Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

Identification of quality indicators for the nutritional management of adult hospitalized patients by a modified Delphi process.

BACKGROUND AND OBJECTIVE: The aim of this study was to identify quality indicators (QI) that measure or evaluate the quality of nutritional management of the adult hospitalized patient irrespective of the primary disease or surgical condition. METHODS: During a modified Delphi procedure consisting of three rounds a 48 member expert panel selected quality indicators applicable to the subject focusing on validity and feasibility from a list of 89 candidate indicators, retrieved from the literature and completed by expert opinion. RESULTS: The following top ten of QIs were selected (weight between brackets): (1) Priority use of enteral route in the absence of contra indications (.95); (2) Patients with malnutrition (risk) receive a nutrition care plan or Nutritional Support (NS) (.935); (3) The hospital has a formulary on enteral formulas, parenteral nutrition (PN) solutions and nutritional supplements (.93); (4) The hospital has a designated nutrition support service (or team) (.922); (5) The hospital has written policies and procedures for the provision of nutrition support therapy (.9); (6) In hospitalized patients on PN the plasma triglycerides are checked weekly (.894); (7) Presence of a protocol for enteral drug administration through a feeding tube (.885); (8) Frequency of periodic reassessment of patients on NS (.883); (9) Enteral and PN orders are regularly revised and adjusted (daily/weekly/twice a week)(.88); (10) There is a hospital wide consensus on the screening method(s) for malnutrition (.88). CONCLUSIONS: Using a three round modified Delphi approach a list of ten best scoring QIs for the management of the adult hospitalized patient was established.

The variability of critical care bed numbers in Europe.

PURPOSE: To quantify the numbers of critical care beds in Europe and to understand the differences in these numbers between countries when corrected for population size and gross domestic product. METHODS: Prospective data collection of critical care bed numbers for each country in Europe from July 2010 to July 2011. Sources were identified in each country that could provide data on numbers of critical care beds (intensive care and intermediate care). These data were then cross-referenced with data from international databases describing population size and age, gross domestic product (GDP), expenditure on healthcare and numbers of acute care beds. RESULTS: We identified 2,068,892 acute care beds and 73,585 (2.8 %) critical care beds. Due to the heterogeneous descriptions of these beds in the individual countries it was not possible to discriminate between intensive care and intermediate care in most cases. On average there were 11.5 critical care beds per 100,000 head of population, with marked differences between countries (Germany 29.2, Portugal 4.2). The numbers of critical care beds per country corrected for population size were positively correlated with GDP (r(2) = 0.16, p = 0.05), numbers of acute care beds corrected for population (r(2) = 0.12, p = 0.05) and the percentage of acute care beds designated as critical care (r(2) = 0.59, p < 0.0001). They were not correlated with the proportion of GDP expended on healthcare. CONCLUSIONS: Critical care bed numbers vary considerably between countries in Europe. Better understanding of these numbers should facilitate improved planning for critical care capacity and utilization in the future.

Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM).

OBJECTIVES: To define a set of indicators that could be used to improve quality in intensive care medicine. METHODOLOGY: An European Society of Intensive Care Medicine Task Force on Quality and Safety identified all commonly used key quality indicators. This international Task Force consisted of 18 experts, all with a self-proclaimed interest in the area. Through a modified Delphi process seeking greater than 90% consensual agreement from this nominal group, the indicators were then refined through a series of iterative processes. RESULTS: A total of 111 indicators of quality were initially found, and these were consolidated into 102 separate items. After five discrete rounds of debate, these indicators were reduced to a subset of nine that all had greater than 90% agreement from the nominal group. These indicators can be used to describe the structures (3), processes (2) and outcomes (4) of intensive care. Across this international group, it was much more difficult to obtain consensual agreement on the indicators describing processes of care than on the structures and outcomes. CONCLUSION: This document contains nine indicators, all of which have a high level of consensual agreement from an international Task Force, which could be used to improve quality in routine intensive care practice.

Living related intestinal transplantation for Churg-Strauss syndrome: a case report.

Exceptionally, gastrointestinal involvement of Churg-Strauss syndrome (CSS) may require extensive bowel resection resulting in a short bowel syndrome. Living related intestinal transplantation (IT) has emerged as an alternative to deceased-donor IT in the management of patients with irreversible short bowel syndrome. Herein, we have presented a 35-year-old patient with isolated intestinal involvement of CSS lesions refractory to steroids and azathioprine requiring multiple abdominal resections resulting in an ultrashort bowel syndrome. A living related IT (from the mother) was performed. She underwent several acute rejection episodes treated with additional immunosuppressive therapy. Despite higher doses of immunosuppression, these repeated acute rejection episodes eventually evolved into a syndrome of chronic allograft rejection. Eventually, owing to her poor general condition and to avoid life-threatening infections, transplantectomy was inevitable. Recent immunologic studies indicate that peripheral mononuclear cells from patients with CSS secrete large amounts of T-helper type 1 and 2 cytokines. It is likely that patients with CSS are at higher risk for acute and chronic rejection after transplantation.

Thrombotic microangiopathy following intestinal transplantation: a single center experience.

BACKGROUND: Transplant-related thrombotic microangiopathy (TMA) is a well-recognized complication of all types of transplantations. Despite its known relationship with immunosuppressive therapy, only a few cases have been reported following intestinal transplantation. METHODS: We retrospectively reviewed the medical files of nine consecutive intestinal transplant patients between 2000 and 2008. RESULTS: The diagnosis of TMA was established in 3 patients (33%). At diagnosis the immunosuppressive therapy consisted of tacrolimus (n = 3), combined with azathioprine (n = 1) or sirolimus (n = 2) and steroids (n = 2). The median time between transplantation and TMA was 104 days (range, 55-167 days). Levels of ADAMTS13, a von Willebrand protease, were within normal ranges in all 3 patients. Treatment consisted of stopping/tapering of tacrolimus, together with initiation of plasma therapy, leading to complete remission in all 3 patients. During further follow-up, all 3 patients showed severe graft rejection necessitating more profound immunosuppressive therapy, leading to graft loss in 1 patient and infection-related death in the 2 others. At a median follow-up of 52 months (range, 9-100 months) all remaining TMA-free patients (n = 6) were alive with functioning grafts under minimal immunosuppression. CONCLUSION: Herein we have described 3 intestinal transplant patients who were diagnosed with transplantation-related TMA. Despite excellent disease control the final outcomes were dismal, which clearly contrasts with the outcome among TMA-free patients, who were all well with functioning grafts at last follow-up.

Selection criteria and outcome of patients referred to intestinal transplantation: an European center experience.

Until 1998, intestinal transplantation (SBT) had not been performed in our region of Flanders, Belgium. Potential SBT activity was not known and selection criteria had not been validated. A multidisciplinary SBT program was launched in 1998. We analyzed requests for SBT and outcomes in these patients whether with or without SBT. Listing for SBT was only considered for patients with irreversible short bowel syndrome who had developed life-threatening complications of total parenteral nutrition, but whose general condition was still thought compatible with surgery and immunosuppression. During the study period 1998 to 2004, one third of the requests for SBT (10/31) were deemed suitable. SBT in this group was lifesaving (100% survival) when performed in time. Mortality in this group without SBT was high (67%). Two thirds of the patients (21/31) did not fulfill the SBT inclusion criteria, either because they were "too moribund" to tolerate transplantation or because they were "too well". This preliminary study emphasized the importance of (1) early referral of potential SBT candidates, (2) adherence to strict criteria for listing patients for SBT, and (3) referral of intestinal donors to procurement organizations.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

Phrenic nerve dysfunction after heart-lung and lung transplantation.

BACKGROUND: Phrenic nerve dysfunction (PND) is a well-known complication after cardiac surgery, but reports on its incidence and consequences after heart-lung and lung transplantation are scarce. METHODS: The incidence and consequences (ventilator days and intensive-care unit length of stay [ICU LOS]) of PND were studied by retrospective chart review of 27 heart-lung (HLTx) and 111 lung (LTx) transplantations performed from July 1991 to June 2001 at the Leuven University Hospital, Leuven, Belgium. On clinical suspicion of diaphragmatic dysfunction, nerve conduction studies were performed, which were completed with a needle electromyogram (EMG) of the diaphragm when the conduction study was non-conclusive. RESULTS: The incidence of PND in 21 evaluable HLTx recipients was 42.8% (9 of 21 patients), resulting in significantly more ventilator days for PND patients (37.6 +/- 36.3 days vs 5.3 +/- 3 days; p < 0.05) and a prolonged ICU LOS (46.8 +/- 33 vs 9.8 +/- 4.9 days; p < 0.05). In the 97 evaluable LTx patients, 9.3% (9 of 97 patients) developed PND. This resulted in more ventilator days for the PND group (30.6 +/- 14.8 days vs non-PND 7.9 +/- 14.8 days. p < 0.05) and a longer ICU LOS (PND 37.8 +/- 18.7 days vs non-PND 12.1 +/- 17.8 p < 0.05). Needle EMG of the diaphragm revealed denervation in 1 HLTx and 5 LTx patients. In LTx patients sustaining PND more tracheostomies were performed (44.4% vs 4.5% for non-PND patients p < 0.005). Eight of 9 LTx patients with PND had sequential single-lung transplantation. CONCLUSIONS: PND represents an important clinical problem after HLTx and LTx and has a considerable influence on both number of ventilator days and ICU resource utilization.

Needs of relatives of critical care patients: perceptions of relatives, physicians and nurses.

OBJECTIVES: This study investigated differences between the perceptions of relatives, physicians and nurses concerning the needs of relatives of critical care patients. DESIGN AND PARTICIPANTS: Perceived needs were assessed in 200 relatives, 38 physicians, and 143 nurses using a 45-item questionnaire. SETTING: Data were gathered at the intensive care unit of the University Hospital Gasthuisberg. RESULTS AND CONCLUSIONS: The overall rankings of the needs by the three groups are very similar. Information emerges as most important factor, with considerably less importance attached to comfort and support. There were significant differences between the groups on all categories and on 24 individual needs. Regarding the need categories, both nurses and physicians underestimate the relatives' need for information and proximity to the patient. Physicians also underestimate the relatives' need for assurance. On the individual need items, relatives' needs are generally underestimated by the staff, but in some cases overestimations are found.

What works in severe head injury?

Traumatic brain injury has an important socioeconomic impact in industrialized countries. However, well-conducted clinical trials are rare. Case-control studies have shown that prevention works. Pathophysiological understanding is becoming more complete as data on chemokines, local brain tissue oxygen tension and hypothermia accumulate. Multimodality monitoring will certainly assume greater importance in the future. Research with targeted therapeutic strategies indicates that secondary ischaemic insults can be prevented. Specific subgroups of patients with traumatic brain injury who will benefit from the use of hypothermia and barbiturates have been identified. Enteral feeding is the preferred nutritional strategy, and the follow-up period should be extended beyond the traditional 1 year.

Intensive insulin therapy in critically ill patients.

BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.

Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.

OBJECTIVE: To evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients. DESIGN: Prospective, randomized, concurrent trial. SETTING: Multidisciplinary intensive care unit (ICU) in a 1,800-bed university hospital. PATIENTS: Consecutive patients (n = 660) who were likely to require mechanical ventilation for at least 48 hrs were randomized to one of three groups: conventional antibiotic regimen (control group A); oral and enteral ofloxacin-amphotericin B (group B); and oral and enteral polymyxin E-tobramycin-amphotericin B (group C). Both treatment groups received systemic antibiotics for 4 days (ofloxacin in group B and cefotaxime in group C). INTERVENTIONS: Patients were randomized to receive standard treatment (control group A, n = 220), selective decontamination regimen B (group B, n = 220), and selective decontamination regimen C (group C, n = 220). After early deaths and exclusions from the study, 185 controls (group A) and 193 (group B)/200 (group C) selective decontamination regimen patients were available for analysis. MEASUREMENTS AND MAIN RESULTS: Measurements included colonization and primary/secondary infection rate, ICU mortality rate, emergence of antibiotic resistance, length of ICU stay, and antimicrobial agent costs. The study duration was 19 months. The patient groups were fully comparable for age, diagnostic category, and severity of illness. One third of patients in each group suffered a nosocomial infection at the time of admission. There was a significant difference between treatment group B and control group A in the number of infected patients (odds ratio of 0.42, 95% confidence interval of 0.27 to 0.64), secondary lower respiratory tract infection (odds ratio of 0.47, 95% confidence interval of 0.26 to 0.82), and urinary tract infection (odds ratio of 0.47, 95% confidence interval of 0.27 to 0.81). Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A (odds ratio of 1.22, 95% confidence interval 0.72 to 2.08). Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups. ICU mortality rate was almost identical (group A 16.8%, group B 17.6%, and group C 15.5%) and was not significantly related to primary or secondary infection. Increased antimicrobial resistance was recorded in both treatment groups: tobramycin-resistant enterobacteriaceae (group C 48% vs. group A 14%, p < .01), ofloxacin-resistant enterobacteriaceae (group B 50% vs. group A 11%, p < .02), ofloxacin-resistant nonfermenters (group B 81% vs. group A 52%, p < .02), and methicillin-resistant Staphylococcus aureus (group C 83% vs. group A 55%, p < .05). Antimicrobial agent costs were comparable in control and group C patients; one third less was spent for group B patients. CONCLUSIONS: In cases of high colonization and infection rates at the time of ICU admission, the preventive benefit of selective decontamination is highly debatable. Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental, colonizing, and infecting bacteria. The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous. No beneficial effect on survival is observed. Moreover, selective decontamination adds substantially to the cost of ICU care.

Thyrotropin-releasing hormone in critical illness: from a dopamine-dependent test to a strategy for increasing low serum triiodothyronine, prolactin, and growth hormone concentrations.

OBJECTIVE: The aim of this study was to examine the effect of dopamine infusion on the thyrotropin (TSH), thyroid hormone, prolactin, and growth hormone responses to thyrotropin-releasing hormone (TRH) in critically ill patients. DESIGN: Prospective, randomized, controlled, open-labeled clinical study. SETTING: The intensive care unit, University Hospital Gasthuisberg, Leuven, over a 1-month period. PATIENTS AND INTERVENTIONS: In 15 critically ill patients receiving dopamine treatment (5 micrograms/kg/min) for a mean of 43.3 +/- 1.2 (SEM) hrs after trauma or cardiac surgery, we studied the TSH, thyroid hormone, prolactin, and growth hormone responses to the administration of two consecutive intravenous TRH boluses of 200 micrograms, with a 6-hr interval. The dopamine infusion was continued in the control group and discontinued in the study group. Serum concentrations of TSH, prolactin, and growth hormone were measured before and 20, 40, 60, and 120 mins after TRH administration. Serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse T3, and thyroid hormone binding globulin were determined before and 120 mins after each TRH injection. MEASUREMENTS AND MAIN RESULTS: There was a > 100-fold interindividual variation in the baseline TSH concentration and in the TSH peak value after TRH administration. Two consecutive doses of TRH evoked a mean 16% increase in serum T4 concentration (p = .003) and a mean 47% increase in T3 (p = .001), whereas serum reverse T3 and thyroid hormone binding globulin values remain unaltered. Each of the TRH boluses increased serum growth hormone concentrations in the continued dopamine and discontinued dopamine groups, by a median of 60% (p = .001) and 68% (p = .001), respectively. Three hours after dopamine withdrawal, there was a three-fold increase of the peak TSH response (p = .001), a higher T3 response (p = .01), and a ten-fold increase of the peak prolactin value (p = .001) in response to TRH administration. CONCLUSIONS: The TSH response to TRH administration in critical illness presents a striking interindividual variation and dopamine dependent. Repeated TRH administration results in a repetitive increase of TSH, prolactin, growth hormone, T4, and T3, without increasing reverse T3. These observations point toward a potential for TRH as a strategy for reversing the euthyroid sick syndrome, growth hormone deficiency, and immune dysfunction associated with critical illness.

Dehydroepiandrosterone sulphate in critical illness: effect of dopamine.

OBJECTIVE: As part of a study on the effect of dopamine therapy on pituitary dependent hormone secretion in critical illness, we documented the impact of this inotropic and vasoactive catecholamine on the serum concentrations of dehydroepiandrosterone sulphate (DHEAS). Concomitantly, serum levels of PRL and cortisol were determined. PATIENTS AND DESIGN: In a prospective, randomized, controlled, open-labelled clinical study, 20 critically ill, adult polytrauma patients receiving dopamine treatment (5 micrograms/kg/mi i.v. for a median 109 hours (range (21-296 hours)), were studied to evaluate the effect of dopamine withdrawal on serum concentrations of DHEAS, PRL and cortisol. The median age of the studied patients was 37 years (range 18-83 years). MEASUREMENTS: Serum DHEAS and cortisol concentrations were measured by RIA and PRL by IRMA. The assessed serum samples were obtained at 0300 h on each of two consecutive study nights. RESULTS: Withdrawal of dopamine infusion was found to elicit a median 25% increase of serum DHEAS concentrations within 24 hours whereas no significant change in DHEAS levels was observed when dopamine infusion was continued throughout both study nights (P = 0.01 continued vs interrupted dopamine). Prolactin levels were undetectable as long as dopamine was infused, and increased to a median of 317 IU/l after 24 hours of dopamine withdrawal (P = 0.0007). Elevated serum cortisol levels remained comparable with continued and interrupted dopamine infusion. CONCLUSIONS: Dopamine infusion appears to suppress serum DHEAS concentrations in critically ill patients without affecting their elevated serum cortisol levels, suggesting a differential regulation of DHEAS and cortisol metabolism in critical illness. The lowering effect of dopamine on DHEAS levels could be linked to the concomitant suppression of circulating PRL. The simultaneous suppression of circulating PRL and DHEAS by dopamine infusion may be an iatrogenic factor maintaining or aggravating the anergic state of prolonged severe illness.

Prevention of postintubation laryngotracheal stenosis.

Laryngotracheal complications after translaryngeal intubation and specifically tracheotomy are a common problem. Surgical correction of PITS is not always successful. Pathogenetic mechanisms of PITS are direct pressure necrosis by overinflated endotracheal tube and cuff material, duration of intubation, macro- and microtrauma during intubation, the specific technique of endotracheal intubation, severity of respiratory failure, infection and poor tissue perfusion due to hemodynamic instability. Following preventive guidelines are proposed: the use of high volume low pressure cuffs, cuff pressure monitoring, ventilatory support with lower airway pressures, prevention of macrotrauma during intubation and microtrauma during maintenance, adapted policy of choice between translaryngeal and tracheotomy techniques, anti-infectious strategy and swift hemodynamic stabilization.