Amyloidosis: a case series and review of the literature.

BACKGROUND: Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis. CASE PRESENTATIONS: In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a  69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges. CONCLUSIONS: Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.

Furosemide and Albumin for Diuresis of Edema (FADE): A parallel-group, blinded, pilot randomized controlled trial.

PURPOSE: To assess the feasibility of a trial evaluating whether hyperoncotic albumin, in addition to diuretics, improves diuresis and facilitates liberation from mechanical ventilation in critically ill adults. MATERIALS AND METHODS: We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100 mL of 25% albumin or 0.9% saline placebo BID, for three days, in blinded fashion. We chose five feasibility measurements: enrolment of 50% of eligible patients, at least one patient/week; administration of study treatment within 2 h of diuretics in 85% of patients; completion of study regimen in 80% of patients; and avoidance of open label albumin in 85% of patients. Clinical outcomes included fluid balance, ventilator-free days, and mortality. RESULTS: We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2 h of diuretics, 69% received all doses of study treatment. Study treatment was held in the albumin and placebo groups because of no further need for diuresis (4 vs. 1), hypotension (2 v. 4), and albumin > 35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups. CONCLUSIONS: The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.

The offering of family presence during resuscitation: a systematic review and meta-analysis.

BACKGROUND: Family members may wish to be present during resuscitation of loved ones, despite concerns that they may interfere with the resuscitation or experience psychological harm. METHODS: We conducted a systematic review to determine whether offering family presence during resuscitation (FPDR) affected patient mortality, resuscitation quality, or family member psychological outcomes. We searched multiple databases up to January 2014 for studies comparing FPDR to usual care. Two reviewers independently assessed eligibility, risk of bias, and extracted data. Data from randomized controlled trial (RCTs) at low or uncertain risk of bias were eligible for pooling. Quality of evidence was assessed using GRADE. RESULTS: Three RCTs evaluated the offering of FPDR in adults, finding no differences in resuscitation duration, prehospital/emergency room mortality (odds ratio [OR] 0.80, 95 % confidence interval [CI] 0.54-1.19), or 28-day mortality (OR 1.24, 95 % CI [0.50-3.03]). Hospital Anxiety and Depression Scale scores for anxiety (mean difference [MD] -0.99, 95 % CI [-1.77, -0.22]) and depression (MD -1.00, 95 % CI [-1.78, -0.23]), along with Impact of Events Scale intrusion score (MD -1.00, 95 % CI [-1.96, -0.03]), were better in family members offered FPDR. One RCT evaluated FPDR in pediatric patients, finding no mortality differences at 28 days (OR 0.30; 95 % CI [0.11-0.79]), but did not report psychological outcomes in family members. CONCLUSIONS: Moderate-quality evidence suggests the offering of FPDR does not affect adult resuscitation outcomes and may improve family member psychological outcomes. Low-quality evidence suggests FPDR does not affect pediatric resuscitation outcomes. The generalizability of these findings outside the prehospital and emergency room setting is limited due to the absence of trials in other health care settings.

Reflecting on Diagnostic Errors: Taking a Second Look is Not Enough.

BACKGROUND: An experimenter controlled form of reflection has been shown to improve the detection and correction of diagnostic errors in some situations; however, the benefits of participant-controlled reflection have not been assessed. OBJECTIVE: The goal of the current study is to examine how experience and a self-directed decision to reflect affect the accuracy of revised diagnoses. DESIGN: Medical residents diagnosed 16 medical cases (pass 1). Participants were then given the opportunity to reflect on each case and revise their diagnoses (pass 2). PARTICIPANTS: Forty-seven medical Residents in post-graduate year (PGY) 1, 2 and 3 were recruited from Hamilton Health Care Centres. MAIN MEASURES: Diagnoses were scored as 0 (incorrect), 1 (partially correct) and 2 (correct). Accuracies and response times in pass 1 were analyzed using an ANOVA with three factors-PGY, Decision to revise yes/no, and Case 1-16, averaged across residents. The extent to which additional reflection affected accuracy was examined by analyzing only those cases that were revised, using a repeated measures ANOVA, with pass 1 or 2 as a within subject factor, and PGY and Case or Resident as a between-subject factor. KEY RESULTS: The mean score at pass 1 for each level was PGY1, 1.17 (SE 0.50); PGY2, 1.35 (SE 0.67) and PGY3, 1.27 (SE 0.94). While there was a trend for increased accuracy with level, this did not achieve significance. The number of residents at each level who revised at least one diagnosis was 12/19 PGY1 (63 %), 9/11 PGY2 (82 %) and 8/17 PGY3 (47 %). Only 8 % of diagnoses were revised resulting in a small but significant increase in scores from Pass 1 to 2, from 1.20/2 to 1.22 /2 (t = 2.15, p = 0.03). CONCLUSIONS: Participants did engage in self-directed reflection for incorrect diagnoses; however, this strategy provided minimal benefits compared to knowing the correct answer. Education strategies should be directed at improving formal and experiential knowledge.

Family presence during resuscitation: A Canadian Critical Care Society position paper.

BACKGROUND: Recent evidence suggests that patient outcomes are not affected by the offering of family presence during resuscitation (FPDR), and that psychological outcomes are neutral or improved in family members of adult patients. The exclusion of family members from the resuscitation area should, therefore, be reassessed. OBJECTIVE: The present Canadian Critical Care Society position paper is designed to help clinicians and institutions decide whether to incorporate FPDR as part of their routine clinical practice, and to offer strategies to implement FPDR successfully. METHODS: The authors conducted a literature search of the perspectives of health care providers, patients and families on the topic of FPDR, and considered the relevant ethical values of beneficence, nonmaleficence, autonomy and justice in light of the clinical evidence for FPDR. They reviewed randomized controlled trials and observational studies of FPDR to determine strategies that have been used to screen family members, select appropriate chaperones and educate staff. RESULTS: FPDR is an ethically sound practice in Canada, and may be considered for the families of adult and pediatric patients in the hospital setting. Hospitals that choose to implement FPDR should develop transparent policies regarding which family members are to be offered the opportunity to be present during the resuscitation. Experienced chaperones should accompany and support family members in the resuscitation area. Intensive educational interventions and increasing experience with FPDR are associated with increased support for the practice from health care providers. CONCLUSIONS: FPDR should be considered to be an important component of patient and family-centred care.

Furosemide and albumin for diuresis of edema (FADE): a study protocol for a randomized controlled trial.

BACKGROUND: Fluid retention is a common complication of critical illness. It typically results from large-volume fluid infusions during acute resuscitation and is worsened by hypoalbuminemia. Recognized as edema, fluid retention is important for its association with delayed weaning and increased mortality. The standard treatment is the administration of diuretics, with or without albumin. We hypothesize that intravenous 25% albumin plus furosemide, by comparison with furosemide alone, improves diuresis, oxygenation, and hemodynamic stability in the deresuscitation of critically ill, hypoalbuminemic patients. We propose a pilot study to determine the feasibility of a trial to investigate this hypothesis. METHODS/DESIGN: FADE is a single-center, parallel, pilot randomized controlled trial. We aim to allocate 50 hemodynamically stable, hypoalbuminemic adult patients receiving diuresis to treatment with either 100 ml of either 25% albumin or normal saline placebo twice daily, for a total of six doses. Diuretics are to be prescribed by the caregiving team at least twice daily, and administered within 2 hours following study treatment. Patients, intensive care unit (ICU) clinicians, data collectors, and outcome adjudicators will be blinded to treatment allocation. Feasibility outcome measures include the proportion of patients receiving albumin within 2 hours of diuretic, the proportion of patients receiving the full six doses of study treatment, the proportion of patients who receive open label 25% albumin, and the rate of recruitment. Physiologic, laboratory, and clinical data are collected until discharge from the ICU or until 30 days. DISCUSSION: This is the first randomized trial to assess the use of hyperoncotic albumin in addition to diuretics in a general ICU population. Should this pilot study demonstrate feasibility, the primary outcome measure of the larger clinical trial will be the number of ventilator-free days, with secondary clinical outcome measures of duration of mechanical ventilation, length of ICU stay, episodes of hemodynamic instability and mortality. The addition of 25% albumin to standard diuretic therapy is a promising treatment in the post-resuscitation care of the critically ill patient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02055872; ISRCTN70191881.

Colloids to improve diuresis in critically ill patients: a systematic review.

BACKGROUND: The background of this study is to determine whether the addition of intravenous colloid to diuretic therapy, in comparison to diuretic therapy alone, improves diuresis and oxygenation and prevents intravascular volume depletion in intensive care unit (ICU) patients without shock. METHODS: We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Google Scholar, conference abstracts of ACCP, SCCM, ATS, and references of relevant articles. Randomized controlled trials (RCTs) of adult ICU patients, not in shock (defined as patients on low dose or no vasopressors, without need for IV fluid bolus or blood transfusion within 24 h), comparing intravenous colloid therapy (human albumin, plasma, synthetic starches, or gels) plus diuretic to control (diuretic alone, or diuretic plus placebo). Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. RESULTS: Seven hundred fifty five studies were found in the initial search; 14 were deemed relevant; 2 were found to be eligible. There was good agreement between reviewers for study relevance (k = 0.869) and eligibility (k = 0.811). One study of heart failure patients showed no evidence of improved mean or hourly urine output in the group receiving albumin. The second studied patients hypoproteinemic with ARDS and demonstrated an improved fluid balance in 3 days, improved oxygenation status, and improved serum albumin level in patients treated with albumin. No significant differences were found for other outcomes. No studies evaluating colloids other than albumin were found. CONCLUSIONS: Our review is limited by the small number of high-quality RCTs available to study this clinical question, both of which only studied albumin. High-quality RCTs are required to evaluate the effect of albumin as well as other colloids as an adjunct to diuresis in a general ICU population.

The ace of spades: reverse takotsubo cardiomyopathy in the context of angiographic embolization of recurrent metastatic serotonin-positive neuroendocrine tumour of the pancreas.

A 62-year-old woman undergoing embolization of recurrent neuroendocrine tumor, positive for serotonin, developed chest pain and bradycardia with lateral ST-segment depression. Cardiac biomarkers were elevated, and echocardiography revealed akinesis of all basal segments with a normally contracting apex. The absence of flow-limiting coronary disease on angiography confirmed the presence of reverse Takotsubo cardiomyopathy. After optimal medical therapy for six weeks, left ventricular function returned to normal. Takotsubo cardiomyopathy has been described across a wide variety of hyperadrenergic states; the description of the reverse-type Takotsubo cardiomyopathy in the setting of embolization of recurrent neuroendocrine with serotonergic positivity tumour is novel.

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance.

Thrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectin-coated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyte-endothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration.