Pediatric males receiving hematopoietic stem cell transplant lose their male disadvantage in disease risk after the procedure: A retrospective observational study.

Sex differences play a relevant role in cancer susceptibility, incidence and survival. Exploring such differences is difficult because of the close interplay of genetic, epigenetic and hormonal factors. However, a better understanding of the role of such disparities in cancer mechanisms could improve its prevention and therapy. Our study explores how sex differences in pediatric outcomes vary after undergoing first and advanced-line therapy for hematological malignancies. The primary goal was to evaluate if sex differences in pediatric outcomes after first-line therapy persist after allogeneic hematopoietic stem cell transplantation (HSCT). The secondary goal was to analyze sex differences in disease risk at onset and pediatric outcomes after first-line therapy to compare our results with the literature's reported results. Among a total of 485 patients (280 males, 205 females) admitted for hematological malignancies, disease risk at the onset was significantly higher in males (P < .05). One hundred and seventy-four patients (111 males and 63 females) had a high-risk disease requiring HSCT. Before HSCT, all patients underwent myeloablative conditioning, which substantially impaired gonadal function. Although the number of boys undergoing HSCT was almost double that of girls, there were no sex-related differences in overall survival, cancer relapse and complications after HSCT exposure (P > .05). These findings suggest that the existing sex differences in cancer risk ab initio can be somehow flattened by a conditioning regimen, shedding new light on the role of hormonal factors in cancer mechanism and management.

Thrombogenesis in Thrombophilic Pregnancy: Evaluation of Low-Molecular-Weight Heparin Prophylaxis.

The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women.

Hepatic Gadolinium Deposition and Reversibility after Contrast Agent-enhanced MR Imaging of Pediatric Hematopoietic Stem Cell Transplant Recipients.

Purpose To determine if hepatic gadolinium deposition occurs in pediatric patients with iron overload but normal renal and hepatic function who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. Materials and Methods Design and execution of this study was approved by the Ethical Committee of Institute for Research in Maternal and Child Health Burlo Garofolo of Trieste (reference no. 1105/2015). Because of the retrospective nature of the study, the requirement to obtain informed consent was waived. Twenty-one recipients of allogeneic hematopoietic stem cell transplants who underwent GBCA-enhanced MR imaging for suspected infection or relapse followed by liver biopsy comprised the study group. The number of GBCA-enhanced MR examinations and cumulative gadolinium dose for each patient was analyzed by comparing liver histologic analysis and iron and gadolinium liver concentration (GLC). Eight patients had siderosis and underwent chelation therapy. The study group was compared with four control patients who were never exposed to GBCA. Statistical analysis was performed with Spearman rank coefficient for correlation. Results All 21 patients had positive correlations between GLC and total GBCA dose (r = 0.4486; P < .05) and between GLC and liver iron concentration (r = 0.56; P < .05). Patients who underwent deferoxamine therapy had a significant reduction of GLC (from 0.64 µg/g ± 0.29 to 0.20 µg/g ± 0.17 [standard deviation]; P < .05). Conclusion In the presence of siderosis, a transmetallation mechanism may be set off between ferric ion and gadoterate meglumine. Deferoxamine appears capable of binding to gadolinium ion. Further studies of the safety of GBCAs in severe siderosis are needed. Chelation should be considered in patients with iron overload and a history of GBCA exposure. © RSNA, 2016.

Pre-Transplant Total Lymphocyte Count Determines Anti-Thymocyte Globulin Exposure, Modifying Graft-versus-Host Disease Incidence and Post-Transplant Thymic Restoration: A Single-Center Retrospective Study.

The use of anti-thymocyte globulin (ATG) as part of conditioning to prevent graft-versus-host disease (GVHD) may severely impair immune reconstitution (IR). We analyzed relationships between ATG exposure, the recipient lymphocyte count, IR, and transplant outcome. We retrospectively reviewed patients aged ≤ 18 years who underwent allogeneic HSCT between April 2005 and April 2020. The outcomes of interest included the incidence of GVHD, overall survival (OS), and IR. IR was analyzed through thymic magnetic resonance imaging (MRI) and by quantifying T CD4+ and recent thymic emigrants (RTEs). The ATG-exposed group was split into a low ATG/lymphocyte ratio subgroup (ratio < 0.01) and a high ATG/lymphocyte ratio subgroup (ratio > 0.01). The low ratio subgroup had a higher incidence of GVHD (29 [59%] vs. 7 [16.6%]) but a better IR in both laboratory and MRI imaging assessments (p < 0.0001). The median thymic volume in the low ratio subgroup was significantly higher (14.7 cm3 vs. 4.5 cm3, p < 0.001). This was associated with a better OS and lower transplant-related mortality (TRM) (80.4% vs. 58.0%, p = 0.031) and (13.1% vs. 33.0%, p = 0.035). An individualized approach to ATG dosing allows for the obtainment of rapid thymic reconstitution and the best transplant-related outcomes.

Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients.

Background: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous (IV) acyclovir in oncologic children. Methods: Patients (age, 8.6 ± 5.0 years, 73 males and 47 females) received IV acyclovir for prophylaxis (n = 94) and therapy (n = 26) under a therapeutic drug monitoring (i.e., minimum and maximal plasma concentrations, >0.5 and <25 mg/L, respectively). Plasma concentrations were fitted by nonlinear mixed effect modeling and a simulation of dosing regimens was performed. Findings were stratified according to an estimated glomerular filtration rate (eGFR) threshold of 250 ml/min/1.73 m2. Results: The final 1-compartment POP/PK model showed that eGFR had a significant effect on drug clearance, while allometric body weight influenced both clearance and volume of distribution. The population clearance (14.0 ± 5.5 L/h) was consistent across occasions. Simulation of standard 1-h IV infusion showed that a 10-mg/kg dose every 6 h achieved target concentrations in children with normal eGFR (i.e., ≤250 ml/min/1.73 m2). Increased eGFR values required higher doses that led to an augmented risk of toxic peak concentrations. On the contrary, simulated prolonged (i.e., 2 and 3-h) or continuous IV infusions at lower doses increased the probability of target attainment while reducing the risk of toxicities. Conclusion: Due to the variable pharmacokinetics of acyclovir, standard dosing regimens may not be effective in some patients. Prospective trials should confirm the therapeutic advantage of prolonged and continuous IV infusions.

SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet procoagulant activity.

Thrombosis of the lung microvasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis that is endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting Spike-induced TMEM16 activation. As TMEM16F plays an important role in stimulating the procoagulant activity of platelets, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Here we show that Spike, present either on the virion envelope or on the cell plasma membrane, promotes platelet activation, adhesion and spreading. Spike was active as a sole agonist or, even more effectively, by enhancing the function of known platelet activators. In particular, Spike-induced a marked procoagulant phenotype in platelets, by enhancing Ca2+ flux, phosphatidylserine externalization on the platelet outer cell membrane, and thrombin generation. Eventually, this increased thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine blocked this Spike-induced procoagulant response. These findings provide a pathogenic mechanism to explain lung thrombosis-associated with severe COVID-19 infection. We propose that Spike, present in SARS-CoV-2 virions or exposed on the surface of infected cells in the lungs, enhances the effects of inflammation and leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing Niclosamide for COVID-19 therapy.

Levofloxacin Versus Ciprofloxacin-Based Prophylaxis during the Pre-Engraftment Phase in Allogeneic Hematopoietic Stem Cell Transplant Pediatric Recipients: A Single-Center Retrospective Matched Analysis.

Infectious complications are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Antibacterial prophylaxis in pediatric cancer patients is a controversial issue. Our study compared the outcomes of levofloxacin versus ciprofloxacin prophylaxis in allogeneic HSCT pediatric recipients treated for hematological malignancies. A total of 120 patients received levofloxacin prophylaxis, and 60 patients received ciprofloxacin prophylaxis. Baseline characteristics such as age, gender, primary diagnosis, type of conditioning, donor type, stem cell source, and supportive care of the patients were similar, and duration of antibiotics prophylaxis was similar. Both prophylaxis regimens demonstrated the same efficacy on the risk of febrile neutropenia and severe complications such as sepsis, the same rate of overall mortality, hospital readmission, and length of hospital stay. Levofloxacin prophylaxis was associated with significantly lower cumulative antibiotic exposure. The median of Gram-positive infection-related antibiotic days was 10 days in the levofloxacin group versus 25 days in the ciprofloxacin group (p < 0.0001). The median of Gram-negative infection-related antibiotics was 10 days in the levofloxacin group compared with 20 days in the ciprofloxacin group (p < 0.0001). The number of days with body temperature ≥38 °C was significantly less in the levofloxacin group (p < 0.001).

Area-under-the-Curve-Based Mycophenolate Mofetil Dosage May Contribute to Decrease the Incidence of Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients.

Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease relapse, in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The medical records of 112 pediatric patients who underwent allo-HSCT from matched unrelated and haploidentical donors were analyzed. Patients were divided into two groups, according to the GvHD prophylactic regimen used. In the control group, GvHD prophylaxis consisted of cyclosporine A (CsA) and methotrexate (MTX) or CsA and mycophenolate mofetil (MMF) at a standard daily dose of 30 mg/kg. All subjects in the study group received tacrolimus (FK506) and MMF. In this group, MMF was subjected to therapeutic drug monitoring (TDM) through mycophenolic acid (MPA) area under the curve AUC0-12. We found a statistically significant difference in both overall acute GvHD (p < 0.0001) and overall chronic GvHD (p < 0.05) incidence between the study and the control group. The initial daily MMF dose and the age at transplant in the study group proved to be inversely correlated (r = -0.523, p < 0.0001). The children under six years of age required a significantly higher daily MMF dose (p < 0.008). This study showed that pharmacological monitoring of MPA AUC0-12 concentration allowed a reduction in the incidence of acute and chronic GvHD. MMF showed age-dependent pharmacokinetics due to greater drug clearance in younger children.

Post-Irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: A Retrospective Single-Centre Cohort Analysis.

BACKGROUND: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. METHODS: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient's age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. RESULTS: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66-0.86; p < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77-0.93; p < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-α, IL-6, and RANTES (p < 0.001). CONCLUSIONS: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.

Leukocytospermia and sperm preparation--a flow cytometric study.

BACKGROUND: Leukocytes represent the predominant source of reactive oxygen species both in seminal plasma and in sperm suspensions and have been demonstrated to negatively influence sperm function and fertilization rate in assisted reproduction procedures. Peroxidase test is the standard method recommended by WHO to detect semen leukocytes but it may be inaccurate. The aims of this study were (i) to compare the efficiency of swim-up and density-gradient centrifugation techniques in removing seminal leukocytes, (ii) to examine the effect of leukocytes on sperm preparation, and (iii) to compare flow cytometry and peroxidase test in determining leukocyte concentration in semen using a multiparameter flow cytometric method. METHODS: Semen samples from 126 male partners of couples undergoing infertility investigations were analyzed for leukocytospermia using standard optical microscopy and flow cytometry. Sixty-nine out of 126 samples were also processed using simultaneously the swim-up and density-gradient centrifugation techniques. A multiparameter flow cytometric analysis to assess simultaneously sperm concentration, sperm viability, sperm apoptosis, and leukocyte concentration was carried out on neat and prepared sperm. RESULTS: Both sperm preparation methods removed most seminal leukocytes. However, the concentration of leukocytes was significantly lower after swim-up compared to that after density-gradient centrifugation preparation. Leukocytes concentration, either initial or in prepared fractions, was not correlated with sperm parameters (optical microscopy and flow cytometry parameters) after semen processing. There was no correlation between leukocyte concentration in the ejaculate and sperm recovery rate, whereas a significant correlation was found between the concentration of the residual leukocytes in prepared fractions and viable sperm recovery rate. Although the overall concordance between the flow cytometry and the optical microscopy was satisfactory, the sensitivity of peroxidase test for the detection of leukocytospermia resulted low. CONCLUSION: Seminal leukocytes do not seem to influence sperm preparation results. However, for assisted conception, semen samples containing leukocytes should be processed using swim-up method. Although peroxidase-test is recommended by WHO as the standard method for determining semen leukocytes, it should not be used in clinical research study.

Drop of Butyrylcholinesterase Activity after Cyclophosphamide Conditioning as a Predictive Marker of Liver Transplant-Related Complications and Its Correlation with Transplant-Related Mortality in Pediatric Hematopoietic Stem Cell Recipients.

Transplant-related liver complications are a potentially fatal condition of hematopoietic stem cell transplantation (HSCT) in pediatric patients, actually representing one of the main factors involved in transplant-related mortality (TRM). The search for a specific marker capable of predicting the development of this condition is a relevant clinical issue. We have observed a variable reduction in serum butyrylcholinesterase (BChE) activity after a cyclophosphamide-containing conditioning regimen. This study aims to determine the cutoff of BChE activity reduction that might be a specific prognostic marker for liver complications after HSCT. Our results show that the reduction of BChE values below 2000 U/L the day before the transplantation is an indicator strongly associated with the transplant-related liver complications (p < 0.0001). The incidence of overall survival at 1 year was significantly higher in the BChE > 2000 U/L group compared to the BChE < 2000 U/L group (84.7% versus 58.5%, p < 0.001), while the TRM rate was significantly lower (8.1% versus 23.1%, p < 0.05). None of the patients undergoing prophylaxis with defibrotide developed severe liver complications. Starting defibrotide treatment at the first signs of hepatic dysfunction in patients with particularly low BChE activity levels reduces severe liver transplant-related complications.

Tapentadol: an analgesic that differs from classic opioids due to its noradrenergic mechanism of action.

Chronic pain treatment represents one of the most complex clinical challenges and even though opioids exhibit particular efficacy on nociceptive pain, their use must be controlled to avoid the risk of adverse reactions. A useful approach, aimed at maintaining analgesia and mitigating side effects, is represented by the use of a new class of analgesics endowed of µ-opioid (MOR) receptor agonism and noradrenaline reuptake inhibition (NRI) mechanisms. Tapentadol is the progenitor of this new class of drugs called MOP-NRI. A literature review has been conducted to gain information about the efficacy and the tolerability profile of tapentadol shifting from MOR agonism (acute pain) to NRI activity (chronic pain). The tolerability and therapeutic safety of tapentadol in neuropathic pain models, as well as in clinical settings, has been analyzed showing a good gastrointestinal tolerability profile, a moderate effect on hormone levels (in healthy volunteers and in patients) and on cognitive performance, a lack of significant alteration of the electrocardiogram recording and no changes of the QT/QTc interval, a minimal effect on serotonin reuptake in vivo with a low risk of serotonin syndrome, a longer time for the onset of analgesic tolerance and a less occurrence of abuse liability compared to formulations containing other comparator compounds. Tapentadol represents a great innovation in chronic pain therapy with a unique analgesic profile different form classical opioids, therefore, thanks to its synergistic MOR-NRI action, it may be a good option for the treatment of chronic, neuropathic and mixed pain.

Monocyte-predominant engraftment, cytokine levels and early transplant-related complications in pediatric hematopoietic stem cell recipients.

Myeloablative conditioning is a well-established procedure that precedes hematopoietic stem cell transplantation (HSCT), particularly in pediatric patients. In the period directly following transplantation, several factors may contribute to complications that lead to the activation or damage of endothelial cells, involved in the pathogenesis of vascular endothelial syndromes (VES). However, to date, sufficiently specific and sensitive diagnostic markers for the various forms of VES have not been identified. This was a retrospective single-center study of patients who underwent allogeneic HSCT. For this cohort of patients, parameters including type of engraftment, donor characteristics, and cytokine production were measured and correlated with a high prevalence of short-term complications after HSCT. The aim of this study was to identify specific parameters useful for improving diagnostics and predicting adverse effects in VES. We confirmed that monocyte-predominant engraftment was related to a higher risk for an early transplant-related complication termed sinusoidal obstruction syndrome (SOS). The increased production of specific cytokines, in particular RANTES, represents a marker associated with prevalent engraftment. In addition, patients undergoing prophylaxis with defibrotide had "classical" engraftment, a common cytokine profile and a lower incidence of life-threatening transplant-related complications. The beneficial effect of defibrotide might be a starting point for developing selective prophylaxis for patients with monocyte engraftment to prevent severe early transplant-related complications.

Meconium-stained amniotic fluid: a risk factor for postpartum hemorrhage.

BACKGROUND/AIM: Clinical data with respect to the impact of meconium on the risk of maternal hemorrhage are scarce. Therefore, in this study, we aimed to determine whether meconium-stained amniotic fluid (MSAF) represents a risk factor for postpartum hemorrhage (PPH) after vaginal delivery in a large unselected population. PATIENTS AND METHODS: A retrospective cohort study evaluated 78,542 consecutive women who had a vaginal delivery between 24th and 44th weeks of gestation. The women who had undergone cesarean section were excluded to avoid possible bias. Postpartum blood loss was measured with graduated blood sack. Postpartum blood loss between 1,000 and 2,000 mL and >2,000 mL were classified as moderate and severe PPH, respectively. RESULTS: A total of 74,144 patients were available for analysis. According to the color of amniotic fluid (AF), two groups of patients were identified: MSAF (n=10,997) and clear AF (n=63,147). The rates of severe and massive PPH were found to be significantly higher in the MSAF group than that of clear AF group (OR=1.3, 95% CI: 1.2-1.5, p<0.001 and OR=2.5, 95% CI: 1.5-4.2, p<0.001). Operative vaginal delivery rate was found to be higher in the MSAF group than that of clear AF group, but the difference was only borderline significant (OR=1.5, 95% CI: 1.0-2.2, p=0.05). There were no significant differences between the MSAF and the clear AF groups with respect to episiotomies, second- or third-degree perineal tears, vaginal-perineal thrombus, cervical lacerations, vaginal births after cesarean section, twin deliveries, and placental retention rates. CONCLUSION: To the best of our knowledge, this is the first clinical study that has investigated the role of MSAF as a risk factor for PPH after vaginal delivery in an unselected population. Our results suggest that MSAF is significantly associated with higher risk of moderate and severe PPH than clear AF.

Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation.

Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 µmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 µmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 µmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy. Based on our data, we suggest that TBI is detrimental for pancreatic functions, and speculate that DFO may contribute to the rapid pancreatic IO observed in these patients.

Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis.

INTRODUCTION: The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against Candida and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT. METHODS: This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3 months after transplantation. RESULTS: Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents. CONCLUSION: These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients: one facility's five years' experience of chelation treatment.

42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135.7 days in the DFX Ctrough < 10 mcg/mL group versus 41.8 days in the DFX Ctrough > 10 mcg/mL group (p<0.0001). The mean tissue iron concentration in the DFX Ctrough < 10 mcg/mL group was 261.9 µmol/g versus 133.4 µmol/g in the DFX Ctrough > 10 mcg/mL group (p < 0.0001). 21 patients (100%) in the DFX Ctrough > 10 mcg/mL group had ductopenia which was complete in 47.6% of them and severe in 52.4%. All patients with particularly high Ctrough (> 25 mcg/mL) were found to have total ductopenia. 90.5% of all deferasirox-related adverse events and 100% of major adverse events occurred in the DFX Ctrough > 10 mcg/mL group. In the DFX Ctrough < 10 mcg/mL group only one patient interrupted chelation therapy versus 16 (84.2%) patients in the DFX Ctrough > 10 mcg/mL group. We would recommend a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasirox-based therapy because we have observed a high incidence of adverse events and discontinuation of chelation treatment.

MRI-based evaluation of multiorgan iron overload is a predictor of adverse outcomes in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 µmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 µmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6.8), pancreatic insufficiency (OR = 17) and metabolic syndrome (OR = 15.1). No statistically significant differences in overall survival, disease-free survival, relapse incidence and incidence of acute or chronic graft-versus host disease were observed between the two groups. Mean times to engraftment of platelets (43.0 ± 35.3 days vs. 22.1 ± 9.5 days, p < 0.05) and neutrophils (23.1 ± 10.4 days vs. 17.8 ± 4.6 days, p < 0.05) appear significantly longer in Group 2 than in Group 1. Time to platelet engraftment showed statistically significant correlation with pre-transplant liver (r = 0.5775; p < 0.001) and bone iron concentration (r = 0.7305; p < 0.001). Post-transplant evaluation pointed out that iron concentration analyzed at the first follow-up peaked in all tissues. The iron accumulation was highest in bone, followed by the spleen, liver and pancreas. One year post transplant 9 of 18 (50%) patients in Group 1 and 6 of 22 (27%) in Group 2 presented with bone and/or spleen iron overload, but not with liver overload. Liver iron concentration is not always a reliable indicator of systemic siderosis or of the efficacy of chelation therapy.

Manual accidents, biological risk control, and quality indicators at a children's hospital in north-east Italy.

BACKGROUND: Working in health care carries the risk of transmission of infected blood to patients by hospital workers and to other health personnel in the form of occupational infections. Conscientious application of the standard precautions is the main method used to avoid needle stick injuries, contamination of skin and mucous membranes, cuts with sharp tools, and inadequate disposal and recapping of needles. The aim of this work was to investigate in Friuli Venezia Giulia, a region in north-east Italy, the enhancement carried out to prevent situations of biologic risk for health care workers, and to verify the related laboratory analyses. METHODS: Biological accidents occurring during the years 2012-2013 in the departments of oncology and pediatric-obstetric surgery, and in the intensive care unit at Burlo Garofolo Children's Hospital in Trieste (a large town in Friuli Venezia Giulia) were reviewed, and a new panel of tests was introduced for patients and health care workers, to also detect human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), and aspartate transaminase and immunoglobulin G. All tests were submitted for external quality assessment. RESULTS: In total, 230 nosocomial events were reported by health care workers in the above-mentioned hospital departments in 2012-2013. There were 158 accidents in 2012, including 55 accidental needle stick injuries (34.81%), 59 blood splashes (37.34%), and 44 cuts with infected instruments (27.84%). The risk of sustaining a cut was related to movement error during surgery when the appropriate procedure was not followed or when devices were being assembled and passed between doctors and nurses. Most accidents happened among physicians compared to nurses; the high percentage of needle stick injuries (34.81%) versus nurses (25.94%) were due to incorrect recapping of needles after use. No cases of health care workers being infected with HCV, HBV, or HIV were identified. In 2013, the number of biological accidents decreased to 61, comprising two needle stick injuries (3.27%), 35 blood splashes (57.37%), and 25 cuts with contaminated instruments (40.98%). The number of subcutaneous abscesses with scarring resulting from cuts with sharp instruments decreased from three in 2012 (one of which was the subject of medicolegal proceedings) to none in 2013. Although our study population was relatively small, we did detect a statistically significant decrease in the number of needle stick injuries (P<0.05, χ(2) test). CONCLUSION: In this early experience at a maternal and child health institution in the Friuli Venezia Giulia region, application of a safety protocol, centralized organization of HIV tests, improved external quality assessment, and introduction of internal quality control for immunoglobulin G contributed to a decrease in the number of work-related biological accidents and their complications, which have the potential to result in medicolegal problems.