Israel Medical Association Journal

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

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: Exposure to silica gel, a common desiccant, is considered common and non-toxic although data are limited.

Objectives: To evaluate the characteristics of silica gel ingestion, and to attempt to estimate the associated health care costs.

Methods: We conducted a one year retrospective review of charts of a national poison information center to characterize ingestions of silica gel and estimate its direct cost to health care services. Cost evaluation was based on emergency department and community clinic tariffs (NIS 807/US$ 213 and NIS 253/US$ 67, respectively).

Results: A total of 546 cases were recorded, 2.1% of the annual calls to the poison information center. Most ingestions occurred in children younger than 6 years old (91.4%, 65.2% < 2 years). Median monthly exposure was 42; the peak (74) occurred in April, before the Passover holiday. Sixty calls (11%) came from health care facilities and the rest were reported by the public; 2.7% were symptomatic, mainly mild self-limited mouth and throat discomfort. The direct annual treatment cost of patients who referred themselves to health care facilities without consulting first with the Poison Center (n=60) was NIS 24,598/US$ 6507 (emergency department and community clinic visit fees). 

Conclusions: Silica gel ingestion is relatively common, occurring mainly in young children; it is rarely symptomatic but is a source of unnecessary referrals to health care facilities. The potential annual saving by preventing unnecessary referrals due to poison information center advice was estimated at NIS 375,678/US$ 99,383. The availability of poison information center services may prevent unnecessary referrals to health care facilities and thus save costs. 

 

Background: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. 

Objectives: To summarize the single-center experience in the treatment of anal carcinoma using various radiation techniques.

Methods: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B).

Results: A total of 42 patients – 25 (59.5%) females and 17 males (40.5%) – underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups, only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. 

Conclusions: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions, but did not differ from 3D with regard to treatment efficacy. 

 

Background: Due to increasing antimicrobial resistance, there has been renewed interest in old drugs that have fallen into disuse because of toxic side effects. One such drug is chloramphenicol. Data on the use and susceptibility patterns to chloramphenicol in developed countries in recent years are limited.

Objectives: To assess the susceptibility of bacteria to chloramphenicol, and evaluate the use of chloramphenicol in Israeli hospitals as influenced by infectious disease specialists’ attitudes with regard to its potential harms.

Methods: A national survey was conducted in all Israeli hospitals. Questionnaires were sent to the directors of infectious disease units and included items on chloramphenicol susceptibility in clinical isolates, use of chloramphenicol for the treatment of inpatients, local recommendations for use of chloramphenicol, and concerns regarding side effects.

Results: Chloramphenicol is used in 83.3% of hospitals, mostly for the treatment of aspiration pneumonia. While 22.2% of infectious disease unit directors believe that chloramphenicol should be avoided because of dangerous side effects, 88.9% believe there is a place for chloramphenicol in the treatment of patients in this era of increasing antibiotic resistance. Chloramphenicol susceptibility is routinely assessed in 44.4% of hospitals, with high susceptibility rates found among gram-positive, gram-negative and anaerobic bacteria.

Conclusions: In an era of increasing antibiotic resistance, many Israeli infectious disease unit directors believe that chloramphenicol has a role in the treatment of respiratory tract and other infections in hospitalized patients.

Background: The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services.

Objectives: To report data on the epidemiology of poisonings and poison exposures in Israel.

Methods: We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012.

Results: A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children < 6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink).

Conclusions: Poison exposures and poisonings have increased significantly and have contributed substantial to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.

Objectives: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy (CRT) or cetuximab (ERT) in the treatment of patients with advanced SCCHN.

Methods: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007–2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events.

Results: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients.

Conclusions: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.