Paediatric haematologists’ attitudes regarding haematopoietic cell transplantation as treatment for sickle cell disease

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists’ attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38–46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.     

Large granular lymphocytic leukaemia after solid organ and haematopoietic stem cell transplantation

T-cell large granular lymphocytic leukaemia (T-LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T-LGLL seen at our institution over the last 10 years, we encountered 15 cases following solid organ or haematopoietic stem cell transplantation. Here, we studied the clinical characterization of these cases and compared them to de novo T-LGLL. This experience represented a clear picture of the intricate nature of the disease manifestation and the complexities of several immune mechanisms triggering the clonal expansion.     

Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging.

OBJECTIVES: The purpose of this study was to evaluate the role of caspase inhibitors on acute resolution of apoptosis in atherosclerotic lesions as evaluated by imaging with annexin A5. BACKGROUND: Extensive apoptosis of macrophages has been reported at the site of plaque rupture in patients dying of acute coronary syndrome. METHODS: Of 31 New Zealand White atherosclerotic rabbits, 6 received broad caspase, 3 received caspase-1, 3 received caspase-3, 3 received caspase-8, and 4 received caspase-9 inhibitors; 12 animals did not receive any caspase inhibitors (treatment control group). Six unmanipulated rabbits were used for comparison (disease control group). Technetium-99m-labeled annexin A5 was used for imaging atherosclerotic lesions; 6 of the 12 uninhibited atherosclerotic rabbits received (99m)Tc-labeled mutant annexin A5 (radiotracer control group). Gamma images were obtained, and quantitative radiotracer uptake was compared with pathologic findings. RESULTS: Atherosclerotic lesions were best visible in untreated atherosclerotic rabbits. Quantitative annexin uptake, defined as the percent of injected dose per g of abdominal aorta tissue, was significantly higher in untreated atherosclerotic animals (mean +/- SD = 0.0515 +/- 0.0099) compared with the normal rabbits (0.0065 +/- 0.0008; p < 0.0001) or atherosclerotic rabbits receiving mutant annexin (0.014 +/- 0.0024; p < 0.0001). Among all caspase inhibitor-treated rabbits, uptake was 39% lower (0.0314 +/- 0.0151) than in untreated atherosclerotic animals (p < 0.01). Uptake was also significantly lower in rabbits receiving broad caspase (0.0206 +/- 0.0058; p < 0.0001) or caspase-1, -3, or -9 (0.0272 +/- 0.0088, p < 0.01; 0.0286 +/- 0.0095, p < 0.01; 0.0300 +/- 0.0021, p < 0.01, respectively) inhibitors. Caspase-8 inhibitor did not affect apoptosis (0.0618 +/- 0.0047; p = NS). Upon histologic characterization, a substantial decrease in macrophage apoptosis was observed in caspase-inhibited animals. CONCLUSIONS: Molecular imaging, using radiolabeled annexin A5, allows the detection of acute resolution of apoptosis as a result of caspase inhibition in experimental atherosclerosis. If proven clinically, this may allow development of novel intervention strategies in acute vascular events.     

Circulatory and hepatic failure at admission predicts mortality of severe scrub typhus patients: A prospective cohort study

Objective: To study the spectrum and outcome of severe scrub typhus in adult patients and to predict the hospital mortality by organ failure on admission.Methods: This was a prospective observational cohort study conducted between July 2017 and October 2020 at the medical emergency centre of PGIMER, Chandigarh, India. One hundred and twenty-six patients aged ≥13 years were diagnosed with scrub typhus. Severe disease was defined as the presence of organ failure based on the Sequential Organ Failure Assessment(SOFA) score on admission.Results: About two-thirds of the patients were from geographic regions outside the endemic sub-Himalayan belt. Fever(99.21%) and dyspnea(79.36%) were the most frequent complaints. Respiratory failure(81.75%) was the most common organ failure, followed by hepatic(52.38%), coagulative(47.62%), circulatory(33.33%), renal(21.43%), and cerebral dysfunction(13.49%). The median(Q1, Q3) SOFA score was 8(6, 9), and 48.41% of the patients had a quick-SOFA score ≥2. Organ supports with invasive ventilation(40.48%), vasopressors(36.51%), and renal replacement therapy(7.14%) were frequently required. The in-hospital mortality was 11.90% and was independently predicted by circulatory and hepatic failures on multivariate logistic regression(OR 11.12, 95% CI 1.73-71.31 and OR 8.49, 95% CI 1.18-61.41, respectively).Conclusions: Most patients had pulmonary dysfunction; circulatory or hepatic failure on admission strongly predicts death.