High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: total metabolic tumor volume is a useful risk factor to stratify patients at baseline

Stage IIB Hodgkin lymphoma (HL) patients, with a mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization have a poor prognosis and are treated either as limited or advanced stage. We compared these two approaches in patients included in two randomized phase III trials enrolling previously untreated early (H10) or advanced stage HL (AHL2011). We included HL patients with Ann-Arbor stage IIB with M/T ≥0.33 or extranodal involvement enrolled in the H10 or AHL2011 trials with available positron emission tomography at baseline (PET0) and after two cycles of chemotherapy (PET2). Baseline total metabolic tumor volume (TMTV) was calculated using the 41% SUV_max method. PET2 response assessment used the Deauville score. One hundred and fourty-eight patients were eligible, including 83 enrolled in the AHL2011 trial and 65 in the H10 trial. The median TMTV value was 155.5 mL (range, 8.3-782.9 mL), 165.6 mL in AHL2011 and 147 mL in H10. PET2 positivity rates were 16.9% (n=14) and 9.2% (n=6) in AHL2011 and H10 patients, respectively. With a median follow-up of 4.1 years (95% confidence interval [CI]: 3.9-4.4), overall 4-year PFS was 88.0%, 87.0% in AHL2011 and 89.2% in H10. In univariate and mutivariate analyses, baseline TMTV and PET2 response influenced significantly progression-free survival (hazard ratio [HR]=4.94, HR=3.49 respectively). Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline ≥155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient’s outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline.     

Effects of trunk muscle activation on trunk stability,arm power,blood pressure and performance in wheelchair rugby players with a spinal cord injury

Objective: In wheelchair rugby (WR) athletes with tetraplegia, wheelchair performance may be impaired due to (partial) loss of innervation of upper extremity and trunk muscles, and low blood pressure (BP). The objective was to assess the effects of electrical stimulation (ES)-induced co-contraction of trunk muscles on trunk stability, arm force/power, BP, and WR performance.Design: Cross-sectional study.Setting: Rehabilitation research laboratory and WR court.Participants: Eleven WR athletes with tetraplegia.Interventions: ES was applied to the rectus abdominis, obliquus externus abdominis and erector spinae muscles. For every test, the ES condition was compared to the non-ES condition.Outcome measures: Stability was assessed with reaching tasks, arm force/power with an isokinetic test on a dynamometer, BP during an ES protocol and WR skill performance with the USA Wheelchair Rugby Skill Assessment.Results: Overall reaching distance (ES 14.6 ± 7.5 cm, non-ES 13.4 ± 8.2 cm), and BP showed a significant increase with ES. Arm force (ES 154 ± 106 N, non-ES 148 ± 102 N) and power (ES 37 ± 26 W, non-ES 36 ± 25 W), and WR skills were not significantly improved.Conclusion: ES-induced trunk muscle activation positively affects trunk stability and BP, but not arm force/power. No effects were found in WR skill performance, probably due to abdominal strapping. More research is needed to assess different ES (training) protocols and longitudinal effects.     

Practical aspects of implementing tight glucose control in the ICU

PURPOSE OF REVIEW: The outcomes of intervention studies implementing intensive insulin therapy aimed at tight glucose control (TGC) are yet not conclusive. There is concern about an increasing incidence of hypoglycemic episodes. Normoglycemia is not easy to obtain in a 'real-life' ICU setting. To facilitate the implementation of TGC, we review its practical aspects. RECENT FINDINGS: Point-of-care blood gas/glucose analyzers currently present the best trade-off between accuracy and speed. A nurse-driven dynamic scale protocol leads to the most efficacious and safe implementation of TGC. Paper protocols have been published and computerized protocols are a new development. Closed-loop systems are not yet available for clinical use. SUMMARY: Clinicians should take care in selecting both the patient group and target blood glucose level. As long as doubts remain about the potential benefits, it is important to perform TGC in a safe way. This can be done with a nurse-driven protocol, using arterial blood samples measured on a point-of-care blood gas analyzer. Insulin administration should be continuous, and guided by a dynamic scale protocol either on paper or on the computer. Periodical monitoring of performance and incremental modification of the protocol leads to best results.     

ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma

We present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20-/CD138+ plasmablast-like cells. In one of the cases, initially diagnosed as a null-type anaplastic large cell lymphoma (ALCL), the B-cell phenotype became evident only at recurrence. Fluorescent in situ hybridization (FISH) and molecular studies led to the detection of a CLTC-ALK rearrangement in all 3 cases, without any evidence of full-length ALK receptor expression. The associated t(2;17)(p23;q23) was demonstrated in the karyotype of 2 cases. Although a similar CLTC-ALK aberration was previously identified in ALK-positive T-/null cell ALCL and inflammatory myofibroblastic tumor, its association with ALK-positive LBCL seems to be specific and intriguing.     

Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/- 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS)     

Navigating double marginalisation: migrant Chinese sexual and gender minority young people’s views on mental health challenges and supports

Sexual and/or gender minority young people who are also members of an ethnic minority can experience unique challenges. Limited research draws directly on the mental health experiences of these ‘double minority’ youth. This study focused on Chinese sexual/gender minority youth in New Zealand. It sought to explore features they found challenging for, or supportive of, their mental health and wellbeing. Semi-structured interviews were conducted with 11 Chinese sexual/gender minority participants aged between 19 and 29 years old and residing in Auckland, New Zealand. An inductive approach to qualitative data analysis was used. Two major domains of findings emerged. Firstly, participants described mental health challenges linked to racism, sexism, cis-heteronormativity and challenges in relation to intersecting identities. Secondly, Chinese culture and community connections, family and peer support and role models seemed to facilitate resiliency. However, the fear of ‘losing face’, unwillingness to disclose distress when unwell and mental health service providers’ lack of cultural and linguistic competency were described as barriers to effective mental health support. In conclusion, Chinese and sexual/gender minority identities were integral parts of participants’ sense of self, and this was associated with their mental health and wellbeing. Further research is required to explore ways to reduce barriers and promote resiliency.     

Recombinant interferon-alpha,but not interferon-gamma is effective therapie for essential thrombocythemia

Summary Recombinant interferon-gamma with a starting dose of 0.5 mg 3×/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172×10⁹/1, range 602–1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to 350×10⁹/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferonalpha_2c at a dose of 5×10⁶ U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferonalpha dosis was reduced to 5× an thereafter to 3× weekly 5×10⁶ U. During an observation period ranging from 12–41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferonalpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.     

The Role of the Fibrinolytic System in Corneal Angiogenesis

The plasminogen activation system has been implicated in angiogenesis and angiogenesis-dependent diseases such as cancer, atherosclerosis and ocular diseases. The identification and development of inhibitors of angiogenesis offer new possibilities for the treatment of these diseases. To clarify the role of proteins involved in the regulation of fibrinolysis during corneal angiogenesis, we have studied corneal vessel formation in mice deficient for urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI). Our results corroborate earlier findings that angiogenesis in the mouse cornea is dependent on PAI-1 and plasminogen. The absence of tPA, uPA or TAFI did not affect the formation of new vessels in the cornea.