiectasis during and after their stay in the intensive care unit (ICU) has seldom been reported in the literature. Managing these patients in the ICU can be challenging because of the complex nature of their disease. This study aims to identify the in-hospital and long-term outcome of patients with bronchiectasis and respiratory failure (RF) in ICU. METHODS: A retrospective study was carried out by studying all bronchiectatic patients admitted to the medical ICU for RF over a 10-year period (1995-2004). RESULTS: The mean (+/- standard deviation) age of 35 patients was 63.5 +/- 11.7 years and APACHE score was 22.3 +/- 7.3. The 4-year mortality was 60%. Among the variables observed, age > 65 years (hazard ratio (HR): 4.15; 95% confidence interval (CI): 3.2-5.1), APACHE II score > 24 (2.6, 95% CI 1.7-3.5), intubation (2.81, 95 %CI 1.9-3.7), inotropic support (2.9, 95% CI 2.0-3.7), Home-O2 (4.0, 95% CI 2.7-5.2) and activity index (4.0, 95% CI 2.8-5.3) were associated with diminished survival in univariate analysis by Cox regression. By long rank test, survival probabilities were significantly low at these strata. Multivariate analysis of Cox proportional hazard model showed that age > 65 years (HR: 5.4, 95% CI 1.9-15.7); activity index (HR: 4.8, 95% CI 1.4-16.6); and inotropic support (HR: 3.8, 95% CI 1.5-10.1) were independently associated with reduced survival. CONCLUSION: The decreased survival of ICU patients was associated with age > 65 years, activity index (bedridden or wheelchair-bound) and use of inotropic support.

Outcome of patients with severe asthma in the intensive care unit.

BACKGROUND: Because little has been reported about the outcome of severe asthma outside the US and western Europe, we performed a retrospective case analysis of patients treated in the medical intensive care unit (MICU) of a university hospital in Riyadh, Saudi Arabia, to determine the management, complications and outcome of severe asthma requiring ICU admission. METHODS: The records of patients with severe asthma admitted to the MICU between the periods of January 1996 to December 2003 were reviewed. Sixty-one episodes from 54 patients were studied, of which 27 (44%) were male. RESULTS: All patients were hypercapnic; 23 (38%) were ventilated. The Acute Physiological and Health Evaluation (APACHE) score II was significantly higher in the ventilated group (P<0.0001). The pH was significantly lower and PaCO2 was significantly higher in the ventilated group (P<0.0001). All patients survived. Only 42% of patients our series received inhaled corticosteroids before admission. CONCLUSION: Our results suggest that severe asthma requiring ICU admission is now safely managed in ICUs. Our results are comparable to recently published data on the treatment of severe asthma in the ICU.

Outcome of patients with hematological malignancies admitted to the intensive care unit with life-threatening complications.

OBJECTIVE: To assess the outcome of patients with hematological malignancies (HM) admitted to medical intensive care unit (MICU) and to identify prognostic factors that may affect patients' outcome. METHODS: Data were collected in 44 patients with HM admitted to the MICU at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia within a 9-year period from 1993 to 2004. Demographic, physiological, clinical, laboratory and therapeutic data were collected on admission to MICU. RESULTS: Thirty-four percent of the patients had acute lymphocytic leukemia; 25% had acute myelocytic leukemia (AML) followed by non-Hodgkin's lymphoma in 20%, only 13.6% of these patients were in remission. The reasons for admission of these patients into MICU were shock (34.15%), respiratory failure (31.8%), cardiac arrest (20.4%), neurological causes (9.1%) and for other causes like small bowel perforation, hepatic failure, acute renal failure and metabolic disorders (4.5%). The overall in-hospital mortality was 72.7%, intensive care unit (ICU) mortality 61%, and the mean length of stay in the MICU was 5.4 +/- 4.8 days. A statistically significant association was demonstrated between both remission status and aspartate aminotransferase values on one side and patient's outcome on the other side. Patients with AML had poorer prognosis with mortality rate of 90.9%. CONCLUSION: Although mortality in patients with HM requiring ICU care is high, our results indicate that critical care support may be lifesaving. Apart from remission status and AML disease, no other prognostic factor could be identified.