Influence of progressive renal dysfunction in chronic heart failure

Chronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important.

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): Protocol for a randomized controlled trial

Background

Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.

This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg^-1.min^-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.

This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.

The Impact of Admissions for the Management of End-stage renal disease on hospital bed occupancy

BACKGROUND:

End-stage renal disease (ESRD) is increasingly prevalent but the inpatient costs associated with this condition are poorly defined due to limitations with data extraction and failure to differentiate between hospitalisation for renal and non-renal disease reasons. The impact of admissions primarily for the management of ESRD on hospital bed utilisation was assessed over a 5-year period in a large teaching hospital.

METHODS:

All admission episodes were reviewed and the ESRD group was identified by a primary International Classification of Diseases code for ESRD or a non-specific primary renal failure code with a secondary code for ESRD. The frequency and duration of hospitalisation and contribution to bed day occupancy of this group with ESRD was determined.

RESULTS:

There were 70,808 patients responsible for a total of 116,915 admissions and 919,212 bed days over the study period. Of these, 988 (1.4%) patients were admitted for the management of ESRD, accounting for 2,387 (2.0%) of admissions and utilisation of 23,011 (2.5%) bed days. After adjustment for age and gender, those admitted for ESRD management were significantly more likely to have a prolonged admission exceeding 30 days (odds ratio 1.46, 95% confidence interval 1.23-1.72, p < 0.001). When the admission was an emergency rather than an elective event, the patient was 4.6 times more likely to be hospitalised for over 30 days.

CONCLUSIONS:

Persons admitted for ESRD management are hospitalised more frequently and for longer than the overall inpatient population, occupying a substantial number of bed days.

Elevated soluble cellular adhesion molecules are associated with increased mortality in a prospective cohort of renal transplant recipients

Increased plasma levels of cellular adhesion molecules (CAMs) have been shown to be predictors of all cause mortality in individuals with chronic renal failure 12 and patients with end-stage renal disease receiving haemodialysis 3. In renal transplant recipients the predictive value of CAMs has not been well characterised. The aim of this study was to assess the relationship between CAMs and all-cause mortality during prospective follow-up of a renal transplant cohort.

Renal replacement treatment for diabetic nephropathy in Northern Ireland 1979-1987

Twenty-three patients with end-stage renal failure due to diabetic nephropathy received renal replacement treatment. All patients had insulin-dependent diabetes mellitus. Nineteen transplants were performed in seventeen patients. Two-year graft survival for all transplants was 74% with a two-year patient survival post-transplantation of 81%. Overall two-year patient survival was 73%, compared with 82% in non-diabetic patients receiving renal replacement treatment. In diabetic patients accepted for treatment there was a high incidence of non-renal complications, particularly vascular disease. An aggressive approach to the treatment of vascular disease in these patients may improve overall survival rates.

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.

Genetic renal abnormalities

Inherited disorders of renal structure and function are relatively common causes of end-stage renal disease requiring renal replacement therapy. A family history of haematuria, urinary tract infection or renal failure can alert the clinician to the possible diagnosis of underlying renal genetic abnormalities. In practice, the commonest inherited renal disorder is autosomal dominant polycystic kidney disease (ADPKD), characterized by multiple kidney cysts associated with hypertension and renal failure. Insights into the cell biology of ADPKD are informing new therapeutic approaches to limit cyst growth and prevent progressive renal failure. Non-visible haematuria is a clinical finding that presents a diagnostic challenge because it has so many possible causes. Mutations in the genes encoding collagen proteins within the glomerular basement membrane (GBM) can disrupt its normal barrier function. Thin basement membrane nephropathy, caused by GBM collagen gene mutations, is a relatively common cause of familial haematuria that normally has a good long-term prognosis. Alport syndrome is a rare and genetically heterogeneous condition leading to renal failure in men inheriting the X-linked gene defect. Single-gene defects may cause diverse renal tubular disorders, such as predisposition to renal calculi, diabetes insipidus, renal tubular acidosis or hypertension with associated electrolyte imbalance. Gene mutations responsible for familial renal cancer syndromes, such as tuberous sclerosis complex and von Hippel–Lindau disease, have also been identified

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries

Importance Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS).

Objectives To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts—for example prone positioning—in routine clinical practice for patients fulfilling the ARDS Berlin Definition.

Design, Setting, and Participants The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents.

Exposures Acute respiratory distress syndrome.

Main Outcomes and Measures The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS.

Results Of 29 144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS.

Conclusions and Relevance Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS.

The challenge of patients’ unmet palliative care needs in the final stages of chronic illness.

Background: There is consensus in the literature that the end of life care for patients with chronic illness is suboptimal, but research on the specific needs of this population is limited. Aim: This study aimed to use a mixed methodology and case study approach to explore the palliative care needs of patients with a non-cancer diagnosis from the perspectives of the patient, their significant other and the clinical team responsible for their care. Patients (n 18) had a diagnosis of either end-stage heart failure, renal failure or respiratory disease. Methods: The Short Form 36 and Hospital and Anxiety and Depression Questionnaire were completed by all patients. Unstructured interviews were (n 35) were conducted separately with each patient and then their significant other. These were followed by a focus group discussion (n 18) with the multiprofessional clinical team. Quantitative data were analysed using simple descriptive statistics and simple descriptive statistics. All qualitative data were taped, transcribed and analysed using Colaizzi’s approach to qualitative analysis. Findings: Deteriorating health status was the central theme derived from this analysis. It led to decreased independence, social isolation and family burden. These problems were mitigated by the limited resources at the individual’s disposal and the availability of support from hospital and community services. Generally resources and support were perceived as lacking. All participants in this study expressed concerns regarding the patients’ future and some patients described feelings of depression or acceptance of the inevitability of imminent death. Conclusion: Patients dying from chronic illness in this study had many concerns and unmet clinical needs. Care teams were frustrated by the lack of resources available to them and admitted they were ill-equipped to provide for the individual’s holistic needs. Some clinicians described difficulty in talking openly with the patient and family regarding the palliative nature of their treatment. An earlier and more effective implementation of the palliative care approach is necessary if the needs of patients in the final stages of chronic illness are to be adequately addressed. Pa

HDL composition and HDL antioxidant capacity in patients on regular haemodialysis

Recent evidence suggests that HDL can directly inhibit LDL oxidation, a key early stage in atherogenesis. Patients with chronic renal failure are at increased cardiovascular risk, have reduced HDL levels and altered HDL composition. We have therefore investigated whether compositional changes in HDL lead to decreased HDL antioxidant capacity in these patients. In comparison to control subject HDL, patient HDL contained less total cholesterol, cholesterol esters, phospholipids and alpha-tocopherol. LDL, HDL and LDL + HDL were standardised for protein and oxidised in the presence of Cu2+. The rate of propagation during HDL oxidation was reduced in the patient group (3.28 +/- 0.65 x 10(-5) vs. 4.60 +/- 0.97 x 10(-5) abs. U/min, P

Cyclin G associated kinase interacts with interleukin 12 receptor beta2 and suppresses interleukin 12 induced IFN-gamma production.

BACKGROUND: Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. METHODS: Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) <10 served as group A and 21 with GCS = 10 as group B. RESULTS: Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P <0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P <0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P <0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P <0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P <0.05 or P <0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1). CONCLUSIONS: Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.

Desmoplastic Small Round Cell Tumor of Major Salivary Glands: Report of 1 Case and a Review of the Literature

Desmoplastic small round cell tumor is a rare malignant neoplasm mostly occurring in the vicinity of or within the peritoneal cavity, and is uncommon in the head and neck region. Tumor location within a major salivary gland is exceptional. We report a case of a 41-year-old Chinese man with a history of diabetes mellitus and end-stage renal failure on peritoneal dialysis with a desmoplastic small round cell tumor occurring in the left submandibular gland. Fine-needle aspiration cytology showed variably cohesive clusters of small cells with hyperchromatic nuclei and fine granular chromatin. On histology the neoplasm displayed classic features of a desmoplastic small round cell tumor with angulated nests of small round blue cells in a fibromyxoid/desmoplastic stroma. Neoplastic cells were immunoreactive for cytokeratins (AE1/3), desmin (paranuclear dot-like), WT-1 (nuclear), epithelial membrane antigen, and CD56. EWS gene translocation and EWS-WT1 gene fusion were detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. The case presented is the sixth case of and the oldest reported patient with a desmoplastic small round cell tumor occurring in a major salivary gland to date. Desmoplastic small round cell tumor should be considered in the differential diagnosis of a salivary gland neoplasm with a basaloid or small cell pattern on fine-needle aspiration cytology.

Factors influencing patients with stage 5 chronic kidney disease to opt for conservative management: a practitioner research study

Aims and objectives. This study explored decision-making experiences of patients with stage 5 chronic kidney disease when opting for conservative management of their renal failure.

Background. Dialysis is an invasive treatment, and for some older patients, there is an associated treatment burden of dialysis-related symptoms. An alternative choice is conservative management, but little is known about those who make this decision and how they are supported through the process.

Design. Qualitative practitioner research study.

Method. Data were generated from nine patients' naturally occurring clinic consultations with a renal clinical nurse specialist between May 2010 - July 2010. Interviews were transcribed verbatim and findings fed back at three multi-disciplinary meetings to check for relevance and resonance. Common themes were identified and codes applied.

Results. Patients reported age and having to travel three times a week to hospital for dialysis as reasons not to opt for treatment. Others felt well without dialysis not wanting to upset the 'status quo' or to burden loved ones. Most felt equipped to make the decision following explanation and discussion with the clinical nurse specialist in the renal clinic.

Conclusions. Patients opting for conservative management give numerous reasons for this including old age, travel limitations, feeling well without dialysis and not wanting to be a burden, but appear content with their decision. One-to-one discussions with the clinical nurse specialist appear helpful during the decision-making process presenting an opportunity for advancing nursing roles in the chronic kidney disease service.

Relevance to clinical practice. Understanding patients' reasons for refusing dialysis assists in supporting until death. There is an opportunity for developing nursing practice to meet the multi-faceted needs of this group.