Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer.

Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved. In particular, whether lysosphingolipids, the deacylated form of sphingolipids, both of which accumulate in these diseases, are simple biomarkers or play an instrumental role is unclear. In the meanwhile, evidence has been provided for a high risk of developing malignancies in patients affected with Gaucher disease, the most common sphingolipidosis. This article aims at analyzing the potential involvement of lysosphingolipids in cancer. Knowledge about lysosphingolipids in the context of lysosomal storage diseases is summarized. Available data on the nature and prevalence of cancers in patients affected with sphingolipidoses are also reviewed. Then, studies investigating the biological effects of lysosphingolipids toward pro or antitumor pathways are discussed. Finally, original findings exploring the role of glucosylsphingosine in the development of melanoma are presented. While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general.

Kinetics of inflammatory biomarkers to predict one-year mortality in older patients hospitalized for pneumonia: a multivariable analysis.

OBJECTIVES: Long-term mortality is increased in older patients with pneumonia. We aimed to test whether residual inflammation is predictive of one-year mortality after pneumonia. METHODS: Inflammation biomarkers (C-reactive protein [CRP], interleukin [IL]-6 and IL-8, tumor necrosis factor-α, serum amyloid A, neopterin, myeloperoxidase, anti-apolipoprotein A-1, and anti-phosphorylcholine IgM) were measured at admission and discharge in older patients hospitalized for pneumonia in a prospective study. Univariate and multivariate analyses were conducted using absolute level at discharge and relative and absolute differences between admission and discharge for all biomarkers, along with usual prognostic factors. RESULTS: In the 133 included patients (median age, 83 years [interquartile range: 78-89]), one-year mortality was 26%. In univariate analysis, the relative difference of CRP levels had the highest area under the receiver operating characteristic curve (0.70; 95% confidence interval [CI] 0.60-0.80). A decrease of CRP levels of more than 67% between admission and discharge had 68% sensitivity and 68% specificity to predict survival. In multivariate analysis, lower body mass index (hazard ratio=0.87 [CI 95% 0.79-0.96], P-value=0.01), higher IL-8 (hazard ratio=1.02 [CI 95% 1.00-1.04], P-value=0.02), and higher CRP (1.01 [95% CI 1.00-1.02], P=0.01) at discharge were independently associated with mortality. CONCLUSION: Higher IL-8 and CRP levels at discharge were independently associated with one-year mortality. The relative CRP difference during hospitalization was the best individual biomarker for predicting one-year mortality.

Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia.

BACKGROUND: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia. METHODS: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. RESULTS: A total of 133 patients were included (median age 83 years [IQR: 78-89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55-0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56-0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00-1.02) and BMI (HR 0.92 (95% CI 0.85-1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality. CONCLUSIONS: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.

[Artrial blood gas analysis is a daily intervention: is it safe, reliable and done properly?] / La gazométrie artérielle est un geste fréquent†; mais est-elle sûre, fiable, et bien réalisée?

Arterial punctures are frequent procedures performed by hospital internists. It provides crucial information on acid-base status, oxygenation and the quality of gas exchanges. Nevertheless, this intervention is often painful and carries potential risks. This review aims to summarize the literature about this subject and to address the accuracy of the results obtained by point-of-care analysis.

Effectuer une gazométrie artérielle est un geste faisant partie du quotidien du médecin interniste hospitalier. Cela apporte des informations cruciales sur l'équilibre acido-basique, l'oxygénation et la qualité des échanges gazeux, mais aussi sur d'autres paramètres biologiques. Néanmoins, la réalisation de ce geste reste souvent douloureuse pour le patient et comporte certains risques potentiels. Cet article a pour objectif une mise à jour des connaissances sur le sujet et d'évaluer le niveau de précision des analyses au lit du malade (point-of-care tests).

Accuracy of C-reactive protein, procalcitonin, serum amyloid A and neopterin for low-dose CT-scan confirmed pneumonia in elderly patients: A prospective cohort study.

OBJECTIVE: The diagnosis of pneumonia based on semiology and chest X-rays is frequently inaccurate, particularly in elderly patients. Older (C-reactive protein (CRP); procalcitonin (PCT)) or newer (Serum amyloid A (SAA); neopterin (NP)) biomarkers may increase the accuracy of pneumonia diagnosis, but data are scarce and conflicting. We assessed the accuracy of CRP, PCT, SAA, NP and the ratios CRP/NP and SAA/NP in a prospective observational cohort of elderly patients with suspected pneumonia. METHODS: We included consecutive patients more than 65 years old, with at least one respiratory symptom and one symptom or laboratory finding suggestive of infection, and a working diagnosis of pneumonia. Low-dose CT scan and comprehensive microbiological testing were done in all patients. The index tests, CRP, PCT, SAA and NP, were obtained within 24 hours. The reference diagnosis was assessed a posteriori by a panel of experts considering all available data, including patients' outcome. We used area under the curve (AUROC) and Youden index to assess the accuracy and obtain optimal cut-off of the index tests. RESULTS: 200 patients (median age 84 years) were included; 133 (67%) had pneumonia. AUROCs for the diagnosis of pneumonia was 0.64 (95% CI: 0.56-0.72) for CRP; 0.59 (95% CI: 0.51-0.68) for PCT; 0.60 (95% CI: 0.52-0.69) for SAA; 0.41 (95% CI: 0.32-0.49) for NP; 0.63 (95% CI: 0.55-0.71) for CRP/NP; and 0.61 (95% CI: 0.53-0.70) for SAA/NP. No cut-off resulted in satisfactory sensitivity or specificity. CONCLUSIONS: Accuracy of traditional (CRP, PCT) and newly proposed biomarkers (SAA, NP) and ratios of CRP/NP and SAA/NP was too low to help diagnosing pneumonia in the elderly. CRP had the highest AUROC. CLINICAL TRIAL REGISTRATION: NCT02467092.

[Gaucher disease]. / Maladie de Gaucher.

Gaucher disease. Gaucher disease is a rare lysosomal autosomal recessive disease, caused by a deficiency of glucocerebrosidase, a lysosomal enzyme. The most frequent symptoms are cytopenia, splenomegaly, hepatomegaly, and potentially severe bone involvement (bone infarcts, avascular osteonecrosis, and pathological fractures). Neurological involvement may occur in type 2 and type 3 Gaucher disease. Patients with type 1 Gaucher disease have an increased risk of Parkinson disease, some solid cancers, and some hematologic malignancies including multiple myeloma. Patients often experience delays before their disease is being diagnosed. Thus, there is a need for physicians to recognize Gaucher disease symptoms to reduce the risk of irreversible complications.

Maladie de gaucher. La maladie de Gaucher est une maladie lysosomale génétique rare à transmission autosomique récessive, due à un déficit enzymatique en glucocérébrosidase. La présentation clinique est très hétérogène, allant de formes asymptomatiques ou très peu symptomatiques à des formes sévères. Elle associe des cytopénies, une hépatosplénomégalie et une atteinte osseuse (ostéonécroses aseptiques, infarctus osseux, fractures pathologiques et ostéoporose). Des atteintes neurologiques potentiellement sévères peuvent se voir dans les maladies de Gaucher de type 2 et 3. Le type 1 est associé à un risque accru de maladie de Parkinson, de certains cancers solides, et d'hémopathies dont le myélome multiple. Le diagnostic est souvent fait avec retard, l'enjeu est donc celui d'une meilleure connaissance des symptômes devant faire évoquer la maladie, afin d'initier un traitement avant les complications potentiellement irréversibles.

Association of patterns of multimorbidity with length of stay: A multinational observational study.

The aim of this study was to identify the combinations of chronic comorbidities associated with length of stay (LOS) among multimorbid medical inpatients.Multinational retrospective cohort of 126,828 medical inpatients with multimorbidity, defined as ≥2 chronic diseases (data collection: 2010-2011). We categorized the chronic diseases into comorbidities using the Clinical Classification Software. We described the 20 combinations of comorbidities with the strongest association with prolonged LOS, defined as longer than or equal to country-specific LOS, and reported the difference in median LOS for those combinations. We also assessed the association between the number of diseases or body systems involved and prolonged LOS.The strongest association with prolonged LOS (odds ratio [OR] 7.25, 95% confidence interval [CI] 6.64-7.91, P < 0.001) and the highest difference in median LOS (13 days, 95% CI 12.8-13.2, P < 0.001) were found for the combination of diseases of white blood cells and hematological malignancy. Other comorbidities found in the 20 top combinations had ORs between 2.37 and 3.65 (all with P < 0.001) and a difference in median LOS of 2 to 5 days (all with P < 0.001), and included mostly neurological disorders and chronic ulcer of skin. Prolonged LOS was associated with the number of chronic diseases and particularly with the number of body systems involved (≥7 body systems: OR 21.50, 95% CI 19.94-23.18, P < 0.001).LOS was strongly associated with specific combinations of comorbidities and particularly with the number of body systems involved. Describing patterns of multimorbidity associated with LOS may help hospitals anticipate resource utilization and judiciously allocate services to shorten LOS.

Immunoglobulin Abnormalities in Gaucher Disease: an Analysis of 278 Patients Included in the French Gaucher Disease Registry.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses.

The roles of ceramide and its catabolites, i.e., sphingosine and sphingosine 1-phosphate, in the development of malignancies and the response to anticancer regimens have been extensively described. Moreover, an abundant literature points to the effects of glucosylceramide synthase, the mammalian enzyme that converts ceramide to ß-glucosylceramide, in protecting tumor cells from chemotherapy. Much less is known about the contribution of ß-glucosylceramide and its breakdown products in cancer progression. In this chapter, we first review published and personal clinical observations that report on the increased risk of developing cancers in patients affected with Gaucher disease, an inborn disorder characterized by defective lysosomal degradation of ß-glucosylceramide. The previously described mechanistic links between lysosomal ß-glucosylceramidase, ß-glucosylceramide and/or ß-glucosylphingosine, and various hallmarks of cancer are reviewed. We further show that melanoma tumor growth is facilitated in a Gaucher disease mouse model. Finally, the potential roles of the ß-glucosylceramidase protein and its lipidic substrates and/or downstream products are discussed.

Iron Deficiency in Acute Decompensated Heart Failure.

The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Consecutive patients admitted with ADHF at a single tertiary center were included. Demographic information, pathology investigations, and metrics regarding hospital stay and readmission were recorded. Patients were classified as having 'absolute' ID if they had a ferritin level <100 ng/mL; or 'functional' ID if they had a ferritin 100-200 ng/mL and a transferrin saturation <20%. Of 503 patients that were recruited, 270 (55%) had HFpEF, 160 (33%) had HFREF, and 57 (12%) had heart failure with mid-range ejection fraction. ID was present in 54% of patients with HFrEF and 56% of patients with HFpEF. In the HFpEF group, ID was associated with a LOS of 11 ± 7.7 vs. 9 ± 6 days in iron replete patients, p = 0.036, and remained an independent predictor of increased LOS in a multivariate linear regression incorporating comorbidities, age, and ID status. This study corroborates a high prevalence of ID in both HFrEF and HFpEF, and further shows that in patients with HFpEF there is a prolongation of LOS not seen in HFrEF which may indicate a more prominent role for ID in HFpEF.

Multimorbidity and healthcare resource utilization in Switzerland: a multicentre cohort study.

BACKGROUND: Multimorbidity is associated with higher healthcare resource utilization, but we lack data on the association of specific combinations of comorbidities with healthcare resource utilization. We aimed to identify the combinations of comorbidities associated with high healthcare resource utilization among multimorbid medical inpatients. METHODS: We performed a multicentre retrospective cohort study including 33,871 multimorbid (≥2 chronic diseases) medical inpatients discharged from three Swiss hospitals in 2010-2011. Healthcare resource utilization was measured as 30-day potentially avoidable readmission (PAR), prolonged length of stay (LOS) and difference in median LOS. We identified the combinations of chronic comorbidities associated with the highest healthcare resource utilization and quantified this association using regression techniques. RESULTS: Three-fourths of the combinations with the strongest association with PAR included chronic kidney disease. Acute and unspecified renal failure combined with solid malignancy was most strongly associated with PAR (OR 2.64, 95%CI 1.79;3.90). Miscellaneous mental health disorders combined with mood disorders was the most strongly associated with LOS (difference in median LOS: 17 days) and prolonged LOS (OR 10.77, 95%CI 8.38;13.84). The number of chronic diseases was strongly associated with prolonged LOS (OR 9.07, 95%CI 8.04;10.24 for ≥10 chronic diseases), and to a lesser extent with PAR (OR 2.16, 95%CI 1.75;2.65 for ≥10 chronic diseases). CONCLUSIONS: Multimorbidity appears to have a higher impact on LOS than on PAR. Combinations of comorbidities most strongly associated with healthcare utilization included kidney disorders for PAR, and mental health disorders for LOS.

Development of a predictive score for potentially avoidable hospital readmissions for general internal medicine patients.

BACKGROUND: Identifying patients at high risk of hospital preventable readmission is an essential step towards selecting those who might benefit from specific transitional interventions. OBJECTIVE: Derive and validate a predictive risk score for potentially avoidable readmission (PAR) based on analysis of readmissions, with a focus on medication. DESIGN/SETTING/PARTICIPANTS: Retrospective analysis of all hospital admissions to internal medicine wards between 2011 and 2014. Comparison between patients readmitted within 30 days and non-readmitted patients, as identified using a specially designed algorithm. Univariate and multivariate regression analyses of demographic data, clinical diagnoses, laboratory results, and the medication data of patients admitted during the first period (2011-2013), to identify factors associated with PAR. Using these, derive a predictive score with a regression coefficient-based scoring method. Subsequently, validate this score with a second cohort of patients admitted in 2013-2014. Variables were identified at hospital discharge. RESULTS: The derivation cohort included 7,317 hospital stays. Multivariate logistic regressions found significant associations with PAR for: [adjusted OR (95% CI)] hospital length of stay > 4 days [1.3 (1.1-1.7)], admission in previous 6 months [2.3 (1.9-2.8)], heart failure [1.3 (1.0-1.7)], chronic ischemic heart disease [1.7 (1.2-2.3)], diabetes with organ damage [2.2 (1.3-3.8)], cancer [1.4 (1.0-1.9)], metastatic carcinoma [1.9 (1.3-3.0)], anemia [1.2 (1.0-1.5)], hypertension [1.3 (1.1-1.7)], arrhythmia [1.3 (1.0-1.6)], hyperkalemia [1.4 (1.0-1.7)], opioid drug prescription [1.3 (1.1-1.6)], and acute myocardial infarction [0.6 (0.4-0.9)]. The PAR-Risk Score, derived from these results, demonstrated fair discriminatory and calibration power (C-statistic = 0.699; Brier Score = 0.069). The results for the validation cohort's operating characteristics were similar (C-statistic = 0.687; Brier Score = 0.064). CONCLUSION: This study identified routinely-available factors that were significantly associated with PAR. A predictive score was derived and internally validated.

Patterns of multimorbidity in internal medicine patients in Swiss university hospitals: a multicentre cohort study.

AIMS OF THE STUDY: Despite the high prevalence of multimorbidity, we lack detailed descriptive data on the most prevalent combinations of chronic comorbidities in Switzerland. We aimed to describe and quantify the most prevalent combinations of comorbidities in internal medicine multimorbid inpatients. METHODS: We conducted a multicentre retrospective cohort study including all consecutive adults (n = 42,739) discharged from the general internal medicine department of three Swiss tertiary teaching hospitals in 2010–2011. We used the Chronic Condition Indicator and the Clinical Classification Software to classify International Classification of Diseases diagnosis codes into chronic or acute diseases, into body system categories and into categories of chronic comorbidities. We defined multimorbidity as ≥2 chronic diseases. We described the most prevalent combinations of comorbidities and their prevalence. RESULTS: Seventy-nine percent (n = 33,871) of the patients were multimorbid, with a median of four chronic diseases. Chronic heart disease, chronic kidney disease, solid malignancy and substance-related disorders were the most prevalent comorbidities, with a prevalence of more than 10% for each. All these comorbidities were frequently found in combination with chronic obstructive pulmonary disease and bronchiectasis, pulmonary heart disease, and peripheral and visceral atherosclerosis. Chronic heart disease was identified in 80% of the most prevalent combinations. Half of the combinations occurred more often than it would have been expected if they were independent. CONCLUSIONS: The vast majority of patients fulfilled the criteria for multimorbidity. Chronic heart disease, chronic kidney disease, solid malignancy and substance-related disorders were each present in at least one tenth of the patients. This in-depth description of the most frequent comorbidities and of their frequent associations in a multicentre population may advise healthcare providers to improve preventive care and develop appropriate guidelines for multimorbid patients.  .

Associations between early handoffs, length of stay and complications in internal medicine wards: A retrospective study.

BACKGROUND: In US healthcare system, handoffs are associated with an increase in medical error and in hospital length of stay. In non-US healthcare systems, this phenomenon has not been well studied. We studied the association between early handoffs (EH) in a non-US internal medicine ward with length of stay (LOS), use of resources, major complication (MC) and discharge to post-acute care (PAC) facility. METHODS: We conducted a retrospective cohort study on patients admitted to the general internal medicine division. Patients with EH (defined as a transfer of responsibility between primary teams within the first 72 h) were compared with patients without EH. The primary outcome was LOS in the general internal medicine division. Secondary outcomes were the use of resources, the incidence of MC (transfer to intensive care, to intermediate care or death) and discharge to a PAC facility. RESULTS: We included 11,869 patients, 38% of whom were in the EH group. Patients were 67.7±16.6 years old and 53% were males. EH was independently associated with an increase of LOS (+6.4% [95% CI, 3.5%-9.5%], P < .001) and with an increased rate of MC (OR 1.3 [95% CI, 1.1-1.7], P = .012). In our subgroup analysis, the association between early handoff and LOS and MC rate were not statistically significant when the admission occurred on public holidays and weekends. CONCLUSIONS: Among patients admitted in our general internal medicine division, early handoffs were associated with significantly higher length of stay and major complication rate, but not in patients admitted during week-ends.

Patterns of multimorbidity associated with 30-day readmission: a multinational study.

BACKGROUND: Multimorbidity is associated with higher healthcare utilization; however, data exploring its association with readmission are scarce. We aimed to investigate which most important patterns of multimorbidity are associated with 30-day readmission. METHODS: We used a multinational retrospective cohort of 126,828 medical inpatients with multimorbidity defined as ≥2 chronic diseases. The primary and secondary outcomes were 30-day potentially avoidable readmission (PAR) and 30-day all-cause readmission (ACR), respectively. Only chronic diseases were included in the analyses. We presented the OR for readmission according to the number of diseases or body systems involved, and the combinations of diseases categories with the highest OR for readmission. RESULTS: Multimorbidity severity, assessed as number of chronic diseases or body systems involved, was strongly associated with PAR, and to a lesser extend with ACR. The strength of association steadily and linearly increased with each additional disease or body system involved. Patients with four body systems involved or nine diseases already had a more than doubled odds for PAR (OR 2.35, 95%CI 2.15-2.57, and OR 2.25, 95%CI 2.05-2.48, respectively). The combinations of diseases categories that were most strongly associated with PAR and ACR were chronic kidney disease with liver disease or chronic ulcer of skin, and hematological malignancy with esophageal disorders or mood disorders, respectively. CONCLUSIONS: Readmission was associated with the number of chronic diseases or body systems involved and with specific combinations of diseases categories. The number of body systems involved may be a particularly interesting measure of the risk for readmission in multimorbid patients.

Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: A systematic review and network meta-analysis.

BACKGROUND: Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT. METHODS: We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications. RESULTS: We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding. CONCLUSIONS: DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.

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.

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD-but also carriers of GBA1 mutation-have been found to be predisposed to developing Parkinson's disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat).

Determining prognosis in acute exacerbation of COPD.

BACKGROUND: Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD. METHODS: This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox). RESULTS: We identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02-1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42-15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003-2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68-4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004-1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003-1.05; P=0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome. CONCLUSION: COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission appears to be the most prognostic clinical parameter. A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission.