Prevention of nosocomial pressure ulcers: a process improvement project.

Nosocomial pressure ulcers (PU) occur in approximately 12% of all hospitalized patients. The risk can be determined by a variety of intrinsic and extrinsic factors. As a first line of defense against nosocomial PU, we use the Braden Scale to determine the potential risk of PU development during hospitalization. Once risk was identified, our standard was to implement an individualized plan of care. However, consistent implementation of PU preventative measures was lacking. As a result, a process improvement project was developed and implemented. The purpose of this process improvement project was to increase communication about and awareness of the need to vigorously intervene and document whenever there is risk of, or development of, a nosocomial PU. By initiating consistent use of a PU Tracking Form, developing unit-based wound champions that serve as experts in ulcer prevention, and creating an individual case analysis process, PU prevention and tracking was institutionalized. Results indicate that our nosocomial PU rate has declined from 7% to 4%.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay

We evaluated a procedure for identifying recent HIV infections, using sequential serum samples from 47 HIV-positive persons for whom the seroconversion date could be accurately estimated. Each serum sample was divided into two aliquots: one diluted with phosphate-buffered saline and the other diluted with 1 M guanidine. We assayed the aliquots with the automated AxSYM HIV1/2gO test (Abbott Diagnostics Division), without modifying the manufacturer's protocol. We then calculated the avidity index (AI): the ratio of the sample/cutoff value for the guanidine aliquot to that of the phosphate-buffered saline aliquot. We analyzed 216 serum samples: 34 samples were collected within 6 months of seroconversion (recent seroconversions), and 182 were collected after 6 months. The mean AIs, by time from seroconversion, were 0.68 +/- 0.16 (within 6 months) and 0.98 +/- 0.10 (after 6 months) (P < 0.0001). AI of <0.90 correctly identified 88.2% of recent infections but misclassified as recent infections 13.2% of serum samples collected afterward. The probability of an infection being classified as recent and having AI of > or = 0.90 would be 0.7% in a population with 5% recent infections. AI can identify with a certain degree of accuracy recent HIV infections, and being a quantitative index, it provides different levels of sensitivity and specificity, depending on the selected cutoff value. The standard assay procedure is not modified. This test is simple and inexpensive and could be used for surveillance, decision-making in treatment, and prevention.     

β3‐Adrenoceptors modulate left ventricular relaxation in the rat heart via the NO‐cGMP‐PKG pathway

Aims: Using a model of isolated and Langendorff‐perfused rat heart we analysed whether activation of β₃‐adrenergic receptors (β₃‐ARs) influences ventricular lusitropic performance. We also focused on the NOS/NO/cGMP/PKG cascade as the signal transduction mechanism. Methods: Hearts were treated with increasing concentrations (from 10^?12 to 10^?6 m ) of BRL₃₇₃₄₄, a selective β₃‐AR agonist, and cardiac performance was evaluated by analysing both lusitropic parameters and coronary motility. Cardiac preparations were also perfused with BRL₃₇₃₄₄ in the presence of either isoproterenol (ISO) or nadolol, or pertussis toxin (PTx), or selective inhibitors of the NOS/NO/cGMP/PKG pathway. Results: BRL₃₇₃₄₄ caused a significant concentration‐dependent reduction in (LVdP/dt)_min, a decrease in half time relaxation significant starting from 10^?12 m , and an increase in (LVdP/dt)_max/(LVdP/dt)_min ratio (T/?t). BRL₃₇₃₄₄ abolished the ISO‐mediated positive lusitropism. β₃‐AR‐dependent effects on relaxation were insensitive to β₁/β₂‐AR inhibition by nadolol (100 nm ), and were abolished by G_i/o protein inhibition by PTx (0.01 nm ). NO scavenging by haemoglobin (10 μm ), and nitric oxide synthase (NOS) inhibition by NG‐monomethyl‐l ‐arginine (10 μm ) revealed the involvement of NO signalling in BRL₃₇₃₄₄ response. Pre‐treatment with inhibitors of either soluble guanylate cyclase (ODQ; 10 μm ) or PKG (KT₅₈₂₃; 100 nm ) abolished β₃‐AR‐dependent negative lusitropism. In contrast, anantin (10 nm ), an inhibitor of particulate guanylate cyclase, did not modify the effect of BRL₃₇₃₄₄ on relaxation. Conclusion: Taken together, our findings provide functional evidence for β₃‐AR modulation of ventricular relaxation in the rat heart which involves PTx‐sensitive inhibitory Gi protein and occurs via an NO‐cGMP‐PKG cascade. Whether the effects of β₃‐AR stimulation on lusitropism are beneficial or detrimental remains to be established.     

Chordoma: Radiological–pathological correlation

This review correlates the imaging findings and histological appearances seen in chordomas in a series of patients presenting at our institution, together with a published literature review. A parallel presentation of photographs of imaging findings and microscopic histological findings is made, with the aim being to enhance recognition of this uncommon but clinically significant entity.     

Prevalence of Delirium in End-of-Life Palliative Care Patients: An Observational Study

ObjectivesThe aim of this study was to assess the prevalence of delirium, using the Assessment Test for Delirium and Cognitive Impairment (4AT) in end-of-life palliative care patients.Subjects and MethodsThis retrospective cross-sectional study was conducted on end-of-life patients in a hospice or at home. All patients were evaluated with the 4AT for the presence of delirium.ResultsOf the 461 patients analyzed, 76 (16.5%) were inpatients and 83.5% (385) outpatients. The median age was 79.5 (72–86) years, and 51.0% were female. According to the 4AT score, 126 patients (27.3%) had delirium (A4T ≥4) at admission, 28 (36.8%) were inpatients, and 98 (25.5%) outpatients. Around 33.8% of the cancer inpatients had delirium, while 20.6% of the cancer outpatients had delirium. The prevalence of delirium varied according to the setting, clinical condition, and life expectancy. In addition, 55.0% (11) actively dying inpatients, within 3 days, had delirium, and 56.7% (17) outpatients had delirium; while among those with life expectancy longer than 4 days, 30.4% (17) inpatients and 22.8% (81) outpatients were with delirium.ConclusionsOur study confirms that delirium is common in cancer and noncancer palliative care patients. Further research on delirium in end-of-life palliative care patients should consider the complexity of palliative care of this population as well as of the characteristics of the settings.     

Direct and reversible inhibitory effect of the tetrapeptide acetyl-N- Ser-Asp-Lys-Pro (Seraspenide) on the growth of human CD34+ subpopulations in response to growth factors

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, Seraspenide; Ipsen- Biotech, Paris, France), an inhibitor of murine spleen colony-forming units reduces the number and the percentage in DNA synthesis of progenitors from human unfractionated bone marrow. To determine whether AcSDKP may directly affect the growth potential of purified progenitors even at the most primitive level, CD34+HLA-DRhigh and CD34++HLA-DRlow cells were highly purified by cell sorting. Then, CD34+ subsets were stimulated in liquid culture with combinations of growth factors (GFs) and AcSDKP was added for 20 hours or 6 days and cells plated in methylcellulose. After a 20-hour incubation, we show that AcSDKP (at 10(-10) mol/L) significantly inhibits the colony formation of both CD34+ subsets. Moreover, when added daily for 6 days, AcSDKP: (1) reduces the proliferation of both CD34+ cell fractions stimulated by 3 or 7 GFs, and (2) decreases the number of progenitors generated from the CD34+HLA-DRhigh and CD34++HLA-DRlow cell fractions. Furthermore, we show for the first time, using both high proliferative potential cell and long-term culture initiating cell assays, that AcSDKP inhibits the most primitive cells contained in the CD34++HLA-DRlow subpopulation. Finally, by using limiting dilution assays we demonstrated that AcSDKP acts directly at a single cell level and that its inhibitory effect is reversible and dose dependent.     

Ixazomib for the treatment of multiple myeloma

Introduction: Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 (ixazomib) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss.

Areas covered: In this review, the authors discuss the rationale for use of PIs. They then summarize the clinical development of ixazomib in MM, from initial Phase I to Phase II studies as a monotherapy and in combination with other chemotherapeutics.

Expert opinion: Preliminary data of Phase I/II trials showed that ixazomib had a good safety profile and exerted anti-myeloma activity as a single agent in relapsed/refractory patients. Furthermore, ixazomib also had efficacy in patients who were refractory to bortezomib. Its use in combination with lenalidomide and dexamethasone was shown to be an effective and well-tolerated regimen in up-front treatment leading to minimal residual disease negativity in a significant number of patients. Results of Phase III trials, evaluating ixazomib in induction or maintenance therapy, are awaited.     

Smoldering multiple myeloma: to treat or not to treat

Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥ 30 g/l serum M-protein and/or ≥ 10% bone marrow plasma cell infiltration. The progression risk to active multiple myeloma (MM) is not uniform, and several prognostic parameters are useful for identifying patients at high risk of progression. A watch-and-wait approach has been the standard of care up to now. However, recently, it has been demonstrated that a subset of high-risk cases can benefit from early treatment with new drugs.

Areas covered: In this editorial, we focus on SMM and evaluate the diagnostic work-up and the prognostic factors predicting progression to symptomatic MM. We also review the studies in which the role of early treatment has been evaluated for patients with SMM.

Expert opinion: After the update performed by the International Myeloma Working Group regarding MM diagnosis, it is now time to change the therapeutic paradigm for this disease. While “ultra high-risk” myeloma should now be considered as active MM, for low-risk patients the “watch-and-wait” strategy is still recommended. More caution is needed for the high-risk group: physicians should continue monitoring patients using every tool now available while waiting for results from ongoing trials that will establish if this group will benefit from an early intervention.     

Rapid discrimination of early CD34+ myeloid progenitors using CD45-RA analysis

Mononuclear cells (MNC) isolated by density centrifugation of cord blood and healthy bone marrow, and of peripheral blood (PB) from patients treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF after chemotherapy, were double-stained with anti CD34 monoclonal antibody (MoAb) (8G12) versus anti CD45, CD45-RB, CD45- RO, and CD45-RA, respectively, and analyzed by flow cytometry. In all specimens, CD34+ MNC co-expressed CD45 at a low level and the expression of CD45-RB was similar or slightly higher. Most CD34+ MNC were negative for CD45-RO, a weak coexpression was only seen in some bone marrow (BM) and blood samples. In contrast, CD45-RA could subdivide the CD34+ population into fractions negative, dim (+), and normal positive (++) for these subgroups, and typical staining patterns were observed for the different sources of hematopoietic cells: in BM, most CD34+ MNC were RA++. In PB, their majority was RA++ after G-CSF but RA+ or RA- after GM-CSF. In cord blood, the hematopoietic progenitors were mainly RA-/RO-. Semisolid culture of sorted CD34+ MNC showed that clusters and dispersed (late) colony-forming unit-GM (CFU- GM) originated from 34+/RA++ cells, while the 34+/RA- MNC formed compact and multicentric, both white and red colonies derived from early progenitors. Addition of 20 ng stem cell factor per milliliter of medium containing 34+/RA- cord blood MNC led to a change of many burst- forming unit-erythrocyte (BFU-E) to CFU-mix which was not, at least to this extent, seen in blood and BM. We conclude that early myeloid CD34+ cells are 45+/RA-. Because this population excludes 34+/19+ B cells and 33+ myeloid cells, both of which are RA++, two-color flow cytometric analysis using CD34 and CD45-RA facilitates the characterization and quantification of early myeloid progenitor cells.