Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial

Purpose

Family members of patients who die in the intensive care unit (ICU) may experience symptoms of stress, anxiety, depression, posttraumatic stress disorder (PTSD), and/or prolonged grief. We evaluated whether grief symptoms were alleviated if the physician and the nurse in charge at the time of death sent the closest relative a handwritten condolence letter.

Methods

Multicenter randomized trial conducted among 242 relatives of patients who died at 22 ICUs in France between December 2014 and October 2015. Relatives were randomly assigned to receiving (n = 123) or not receiving (n = 119) a condolence letter. The primary endpoint was the Hospital Anxiety and Depression Score (HADS) at 1 month. Secondary endpoints included HADS, complicated grief (ICG), and PTSD-related symptoms (IES-R) at 6 months. Observers were blinded to group allocation.

Results

At 1 month, 208 (85.9%) relatives completed the HADS; median score was 16 [IQR, 10–22] with and 14 [8–21.5] without the letter (P = 0.36). Although scores were higher in the intervention group, there were no significant differences regarding the HADS-depression subscale (8 [4–12] vs. 6 [2–12], mean difference 1.1 [?0.5 to 2.6]; P = 0.09) and prevalence of depression symptoms (56.0 vs. 42.4%, RR 0.76 [0.57–1.00]; P = 0.05). At 6 months, 190 (78.5%) relatives were interviewed. The intervention significantly increased the HADS (13 [7–19] vs. 10 [4–17.5], P = 0.04), HADS-depression subscale (6 [2–10] vs. 3 [1–9], P = 0.02), prevalence of depression symptoms (36.6 vs. 24.7%, P = 0.05) and PTSD-related symptoms (52.4 vs. 37.1%, P = 0.03).

Conclusions

In relatives of patients who died in the ICU, a condolence letter failed to alleviate grief symptoms and may have worsened depression and PTSD-related symptoms. Trial registration Clinicaltrials.gov Identifier: NCT02325297.

     

Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

Purpose

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.

Methods

Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.

Results

Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10^?4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10^?3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10^?5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10^?3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10^?3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10^?3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313).

Conclusions

Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

     

A multicenter multinational study of abdominal candidiasis: epidemiology,outcomes and predictors of mortality

Purpose

Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce.

Methods

We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011–2013) including patients from ICU, medical, and surgical wards.

Results

A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64 %) and C. glabrata (n = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08, P = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89, P = 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy.

Conclusions

Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

     

Renal shear wave elastography for the assessment of nephron hypertrophy: a cross-sectional study in chronic kidney disease

Purpose

To investigate the association of renal elasticity to microscopic findings of nephron hypertrophy and nephrosclerosis.

Methods

Patients who underwent renal biopsy were enrolled. Renal elasticity was measured by acoustic radiation force impulse, and nephron size (glomerular volume, non-sclerotic glomerular density, and mean profile tubular area) and nephrosclerosis (globally sclerotic glomeruli and interstitial fibrosis) were estimated. Nephron hypertrophy was indicated by larger glomerular volume, larger tubular area, and lower non-sclerotic glomerular density. Nephrosclerosis was indicated by a higher percentage of globally sclerotic glomeruli and higher severity of fibrosis.

Results

Renal elasticity was negatively correlated with glomerular volume (r = ? 0.480, P = 0.024) and mean tubular area (r = ? 0.469, P = 0.028), but it was not correlated with non-sclerotic glomerular density (r = 0.205, P = 0.359), percentage of globally sclerotic glomeruli (r = 0.057, P = 0.800), and severity of fibrosis (r = 0.014, P = 0.950). In a multiple linear regression analysis, glomerular volume and mean tubular area were independently associated with renal elasticity (std β = ? 0.454, P = 0.015 and std β = ? 0.577, P = 0.007, respectively).

Conclusion

Renal elasticity was correlated with microstructural findings of nephron hypertrophy. Measuring renal elasticity could help in detecting kidney disease.

     

Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial

Importance

Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness.

Objective

To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients.

Design, setting, and participants

Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days.

Interventions

Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care.

Main outcomes and measures

Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function.

Results

474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI ?0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m² (95 % CI 1.0–14.5 mL/min/1.73 m², P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145–455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21).

Conclusion and relevance

Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction.

Trial registration

anzctr.org.au Identifier: ACTRN12609001015235.

     

Monitoring dynamic arterial elastance as a means of decreasing the duration of norepinephrine treatment in vasoplegic syndrome following cardiac surgery: a prospective,randomized trial

Purpose

To evaluate the ability of an algorithm based on dynamic arterial elastance to decrease the duration of norepinephrine treatment.

Methods

We performed a prospective, open-label, randomized study in patients requiring norepinephrine for vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass. Patients were randomized to an algorithm-based intervention group or a control group. The primary outcome was the duration of norepinephrine treatment. The secondary outcomes included the total dose of norepinephrine, the length of stay (LOS) in the ICU, central venous oxygen saturation, arterial lactate levels, arrhythmia and diuresis.

Results

Of 130 included patients, 118 were analysed on an intention-to-treat basis (intervention group: n = 59; control group: n = 59). On inclusion, the intervention and control groups did not differ significantly in terms of demographic characteristics, surgical data or the prior duration of norepinephrine treatment [5 h (4–10) vs. 5 h (5–7), respectively; P = 0.543]. The cumulative duration of norepinephrine treatment after inclusion was shorter in the intervention group than in the control group [17 h (13–26)] vs. 39 h (19–58), respectively; (P < 0.001). The cumulative dose of norepinephrine and the LOS in the ICU were also lower in the intervention group (P < 0.05). There were no intergroup differences for other outcomes (the sepsis-related organ failure score, central venous oxygen saturation, arrhythmia, and arterial lactate levels).

Conclusion

A haemodynamic algorithm based on dynamic arterial elastance was associated with a shorter duration of norepinephrine treatment and a shorter LOS in the ICU. Use of the algorithm did not alter perfusion parameters or increase the volume of fluid infused. ClinicalTrials.gov Identifier: NCT02479529.

     

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Purpose

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS_CRF?) in comparison with others (ARDS_CRF+).

Methods

Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.

Results

The prevalence of ARDS_CRF? was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS_CRF? patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDS_CRF? patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.

Conclusions

The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

     

The association of duration of boarding in the emergency room and the outcome of patients admitted to the intensive care unit

Background

The demand for critical care beds is increasing out of proportion to bed availability. As a result, some critically ill patients are kept in the Emergency Department (ED boarding) awaiting bed availability. The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU).

Methods

This was a retrospective analysis of ICU data collected prospectively at King Abdulaziz Medical City, Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding. Patients were stratified into three groups according to the duration of boarding from ED. Those admitted less than 6 h were classified as Group I, between 6 and 24 h, Group II and more than 24 h as Group III. We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age, sex, APACHE, Mechanical ventilation, Creatinine, Platelets, INR.

Results

During the study period, 940 patients were admitted from the ED to ICU, amongst whom 227 (25%) were admitted to ICU within 6 h, 358 (39%) within 6–24 h and 355 (38%) after 24 h. Patients admitted to ICU within 6 h were younger [48.7 ± 22.2(group I) years, 50.6 ± 22.6 (group II), 58.2 ± 20.9 (group III) (P = 0.04)]with less mechanical ventilation duration[5.9 ± 8.9 days (Group I), 6.5 ± 8.1 (Group II) and 10.6 ± 10.5 (Group III), P = 0.04]. There was a significant increase in hospital mortality [51(22.5), 104(29.1), 132(37.2), P = 0.0006) and the ICU length of stay(LOS) [9.55 days (Group I), 9.8 (Group II) and 10.6 (Group III), (P = 0.002)] with increase in boarding duration. In addition, the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90, P = 0.04) and hospital mortality(OR for group III vs Group I is 2.09, P = 0.007).

Conclusion

Boarding in the ED is associated with higher mortality. This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow.

     

Histogram Analysis of T1-Weighted,T2-Weighted,and Postcontrast T1-Weighted Images in Primary CNS Lymphoma: Correlations with Histopathological Findings—a Preliminary Study

Purpose

Previously, some reports mentioned that magnetic resonance imaging (MRI) can predict histopathological features in primary CNS lymphoma (PCNSL). The reported data analyzed diffusion-weighted imaging findings. The aim of this study was to investigate possible associations between histopathological findings, such as tumor cellularity, nucleic areas and proliferation index Ki-67, and signal intensity on T1-weighted and T2-weighted images in PCNSL.

Procedures

For this study, 18 patients with PCNSL were retrospectively investigated by histogram analysis on precontrast and postcontrast T1-weighted and fluid-attenuated inversion recovery (FLAIR) images. For every patient, histopathology parameters, nucleic count, total nucleic area, and average nucleic area, as well as Ki-67 index, were estimated.

Results

Correlation analysis identified several statistically significant associations. Skewness derived from precontrast T1-weighted images correlated with Ki-67 index (p = ? 0.55, P = 0.028). Furthermore, entropy derived from precontrast T1-weighted images correlated with average nucleic area (p = 0.53, P = 0.04). Several parameters from postcontrast T1-weighted images correlated with nucleic count: maximum signal intensity (p = 0.59, P = 0.017), P75 (p = 0.56, P = 0.02), and P90 (p = 0.52, P = 0.04) as well as SD (p = 0.58, P = 0.02). Maximum signal intensity derived from FLAIR sequence correlated with nucleic count (p = 0.50, P = 0.03).

Conclusion

Histogram-derived parameters of conventional MRI sequences can reflect different histopathological features in PSNCL.

     

Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised,parallel-group,multicentre feasibility trial

Purpose

We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock.

Methods

We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction group fluid boluses were permitted only if signs of severe hypoperfusion occurred, while in the standard care group fluid boluses were permitted as long as circulation continued to improve.

Results

The co-primary outcome measures, resuscitation fluid volumes at day 5 and during ICU stay, were lower in the fluid restriction group than in the standard care group [mean differences ?1.2 L (95 % confidence interval ?2.0 to ?0.4); p < 0.001 and ?1.4 L (?2.4 to ?0.4) respectively; p < 0.001]. Neither total fluid inputs and balances nor serious adverse reactions differed statistically significantly between the groups. Major protocol violations occurred in 27/75 patients in the fluid restriction group. Ischaemic events occurred in 3/75 in the fluid restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08–1.27; p = 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23–0.92; p = 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36–1.40; p = 0.32).

Conclusions

A protocol restricting resuscitation fluid successfully reduced volumes of resuscitation fluid compared with a standard care protocol in adult ICU patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes.

Trial registration

NCT02079402.

     

Fat-free mass at admission predicts 28-day mortality in intensive care unit patients: the international prospective observational study Phase Angle Project

Purpose

Phase angle as measured by bioelectrical impedance analysis reflects fat-free mass. Fat-free mass loss relates to worse prognosis in chronic diseases. Primary aim of this study was: to determine the association between fat-free mass at intensive care unit admission and 28-day mortality.

Methods

Ten centres in nine countries participated in this multicentre prospective observational study. The inclusion criteria were age >18 years; expected length of stay >48 h; absence of pacemaker, heart defibrillator implant, pregnancy and lactation. Fat-free mass was assessed by measurement of the 50-kHz phase angle at admission. The primary endpoint was 28-day mortality. The area under the receiver operating characteristic curve (AUC) was used to assess prediction of 28-day mortality by fat-free mass at ICU admission. The variables associated with 28-day mortality were analysed by means of multivariable logistic regression.

Results

Of the 3605 patients screened, 931 were analysed: age 61 ± 16 years, male 60 %, APACHE II 19 ± 9, body mass index 26 ± 6, day 1 phase angle 4.5° ± 1.9°. Day 1 phase angle was lower in patients who eventually died than in survivors (4.1° ± 2.0° vs. 4.6° ± 1.8°, P = 0.001). The day 1 phase angle AUC for 28-day mortality was 0.63 [0.58–0.67]. In multivariable analysis, the following were independently associated with 28-day mortality: age (adjusted odds ratio (aOR) 1.014 [95 % confidence interval 1.002–1.027], P = 0.03), day 1 phase angle (aOR 0.86 [0.78–0.96], P = 0.008), APACHE II (aOR 1.08 [1.06–1.11], P < 0.001), surgical patient (aOR 0.51 [0.33–0.79], P = 0.002), and admission for other diagnosis (aOR 0.39 [0.21–0.72], P = 0.003). A multivariable combined score improved the predictability of 28-day mortality: AUC = 0.79 [0.75–0.82].

Conclusion

Low fat-free mass at ICU admission is associated with 28-day mortality. A combined score improves mortality predictability. Trial registration: NCT01907347 (http://www.clinicaltrials.gov).

     

Increased incidence of co-infection in critically ill patients with influenza

Background

Co-infection is frequently seen in critically ill patients with influenza, although the exact rate is unknown. We determined the rate of co-infection, the risk factors and the outcomes associated with co-infection in critically ill patients with influenza over a 7-year period in 148 Spanish intensive care units (ICUs).

Methods

This was a prospective, observational, multicentre study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint of this analysis was the presence of community-acquired co-infection, with secondary endpoints including ICU, 28-day and hospital mortality.

Results

Of 2901 ICU patients diagnosed with influenza, 482 (16.6 %) had a co-infection. The proportion of cases of co-infection increased from 11.4 % (110/968) in 2009 to 23.4 % (80/342) in 2015 (P < 0.001). Compared with patients without co-infection, patients with co-infection were older [adjusted odds ratio (aOR) 1.1, 95 % confidence interval 1.1–1.2; P < 0.001] and were more frequently immunosuppressed due to existing HIV infection (aOR 2.6 [1.5–4.5]; P < 0.001) or preceding medication (aOR 1.4 [1.1–1.9]; P = 0.03). Co-infection was an independent risk factor for ICU mortality (aOR 1.4 [1.1–1.8]; P < 0.02), 28-day mortality (aOR 1.3 [1.1–1.7]; P = 0.04) and hospital mortality (aOR 1.9 [1.5–2.5]; P < 0.001).

Conclusions

Co-infection in critically ill patients with influenza has increased in recent years. In this Spanish cohort, age and immunosuppression were risk factors for co-infection, and co-infection was an independent risk factor for ICU, 28-day and hospital mortality.

     

The impact of disability in survivors of critical illness

Purpose

To use the World Health Organisation’s International Classification of Functioning to measure disability following critical illness using patient-reported outcomes.

Methods

A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation’s Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU.

Results

We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P < 0.002), and reduced health-related quality of life (P < 0.001).

Conclusion

Disability measured using patient-reported outcomes was prevalent at 6 months after critical illness in survivors and was associated with reduced health-related quality of life. Predictors of moderate or severe disability included a prior history of anxiety or depression, separation or divorce and a longer duration of mechanical ventilation.Trial registration: NCT02225938.

     

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3–42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066–1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.     

Partially-covered stent placement versus surgical gastrojejunostomy for the palliation of malignant gastroduodenal obstruction secondary to pancreatic cancer

Purpose

To compare the outcomes of partially covered self-expandable metallic stent (SEMS) placement with surgical gastrojejunostomy (GJ) in patients with gastroduodenal obstruction caused by pancreatic cancer.

Methods

The medical records of 107 patients with gastroduodenal obstruction caused by pancreatic cancer who underwent fluoroscopic partially covered SEMS placement (n = 75) or surgical GJ (n = 32) at our institution were reviewed.

Results

The technical (100% vs. 100%; P > 0.999) and clinical (98.7% vs. 96.9%; P = 0.511) success rates were similar between the SEMS and GJ group. The mean gastric outlet obstruction scoring system score was higher in the SEMS group at 1 week after treatment (2.3 ± 0.5 vs. 1.2 ± 0.4; P < 0.001) but was similar between the two groups at 1 month (2.7 ± 0.5 vs. 2.8 ± 0.5; P = 0.242). The median hospital stay was shorter in the SEMS group than in the GJ group (7 vs. 14 days; P < 0.001). The overall complication (22.7% vs. 28.1%; P = 0.547) and reintervention (21.3% vs. 25.0%; P = 0.677) rates were similar between the two groups. The median patency (99 vs. 138 days; P = 0.102) and survival (106 vs. 140 days; P = 0.245) were also similar between the two groups.

Conclusion

The outcomes of partially covered SEMS placement seem to be more favorable than surgical GJ in patients with gastroduodenal obstruction caused by pancreatic cancer.

     

The relationship between electrocardiographic changes and CMR features in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy

To investigate the relationship between electrocardiographic (ECG) abnormalities and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). 118 asymptomatic or mildly symptomatic patients with HCM were examined with late gadolinium enhancement (LGE) CMR, 12-lead ECG, and echocardiography. The distribution and magnitude of LV segmental hypertrophy and LGE were assessed and analyzed in relation to ECG abnormalities. Abnormal electrocardiograms were found in 113 of 118 (95 %) patients. Negative T waves were associated with greater apical septal thickness (P = 0.009) and an increased ratio of LV septum to free wall thickness (P = 0.01). Giant negative T waves (GNT) were found in 19 patients (16 %), and were associated with apical HCM (P < 0.001), greater apical thickness (P = 0.004), and increased ratio of LV apical to basal wall thickness (P < 0.001). However, no significant association was demonstrated between GNT and apical LGE (P = 0.71). Abnormal Q waves were associated with greater basal anteroseptal thickness (P = 0.001), maximal basal thickness (P = 0.004), and more segments with extensive LGE (>75 % wall thickness involved) (P = 0.001). LV hypertrophy was related to greater LV mass (P = 0.002) and LV end diastolic volume (P = 0.002). In addition, a modest but significant correlation was observed between maximum LV wall thickness and the Romhilt-Estes score (r = 0.41, P < 0.001). GNT were associated with apical HCM and an increased ratio of LV apical to basal wall thickness. Abnormal Q waves were related to basal anteroseptal hypertrophy and segmental extensive LGE.     

Small volume resuscitation with 20% albumin in intensive care: physiological effects

Purpose

We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4–5% albumin.

Methods

We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK.

Results

The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4–5% albumin group [median difference ??600 ml, 95% confidence interval (CI) ??800 to ??400; P?<?0.001]. The 20% albumin group had lower cumulative fluid balance at 48 h (mean difference ??576 ml, 95% CI ??1033 to ??119; P?=?0.01). Peak albumin levels were higher but sodium and chloride levels lower in the 20% albumin group. Median (interquartile range) duration of mechanical ventilation was 12.0 h (7.6, 33.1) in the 20% albumin group and 15.3 h (7.7, 58.1) in the 4–5% albumin group (P?=?0.13); the proportion of patients commenced on renal replacement therapy after randomization was 3.3% and 4.2% (P?=?0.67), respectively, and the proportion discharged alive from ICU was 97.4% and 91.1% (P?=?0.02).

Conclusions

Resuscitation with 20% albumin decreased resuscitation fluid requirements, minimized positive early fluid balance and was not associated with any evidence of harm compared with 4–5% albumin. These findings support the safety of further exploration of resuscitation with 20% albumin in larger randomised trials.

Trial registration

http://www.anzctr.org.au. Identifier ACTRN12615000349549.

     

3′-Deoxy-3′-[<Superscript>18</Superscript>F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

Purpose

We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models.

Procedures

Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [¹⁸F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations.

Results

Expression of TP correlated positively with [¹⁸F]FLT SUV_max (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = ??0.939, P < 0.001).

Conclusions

In a broad range of tumors, [¹⁸F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [¹⁸F]FLT uptake.

     

Evaluation of the treatment of chronic chemotherapy-induced peripheral neuropathy using long-wave diathermy and interferential currents: a randomized controlled trial

Purpose

The purpose was to investigate the effects of long-wave diathermy in combination with interferential currents (interferential therapy and long-wave diathermy at high power (ITH)) in comparison with long-wave diathermy at a power below the active treatment dose (long-wave diathermy at low power (LDL), control group) on sensory and motor symptoms in patients with chronic chemotherapy-induced peripheral neuropathy (CIPN) in the lower extremities.

Methods

Sixty-seven patients with chronic CIPN were randomized to 12 weeks of either ITH or LDL. Follow-up assessments were performed after the treatment period and at 37 weeks after randomization. The primary outcome was pain (Numeric Rating Scale (NRS)), and the secondary outcomes were discomfort, nerve symptoms, subjective measurement of dizziness (Dizziness Handicap Inventory), and balance. Differences within and between groups were analyzed.

Results

Pain intensity decreased significantly only in the LDL group directly after the treatment period from NRS median 25 to median 12.5 (P = 0.017). At the 37-week follow-up, no changes were detected, irrespective of group (NRS 13 vs. 20, P = 0.885). Discomfort decreased significantly in both groups at both 12 and 37 weeks after the baseline (P < 0.05). Balance disability showed significant declines in both groups at 12 and 37 weeks (P = 0.001/0.025 in the ITH group vs P = 0.001/<0.001 in the LDL group). Balance ability (tightened Romberg test) increased significantly at both 12 and 37 weeks in both groups (P = 0.004/<0.040 in the ITH group) but did not improve in the LDL group at any of the follow-up time points (P = 0.203 vs P = 0.383). The one-legged stance test was unchanged in the ITH group after 12 weeks but improved 37 weeks after baseline (P = 0.03). No significant changes were observed in the LDL group at any of the follow-up time points.

Conclusion

This study provides no support for the use of a combination of long-wave diathermy and ITH as a treatment option for patients with chronic CIPN. However, the chronic CIPN symptoms decreased with time irrespective of the treatment.

     

Efficacy of bioelectrical impedance analysis during the perioperative period in children

We evaluated the efficacy of bioelectrical impedance analysis (BIA) during the perioperative period by estimating the preoperative and postoperative body fluid status. After obtaining informed consent, we enrolled 100 children (3–12 years of age) scheduled for elective surgeries. All children had been fasted preoperatively. The children’s body fluid status was estimated using a BIA machine (InBody S10; Biospace, Korea) in the ward on the afternoon before surgery (baseline), just before surgery and immediately after surgery. The total administered fluid volume during the fasting period, total administered fluid volume during the operation and fasting time were recorded. Continuous data are shown as mean ± standard deviation, and Pearson’s correlation analysis was used to assess relationships between the preoperative fluid deficit and intracellular water (ICW)/extracellular water (ECW) changes. The mean fasting period was 13.3 h (range 5.8–19.7 h). A weak positive correlation was shown between the ICW and fluid deficit during the fasting period (Pearson correlation coefficient = 0.254; P = 0.010). A stronger positive correlation was shown between the ECW and fluid deficit during the fasting period (Pearson correlation coefficient = 0.359; P < 0.001). The baseline and postoperative ICW showed a strong positive correlation (Pearson correlation coefficient = 0.992, P < 0.001), as did the baseline and postoperative ECW (Pearson correlation coefficient = 0.990, P < 0.001). Also there was no dehydration and irritability on medical recording preoperatively. BIA may be an alternative method for estimating the perioperative fluid status in children and determining details of fluid administration.