Israel Medical Association Journal

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immune deficiency of adulthood. Besides recurrent infections, autoimmune disorders–mainly cytopenias–affect 30% of patients with CVID.

Objectives: To describe the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIg), which is a combination of 10% [human] SCIg with recombinant human hyaluronidase for the treatment of CVID-linked cytopenias. 

Methods: We describe four women (mean age 54 years) with CVID associated with idiopathic thrombocytopenic purpura (ITP) (n=3) and autoimmune hemolytic anemia (AIHA) (n=1). Diagnosis of CVID was made according to the European Society of Immune Deficiencies / Pan-American Group for Immune Deficiency criteria. All were treated with fSCIg (bi-monthly, 20 g).

Results: After a median follow-up of 22 months, all patients achieved a stable remission from the cytopenias, characterized by increased platelet values in ITP (mean values 93000/mmc), and resolution of anemia. A reduction of the daily prednisone dose was documented in the patient with AIHA. No systemic adverse drug reactions were observed. 

Conclusions: Our preliminary data documented the efficacy and safety of fSCIg in the treatment of CVID associated with autoimmune cytopenias, with a good tolerability. We also noted the role of fSCIg as a steroid sparing agent. It is thus possible to suppose an immunomodulatory role for fSCIg, but linked to different mechanisms than IVIg, due to the peculiar pharmacokinetic and administration route of fSCIg. 

 

Background: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. 

Objectives: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients.

Methods: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only.

Results: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12).

Conclusions: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.

 

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: Accurate assessment of liver fibrosis is crucial for the management of patients with hepatitis C virus (HCV) infection.

Objectives: To evaluate the performance of liver segment-to-spleen volume ratio in predicting the severity of liver fibrosis.

Methods: Sixty-four consecutive HCV patients were enrolled in this retrospective study. All patients underwent contrast-enhanced computed tomography (CT) and were divided into three groups based on their hepatic fibrosis stage evaluated by shear-wave elastography (SWE): non-advanced (F0–F1, n=29), advanced (F2, n=19) and severe fibrosis (F3–F4, n=16). Using semi-automated liver segmentation software, we calculated the following liver segments and spleen volumes for each participant: total liver volume (TLV), caudate lobe (CV), left lateral segment (LLV), left medial segment (LMV), right lobe (RV) and spleen (SV), a well as their ratios: CV/SV, RV/SV, LLV/SV, LMV/SV and TLV/SV.

Results: RV/SV was found to discriminate between patients with non-advanced and advanced fibrosis (P = 0.001), whereas SV, CV, RV, TLV/SV, LMV/SV and RV/SV discriminated between patients with advanced and severe fibrosis (P < 0.05). RV/SV ≤ 3.6 and RV ≤ 2.9 were identified as the best cutoff values to differentiate non-advanced from advanced fibrosis and advanced from severe fibrosis with sensitivities of 72.2% and 92.7%, specificities of 72.7% and 77.8%, and with an area under the receiver operating characteristic (ROC) curve of 0.797 and 0.847, respectively (P ≤ 0.002).

Conclusions: RV/SV may be used for the assessment and monitoring of liver fibrosis in HCV patients prior to the administration of antiviral therapy, considering SWE as the reference method.

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the “real-life” safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3–4 months. Adverse events were obtained from patients’ medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1–7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Pseudoexfoliation syndrome (PES) is a common age-related disorder affecting 60–70 million people worldwide. Patients with PES have abnormal production and deposition of fibrillar material in the anterior chamber of the eye. These exfoliated fibrils, easily detected by ocular slit-lamp examination, have also been found to exist systematically in the skin, heart, lungs, liver and kidneys. Recently, myriad studies have associated PES with systemic conditions such as increased vascular risk, risk of dementia and inflammatory state. We review here the most current literature on the systemic implications of PES. Our aim is to encourage further studies on this important clinical entity.

Background: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2.

Objectives: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic.

Methods: A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza.

Results: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010–2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010–11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups.

Conclusions: The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.