Renal artery reconstruction and kidney autotransplantation for Takayasu arteritis-induced renal artery stenosis.

A young woman with Takayasu arteritis and complex renal artery stenosis in a solitary functional kidney underwent an ex vivo revascularization with autologous saphenous vein graft and renal autotransplantation. Before surgery, she had resistant hypertension and recurrent episodes of acute kidney injury. Two years later, her blood pressure is 123/77 mm Hg, and there have been no acute kidney injury episodes. Computed tomography scan demonstrates no abnormal thickening of the graft despite proximal progression of disease to involve the superior mesenteric artery. As Takayasu arteritis is a progressive disease, use of autologous vein graft, which is unlikely to become involved, is of paramount importance.

Can Early Introduction of Palliative Care Limit Intensive Care, Emergency and Hospital Admissions in Patients with Severe Chronic Obstructive Pulmonary Disease? A Pilot Randomized Study.

BACKGROUND: Despite their poor prognosis, patients with severe chronic obstructive pulmonary disease (COPD) have little access to palliative care and tend to have a high rate of hospital and intensive care unit (ICU) admissions during their last year of life. OBJECTIVES: To determine the feasibility of a home palliative care intervention during 1 year versus usual care, and the possible impact of this intervention on emergency, hospital and ICU admissions, survival, mood, and health-related quality of life (HRQL). METHODS: Prospective controlled study of patients with severe COPD (GOLD stage III or IV) and long-term oxygen therapy and/or home noninvasive ventilation and/or one or more hospital admissions in the previous year for acute exacerbation, randomized to usual care versus usual care with add-on monthly intervention by palliative care specialists at home for 12 months. RESULTS: Of 315 patients screened, 49 (15.5%) were randomized (26 to early palliative care; 23 to the control group); aged (mean ± SD) 71 ± 8 years; FEV1 was 37 ± 14% predicted; 88% with a COPD assessment test score > 10; 69% on long-term oxygen therapy or home noninvasive ventilation. The patients accepted the intervention and completed the assessment scales. After 1 year, there was no difference between groups in symptoms, HRQL and mood, and there was a nonsignificant trend for higher admission rates to hospital and emergency wards in the intervention group. CONCLUSION: Although this pilot study was underpowered to formally exclude a benefit from palliative care in severe COPD, it raises several questions as to patient selection, reluctance to palliative care in this group, and modalities of future trials.

Recollection of participating in a trial: A qualitative study of patients with severe and very severe chronic obstructive pulmonary disease.

BACKGROUND: Despite having similar palliative needs to patients with lung cancer, advanced chronic obstructive pulmonary disease (COPD) patients are less likely to receive palliative care. To evaluate the effect of introducing specialized palliative care with severe to very severe COPD patients, a randomized controlled trial (RCT) was conducted in Switzerland. AIM: To explore COPD patients' recollection of the trial, their needs and the usefulness of the palliative care interventions. DESIGN AND SETTING: Qualitative study with advanced COPD patients who participated in a specialized palliative care intervention, conducted in a general hospital. METHOD: Eighteen patients with severe to very severe COPD were interviewed about their experiences. Interviews were transcribed and thematic content analysis was performed. RESULTS: Patients had poor recollection of the trial and difficulties understanding the palliative care intervention. No major differences were observed between patients who received the specialized intervention and those who did not. Content analysis emphasized that although they experienced disabling symptoms, participants tended to attribute their limitations to problems other than COPD and some declared that they were not sick. Patients reported restrictions due to oxygen therapy, and the burden of becoming dependent on it. This dependence resulted in intense anxiety, leading participants to focus on the present only. A strong feeling of perceived helplessness emerged from the patients' interviews. CONCLUSIONS: Our findings suggest that poor recollection and understanding of the palliative care intervention act as barriers to the conduct of clinical trials with severe and very severe COPD patients. Their cognitive difficulties, perception of COPD, functional limitations, overwhelming anxiety, focus on the present and perceived helplessness also seem to hinder the implementation of such care.

Acute hemodialysis in a young man with severe symptomatic hyponatremia and kidney injury.

A 35-year-old man presented with severe hypo-osmolar hyponatremia (serum sodium 99 mmol/L), profound nonoliguric renal failure (serum creatinine 1240 µmol/L), and nephrotic range proteinuria. Computed tomography of the abdomen revealed nephromegaly and no obstruction. The patient was admitted to the intensive care unit (ICU) and conventional hemodialysis was initiated. To avoid rapid sodium correction, we prescribed concurrent dialysate flow, a low dialysate sodium concentration, a small surface area dialyzer, and a low blood flow rate. We infused dextrose 5% water into the venous return line and adjusted the infusion rate according to hourly sodium concentration. The rate of sodium correction was 7.7 mmol/day over the first 3 days of admission. A subsequent renal biopsy revealed focal segmental glomerulosclerosis and interstitial infiltration with extranodal NK/T-cell lymphoma nasal type. The patient died of massive lower gastrointestinal bleeding secondary to lymphomatous involvement day 19 in the ICU. In the setting of acute kidney injury requiring renal replacement therapy and concomitant severe hyponatremia, it is challenging to avoid overcorrection of serum sodium. We describe several key prescription modifications to conventional hemodialysis, factors that affect sodium diffusion at the level of the dialyzer membrane, and the importance of frequent laboratory monitoring.

[Integration of a palliative care approach in the management patients with polymorbidity]. / Intégration d'une approche palliative dans la prise en charge des patients atteints de multimorbidités.

The number of patients with multimorbidity is steadily increasing due to medical progress and increased life expectancy. A palliative approach may be offered to some of these patients. It includes the detection and management of somatic and mental symptoms, the management of social and spiritual problems, the anticipation of care and support of the relatives. Its main goal is to improve patient's quality of life and reduce interventions that are unnecessary, or undesired by patients themselves.

Reducing Time to Antibiotic Administration for Febrile Neutropenia in the Emergency Department.

PURPOSE: Febrile neutropenia (FN) is an oncologic emergency, and prolonged time to antibiotic administration (TTA) is associated with increased hospital length of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia pathway (FNP) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department (ED). METHODS: This prospective study compared ED FNP patients (> 18 years old), between June 2012 and June 2013 with both historical and direct admissions (DA) cohorts at a multispecialty academic center. Interventions included providing patients with FN-Alert cards, standardizing the definition of FN and recognizing it as a distinct chief complaint, revising ED triage level for FN, creating electronic FN order sets, administering empiric antibiotics before neutrophil count result, and relocating FN antibiotics to the ED. The primary outcome was TTA, with a target goal of 90 minutes after ED presentation. RESULTS: In total, 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68 minutes when the order set was not used versus used in the FNP group (P < .001 for all comparisons). Decrease in hospital LOS was not statistically significant. CONCLUSION: The ED FNP is a significant quality initiative with sustainable interventions, and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED.

The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes.

Studies of paediatric cancers have shown a high frequency of mutation across epigenetic regulators. Here we sequence 633 genes, encoding the majority of known epigenetic regulatory proteins, in over 1,000 paediatric tumours to define the landscape of somatic mutations in epigenetic regulators in paediatric cancer. Our results demonstrate a marked variation in the frequency of gene mutations across 21 different paediatric cancer subtypes, with the highest frequency of mutations detected in high-grade gliomas, T-lineage acute lymphoblastic leukaemia and medulloblastoma, and a paucity of mutations in low-grade glioma and retinoblastoma. The most frequently mutated genes are H3F3A, PHF6, ATRX, KDM6A, SMARCA4, ASXL2, CREBBP, EZH2, MLL2, USP7, ASXL1, NSD2, SETD2, SMC1A and ZMYM3. We identify novel loss-of-function mutations in the ubiquitin-specific processing protease 7 (USP7) in paediatric leukaemia, which result in decreased deubiquitination activity. Collectively, our results help to define the landscape of mutations in epigenetic regulatory genes in paediatric cancer and yield a valuable new database for investigating the role of epigenetic dysregulations in cancer.

Can early introduction of specialized palliative care limit intensive care, emergency and hospital admissions in patients with severe and very severe COPD? a randomized study.

BACKGROUND: COPD is a progressive lung disorder with rates of mortality between 36-50%, within 2 years after admission for an acute exacerbation. While treatment with inhaled bronchodilators and steroids may partially relieve symptoms and oxygen therapy may prolong life, for many patients the course of the disease is one of inexorable decline. Very few palliative care intervention studies are available for this population. This trial seeks to determine the effectiveness of the introduction of specialized palliative care on hospital, intensive care unit and emergency admissions of patients with severe and very severe COPD. METHODS/DESIGN: The study is a three year single centre, randomized controlled trial using a 2 arms parallel groups design conducted in a tertiary center (University Hospitals; Geneva). For the intervention group, an early palliative care consultation is added to standard care; the control group benefits from standard care only. Patients with COPD defined according to GOLD criteria with a stage III or IV disease and/or long term treatment with domiciliary oxygen and/or home mechanical ventilation and/or one or more hospital admissions in the previous year for an acute exacerbation are eligible to participate. Allocation concealment is achieved using randomisation by sealed envelopes. Our sample size of 90 patients/group gives the study a 80% power to detect a 20% decrease in intensive care unit and emergency admissions--the primary endpoint. All data regarding participants will be analysed by a researcher blinded to treatment allocation, according to the "Intention to treat" principle. DISCUSSION: Given the trends toward aggressive and costly care near end-of-life among patients with COPD, a timely introduction of palliative care may limit unnecessary and burdensome personal and societal costs, and invasive approaches. The results of this study may provide directions for future palliative care interventions in this particular population. TRIAL REGISTRATION: This trial has been registered at clinicaltrials.gov under NCT02223780.

Anatomopathological causes of death in patients with advanced cancer: association with the use of anticoagulation and antibiotics at the end of life.

BACKGROUND: Anatomopathological studies that described the immediate causes of death of patients with advanced cancer were first published approximately 20 years ago. OBJECTIVE: Our objective was to analyze if causes of death changed with a wider use of broad spectrum antibiotics and prophylactic anticoagulation. METHODS: We conducted a retrospective study of all patients with an advanced cancer hospitalized in the Division of Palliative Medicine at the University Hospital Geneva from 2004 to 2010 who had an autopsy. RESULTS: Two hundred forty patients were included (130 men, mean age: 74±13). Main causes of death discovered at the autopsy were pulmonary infection (n=131; 55%), advanced cancer (n=39; 16%), pulmonary infection together with pulmonary embolism (PE) (n=27; 12%), PE alone (n=22; 9%), cardiac complications (n=19; 5%) and others (n=2; 1%). In a logistic regression model, with adjusting for age, gender, main diagnosis, comorbidities, blood count, corticosteroids, and antibiotics, there were no independent factors associated with pulmonary infection at autopsy. In a similar model, with adjusting for age, gender, main diagnosis, comorbidities, and anticoagulation, the only independent factor associated with PE at autopsy was the history of thrombo-embolic disease and therapeutic anticoagulation. CONCLUSION: The results of this retrospective study demonstrate that causes of death did not change with the modification of our practice. The high rate of pulmonary infection and embolism in this population, including in patients who received broad spectrum and prophylactic anticoagulation should encourage us to pursue other prospective studies to actually demonstrate the benefit of these treatments in this population.

Primary pulmonary malignant meningioma with lymph node and liver metastasis in a centenary woman, an autopsy case.

Primary meningiomas arising outside the central nervous system are very rare. They have been reported in the head and neck region, in the thorax, the retroperitoneum, and the pelvis. Usually, they behave as slow-growing tumors with a good prognosis. Herein, we report an autopsy case of a 108-year-old woman, known for a right-sided slowly growing lung nodule for 39 years. Death was attributed to cachexia. At post-mortem, a 15-cm mass was present in the right inferior lobe of the lung, associated with an ipsilateral hilar lymphadenopathy, and another 10-cm mass in the liver. Histology revealed a WHO grade III meningioma. No tumor was observed in the cranial cavity. This case illustrates a rare location of meningioma and highlights its biological behavior, with a very slow progression from a most probably benign tumor to a malignant lesion with metastasis over four decades.

Successful hematopoietic stem cell transplantation following a cyclophosphamide-containing preparative regimen with concomitant phenobarbital administration.

Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

Urinary NGAL levels before and after coronary angiography: a complex story.

BACKGROUND: We describe urinary neutrophil gelatinase-associated lipocalin (uNGAL) values in association with clinical characteristics and urinary parameters in adults undergoing coronary angiography. METHODS: This is an observational study of consecutive patients who underwent elective coronary angiography during a 4-month period in a large urban tertiary care hospital. RESULTS: One hundred and thirteen patients were enrolled, and 100 had sufficient data to be included in the analyses. A large range of preprocedural uNGAL levels were observed (range 1-269 ng/mg Cr). Median preprocedural uNGAL was 8 ng/mg Cr. Age (P = 0.009), serum creatinine (P = 0.077) and albumin excretion (P = 0.009) were significant predictors of baseline uNGAL. Half the cohort demonstrated an increase and half a decrease in the absolute values of uNGAL after angiography, irrespective of preprocedural levels. CONCLUSIONS: We observed variable, but relatively low absolute levels of uNGAL prior to angiography in this 'cardiac' cohort. Only age, serum creatinine and albumin excretion could explain some of this variability. When designing studies of at-risk individuals where uNGAL may be used as a marker for acute kidney injury, this variability should be taken into account.

[Demands for death (suicide assistance and euthanasia) in palliative medicine]. / Demandes d'aide au décès (assistance au suicide et euthanasie) en médecine palliative.

During a prospective open survey over 12 months of hospitalized patients, 44 death demands were registered for 39 patients (25 cancer, 6 cardiovascular disorder, 2 Parkinson's disease, 3 arthritis, 1 COPD, 1 dementia and 1 severe depression). 14 patients were also depressed. 28 requested euthanasia, 16 suicide assistance. At 1 month, 3 persisted, 16 had abandoned, 16 had died and 4 were not questioned. At 6 months, 7 were alive but had abandoned and 2 had committed suicide at their home. The majority of death demands correspond to euthanasia which is a murder according to the penal code. In front of such demand, realistic short-term objectives must be established. Many patients give up their project. This indicates great uncertainty in front of care and greatest ambivalence in front of life.

Focal segmental glomerulosclerosis in mild IgA nephropathy: a clinical-pathologic study.

BACKGROUND: The significance of focal segmental glomerulosclerosis (FSGS) in mild IgA nephropathy is uncertain. METHODS: All consecutive renal biopsies performed between 1996 and 2005 in adults with a diagnosis of mild IgA nephropathy (Lee Grade 1 or 2) at St Paul's Hospital, Vancouver, Canada, were reviewed. RESULTS: Seventy-five patients were included, 26 (35%) with IgA nephropathy and FSGS (FSGS+ group) and 49 (65%) with IgA nephropathy without FSGS (FSGS- group). The mean follow-up was 3 years. At the time of renal biopsy the FSGS+ group had a lower eGFR (60 versus 73 mL/min, P = 0.02), lower serum albumin (38 versus 41 g/L, P = 0.02), higher mean arterial pressure (103 versus 97 mmHg, P = 0.03) and greater protein excretion (3.0 versus 1.3 g/day, P < 0.01) than the FSGS- group. On histology, the FSGS+ group had a higher percentage of obsolete glomeruli (23.4% versus 12.7%, P < 0.01), and 31% of FSGS+ biopsies had >or=25% tubular atrophy/interstitial fibrosis while this was not observed in the FSGS- group (P < 0.01). The primary outcome measure, DeltaGFR, was -2.56 mL/ min/year in the FSGS+ group and +1.14 mL/min/year in the FSGS- group, difference: 3.70 mL/min/year (P = 0.03) (univariate). In the multivariate model, the FSGS+ group declined at 0.19 mL/min/year (-14.16, 13.78) and the FSGS- group improved at 2.85 mL/min/year (-11.64, 17.34), difference 3.04 mL/min/year, P = 0.18. CONCLUSIONS: Our study suggests that the focal segmental glomerulosclerosis lesion and associated clinical and pathologic findings in patients with mild IgA nephropathy are associated with a worse renal outcome.

Malignant irreversible intestinal obstruction: the powerful association of octreotide to corticosteroids, antiemetics, and analgesics.

In the case of malignant intestinal obstruction, surgery often carries important mortality and morbidity risks, and feasibility is neither realistic nor reasonable. A total of 4 clinical cases of intestinal obstruction caused by advanced gastrointestinal cancers in their terminal phase are described. The association of analgesics, corticosteroids, antiemetics, and octreotide was effective to relieve symptoms of intestinal obstruction for the remaining lifetime. The insertion of a nasogastric tube was avoided in 3 of 4 cases. Death occurred 51, 56, and 64 days after clinical and radiological diagnosis of irreversible intestinal obstruction. This combination of drugs appears very powerful and well tolerated. The relatively long survival that was observed should encourage future studies of longer half-life somatostatin analogues with no need of continuous infusion or multiple daily injections.

Prophylactic anti-coagulation in cancer palliative care: a prospective randomised study.

GOALS: The objective of this study was to determine utility of prophylactic anti-coagulation in cancer patients hospitalised for palliative care in a specialised centre. MATERIALS AND METHODS: Prospective 1:1 open randomised study was designed. Twenty patients aged 55 to 88 years with advanced cancer and an estimated life expectancy of less than 6 months were assigned to either receive treatment with 2,850/3,800 U (<70/>70 kg) of daily subcutaneous nadroparin or no treatment. Suspicion of venous thrombo-embolism (deep vein thrombosis and pulmonary embolism) was confirmed by echo-Doppler examination of the lower limbs and/or by spiral computed tomography scan of the lungs. Bleeding episodes were recorded. Platelet count was measured on days 7 and 14. Survival time from study entry was determined. MAIN RESULTS: One venous thrombo-embolism and one major bleeding occurred in the group receiving nadroparin, whereas two minor bleedings occurred in the control group. At 3 months, nine of ten participants had died in the control group vs five of ten in the group receiving nadroparin (P = 0.141). Five participants could be discharged home (P = 0.141). CONCLUSIONS: Decision to administer prophylactic nadroparin in hospitalised cancer patients under palliative care remains a challenge. Better mobility score at admission and the likelihood to be discharged home may be useful for practical purposes. The observation of a potential influence of prophylactic nadroparin on survival deserves further studies.

Oral health risks associated with HLA-types of patients undergoing hematopoietic stem cell transplantation.

AIM: Dental caries, gingivitis and periodontitis are frequent long-term complications after hematopoietic stem cell transplantation (HSCT). Not all patients are affected equally. As HLA-genotypes are associated with many functions of the immune system we made use of our long-standing oral health program in HSCT recipients to compare oral health data with recipient HLA-antigens. PATIENTS AND METHODS: This study includes 267 patients evaluated prior to a planned HSCT at our institution between March 1987 and March 2002. Standardized oral examinations were undertaken at fixed time points: pre-HSCT and at 6 and 12 months post-HSCT. Evaluation included loss of radiologic attachment level, decayed, missing, filled teeth (DMFT) index, and salivary flow rate. For 241 patients (120 males, 121 females) baseline values of these parameters were compared with recipient HLA-A, -B, -C and -DR-antigens. RESULTS: Significant correlations were found between increased DMFT and HLA-A32 (P = 0.05), -B5 (0.04), and -DR2 (0.05) as well as decreased DMFT with HLA-B35 (0.02) and -C4 (0.04). Significant associations were also found between certain HLA-antigens and loss of radiologic periodontal attachment level [HLA-A1 (<0.01), -C7 (0.04), and -B60 (0.05)], and saliva flow rate [HLA-A30 (0.02)]. CONCLUSIONS: These data suggest that there may be associations between pretransplant caries, other oral parameters and HLA in patients at HSCT. Confirmatory studies concerning the associations of certain HLA-antigens with caries and periodontal diseases will be needed.