Leukocyte Cell Population Data for Hematology Analyzer-Based Distinction of Clonal-versus-Non-Clonal Lymphocytosis: A Real-World Testing Experience

Automated blood counts revealing lymphocytosis necessitate smear reviews. Even expert morphological evaluation may however, fail to differentiate a benign-versus-malignant etiology without further testing. Automated analyser-derived quantitative data on leukocyte cell populations remain undertested for distinguishing such etiologies. Instrument manufacturers claim that if successful, they may be used to generate software flags that help under-resourced laboratories better triage hemogram specimens requiring further testing. We tested the diagnostic accuracy of volume-conductivity-scatter (VCS) indices together with complete blood count (CBC) parameters in such scenarios. We compared LH780-derived (Beckman Coulter, FL, USA) CBC + VCS parameters from patients with clonal lymphoproliferations (n = 42, including 30 chronic lymphocytic leukemia cases) versus 83 controls with absolute or relative lymphocytosis (derivation cohort). Diagnostic performances of 11 logistic regression equations derived were subsequently evaluated on two specific validation cohorts (n = 130 and n = 1465). Clonal lymphocytoses showed significantly lower hemoglobin and higher leukocyte counts but similar lymphocyte percentages (LY %) vis-à-vis controls. The most significant, albeit overlapping predictor of clonality was the absolute lymphocyte count, LY# (47.8 ± 48.4 × 10⁹/L vs. 2.9 ± 1.4 × 10⁹/L in clonal vs. benign cases). In eleven logistic regression equations constructed using four combinatorial approaches, only the models with LY# (highest sensitivity/specificity of 99.3%/100%) and the lymphocytic VCS parameters alone (highest sensitivity/specificity of 76.2%/90.2%) performed consistently in both validation cohorts. Lymphocytic VCS parameters were moderately successful in distinguishing benign-versus-malignant lymphocytes. Other approaches of CBC-plus-VCS parameters did not sustain their initial excellent performances in the validation cohorts, highlighting a need for careful appraisal and better standardization of automated cellular analysis technologies.     

COPD-related Bronchiectasis; Independent Impact on Disease Course and Outcomes

Background: COPD and radiographic bronchiectasis frequently coexist but the effect of this on the clinical course of COPD is not fully understood. We determined the impact of bronchiectasis on clinical outcomes in COPD patients, independent of coexisting emphysema and bronchial wall thickening (BWT). Methods: COPD patients admitted with first exacerbation 1998–2008 were identified retrospectively using ICD10 codes J44.0,1,8,9. Patients with suitable CT scans were graded for severity of bronchiectasis, emphysema and BWT on a 5 point scale (0-absent, 1-minor, 2-mild, 3-moderate, 4-severe). Results: 406 patients (71 ± 11 years, 56% male, FEV₁ 52 ± 23% predicted) were included; 278 (69%) patients had bronchiectasis: minor, 112 (40%); mild, 81 (29%); moderate, 62 (22%); severe 23 (8%). Bronchiectasis severity correlated with severity of BWT (p < 0.001) but not emphysema (p = 0.090). Bronchiectasis independently determined sputum isolation of Pseudomonas aeruginosa (Odds ratio (OR) 1.39 (95% CI 1.07 to 1.80), p = 0.013) and atypical mycobacteria (OR 2.44 (95% CI 1.04 to 5.69), p = 0.040), annual respiratory admissions (p = 0.044) and inpatient days (p < 0.001), but did not predict survival (p = 0.256). Conclusions: Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore an important diagnosis with potential implications for treatment.     

Response to androgen therapy in patients with dyskeratosis congenita

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age‐related decline in telomere length was noted in androgen‐treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment‐related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre‐pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen‐treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored.     

Gastrointestinal mucormycosis—four cases with different risk factors, involving different anatomical sites

Mucormycosis of the gastrointestinal tract is a rare infection that usually occurs in patients who are immunocompromised and carries a high mortality. We report four cases of gastrointestinal mucormycosis seen over a one year period with different presentations, risk factors and different anatomical sites of involvement. A preoperative diagnosis was made only in one patient. All underwent surgery, three survived and one died postoperatively from multiorgan failure.     

Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP(+) corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-alpha induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs.