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: 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: 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.

Background: A clavicular fracture accounts for 2.6%–5% of adult fractures. Fractures in the middle-third (OTA 15-B) represent 69%–82% of all clavicular fractures. There is no consensus among orthopedic surgeons regarding treatment for these fractures; many support conservative treatment even for displaced middle-third clavicular fractures, while others choose operative treatment.

Objectives: To assess the attitudes of orthopedic surgeons regarding treatment of displaced mid-shaft clavicular fractures.

Methods: We conducted a survey in which we interviewed orthopedic surgeons from various countries during the 2012 EFORT meeting in Berlin. The questionnaire included an X-ray of a displaced middle-third clavicular fracture, as well as questions regarding the surgeon’s proposed treatment plan.

Results: A total of 177 orthopedic surgeons completed the questionnaire; 49% preferred operative treatment for a displaced middle-third clavicular fracture. Among the orthopedic trauma specialists, 58% suggested operative treatment, as did 82% of shoulder specialists. Most surgeons preferred a locking plate for fixation.

Conclusions: The treatment approach for a displaced middle-third clavicular fracture seems to be evenly split between conservative and operative approaches. The tendency toward operative treatment was even more remarkable among orthopedic trauma specialists and shoulder specialists who completed the questionnaire. Most surgeons prefer a locking plate as a fixation system for this type of fracture. 

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Background: The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.

Objectives: To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.

Methods: The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n=205), intermediate 22–31 (n=138), and high ≥ 32 (n=63). Five year mortality was derived from the National Mortality Database.

Results: Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P < 0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P < 0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.

Conclusion: Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.

Background: Trachea esophageal puncture (TEP) is performed following total laryngectomy to allow speech and communication. The most common reason for long-term speech failure in this population is hypertonicity of the constrictor muscle.

Objectives: To present our experience with the treatment of aphonic patients after total laryngectomy and TEP and suggest a protocol for treatment.

Methods: Of 50 patients who underwent total laryngectomy and TEP, 6 suffered from aphonia after surgery. All patients underwent radiotherapy with or without chemotherapy. Delay in speech continued for more than 6 months after surgery. The patients received percutaneous lidocaine injection to the neopharynx in different locations around the stoma in order to map the hypertonic segments in the neopharynx.

Results: Lidocaine injection immediately enabled free speech in five patients. One patient (patient 6) suffered from aphonia and from severe dysphagia and required a feeding tube. This patient succeeded to pronounce abbreviations after lidocaine injection. Another (patient 4) gained permanent ability to speak following a single lidocaine injection; this patient was not injected with botolinium toxin (BTX). For the other five, lidocaine had a transient effect on speech. These patients received BTX percutaneous injections. After BTX injections four regained free speech within 14 days. The fifth patient (patient 6) gained a conversational voice and experienced improvement in swallowing only after additional intensive speech therapy.

Conclusions: Percutaneous lidocaine and BTX injections represent first-line treatment in this population, with good success and minimal complications.