Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increased bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparathyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss and to reduce vertebral fracture risk. Calcitonin may be of interest in situations where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be managed. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatmen

Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: Derivation of a clinical algorithm

Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI

Doping of thiolate protected gold clusters through reaction with metal surfaces

A new technique is introduced for doping gold nanoclusters by using a metal surface such as Ag, Cu and Cd as a source of heteroatoms. The importance of the thiol ligand in the doping process is examined by following the reactions with MALDI-TOF mass spectrometry in the presence and the absence of the thiols on the surface. The doping reactions depend greatly on the type of the cluster and the availability of the ligand which is a crucial element for alloying. The thiol acts as a messenger exchanging the metal atoms between the cluster and the metal surface as revealed by the XPS studies performed on the metal surfaces

A case report of Clarkson's disease: If you don't know it, you'll miss it

The systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare disorder characterized by paroxysmal capillary hyperpermeability with a shift of plasma fluid from the intravascular to the interstitial space. A 35-year-old previously healthy woman was admitted with rapidly developing hypovolemic shock syndrome, rhabdomyolysis, and diffuse edema. Laboratory analysis revealed a severe hemoconcentration, renal insufficiency, and paraproteinemia. After exclusion of infection, allergy, burning or drug-induced conditions, the clinical presentation was consistent with the diagnosis of SCLS. Though this is a rare entity, the substantial morbidity and mortality associated with it necessitate the physician's awareness in order to provide timely therapy. This report is meant to enhance awareness of SCLS

ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression

Tightly regulated expression of the transcription factor PU.1 is crucial for normal hematopoiesis. PU.1 knockdown mice develop acute myeloid leukemia (AML), and PU.1 mutations have been observed in some populations of patients with AML. Here we found that conditional expression of promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA), the protein encoded by the t(15;17) translocation found in acute promyelocytic leukemia (APL), suppressed PU.1 expression, while treatment of APL cell lines and primary cells with all-trans retinoic acid (ATRA) restored PU.1 expression and induced neutrophil differentiation. ATRA-induced activation was mediated by a region in the PU.1 promoter to which CEBPB and OCT-1 binding were induced. Finally, conditional expression of PU.1 in human APL cells was sufficient to trigger neutrophil differentiation, whereas reduction of PU.1 by small interfering RNA (siRNA) blocked ATRA-induced neutrophil differentiation. This is the first report to show that PU.1 is suppressed in acute promyelocytic leukemia, and that ATRA restores PU.1 expression in cells harboring t(15;17)

Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial

Concerns about inadequate performance and complexity limit routine use of clinical risk scores in lower respiratory tract infections. Our aim was to study feasibility and effects of adding the biomarker proadrenomedullin (proADM) to the confusion, urea>7 mmol·L(-1), respiratory rate≥30 breaths·min(-1), blood pressure<90 mmHg (systolic) or ≤60 mmHg (diastolic), age≥65 years (CURB-65) score on triage decisions and length of stay. In a randomised controlled proof-of-concept intervention trial, triage and discharge decisions were made for adults with lower respiratory tract infection according to interprofessional assessment using medical and nursing risk scores either without (control group) or with (proADM group) knowledge of proADM values, measured on admission, and on days 3 and 6. An adjusted generalised linear model was calculated to investigate the effect of our intervention. On initial presentation the algorithms were overruled in 123 (39.3%) of the cases. Mean length of stay tended to be shorter in the proADM (n=154, 6.3 days) compared with the control group (n=159, 6.8 days; adjusted regression coefficient -0.19, 95% CI -0.41-0.04; p=0.1). This trend was robust in subgroup analyses and for overall length of stay within 90 days (7.2 versus 7.9 days; adjusted regression coefficient -0.18, 95% CI -0.40-0.05; p=0.13). There were no differences in adverse outcomes or readmission. Logistic obstacles and overruling are major challenges to implement biomarker-enhanced algorithms in clinical settings and need to be addressed to shorten length of stay.status: publishe

Prediction of post-acute care demand in medical and neurological inpatients: diagnostic assessment of the post-acute discharge score - a prospective cohort study

BACKGROUND: Early identification of patients requiring transfer to post-acute care (PAC) facilities shortens hospital stays. With a focus on interprofessional assessment of biopsychosocial risk, this study's aim was to assess medical and neurological patients' post-acute care discharge (PACD) scores on days 1 and 3 after hospital admission regarding diagnostic accuracy and effectiveness as an early screening tool. The transfer to PAC facilities served as the outcome ("gold standard"). METHODS: In this prospective cohort study, registered at ClinicalTrial.gov (NCT01768494) on January 2013, 1432 medical and 464 neurological patients (total n = 1896) were included consecutively between February and October 2013. PACD scores and other relevant data were extracted from electronic records of patient admissions, hospital stays, and interviews at day 30 post-hospital admission. To gauge the scores' accuracy, we plotted receiver operating characteristic (ROC) curves, calculated area under the curve (AUC), and determined sensitivity and specificity at various cut-off levels. RESULTS: Medical patients' day 1 and day 3 PACD scores accurately predicted discharge to PAC facilities, with respective discriminating powers (AUC) of 0.77 and 0.82. With a PACD cut-off of ≥8 points, day 1 and 3 sensitivities were respectively 72.6% and 83.6%, with respective specificities of 66.5% and 70.0%. Neurological patients' scores showed lower accuracy both days: using the same cut-off, respective day 1 and day 3 AUCs were 0.68 and 0.78, sensitivities 41.4% and 68.7% and specificities 81.4% and 83.4%. CONCLUSION: PACD scores at days 1 and 3 accurately predicted transfer to PAC facilities, especially in medical patients on day 3. To confirm and refine these results, PACD scores' value to guide discharge planning interventions and subsequent impact on hospital stay warrants further investigation. TRIAL REGISTRATION: ClinialTrials.gov Identifier, NCT01768494 .status: publishe

Prediction of post-acute care demand in medical and neurological inpatients: diagnostic assessment of the post-acute discharge score – a prospective cohort study

Abstract Background Early identification of patients requiring transfer to post-acute care (PAC) facilities shortens hospital stays. With a focus on interprofessional assessment of biopsychosocial risk, this study’s aim was to assess medical and neurological patients’ post-acute care discharge (PACD) scores on days 1 and 3 after hospital admission regarding diagnostic accuracy and effectiveness as an early screening tool. The transfer to PAC facilities served as the outcome (“gold standard”). Methods In this prospective cohort study, registered at ClinicalTrial.gov (NCT01768494) on January 2013, 1432 medical and 464 neurological patients (total n = 1896) were included consecutively between February and October 2013. PACD scores and other relevant data were extracted from electronic records of patient admissions, hospital stays, and interviews at day 30 post-hospital admission. To gauge the scores’ accuracy, we plotted receiver operating characteristic (ROC) curves, calculated area under the curve (AUC), and determined sensitivity and specificity at various cut-off levels. Results Medical patients’ day 1 and day 3 PACD scores accurately predicted discharge to PAC facilities, with respective discriminating powers (AUC) of 0.77 and 0.82. With a PACD cut-off of ≥8 points, day 1 and 3 sensitivities were respectively 72.6% and 83.6%, with respective specificities of 66.5% and 70.0%. Neurological patients’ scores showed lower accuracy both days: using the same cut-off, respective day 1 and day 3 AUCs were 0.68 and 0.78, sensitivities 41.4% and 68.7% and specificities 81.4% and 83.4%. Conclusion PACD scores at days 1 and 3 accurately predicted transfer to PAC facilities, especially in medical patients on day 3. To confirm and refine these results, PACD scores’ value to guide discharge planning interventions and subsequent impact on hospital stay warrants further investigation. Trial registration ClinialTrials.gov Identifier, NCT01768494