Rituximab for the treatment of refractory autoimmune hemolytic anemia in children

Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment. Fifteen children with AIHA were given rituximab, 375 mg/m(2)/dose for a median of 3 weekly doses. All patients had previously received 2 or more courses of immunosuppressive therapy; 2 patients had undergone splenectomy. After completing treatment, all children received intravenous immunoglobulin for 6 months. Treatment was well tolerated. With a median follow-up of 13 months, 13 patients (87%) responded, whereas 2 patients did not show any improvement. Median hemoglobin levels increased from 7.7 g/dL to a 2-month posttreatment level of 11.8 g/dL (P <.001). Median absolute reticulocyte counts decreased from 236 to 109 x 10(9)/L (P <.01). An increase in platelet count was observed in patients with concomitant thrombocytopenia (Evans syndrome). Three responder patients had relapse, 7, 8, and 10 months after rituximab infusion, respectively. All 3 children received a second course of rituximab, again achieving disease remission. Our data indicate that rituximab is both safe and effective in reducing or even abolishing hemolysis in children with AIHA and that a sustained response can be achieved in the majority of cases. Disease may recur, but a second treatment course may be successful in controlling the disease.     

Giant Spermatic Cord Liposarcoma

We report a case of giant spermatic cord liposarcoma (SCL) in an 81-year-old patient, presenting with a huge scrotal mass that reached up to the knee joint. SCL is a rare tumor, and about 200 cases have been reported in the literature so far. Although 20% of liposarcomas arise in the retroperitoneum, only 0.1% present as incidental inguinal hernias. The occasional presence of myxoid stroma in well-differentiated liposarcomas can lead to confusion with myxoid sarcoma subtypes. Correct diagnosis is critical and reflects remarkable differences in behavior and therapeutic choices.Key words: Liposarcoma, Spermatic cord, Scrotal massSpermatic cord liposarcoma (SCL) is a very rare tumor, and about 200 cases have been described in the literature up to date. Clinically, these tumors can sometimes mimic the common scrotal masses such as hernias, testicular cancer, and hydrocele. Their histologic heterogeneity reflects remarkable differences in both prognosis and treatment. We report a case of SCL in an 81-year-old patient presenting with a huge scrotal mass.     

Exploiting pre‐rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single‐copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre‐rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre‐rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre‐60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. Am. J. Hematol. 89:985–991, 2014. © 2014 Wiley Periodicals, Inc.     

Left-Atrial-Appendage Occluder Migrates in an Asymptomatic Patient

Percutaneous closure of the left atrial appendage (LAA) is a new approach to the prevention of cardioembolic events in patients with atrial fibrillation. We implanted an LAA occlusion device (Amplatzer™ Cardiac Plug) in a 70-year-old woman via a transseptal approach. Upon her discharge from the hospital, a transthoracic echocardiogram showed stable anchoring of the device; 6 months after implantation, a routine transthoracic echocardiogram revealed migration of the occluder into the left ventricular outflow tract, in the absence of symptoms. We surgically removed the device from the mitral subvalvular apparatus and closed the LAA with sutures. This case shows that percutaneous LAA occlusion can result in serious adverse events, including device migration in the absence of signs or symptoms; therefore, careful follow-up monitoring is mandatory.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Long-term safety of anti-TNF-α in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.     

Perioperative outcomes of laparoscopic and robot-assisted major hepatectomies: an Italian multi-institutional comparative study

Background

Laparoscopic major hepatectomy (LMH), although safely feasible in experienced hands and in selected patients, is a formidable challenge because of the technical demands of controlling hemorrhage, sealing bile ducts, avoiding gas embolism, and maintaining oncologic surgical principles. The enhanced surgical dexterity offered by robotic assistance could improve feasibility and/or safety of minimally invasive major hepatectomy. The aim of this study was to compare perioperative outcomes of LMH and robotic-assisted major hepatectomy (RMH).

Methods

Pooled data from four Italian hepatobiliary centers were analyzed retrospectively. Demographic data, operative, and postoperative outcomes were collected from prospectively maintained databases and compared.

Results

Between January 2009 and December 2012, 25 patients underwent LMH and 25 RMH. The two groups were comparable for all baseline characteristics including type of resection and underlying pathology. Conversion to open surgery was required in one patient in each group (4 %). No difference was noted in operative time, estimated blood, and need for allogenic blood transfusions. Intermittent pedicle occlusion was required only in LMH (32 % vs. 0; p = 0.004). Length of hospital stay, including time spent in intensive care unit, was similar between the two groups, but patients undergoing LMH showed quicker recovery of bowel activity, with shorter time to first flatus (1 vs. 3 days; p = 0.023) and earlier tolerance to oral liquid diet (1 vs. 2 days; p = 0.001). No difference was noted in complication rate, 90-day mortality, and readmission rate.

Conclusions

This retrospective multi-institution study confirms that selected patients can safely undergo minimally invasive major hepatectomy, either LMH or RMH. The fact that intermittent pedicle occlusion could be avoided in RMH suggests improved surgical ability to deal with bleeding during liver transection, but further studies are needed before any final conclusion can be drawn.     

Association between nocturnal blood pressure dipping and insulin resistance in children affected by NAFLD

The aim of this study was to analyse the relationship between insulin–glucose metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease (NAFLD) in obese adolescents without diabetes. One hundred one consecutive children, with biopsy-proven NAFLD, were included in this study. Blood samples were drawn for the analyses of liver function tests, insulin–glucose metabolism and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them were diastolic nondippers (30.3 %). No differences were found in the anthropometric parameters between the two groups. When compared to the systolic dippers, the systolic nondippers had higher medians of mean nocturnal blood pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT), OGTT insulin at all time points and insulin-resistance values. No correlation of histopathological features with dipping/nondipping statuses was found. Conclusions: We found an association between a nocturnal blood pressure fall and measures of insulin levels, independent of obesity, or daytime blood pressure levels, among the obese patients with NAFLD. Although no association between nondipping profiles and NAFLD was observed in our study, further studies with a longer term follow-up are needed, to better elucidate the complex link between these particular entities.