Clinico-haematological profile of HbE syndrome in adults and children

Haemoglobin E beta thalassemia (HbE beta thalassemia) has a remarkable variability in clinical expression ranging from a mild form of thalassemia intermedia to a transfusion dependent condition. An overlap between the mild variety of HbE beta thalassemia and homozygous HbE disease is common, however, differentiation is required for early institution of therapy and for predicting the later clinical course. Fifty cases of Hb E syndrome comprising of 43 cases of Hb E beta thalassemia and 7 cases of homozygous HbE disease were studied. Their clinico- haematological features and results of high performance liquid chromatography (HPLC) were analysed.     

Tuberculosis in acute leukemia: a clinico-hematological profile

We studied 130 consecutive cases of acute leukemia over a 2-year period and identified 9 cases (6.9%) with active tuberculosis (TB). Eight patients with TB had acute myeloid leukemia (AML). Patients with AML were more likely to develop TB as compared to patients with acute lymphoblastic leukemia (ALL) despite the wider use of steroids and radiotherapy in ALL protocols {OR 4.41 (CI 0.53-36.44)}. Only 1 patient died of disseminated TB during post induction neutropenia. All other patients were successfully managed using current anti-tuberculous therapy (ATT). On the whole, TB did not cause any undue delay in chemotherapy and did not flare up during subsequent chemotherapy cycles. However it is not a commonly described infection in acute leukemia and a high index of suspicion is warranted especially in areas endemic for TB.     

Perceived Burdens and Benefits Associated With Continuous Glucose Monitor Use in Type 1 Diabetes Across the Lifespan

Background:Continuous glucose monitors (CGMs) help people with type 1 diabetes (T1D) improve their glycemic profiles but are underutilized. To better understand why, perceived CGM burdens and benefits in nonusers versus users with type 1 diabetes across the lifespan were assessed.Methods:Burdens (BurCGM) and benefits of CGM (BenCGM) questionnaires were completed during T1D outpatient visits (n = 1334) from February 2019 to February 2020. Mean scores were calculated (scale one to five; higher scores reflect greater perceived burdens/benefits). Data were collected from medical records including glycated hemoglobin (HbA1c) within 3 months of the visit.Results:Individuals of all ages using CGM described more benefits and less burdens (mean scores 4.48 and 1.69, respectively) when compared with those who were not using CGM (mean score 4.19 and 2.35, respectively) (P < .001). There were no differences in burdens or benefits by sex. Non-CGM users aged ≥50 years had higher mean BurCGM scores than those aged <50 years (P = .004); the cost was the greatest barrier in those aged 27+ years. Other burdens were readings not trusted, painful to wear, and takes too much time to use. For those aged 65+, nonusers versus users, 18.5% versus 3.1% agreed with “it was too hard to understand CGM information,” and 21.4% versus 7.7% agreed that CGM causes too much worry. Mean HbA1C was lower in CGM users (8.1%) versus non-CGM users (mean A1c 9.1%; P < .001).Conclusions:CGM was perceived as having more burdens and less benefits in nonusers, with differences in concerns varying across the lifespan. Lower costs and age-appropriate education are needed to address these barriers.     

Fludarabine, cyclophosphamide and horse antithymocyte globulin conditioning regimen for allogeneic peripheral blood stem cell transplantation performed in non-HEPA filter rooms for multiply transfused patients with severe aplastic anemia

Multiply transfused patients of severe aplastic anemia are at increased risk of graft rejection. Five such patients underwent peripheral blood stem cell transplantation from HLA-identical siblings with a fludarabine-based protocol. The conditioning consisted of fludarabine 30 mg/m(2)/day x 6 days, cyclophosphamide 60 mg/kg/day x 2 days and horse antithymocyte globulin (ATG) x 4 days. Two different ATG preparations were used: ATGAM (dose 30 mg/kg/day x 4 days) or Thymogam (dose 40 mg/kg/day x 4 days). Engraftment: median time to absolute neutrophil count (ANC) >0.5 x 10(9)/l was 11 days (range: 8-17) and median time to platelet count >20 x 10(9)/l was 11 days (range: 9-17). At a median follow-up of 171 days (range: 47-389), there has been no graft rejection and all patients are in complete remission. Acute GVHD (grade 1) occurred in one patient only. Chronic GVHD developed in two patients (extensive in one and limited in another). The transplants were performed in non-HEPA filter rooms. In only one patient, systemic antifungal therapy (voriconazole) was used. The use of Thymogam brand of ATG for conditioning is being reported for the first time. Our experience suggests that this fludarabine-based protocol allows rapid sustained engraftment in high-risk patients without significant immediate toxicity.     

Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute

Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French-American-British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6-yr period (1996-2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long-term survival estimate.     

Development of Vero cell miniculture assay for detection of heat-labile enterotoxin of Escherichia coli and its significance

In the present study the Vero cell miniculture assay was developed for the detection of heat-labile enterotoxin of E. coli. The test was found to be reliable and efficient and was comparable with other tissue culture assays. The new cell lines BHK21, MDBK, LM and CK included in the present study did not respond positively to the E. coli toxins.     

Decreased Pulmonary Inflammation Following Ethanol and Burn Injury in Mice Deficient in TLR4 but not TLR2 Signaling

Background: Clinical and laboratory evidence suggests that alcohol consumption prior to burn injury leads to dysregulated immune function and subsequent higher rates of morbidity and mortality. Our laboratory previously observed higher levels of pro‐inflammatory cytokines and leukocyte infiltration in the lungs of mice following ethanol and burn injury. To understand the mechanism of the increased inflammatory response, we looked at different signaling initiators of inflammation including toll‐like receptors 2 and 4 (TLR2 and 4) pathways. Methods: Wild‐type, TLR2, and TLR4 knockout mice were treated with vehicle or a single binge dose of ethanol (1.11 g/kg) and subsequently given a sham or burn injury. Twenty‐four hours postinjury, systemic and pulmonary levels of pro‐inflammatory cytokines were quantified, and differences in neutrophil infiltration were determined by histological examination. Results: Higher numbers of neutrophils were observed in the lungs of wild‐type mice following the combined insult of ethanol and burn injury relative to either injury alone. This increase in leukocyte accumulation was absent in the TLR4 knockout mice. Circulating levels of IL‐6 and tumor necrosis factor‐α were also elevated in wild‐type mice but not in TLR4 knockout mice. Consistent with these findings, pulmonary levels of KC and IL‐6 were increased in wild‐type mice following burn and ethanol compared to burn injury alone as well as to their TLR4 knockout counterparts. In contrast, TLR2 knockout mice displayed similar levels, to wild‐type mice, of neutrophil infiltration as well as IL‐6 and KC in the lung. Conclusions: These data suggest that TLR4 signaling is a crucial contributory component in the exuberant inflammation after ethanol and burn injury. However, TLR2 does not appear to play a vital role in the aberrant pulmonary inflammation.     

Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus

Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus of the family Paramyxoviridae and are unique in that they exhibit a broad species tropism and cause fatal disease in both animals and humans. They infect cells through a pH-independent membrane fusion process mediated by their fusion and attachment glycoproteins. Previously, we demonstrated identical cell fusion tropisms for HeV and NiV and the protease-sensitive nature of their unknown cell receptor and identified a human cell line (HeLa-USU) that was nonpermissive for fusion and virus infection. Here, a microarray analysis was performed on the HeLa-USU cells, permissive HeLa-CCL2 cells, and two other permissive human cell lines. From this analysis, we identified a list of genes encoding known and predicted plasma membrane surface-expressed proteins that were highly expressed in all permissive cells and absent from the HeLa-USU cells and rank-ordered them based on their relative levels. Available expression vectors containing the first 10 genes were obtained and individually transfected into HeLa-USU cells. One clone, encoding human ephrin-B2 (EFNB2), was found capable of rendering HeLa-USU cells permissive for HeV- and NiV-mediated cell fusion as well as infection by live virus. A soluble recombinant EFNB2 could potently block fusion and infection and bind soluble recombinant HeV and NiV attachment glycoproteins with high affinity. Together, these data indicate that EFNB2 serves as a functional receptor for both HeV and NiV. The highly conserved nature of EFNB2 in humans and animals is consistent with the broad tropism exhibited by these emerging zoonotic viruses.     

Clinico-haematological Profile of HbE Syndrome in Adults and Children

Haemoglobin E beta thalassemia (HbE β thalassemia) has a remarkable variability in clinical expression ranging from a mild form of thalassemia intermedia to a transfusion dependent condition. An overlap between the mild variety of HbE beta thalassemia and homozygous HbE disease is common, however, differentiation is required for early institution of therapy and for predicting the later clinical course. Fifty cases of Hb E syndrome comprising of 43 cases of Hb E beta thalassemia and 7 cases of homozygous HbE disease were studied. Their clinico- haematological features and results of high performance liquid chromatography (HPLC) were analysed.