Israel Medical Association Journal

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Background: Since 2006 more than 60,000 migrants arrived in Israel from the Horn of Africa (HoA: Sudan, Eritrea, Ethiopia). They were detained in prison and screened for tuberculosis (TB) by means of an interview and chest X-ray (CXR).

Objectives: To evaluate the yield of this screening process.

Methods: This cross-sectional study evaluated the validity of CXR in a random sample of 1087 of the 5335 HoA migrants (20.4%) who arrived in 2009, and assessed its related costs.

Results: Sixty-two migrants (5.7%) had CXRs with TB-suspicious findings, and 11 of them were finally diagnosed with TB (17.7% of all TB-suspicious CXRs). TB point-prevalence was 1000 cases per 100,000 migrants (1.0%). As no additional TB cases were diagnosed on arrival, CXR sensitivity, specificity and positive predictive value were 100%, 96.1% and 17.7%, respectively. The interview did not contribute to the detection of migrants with TB. Direct costs related to the detection of single TB cases in prison was 17,970 shekels (US$ 4585), lower than the treating cost of 28,745 shekels ($ 7335). During 2008–2010, 88 HoA migrants who had been screened at the prison after crossing the border were later diagnosed with TB in the community. The average annual TB incidence was 132 cases/100,000 migrants. We traced 56 (63.6%) of the CXRs that were performed during detention. Of those, 41 (73.2%) were unremarkable, 8 (14.2%) were TB suspicious and 7 (12.5%) had non-TB-related abnormalities.

Conclusions: CXR-based screening is a valid and cost-saving tool for screening  HoA migrants for TB; the interview has significant limitations. 

Background: Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the course of the disease and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.

Objectives: To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.

Methods: We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.

Results: Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P < 0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.

Conclusions: Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment. 

Background: New animal models provide insights into the pathogenesis of different types of inflammatory bowel disease as well as novel pathways for new therapeutic options. However, the scarcity of large animal models hinders the research and development of new surgical procedures and technological devices in inflammatory bowel disease surgery. Common small animal inducible models involve chemical agents that result in the development of acute intestinal inflammation.

Objectives: To assess a novel method for the induction of Crohn’s-like colitis using intramural injection of sclerosants in a porcine model.

Methods: Seven domestic pigs underwent several experimental protocols to assess the efficacy of intramural colonic injections of two different compounds (lauromacrogol, and phenol in almond oil). Twenty-five different large bowel segments were treated with intramural injections of the compounds. The animals were followed for 6 weeks, and treated colonic segments were resected for histopathological examination.

Results: Intramural injection of lauromacrogol resulted in non-specific, mild reactive foreign body changes only. Injection of various dosages of 5% phenol in almond oil caused a range of histopathological changes varying from focal fibrosis to Crohn’s-like reactions comprising acute and chronic infiltrates, mucosal ulceration and focal necrosis with enteric and lymphoid non-caseating granulomas.

Conclusions: Intramural colonic phenol in almond oil injection in pigs induces inflammatory reactions that histologically resemble Crohn's disease in humans. 

Background: The prevalence of heart failure (HF) is increasing rapidly with high readmission rates, mainly due to fluid retention. Ultrafiltration (UF) is a mechanical method for removing fluids. Introduced only recently in Israel, the skill and experience required for outpatient congested HF patients are scarce.

Objectives: To evaluate the feasibility and safety of UF therapy in congested HF patients in outpatient clinics under a strict protocol of monitoring and therapy that we developed.

Methods: Between April and September 2013 we applied UF in our outpatient clinic to seven chronically congested HF patients with NYHA III-IV who did not respond adequately to diuretics. We administered a total of 38 courses.

Results: On average, 1982 ml fluid per course was removed without significant adverse events and with patients' subjective feeling of improvement. Only two courses were interrupted prematurely due to mechanical problems but were completed without harm to the patients.

Conclusions: Under appropriate professional medical supervision, UF therapy in an outpatient setting is a safe and effective procedure and serves as an additional tool for managing congested HF patients who do not respond adequately to diuretics.

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: Congenital hepatic hilar cysts are rare. Some are simple and do not require intervention, but some biliary cystic malformations impose the risk of morbidity and mortality. Objectives: To assess a series of five patients presenting with congenital hepatic hilar cysts. 

Methods: We retrospectively reviewed all cases presenting to our pediatric surgical service between January 2010 and December 2012 and found to have a congenital hepatic hilar cyst. Data regarding clinical, radiological, operative and pathological features were analyzed.

Results: Five children with congenital cyst of the hepatic hilum were identified; four of them were diagnosed prenatally. Four children had undergone surgical intervention: one with intrahepatic choledochal cyst, one with epidermoid cyst, and two with biliary atresia and an associated cyst of the common bile duct. In another case of choledochal cyst the treatment was conservative. All children except one had a good prognosis; one child with biliary atresia required liver transplantation.

Conclusions: The differential diagnosis of congenital hepatic hilar cyst includes a broad spectrum of pathologies. It is essential to diagnose biliary atresia as early as possible. Signs such as smaller cysts in association with a hypoplastic gallbladder and direct hyperbilirubinemia may be suggestive of biliary atresia.

Background: Most spine tumors are resistant to radiation and chemotherapy. Complete surgical removal provides the best chance for long-term control of the tumor. Total en bloc spondylectomy (TES) is a radical new technique that entails total removal of the tumor and affected vertebras with clean margins.

Objectives: To review our initial experience with TES, focusing on feasibility, surgical challenges and the short-term outcome.

Methods: We retrospectively reviewed the hospitalization charts and follow-up data of all patients treated with TES for spine tumors in the spine unit at Tel Aviv Medical Center.

Results: TES was performed in 12 patients aged 13–78 years. Nine patients had primary spinal tumors and three had metastasis. Total en bloc removal was achieved in all cases with spondylectomy of one to three affected vertebras. There was no perioperative mortality and only one major intraoperative complication of injury to a major blood vessel. Late complications were mainly related to hardware failure.

Conclusions: Total en bloc spondylectomy is feasible and effective for the management of selected patients with extradural spinal tumors. Since the surgical procedure is demanding and carries significant risk, careful preoperative evaluation and collaboration with colleagues from other specialties are crucial.