Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS)

The aim of this study was to evaluate the role of markers of bone remodelling, and osteoclast activation/function in patients with monoclonal gammopathy of undetermined significance (MGUS). We have measured serum levels of soluble RANKL (sRANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alpha), markers of bone resorption [N-telopeptide of collagen type-I (NTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)] and bone formation [bone-alkaline phosphatase (bALP)] in 40 MGUS patients. These parameters were compared with those of 42 newly diagnosed myeloma patients, and 45 healthy, gender- and age-matched controls. MGUS patients had elevated levels of NTX, sRANKL, and sRANKL/OPG ratio compared with controls (P < 0.0001). Furthermore, TRACP-5b, MIP-1alpha and NTX were decreased in patients with MGUS compared with myeloma patients (P < 0.001), while OPG and bALP were increased (P < 0.001). Serum levels of MIP-1alpha, as well as TRACP-5b, and sRANKL/OPG ratio were reduced, while bALP was increased in MGUS patients, even when compared with myeloma patients who had stage I/II disease. These results demonstrate that increased osteoclastogenesis leading to increased bone resorption is present in MGUS but seems to be compensated for by normal bone formation, which is absent in MM. Furthermore MIP-1alpha, bALP, and sRANKL/OPG may be useful tools for distinguishing between cases of MGUS and early myeloma.     

The impact of deep sternal wound infection on long-term survival after coronary artery bypass grafting

OBJECTIVES: To identify the impact of deep sternal wound infection (DSWI) on long-term survival after coronary artery bypass grafting (CABG). BACKGROUND: DSWI following CABG is an infrequent, yet devastating complication with increased morbidity and mortality. However, little has been published regarding the impact of DSWI on long-term mortality. METHODS: We studied 3,760 consecutive patients who underwent isolated CABG between 1992 and 2002. Patients with CABG and no DSWI were compared with those in whom DSWI developed. Long-term survival data (mean follow-up, 5.2 years) were obtained from the National Death Index. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for DSWI was determined by logistic regression analysis, and each patient with DSWI was then matched to 10 patients without DSWI. RESULTS: DSWI developed in 40 of 3,760 patients (1.1%). Independent predictors for DSWI were diabetes (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.7 to 11.6; p < 0.001), hemodynamic instability preoperatively (OR, 4.0; 95% CI, 1.2 to 13.9; p = 0.026), preoperative renal failure on dialysis (OR, 3.4; 95% CI, 1.0 to 13.6; p = 0.049), use of bilateral internal thoracic arteries (OR, 2.6; 95% CI, 1.3 to 5.3; p = 0.010), and sepsis and/or endocarditis after CABG (OR, 29.9; 95% CI, 11.7 to 76.4; p < 0.001). Patients with DSWI had prolonged length of stay (35.0 days vs 16.4 days; p < 0.001); however, there was no difference in early mortality between matched groups. After adjustment for preoperative, intraoperative, and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 2.44 (95% CI, 1.51 to 3.92; p < 0.001). Patients without DSWI had a better 5-year survival rate (72.8 +/- 2.4% vs 50.8.6 +/- 8.5% [mean +/- SE]; p = 0.0007 between matched groups). CONCLUSIONS: We found that DSWI following CABG was associated with increased long-term mortality during a 10-year follow-up study.     

Phenotype and genotype frequency of β-thalassemia and sickle cell disease carriers in Halkidiki, Northern Greece

A decade of screening (years 2000 to 2010) for hemoglobinopathies in 3,931 patients was performed at the General Hospital of Poligiros, Halkidiki, Northern Greece. Among the patients examined, 10.8% heterozygotes for β-thalassemia (β-thal) were found, as well as 4.1% with sickle cell disease and 1.2% with double β-thal/Hb S [β6(A3)Glu→Val] heterozygosity. Iron deficiency was observed in 23.4%. The geographical distribution in the region revealed a substantial incidence of hemoglobinopathies even in mountainous areas. This pattern did not follow the typical distribution according to the malaria hypothesis, as incidence did not dovetail with swamp locations recorded in the past. The HBB gene mutations for 85 patients were also analyzed. Most prevalent in Halkidiki, Northern Greece, was the codon 39 (C>T) mutation (27.1%) followed by the IVS-I-110 (G>A) mutation (22.4%); this was in direct contrast to the current distribution of the same mutations seen in the rest of Greece (Greek National Genetic Database, GNGD). This frequency inversion was statistically significant, with the difference from the GNGD being 20.6% for the IVS-I-110 mutation (p <0.0005) and 7.6% for the codon 39 mutation (p = 0.0238). The history of Halkidiki, denoting a clear example of geographical isolation from the rest of the country, may possibly account for a potentially diverse genetical identity of the disease in this region.     

ESCAP CovCAP survey of heads of academic departments to assess the perceived initial (April/May 2020) impact of the COVID-19 pandemic on child and adolescent psychiatry services

In April 2020, the European Society for Child and Adolescent Psychiatry (ESCAP) Research Academy and the ESCAP Board launched the first of three scheduled surveys to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on child and adolescent psychiatry (CAP) services in Europe and to assess the abilities of CAP centers to meet the new challenges brought on by the crisis. The survey was a self-report questionnaire, using a multistage process, which was sent to 168 heads of academic CAP services in 24 European countries. Eighty-two responses (56 complete) from 20 countries, representing the subjective judgement of heads of CAP centers, were received between mid-April and mid-May 2020. Most respondents judged the impact of the crisis on the mental health of their patients as medium (52%) or strong (33%). A large majority of CAP services reported no COVID-19 positive cases among their inpatients and most respondents declared no or limited sick leaves in their team due to COVID-19. Outpatient, daycare, and inpatient units experienced closures or reductions in the number of treated patients throughout Europe. In addition, a lower referral rate was observed in most countries. Respondents considered that they were well equipped to handle COVID-19 patients despite a lack of protective equipment. Telemedicine was adopted by almost every team despite its sparse use prior to the crisis. Overall, these first results were surprisingly homogeneous, showing a substantially reduced patient load and a moderate effect of the COVID-19 crisis on psychopathology. The effect on the organization of CAP services appears profound. COVID-19 crisis has accelerated the adoption of new technologies, including telepsychiatry.

     

Translocation (X;12)(p11;p13) as a sole abnormality in biphenotypic acute leukemia

A reciprocal t(X;12)(p11;p13) was found as the sole clonal abnormality in biphenotypic leukemia with myeloid and B-lymphoid differentiation. With fluorescence in situ hybridization analysis, the ETV6 gene (previously TEL) was found to be translocated intact to the derivative X chromosome; no MLL and BCR/ABL rearrangements were found. The patient achieved complete remission after induction chemotherapy. To our knowledge, this cytogenetic aberration has not been reported previously as a sole abnormality in hematological malignancies. Its presence may suggest an important role in the pathogenesis of biphenotypic leukemia.     

Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In vitro testing of response

Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2 (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 microM amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.     

Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin

Lymphomatoid papulosis (LyP) represents an intriguing cutaneous T-cell lymphoproliferative disorder with a histologic appearance resembling malignant lymphoma. This finding strongly contrasts with the benign clinical course of the disease. However, in 10% to 20% of cases, LyP can precede, coexist with, or follow malignant lymphoma. In these cases, the same T-cell population has been shown to be present in the LyP as well as in the associated lymphoma. In most LyP cases, there is-despite the sometimes extremely long course of the disease-no evolution of a secondary lymphoma. The investigation of these uncomplicated LyP cases for the presence of clonal T-cell receptor rearrangements has produced heterogeneous results. This might be explained by biologic or technical reasons arising from analyzing whole tissue DNA extracts. To definitively clarify whether the large atypical CD30(+) cells in LyP without associated lymphoma all belong to the same clone or represent individually rearranged T cells, we analyzed the T-cell receptor-gamma rearrangements of single CD30+ as well as of single CD30- cells isolated from 14 LyP lesions of 11 patients. By using this approach we could demonstrate that the CD30+ cells represent members of a single T-cell clone in all LyP cases. Moreover, in 3 patients the same CD30+ cell clone was found in anatomically and temporally separate lesions. In contrast, with only a few exceptions, the CD30- cells were polyclonal in all instances and unrelated to the CD30+ cell clone. Our results demonstrate that LyP unequivocally represents a monoclonal T-cell disorder of CD30+ cells in all instances.