Natalia Maximova

Neutrophils Engraftment Delay During Tigecycline Treatment in 2 Bone Marrow-transplanted Patients

Background: Tigecycline is the first available drug of glycylcycline family. Because of recent introduction, some of its adverse effects could be still unexplored. Observation: We report the cases of 2 boys who underwent an allogenic bone marrow transplantation for acute myeloid leukemia and were treated with tigecycline. Erythrocyte and platelet engraftment followed a normal course, but the neutrophil count remained low despite the increase in leukocyte count. After tigecycline interruption, the neutrophil count rapidly raised in both cases. Conclusions: Neutropenia was suspected to be secondary to tigecycline exposure. In vitro experiments were performed, which suggested tigecycline influence on myeloid cells survival.

Glutamine-Enriched Nutrition Does Not Reduce Mucosal Morbidity or Complications After Stem-Cell Transplantation for Childhood Malignancies: A Prospective Randomized Study

Background. Intravenous glutamine-enriched solution seems to be effective in posttransplant period in decreasing the severity and duration of mucositis. The aim of this randomized study was to determine the benefit of glutamine supplementation both on mucosal morbidity and in posttransplant associated complications. Methods. Children undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) for malignant hematological diseases were randomly assigned to standard total parenteral nutrition (S-TPN) or glutamine-enriched (GE)-TPN solution consisting of 0.4 g/kg/day of l-alanine-glutamine dipeptide. This treatment started on the day of HSCT and ended when the patients could orally cover more than 50% of their daily energy requirements. The severity and the rate of post-HSCT mucositis were based on World Health Organization criteria. All the analyses were conducted on intention-to-treat principle. Results. One hundred twenty consecutive patients (83 men; median age, 8.1 years) were enrolled. The mean duration of treatment was 23.5 and 23 days in the two treatment arms. The mean calorie intake was 1538 kcal/d in the S-TPN group and 1512 kcal/d in GE-TPN group. All patients were well nourished before and after HSCT. Mucositis occurred in 91.4% and 91.7% of patients in S-TPN and GE-TPN arm, respectively (P=0.98). Odds ratio adjusted by type of HSCT was 0.98 (95% confidence interval, 0.26–2.63). Type and duration of analgesic treatment, clinical outcome (engraftment, graft versus host disease, early morbidity, and mortality, relapse rate up to 180 days post-HSCT) were not significantly different in the two treatment arms. Conclusion. GE-TPN solution does not affect mucositis and outcome in well-nourished HSCT allogeneic patients.

First description of Merkel Cell polyomavirus DNA detection in a patient with Stevens-Johnson syndrome.

Merkel Cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukaemia while other associations are still being explored. MCPyV sequences have also been detected in normal tissues of tumor patients and in the blood of healthy donors. This report documents a new MCPyV association with the Stevens–Johnson syndrome, a rare immune‐modulated mucocutaneous process particularly associated with specific drugs and infective agents. A high MCPyV viral load was detected simultaneously in fluid from skin lesions (2.0 × 104 copies/ml) and in matched blood (7.4 × 105 copies/ml) from a young adult patient after bone marrow transplant for a relapsed T‐cell acute lymphatic leukaemia. MCPyV clearance concurred with the complete resolution of skin lesions after 5 days of cidofovir treatment. DNA sequencing classified the amplicons as the European/Italian MKL‐1 strain. Given its ubiquitous nature, MCPyV could account for part of Stevens–Johnson syndrome idiopathic cases. J. Med. Virol. 85:918–923, 2013.

Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients

Invasive fungal infection (IFI) is a cause of morbidity, mortality and increased health costs in children undergoing chemotherapy or hematopoietic stem cell transplant (HSCT).

Polyclonal gammopathy after BKV infection in HSCT recipient: a novel trigger for plasma cells replication?

BackgroundBK polyomavirus infects most of the general population. However, its clinical manifestations are almost exclusively seen in immunocompromised patients, particularly in kidney and hematopoietic stem cell transplantation recipients.Case presentationA 15-y-old female suffering from common B-cell acute lymphoblastic leukaemia underwent hematopoietic stem cell transplantation. The patient had reactivation of BKPyV infection and developed an haemorrhagic cystitis. Three months after transplant, BKPyV viremia and viruria increased and she developed a severe nephropathy associated to a polyclonal gammopathy with high levels of isolated IgM.ConclusionThis case report describes a rare and unexpected polyclonal gammopathy developed during a polyomavirus-associated nephropathy confirmed by immunohistochemical and laboratory analyses.

Does Teno Torque Virus Induce Autoimmunity After Hematopoietic Stem Cell Transplantation? A Case Report.

Teno Torque virus, member of the family of Anelloviridae, has been associated with many autoimmune diseases such as idiopathic hepatitis, systemic lupus erythematosus, and multiple sclerosis. Its viral load tends to be higher in the bone marrow and in tissues with high turnover rate. We report here a case of an 11-month-old infant affected by acute myeloid leukemia who underwent hematopoietic stem cell transplantation, and after 6 months had autoimmune hepatitis and atopic dermatitis. Extremely high-cytokine IP-10 and eotaxin levels were found in her sera, and serological tests and RT-PCR for viruses showed positive results exclusively for Teno Torque virus.

Metal accumulation in the renal cortex of a pediatric patient with sickle cell disease: a case report and review of the literature.

Background: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascular injury due to vasoocclusion and hemolysis, as well as infectious complications and iron overload, all of which contribute to high morbidity and mortality rates among children. In these patients, some authors have previously described iron cortical deposition in the kidney. We here report the first case in the literature of a girl affected by SCD showing an anomalous metal and rare element retention in the renal cortex. Case Presentation: A 10-year-old white girl affected by SCD underwent a routine magnetic resonance imaging investigation that evidenced a reduced signal intensity in the renal cortex, compatible with hemosiderin precipitation. Histologic and elemental analyses of the hepatic and the renal biotic samples, performed with inductively coupled plasma mass spectrometry, revealed that concomitant with the high iron deposition, toxic and potentially carcinogenic elements such as nickel, magnesium, rubidium, and gadolinuim were anomalously retained particularly in the kidney. Conclusions: The finding of rare and toxic elements in the kidney of SCD patients might be linked to the development of specific neoplastic transformations already described in this patient cohort. To be confirmed, our speculations need to be demonstrated in large sampling of patients.

Combination of intranasal dexmedetomidine and oral midazolam as sedation for pediatric MRI

passage of the ETT, the length of the bougie should be long enough to accommodate the full length of the ETT as well as extend beyond the proximal end of the tube, so that an assistant can hold it firmly while threading the ETT. In children, one of the commonly used introducer is Cook’s 8 French Frova introducer with a length of 35 cm. It is recommended for ETTs with an internal diameter of 3.5 to 5 mm. The length of a pediatric Frova is adequate when used with endotracheal tubes of internal diameter up to 4.5 mm ID but its length falls short with larger tubes. The average length of 5 mm ID ETT from various manufacturers varies from 24 to 25 cm with the exclusion of the universal circuit adaptor, which makes it impossible to hold the proximal end of introducer once the ETT is railroaded over it (Figure 1). This necessitates discontinuing the current attempt of intubation. As the intubation attempts increase, the risk of airway trauma and desaturation also increases. To ensure smooth railroading of the ETT, the pediatric airway introducer should be at least twice the length of the ETT. Otherwise one simple solution to avoid these problems would be to use a preshortened tube cut to the length appropriate for the age and height of the child. The shortened ETT provides an additional benefit of reducing the airway resistance. Another option is to preload the regular length ETT on the introducer with its bent tip extending just beyond the bevel of ETT. The manufacturer recommends preloading of the ETT over Frova while using as an intubation aid. This technique provides ample length of the introducer beyond the proximal end of the tube but if tube exchange is needed due to improper size, the same problem of inadequate length will crop up; therefore, a shortened tube should be kept standby. This simple step of shortening the ETT while using pediatric Frova introducer can avoid unwanted stress while managing a difficult airway in children and smoothen the process of intubation.

Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation

Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V‐GCV), a valine ester pro‐drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella‐like illness. First‐line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V‐GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox‐like illness treated successfully with V‐GCV.

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.