The Hospital Anxiety and Depression Scale in Greek cancer patients: psychometric analyses and applicability

Goals of work The aim of the present study was to validate the Greek version of the Hospital Anxiety and Depression Scale (HAD) in a palliative care unit.Patients and methods The scale was translated with the forward-backward procedure to Greek. It was administered twice, with a 1-week interval, to 120 patients with advanced cancer. Together with the HAD scale, the patients also completed the Spielberger State-Anxiety Scale (STAI-S).Main results Factor analyses identified a two-factor solution corresponding to the original two subscales of the HAD, which were found to be correlated. The Greek version of the HAD had Cronbachs alphas for the anxiety and depression scales of 0.887 and 0.703, respectively. Validity as performed using known-group analysis showed good results. Both anxiety and depression subscales discriminated well between subgroups of patients differing in disease severity as defined by ECOG performance status. Correlations between the HAD scale and the STAI-S was 0.681 for the anxiety subscale and 0.485 for the depression subscale.Conclusions These psychometric properties of the Greek version of the HAD scale confirm it as a valid and reliable measure when administered to patients with advanced cancer.     

Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.     

Orofacial Pain--Part II: Assessment and management of vascular, neurovascular, idiopathic, secondary, and psychogenic causes

Chronic orofacial pain is a common health complaint faced by health practitioners today and constitutes a challenging diagnostic problem that often requires a multidisciplinary approach to diagnosis and treatment. The previous article by the same authors in this issue discussed the major clinical characteristics and the treatment of various musculoskeletal and neuropathic orofacial pain conditions. This second article presents aspects of vascular, neurovascular, and idiopathic orofacial pain, as well as orofacial pain due to various local, distant, or systemic diseases and psychogenic orofacial pain. The emphasis in this article is on the general differential diagnosis and various therapeutic regimens of each of these conditions. An accurate diagnosis is the key to successful treatment of chronic orofacial pain. Given that for many of the entities discussed in this article no curative treatment is available, current standards of management are emphasized. A comprehensive reference section has been included for those who wish to gain further information on a particular entity.     

Myocardial and hepatic T2* magnetic resonance evaluation in ex-thalassemic patients after bone-marrow transplantation

Bone marrow transplantation (BMT) is the only complete cure for b-thalassemia. Iron depletion therapy is still required to remove excess iron, accumulated before BMT. Hepatic and myocardial iron load were evaluated using T2* magnetic resonance in 8 ex-thalassemic patients after BMT, aged 19.5 ± 4.25 years, who were in iron depletion therapy. Average hepatic T2* was 18.8 ± 11.0 msec (4.1–35.0 msec). In 4 out of 8 patients iron overload was detected, not exceeding however 4 mg/gr dry tissue. Average heart T2* was 31.0 ± 4.6 msec (25.6–35.2 msec), not significantly different (P = 0.18) from our age-matched normal population (33.0 ± 4.0). Normal left ventricular ejection fraction was found in 7 out of 8 patients (mean 64.5 ± 7.0%) with the remaining having a marginal value of 54.1%. Ferritin level before BMT was 1748 ± 451 μg/l and dropped to 536 ± 260 μg/l at the end of iron depletion therapy after BMT. Current ferritin level was 271 ± 253 μg/l and although it was significant lower compared to both ferritin before BMT (P < 0.001) and after iron depletion (P < 0.001), evidence of residual hepatic iron load was identified by T2*. Hepatic and myocardial T2* magnetic resonance can be used as a more reliable index than ferritin for evaluation of iron depletion therapy in ex-thalassemic patients after BMT.     

Engraftment of NOD/SCID-beta2 microglobulin null mice with multilineage neoplastic cells from patients with myelodysplastic syndrome

The development of immunodeficient mouse xenograft models has greatly facilitated the investigation of some human hematopoietic malignancies, but application of this approach to the myelodysplastic syndromes (MDSs) has proven difficult. We now show that cells from most MDS patients (including all subtypes) repopulate nonobese diabetic-severe combined immunodeficient (scid)/scid-beta2 microglobulin null (NOD/SCID-beta2m(-/-)) mice at least transiently and produce abnormal differentiation patterns in this model. Normal marrow transplants initially produce predominantly erythroid cells and later predominantly B-lymphoid cells in these mice, whereas most MDS samples produced predominantly granulopoietic cells. In 4 of 4 MDS cases, the regenerated cells showed the same clonal markers (trisomy 8, n = 3; and 5q-, n = 1) as the original sample and, in one instance, regenerated trisomy 8(+) B-lymphoid as well as myeloid cells were identified. Interestingly, the enhanced growth of normal marrow obtained in NOD/SCID-beta2m(-/-) mice engineered to produce human interleukin-3, granulocyte-macrophage colony-stimulating factor, and Steel factor was seen only with 1 of 7 MDS samples. These findings support the concept that human MDS originates in a transplantable multilineage hematopoietic stem cell whose genetic alteration may affect patterns of differentiation and responsiveness to hematopoietic growth factors. They also demonstrate the potential of this new murine xenotransplant model for future investigations of MDS.     

Coagulation and inflammation biomarkers may help predict the severity of community‐acquired pneumonia

Background and objective: There are limited data on the relationship between the severity of community‐acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT‐III), protein C (P‐C), D‐dimers (D‐D) and CRP, at hospital admission. Methods: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate ≥30 breaths/min, low blood pressure, age ≥65 years (CURB‐65) score. Results: Forty patients (52%) had severe CAP (CURB‐65 score 3–5). Serum levels of AT‐III were lower and levels of D‐D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB‐65 score 0–2) (P < 0.001 for all comparisons). Levels of P‐C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut‐off point of 85%, AT‐III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut‐off point of 600 ng/mL, D‐D showed a sensitivity of 90% and a specificity of 75% and at a cut‐off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization. Conclusions: Serum levels of AT‐III, D‐D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.     

Unusual presentation of M?nckeberg’s sclerosis in the thyroid vessels of three female patients

Histopathological findings of Mönckeberg’s sclerosis in the thyroid vessels of three female patients are described. Two of the patients presented with papillary carcinoma and the third presented with two cystic adenomatous nodules. Lesions of chronic lymphocytic thyroiditis were observed in two of the cases. The presence of Mönckeberg’s sclerosis is an indication for further examination of patients’ vascular systems because of the high risk for cardiovascular events.     

Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial

One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT.     

Safety assessment of allergic contact dermatitis hazards: an analysis supporting reduced animal use for the murine local lymph node assay

The original Organisation for Economic Co-operation and Development Test Guideline 429 (OECD TG 429) for the murine local lymph node assay (LLNA) required five mice/group if mice were processed individually. We used data from 83 LLNA tests (275 treated groups) to determine the impact on the LLNA outcome of reducing the group size from five to four. From DPM measurements, we formed all possible four- and five-mice combinations for the treated and control groups. Stimulation index (SI) values from each four-mice combination were compared with those from five-mice combinations, and agreement (both SI<3 or both SI ≥ 3) determined. Average agreement between group sizes was 97.5% for the 275 treated groups. Compared test-by-test, 90% (75/83) of the tests had 100% agreement; agreement was 83% for the remaining eight tests. Disagreement was due primarily to variability in animal responses and closeness of the SI to three (positive response threshold) rather than to group size reduction. We conclude that using four rather than five mice per group would reduce animal use by 20% without adversely impacting LLNA performance. This analysis supported the recent update to OECD TG 429 allowing a minimum of four mice/group when each mouse is processed individually.     

The binding affinity of anti-Aβ1-42 MAb-decorated nanoliposomes to Aβ1-42 peptides in vitro and to amyloid deposits in post-mortem tissue

Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD), and nanoparticles functionalized with Aβ-specific ligands are considered promising vehicles for imaging probes and therapeutic agents. Herein, we characterized the binding properties of nanoliposomes decorated with an anti-Aβ monoclonal antibody (Aβ-MAb). The Aβ-MAb was obtained in mice by immunization with Aβ antigen followed by hybridoma fusion. Surface Plasmon Resonance (SPR) studies confirmed the very high affinity of purified Aβ-MAb for both Aβ monomers and fibrils (K(D)?=?0.08?and 0.13?nm, respectively). The affinity of the biotinylated Aβ-MAb, used thereafter for liposome decoration, was lower although still in the low nanomolar range (K(D)?=?2.1?and 1.6?nm, respectively). Biotin-streptavidin ligation method was used to decorate nanoliposomes with Aβ-MAb, at different densities. IgG-decorated liposomes were generated by the same methodology, as control. Vesicles were monodisperse with mean diameters 124-134?nm and demonstrated good colloidal stability and integrity when incubated with serum proteins. When studied by SPR, Aβ-MAb-liposomes, but not IgG-liposomes, markedly bound to Aβ monomers and fibrils, immobilized on the chip. K(D) values (calculated on Aβ-MAb content) were about 0.5?and 2?nm with liposomes at high and low Aβ-MAb density, respectively. Aβ-MAb-liposome binding to Aβ fibrils was additionally confirmed by ultracentrifugation technique, in which interactions occur in solution under physiological conditions. Moreover, Aβ-MAb-liposomes bound amyloid deposits in post-mortem AD brain samples, confirming the potential of these nanoparticles for the diagnosis and therapy of AD.