Extracellular vesicles as potential biomarkers of acute graft-vs-host disease.

Acute graft-vs-host disease (GVHD) is a serious complication after allografting. We carried out an exploratory study to investigate a potential correlation of surface antigens on extracellular vesicles (EVs) and acute GVHD. EVs were extracted from serum samples from 41 multiple myeloma patients who underwent allografting. EVs were characterized by flow cytometry using a panel of 13 antibodies against specific membrane proteins that were reported to be predictive of acute GVHD. We observed a correlation between three potential biomarkers expressed on EV surface and acute GVHD onset by both logistic regression analysis and Cox proportional hazard model. In our study, CD146 (MCAM-1) was correlated with an increased risk-by almost 60%-of developing GVHD, whereas CD31 and CD140-α (PECAM-1 and PDGFR-α) with a decreased risk-by almost 40 and 60%, respectively. These biomarkers also showed a significant change in signal level from baseline to the onset of acute GVHD. Our novel study encourages future investigations into the potential correlation between EVs and acute GVHD. Larger prospective multicenter studies are currently in progress.

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation.

The physio-pathologic interrelationships between endothelium and GvHD have been better elucidated and have led to definition of the entity 'endothelial GvHD' as an essential early phase prior to the clinical presentation of acute GvHD. Using the CellSearch system, we analyzed circulating endothelial cells (CEC) in 90 allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients at the following time-points: T1 (pre-conditioning), T2 (pre-transplant), T3 (engraftment), T4 (onset of GvHD) and T5 (1 week after steroid treatment). Although CEC changes in allo-HSCT represent a dynamic phenomenon influenced by many variables (that is, conditioning, immunosuppressive treatments, engraftment syndrome and infections), we showed that CEC peaks were constantly seen at onset of acute GvHD and invariably returned to pre-transplant values after treatment response. Since we showed that CEC changes during allo-HSCT has rapid kinetics that may be easily missed if blood samples are drawn at pre-fixed time-points, we rather suggest an 'on demand' evaluation of CEC counts right at onset of GvHD clinical symptoms to possibly help differentiate GvHD from other non-endothelial complications. We confirm that CEC changes are a suitable biomarker to monitor endothelial damage in patients undergoing allo-transplantation and hold the potential to become a useful tool to support GvHD diagnosis (ClinicalTrials.gov NCT02064972).

Clinical impact of immunophenotypic remission after allogeneic hematopoietic cell transplantation in multiple myeloma.

Immunophenotypic remission (IR) is a strong prognostic factor in myeloma patients. The combination of IR and conventional CR was retrospectively evaluated in 66 patients after allografting. IR was defined as the absence of monoclonal plasma cells in BM aspirates by multiparameter flow cytometry. Conditioning was non-myeloablative in 55 patients; reduced-intensity in 10 and myeloablative in 1 patient. The allograft was given upfront in 35/66 (53%) patients. After a median follow-up of 7.1 years, 24 patients achieved both CR and IR (CR/IR group), 21 achieved IR but not CR with persistence of a urine/serum M-component (no CR/IR group) and 21 did not achieve either CR or IR (no CR/no IR group). Median OS and EFS were 'not reached' and 59 months in the CR/IR group; 64 and 16 months in the no CR/IR; and 36 and 6 months in the no CR/no IR, respectively (P<0.001). Cumulative incidence of extramedullary disease was 4.4% in the CR/IR, 38.1% in the no CR/IR and 14.3% in the no CR/no IR groups, respectively, at 4 years (P<0.001). IR was a valid tool to monitor residual disease after allografting, and allowed definition of a cohort of patients at higher incidence of extramedullary relapse.

Trichoderma species fungemia after high-dose chemotherapy and autologous stem cell transplantation: a case report.

We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high-dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.

Behavioral and functional abnormalities linked with recurrent urinary tract infections in girls.

BACKGROUND: Most girls with recurrent urinary tract infections do not have major urinary tract abnormalities. Recent studies focus on predisposing behavioral and functional abnormalities: infrequent voiding, inadequate fluid intake, stool retention, poor genital hygiene and voiding dysfunction. METHODS: Complete history, bladder and bowel questionnaire, physical examination, voiding-drinking diary, sonography and uroflowmetry were used to assess infrequent voiding, functional stool retention, poor fluid intake, inadequate hygiene, or voiding dysfunction in girls referred for evaluation of three or more symptomatic urinary tract infections (with a first infection at the age of more than 36 months). RESULTS: A total of 141 girls aged 3.9 to 18 years were evaluated between 1996 and 1999; 212 abnormalities were noted in 120 patients: infrequent voiding (isolated, 16; combined with other abnormalities, 47), poor fluid intake (isolated, 10; combined, 50), functional stool retention (isolated, 5; combined, 25), inadequate hygiene or toilet habits (isolated, 3; combined, 24), dysfunctional voiding (isolated, 15; combined, 10), bladder overactivity (isolated, 5; combined, 2). CONCLUSIONS: Most girls referred for evaluation of three or more urinary tract infections have host-mediated predisposing abnormalities: infrequent voiding, poor fluid intake, functional stool retention or voiding dysfunction. Poor genital hygiene and toilet habits were almost always combined with other abnormalities, suggesting that infections are not necessarily related to poor genital hygiene or toilet habits. Two or more indications of predisposing behavior often concur in the same patient.

Long-term calcineurin inhibition and magnesium balance after renal transplantation.

Regulation of magnesium balance is achieved by a steady-state mechanism in which intake and output are maintained at an equal level. Dietary magnesium intake, total and ionized plasma magnesium levels, and urinary magnesium were assessed in 46 renal transplant recipients treated with cyclosporine, nine transplant recipients who had never been on cyclosporine, and 31 healthy volunteers. Dietary magnesium intake [13.5 (11.0-15.1) mmol/day vs 13.0 (11.1-16.0) mmol/day and 13.7 (11.4-16.7) mmol/day, respectively; median and interquartile range] and urinary magnesium excretion [4.31 (3.57-5.89) vs 4.39 (3.56-6.02) and 5.01 (3.73-6.01) mmol/day, respectively] were similar in renal transplant recipients treated with cyclosporine, transplant recipients who had never been on cyclosporine, and control subjects. Total [0.74 (0.70-0.78) vs 0.80 (0.74-0.84) and 0.81 (0.79-0.87) mmol/l), respectively] and ionized [0.49 (0.46-0.52) vs 0.53 (0.50-0.58) and 0.54 (0.52-0.59) mmol/l, respectively] plasma magnesium were significantly lower in renal transplant recipients on cyclosporine than in transplant recipients without cyclosporine, and healthy controls. These observations indicate a modified magnesium steady state in renal transplant recipients treated with cyclosporine.

The antenatal diagnosis of hyperplacentosis, hydramnios and fetal ascites.

The diagnostic value of volumetric analysis of the products of conception by compound ultrasonic scanning is illustrated by a case of hyperplacentosis, hydramnios, and fetal ascites. The use of this method in the diagnosis of fetal conditions is discussed.