Israel Medical Association Journal

Abstract

Background: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.

Objective: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.

Methods: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006–June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.

Results: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.

Conclusions: HHV6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Background: The number of patients awaiting organ transplantation continues to exceed the number of available organs. 

Objectives: To document changes in the demographic characteristics of brain-dead, heart-beating organ donors over the past 10 years which may impact on organ utilization. 

Methods: Data were extracted from the Israel Transplant Registry and the Donor Action database for the 10 year period 2004–2013, inclusive. 

Results: The median age of the donors increased from 44 (range 3–73 years) to 53.5 years (range 1–79 years) (P < 0.001). There was a significant increase in the median age of donors of kidney (33 to 51 years, P < 0.001), liver (41 to 53 years, P < 0.001) and lung (40 to 49.5 years, P < 0.001). The number of donors dying from trauma decreased (34.5% to 20%, P < 0.001), while those with anoxic brain damage increased (14.5% to 25%, P < 0.001). The percent of male donors decreased over the study period, from 63% to 53%. An increase was noted in the mean number of organs transplanted per donor, from 3.29 to 3.82 per donor, due mainly to a significant increase in the utilization of lungs (31.5% to 51.3%, P < 0.001) and livers (76.3% to 82.4%, P < 0.001) while heart utilization decreased significantly since 2006 (40.9% to 17.5%, P < 0.001). 

Conclusion: Trends in the heart-beating, brain-dead organ donor pool in Israel over the past 10 years reveal significant changes in demographic characteristics which in the future will impact on the number of organs available for transplantation. 

 

Objective: To assess the ability of TREC and KREC counts to identify patients with combined T and B cell immunodeficiency in a pilot study in Israel.

Methods: We studied seven children born in Israel during the years 2010–2011 and later diagnosed with SCID, and an additional patient with pure B cell immunodeficiency. TREC and KREC in peripheral blood upon diagnosis and in their neonatal Guthrie cards were analyzed using real-time quantitative polymerase chain reaction, as were Guthrie cards with dried blood spots from healthy newborns and from normal and SCID-like controls.

Results: The first features suggestive of SCID presented at age 3.1 ± 2.4 months in all patients. Yet, the diagnosis was made 4.1 ± 2.9 months later. Their TREC were undetectable or significantly low at their clinical diagnosis and in their originally stored Guthrie cards, irrespective of the amount of their circulating T cells. KREC were undetectable in six SCID patients who displayed B cell lymphopenia in addition to T cell lymphopenia. KREC were also undetectable in one patient with pure B cell immunodeficiency.

Conclusions: TREC and KREC quantification are useful screening tests for severe T and B cell immunodeficiency. Implementation of these tests is highly important especially in countries such as Israel where a high frequency of consanguinity is known to exist. 

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

Background: Appropriate antibiotic use is of both clinical and economic significance to any health system and should be given adequate attention. Prior to this study, no in-depth information was available on antibiotic use patterns in the emergency department of Hadassah Medical Center.

Objectives: To describe the use and misuse of antibiotics and their associated costs in the emergency department of Hadassah Medical Center.

Methods: We analyzed the charts of 657 discharged patients and 45 admitted patients who received antibiotics in Hadassah Medical Center’s emergency department during a 6 week period (29 April – 11 June 2007). A prescription was considered appropriate or inappropriate if the choice of antibiotic, dose and duration by the prescribing physician after diagnosis was considered suitable or wrong by the infectious diseases consultant evaluating the prescriptions according to Kunin’s criteria.

Results: The overall prescribing rate of antibiotics was 14.5% (702/4830) of which 42% were broad- spectrum antibiotics. The evaluated antibiotic prescriptions numbered 1105 (96 prescriptions containing 2 antibiotics, 2 prescriptions containing 3 antibiotics), and 54% of them were considered appropriate. The total inappropriate cost was 3583 NIS[1] (1109 USD PPP[2]) out of the total antibiotic costs of 27,300 NIS (8452 USD PPP). The annual total antibiotic cost was 237,510 NIS (73,532 USD PPP) and the annual total inappropriate cost was 31,172 NIS (9648 USD PPP). The mean costs of inappropriate prescriptions were highest for respiratory (112 NIS, 35 USD PPP) and urinary tract infection (93 NIS, 29 USD PPP). There were more cases when the optimal cost was lower than the actual cost (N=171) than when optimal cost was higher than the actual cost (N=9). In the first case, the total inappropriate costs were 3805 NIS (1,178 USD PPP), and in the second case, -222 NIS (68.7 USD PPP).

Conclusions: The use of antibiotics in emergency departments should be monitored, especially in severely ill patients who require broad-spectrum antibiotics and for antibiotics otherwise restricted in the hospital wards. Our findings indicate that 12% of the total antibiotic costs could have been avoided if all prescriptions were optimal.

Background: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT[1] in Israel is not known.

Objective: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection.

Methods: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR[2]. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records.

Results: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03).

Conclusions: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT. 

Background: There is currently no standard salvage chemotherapy for the 40–50% of patients with non-Hodgkin’s lymphoma who fail first-line treatment.

Objectives: To review the experience of a major tertiary medical center with DVIP (dexamethasone, etoposide, ifosfamide and cisplatin) salvage therapy for primary refractory/relapsing NHL[1].

Methods: We reviewed the records of all patients with NHL who received DVIP salvage therapy during the period 1993 to 2005.

Results: We identified 37 adult patients (mean age 56.3 years): 29 with aggressive lymphoma and 8 with indolent lymphoma. Mean event-free survival was 13.5 months (range 0–82 months), mean time between diagnosis and DVIP treatment 18.5 months (range 2–101), and mean number of DVIP cycles 1.9. Four patients (11%) achieved a complete response and 9 (24%) a partial response (overall response 35%). Consolidation with stem cell transplantation was used in 14 patients with aggressive lymphoma and 4 with indolent lymphoma; 14 patients, all with aggressive lymphoma, responded (12 complete, 2 partial). Of the 10 patients who underwent SCT[2] despite no response to salvage DVIP, 6 achieved a complete response. Five year overall survival from diagnosis for the whole sample was 39.4 ± 8.7%, and 5 year post-DVIP overall survival 37.6 ± 8.0%. On multivariate analysis, SCT was the strongest predictor of survival (relative risk 0.73, P < 0.0001) followed by a high score on the International Prognostic Index (RR[3] 3.71, P = 0.032).

Conclusions: DVIP salvage therapy for NHL was associated with a low response rate of 35% but a 5 year post-DVIP survival rate of 37.6%. Patients who are refractory to salvage treatment with DVIP might still be salvaged with SCT.