Israel Medical Association Journal

Carbamoyl phosphate synthetase 1 (CPS1; MIM *608307; E.C. 6.3.4.16) is the first rate-limiting enzyme of the urea cycle, an essential metabolic pathway for ammonia detoxification. CPS1 deficiency (CPS1-D) is characterized by severe hyperammonemia during disease exacerbations. During a metabolic crisis, children with CPS1-D are admitted with vomiting, altered mental status, and high serum levels of ammonia. Rapid normalization of ammonia level ameliorates neurological outcome [1,2]. The first-line treatment for hyperammonemia in these patients is ammonia scavengers in combination with citrulline or arginine and high-calorie supplementation while controlling protein intake [1].

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs.

Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type.

Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration.

Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route.

Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: Temporary abdominal closure (TAC) surgical technique relates to a procedure in which the post-surgical abdominal wall remains open in certain indications. The Bogota bag (BB) technique is a tension-free TAC method that covers the abdominal contents with a sterilized fluid bag. There are very few reports of pediatric patients treated with this technique.

Objectives: To describe our institution’s 15 years of experience using the BB technique on pediatric patients.

Methods: A retrospective cohort study describing our experience treating patients with BB was conducted. The medical files of 17 pediatric patients aged 0–18 years were reviewed.

Results: Between January 2000 and December 2014, 17 patients were treated with BB at our medical center (6 females, median age 12 years). Indications for BB were a need for a surgical site re-exploration, mechanical inability for primary abdominal closure, and high risk for ACS development. Median BB duration was 5 days and median bag replacement was 2 days. Median ICU length of stay (LOS) was 10 days and hospital LOS was 27 days. The ICU admission and BB procedure was tolerated well by 6 patients who were discharged home without complications. Of the remaining 11 patients, 6 patients died during the admission (35%) and the others presented with major complications not related to the BB but to the patient's primary disease.

Conclusions: This report represents the largest series of children treated with BB. The technique is simple to perform, inexpensive, and has very few complications.

The identification and prompt diagnosis of Horner syndrome (HS) is essential for preventing permanent damage. HS may arise when a lesion presents anywhere along the three-neuron oculosympathetic pathway that begins at the posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We present four cases and review the literature to familiarize the reader with the identification, diagnosis and treatment of Horner syndrome. The four patients, three adults and one child, were followed for at least 6 months following the initial diagnosis (range 6–18 months). There was partial resolution in three of the four cases, while the fourth resolved completely. There are numerous causes of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both adults and children, HS is seen more often following surgical procedures. Prompt recognition of the syndrome and correction of the offending agent may prevent permanent damage to the neuronal pathway. It is therefore recommended that practitioners be aware of the risks for development of iatrogenic HS and the signs for early detection.

Background: Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service. 

Objectives: To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D. 

Methods: Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA). 

Results: Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group. 

Conclusions: Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers. 

 

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.

Background: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on both the pubertal development and the final outcome of growth and sexual maturation.

Objective: To investigate the natural pattern of growth and puberty in patients with Gaucher disease type 1 and the effect of splenectomy and enzyme replacement therapy.

Methods: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we considered severity of disease, time of splenectomy, and start of enzyme replacement therapy.

Results: Deceleration of growth at age 3–5 years was observed in 30 of 57 patients followed since early childhood while untreated: height-SDS decreased from -0.34±0.42 at age 0–3 years to -1.93±0.95 (P<0.01) at age 7–10 years and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observed in 47 patients followed before and throughout puberty. No primary endocrine pathology was found. All patients, untreated as well as treated, with growth and pubertal delay had a spontaneous catch-up, achieved full sexual maturation, and most (83.3%) reached a final height within the range of parental height–standard deviation score. Splenectomy (partial and/or total) performed in 20 patients while still growing had a beneficial effect on growth, which was temporary in some and did not affect puberty. ERT improved growth in 11 patients who started therapy before puberty, as evidenced by a progressive increase in the height-SDS, and seemed to normalize the onset of puberty.

Conclusions: Growth retardation in childhood and delay of puberty are characteristic of Gaucher disease type 1 and are more frequent with severe disease. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement therapy apparently normalizes growth and possibly also the onset of puberty.

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ERT = enzyme replacement therapy

SDS = standard deviation score