Showing papers in "Israel Medical Association Journal in 2014"

Association between vitamin D levels and alopecia areata.

Abstract: BACKGROUND Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely studied. OBJECTIVES To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata. METHODS The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels. RESULTS Mean CRP values were significantly higher in the AA group than the control group (1.1 +/- 0.7 mg/dl vs. 0.4 +/- 0.8 mg/ dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 +/- 10.18 ng/ml vs. 21.55 +/- 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6-4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95% CI 2.2-3.1, P = 0.02) were associated with AA. CONCLUSIONS We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be a significant risk factor for AA occurrence.

Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients.

Abstract: Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients. Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH > or = 800 IU/ml without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients. Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality. Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies, and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. lactate dehydrogenase (LDH), cancer, internal medicine

Long-term health effects in adults born during the Holocaust.

Abstract: BACKGROUND Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease. OBJECTIVES To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood. METHODS This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940-1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups. RESULTS The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 +/- 3.2 vs. 26.97 +/- 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group. CONCLUSIONS These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

The Istanbul protocol (manual on the effective investigation and documentation of torture and other cruel, inhuman or degrading treatment or punishment): implementation and education in Israel.

Abstract: All victims of violence encountered in our emergency rooms and clinics need to be recognized and documented as such. Although there has been progress in the implementation of rules concerning (domestic) violence against women, children and the elderly, the management of cases where patients have been subjected to violence while under the custody of legal enforcement agencies, or patients who have been victims of torture, is still not sufficiently standardized. We describe the Istanbul Protocol of the United Nations, an excellent tool that can help physicians and health professionals recognize and treat cases of torture or institutional violence.

Comparison of the effectiveness of high flow nasal oxygen cannula vs. standard non-rebreather oxygen face mask in post-extubation intensive care unit patients

Abstract: BACKGROUND Optimal oxygen supply is the cornerstone of the management of critically ill patients after extubation, especially in patients at high risk for extubation failure. In recent years, high flow oxygen system devices have offered an appropriate alternative to standard oxygen therapy devices such as conventional face masks and nasal prongs. OBJECTIVES To assess the clinical effects of high flow nasal cannula (HFNC) compared with standard oxygen face masks in Intensive Care Unit (ICU) patients after extubation. METHODS We retrospectively analyzed 67 consecutive ventilated critical care patients in the ICU over a period of 1 year. The patients were allocated to two treatment groups: HFNC (34 patients, group 1) and non-rebreathing oxygen face mask (NRB) (33 patients, group 2). Vital respiratory and hemodynamic parameters were assessed prior to extubation and 6 hours after extubation. The primary clinical outcomes measured were improvement in oxygenation, ventilation-free days, re-intubation, ICU length of stay, and mortality. RESULTS The two groups demonstrated similar hemodynamic patterns before and after extubation. The respiratory rate was slightly elevated in both groups after extubation with no differences observed between groups. There were no statistically significant clinical differences in PaCO2. However, the use of HFNC resulted in improved PaO2/FiO2 post-extubation (P < 0.05). There were more ventilator-free days in the HFNC group (P< 0.05) and fewer patients required reintubation (1 vs. 6). There were no differences in ICU length of stay or mortality. CONCLUSION This study demonstrated better oxygenation for patients treated with HFNC compared with NRB after extubation. HFNC may be more effective than standard oxygen supply devices for oxygenation in the post-extubation period.

Type I interferon signature in systemic lupus erythematosus.

Abstract: Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNalpha, plays a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNalpha in the pathogenesis and course of SLE and the possible role of IFNalpha inhibition as a novel treatment for lupus patients.

Cryopyrin-associated periodic syndrome.

Abstract: CAPS is a rare autoinflammatory disease associated with mutations in the NLRP3 gene that result in overactivation of the inflammasome, increased secretion of IL-1beta and IL-18, and systemic inflammation. Genetic testing has allowed for grouping of the three, previously distinct clinical syndromes of FCAS, MWS and NOMID, into a single syndrome termed CAPS. The clinical features include urticarial rash and fever, CNS and musculoskeletal involvement, ocular disorders and progressive deafness. Onset, severity and complications (mainly retardation, seizures, destructive arthropathy and amyloidosis) depend on the specific mutation. Diagnosis is determined by genetic tests but is often delayed due to lack of awareness. In Israel, the relative abundance of other autoinflammatory disorders (FMF, Behcet's disease) may result in misdiagnosis. Treatment is based on IL-1 antagonism, which usually results in prompt clinical response and may prevent amyloidosis.

A phase IB clinical trial with Dekavil (F8-IL10), an immunoregulatory 'armed antibody' for the treatment of rheumatoid arthritis, used in combination wiIh methotrexate.

Abstract: A therapeutic strategy based on the selective delivery of an immunoregulatory cytokine to the sites of inflammatory disease has been developed. Dekavil is an ‘armed antibody’, composed of the human F8 antibody (specific to the EDA domain of fibronectin, a marker of angiogenesis) fused to the anti-inflammatory cytokine interleukin-10 (IL-10), enabling delivery and accumulation of the cytokine at sites of disease [1,2]. A Phase Ib clinical trial is now underway, which features the administration of weekly escalating doses (6, 15, 30, 60, 110, 160, 210 and 300 μg/kg) of Dekavil in combination with a fixed dose of methotrexate (MTX) to cohorts of three to six rheumatoid arthritis (RA) patients who have previously failed at least one line of anti-tumor necrosis factor (TNF) therapy. This is not a placebo-controlled trial. The objective is to establish the maximum tolerated dose (MTD) and the recommended dose (RD) of the combined treatment, to study safety and tolerability, and to obtain preliminary therapeutic information. The treatment is given as a once-weekly subcutaneous injection for up to 8 weeks. As of today, 24 patients have received at least one drug administration of F8IL10, from dose levels of between 6 and 300 μg/kg, in combination with MTX, and were therefore evaluable for safety. No dose limiting toxicities (DLTs), serious adverse events (SAEs), or Serious unexpected suspected adverse reactions (SUSARs) have been recorded. No MTD has been reached. The dose level of 300 μg/kg is currently being used. Twelve of 24 treated patients reported mild reactions at the injection sites. A single systemic adverse reaction, progressive anemia, was reported in one patient treated with the 160 μg/kg dose level. All adverse reactions recorded resolved after the end of treatment with little to no therapeutic interventions. Initial signs of therapeutic benefit have been observed in the treated patients, even at the low drug dosages of the initial steps of the dose escalation. Overall, 15 of 23 patients evaluable for efficacy have experienced therapeutic benefit (in terms of American College of Rheumatology responses). Among these, 15 patients experienced ACR 20 response, 7 experienced ACR 50 response, and 3 achieved ACR 70 response (15 μg/kg, 30 μg/kg and 60 μg/kg cohorts). Variation in the duration of the response was observed. Of note, two patients in the 30 μg/kg cohort and in the 60 μg/kg cohort achieved long-lasting remission (ACR 70 maintained in excess of one year from the last study drug administration). The promising safety data, together with preliminary positive signs of activity, suggest that the targeted delivery of IL-10 to the sites of inflammation may be beneficial to patients with RA with a possibility for a long-lasting therapeutic potential. These results warrant future clinical investigations in dedicated randomized trials.

Omalizumab therapy for chronic spontaneous urticaria: the Israeli experience.

Abstract: BACKGROUND Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monclonal antibody, was recently shown to be effective in treating resistant CSU. OBJECTIVES To investigated the treatment of CSU with omalizumab in Israel. METHODS We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012-2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients' condition improved but required regular or intermittent doses of antihistamines. RESULTS Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 +/- 12 years and CSU duration was 4.3 +/- 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/ or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 +/- 3.2 injections; 30 patients received 150 mg/ month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005). CONCLUSIONS Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy.

Mortality and reoperations following lower limb amputations.

Abstract: Background Above-the-knee amputations (AKA) and below-the-knee amputations (BKA) are commonly indicated in patients with ischemia, extensive tissue loss, or infection. AKA were previously reported to have better wound-healing rates but poorer rehabilitation rates than BKA. Objectives To compare the outcomes of AKA and BKA and to identify risk factors for poor outcome following leg amputation. Methods This retrospective cohort study comprised 188 consecutive patients (mean age 72 years, range 25-103, 71 males) who underwent 198 amputations (91 AKA, 107 BK 10 bilateral procedures) between February 2007 and May 2010. Included were male and female adults who underwent amputations for ischemic, infected or gangrenotic foot. Excluded were patients whose surgery was performed for other indications (trauma, tumors). Mortality and reoperations (wound debridement or need for conversion to a higher levelof amputation) were evaluated as outcomes. Patient- and surgery-related risk factors were studied in relation to these primary outcomes. Results The risk factors for mortality were dementia [hazard ratio (HR) 2.769], non-ambulatory status preoperatively (HR 2.281), heart failure (HR 2.013) and renal failure (HR 1.87). Resistant bacterial infection (HR 3.083) emerged as a risk factor for reoperation. Neither AKA nor BKA was found to be an independent predictor of mortality or reoperation. Conclusions Both AKA and BKA are associated with very high mortality rates. Mortality is most probably related to serious comorbidities (renal and heart disease) and to reduced functional status and dementia. Resistant bacterial infections are associated with high rates of reoperation. The risk factors identified can aid surgeons and patients to better anticipate and possibly prevent severe complications.

Cogan's syndrome: Anti-Hsp70 antibodies are a serological marker in the typical form.

Abstract: Background Cogan's syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a "typical" form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an "atypical" form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL). Objectives To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups. Methods We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70. Results Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups. Conclusions Anti-Hsp70 antibodies can be considered a serological marker of "typical" CS. "Atypical" CS is conceivably a sort of "melting pot" of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

The role of cardiac computed tomography in infants with congenital heart disease.

Abstract: Background Patients with complex congenital heart disease (CHD) have a high incidence of extracardiac vascular and non-vascular malformations. Those additional abnormalities may have an impact on the precise planning of surgical or non-surgical treatment. Objectives To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings. Methods The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan. Results Median age was 28 +/- 88 days and mean weight 3.7 +/- 1.5 kg. Diagnostic quality was good or excellent (visual image score 3-4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information on extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 +/- 0.07 mSv (range 1.014-2.3 mSv). Conclusions ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE with regard to extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose.

Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment.

Abstract: Background: The multiple symptoms of chronic fatigue syndrome (CFS) and fibromyalgia resemble those described in patients suffering from autoimmune/inflammatory syndrome induced by adjuvants (ASIA) ...

Low plasma vitamin D levels and muscle-related adverse effects in statin users.

Abstract: BACKGROUND Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. OBJECTIVES To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. METHODS Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. RESULTS The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). CONCLUSIONS There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

Methemoglobinemia induced by lidocaine-prilocaine cream.

Abstract: With growing awareness of the importance of pain control in all procedures, the use of lidocaine-prilocaine cream (EMLA) for all ages is increasing Lidocaine-prilocaine cream has been implicated as a cause of methemoglobinemia Diagnostic clues may be oxygen-resistant cyanosis and an oxygen "saturation gap" between arterial blood saturation and pulse oximetry Treatment with intravenous methylene blue is often effective Since EMLA is often mistakenly considered risk-free it is routinely applied by medical staff in the emergency room Subsequent to the case of EMLA-induced methemoglobinemia in an 8 year old girl we wish to alert the medical community to this phenomenon, and in this work review the relevant literature

Blood pressure in obese and overweight children and adolescents.

Abstract: Background The prevalence of obesity in children and adolescents has increased dramatically in the last few decades. Primary hypertension, a known secondary complication among obese adults, has been considered rare in children. Objectives To investigate the prevalence of hypertension and its relation to body mass index (BMI) in obese children aged 9-17 years in Israel. Methods Weight, height, BMI, and systolic and diastolic blood pressure (BP) (twice) were measured in children attending general and pediatric endocrine clinics. Obesity was defined as BMI > or = 95th percentile and overweight as BMI > or = 85th percentile. Pre-hypertension and hypertension were defined as systolic and/or diastolic BP > or = 90th percentile for age, gender and height and BP > or = 95th percentile respectively. In children with pre-hypertension or hypertension, repeated measurements were performed. Results We evaluated 264 children of whom 152 had BMI > or = 85th percentile (study group). Their mean age was 12.5 years. The prevalence of elevated BP (both pre-hypertension and hypertension) in the study group was 44.1% and 31% at the first and second measurements respectively, compared to 11.6% and 1.9% in the normal-weight group. Hypertension was documented in 17.2% of the study group at the second measurement. Conclusions Elevated BP was diagnosed in 31% of overweight and obese children and adolescents. Increased awareness and early diagnosis and treatment are essential.

Treatment of familial Mediterranean fever: colchicine and beyond.

Abstract: F amilial Mediterranean fever, the most common form of hereditary autoinflammatory disorders, is characterized by recurrent episodes of fever and sterile inflammation resulting in peritonitis, pleuritis, arthritis, and/or erysipelas-like erythema. In addition to these self-limited inflammatory episodes that last 1–3 days and mainly affect serosal membranes, FMF has also been associated with an increased risk for reactive (AA type) amyloidosis [1]. FMF is considerably common in eastern Mediterranean countries and exerts a significant disease burden. Colchicine has been accepted as the standard of care for prophylactic treatment of inflammatory episodes and prevention of reactive amyloidosis in FMF patients long before the elucidation of the genetic basis of FMF [2-5]. Identification of the pathogenic mechanisms of FMF, after the MEFV gene variations were found to be the cause of the autosomal recessively inherited disease, enables the optimum use of colchicine as well as the development of more targeted therapies for patients with inadequate response to colchicine. This review updates the treatment options for patients with FMF by summarizing the available data on colchicine and its current alternatives.

Belimumab for the Treatment of Refractory Systemic lupus Erythematosus: Real-life Experience in the First Year of use in 18 Italian Patients

Abstract: T o date, it has been estimated that more than 50% of patients affected by systemic lupus erythematosus (SLE) have suboptimal disease control: while 40% of them have chronic active disease (CAD), the remaining 10% suffer from relapsingremitting disease (RRD) with frequent exacerbations [1,2]. This situation requires frequent changes of therapy and, in particular, increased steroid dosage, along with the obvious risk of one or more of the well-known related side effects [3,4]. In this scenario the need for new treatment options is even more evident than in other rheumatic diseases. After 50 years with no new drug licensed for SLE, belimumab was recently approved for the treatment of active and refractory SLE. Belimumab is a human immunoglobulin G (IgG)1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS) able to inhibit the survival of B cells, including autoreactive B cells, and it reduces the differentiation of B cells into Ig-producing plasma cells. It is indicated in active SLE in the presence of hypocomplementemia and anti-ds-DNA antibody positivity, in addition to the standard treatment regimen. The recommended dose is 10 mg/ kg belimumab in intravenous administration on day 0, 14 and 28, and once a month thereafter. The development of belimumab represents the largest trial ever conducted in SLE patients, with 2200 patients enrolled in clinical studies with long-term treatment, in some cases for more than 7 years [5]. The aim of the study was to evaluate the efficacy and safety of belimumab in the real-life experience of a single tertiary referral center of rheumatology after the first year of licensed use in Italy. METHodS

Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial.

Abstract: Familial Mediterranean fever (FMF) is a genetic auto-inflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%-10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1beta (IL-1beta) as the major cytokine involved in the pathogenesis of FMF, IL-1beta blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1beta blockade have been reported. At the Israel Center for FMF at the Sheba Medical Centerthe first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1beta blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

Exercise and fatigue in rheumatoid arthritis.

Abstract: Fatigue, the enduring sensation of weakness, lack of energy, tiredness or exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as their most disabling symptom with wide-ranging consequences for quality of life. Little attention has been paid to its multidimensional nature or to its reliability as a measure to evaluate progression of the disease. Low impact aerobic exercise affects the level of fatigue, and this same level of fatigue influences the exercise itself. We searched Medline, Cochrane Collaboration Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for randomized controlled trials (with appropriate description of methods, materials and results) on the assessment of fatigue and exercise. Review articles, case reports, letters to the editor and editorials were excluded. Of 121 references initially identified, 4 randomized controlled trials met the inclusion criteria. Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week program of two to three times/ week and different periods of follow-up. Two studies used low impact aerobic exercise, one used dance-based exercise, and another study followed a home cardiopulmonary conditioning program using a stationary bicycle. While fatigue appears to be a reliable outcome measure in the clinical management of RA, especially when related to exercise prescription, further research is needed to evaluate the correlation between exercise, fatigue and quality of life, using fatigue scales validated to explore the different components of fatigue and its wide-ranging consequences.

Effect of seasonality, weather and holidays on the incidence of proximal hip fracture.

Abstract: Background: Proximal hip fractures in the elderly are common and place a heavy burden on health resources. Researching the timing of these fractures could contribute to diverting resources towards peaks in incidence and investing in prevention at certain times. objectives: To examine the effect of seasonality, weather and Jewish holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture. Methods: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals.

Association of Helicobacter pylori with coronary artery disease and myocardial infarction assessed by myocardial perfusion imaging.

Abstract: BACKGROUND The relationship between Helicobacter pylori infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD. OBJECTIVES To investigate the association between CAD and H. pylori infection using MPI. METHODS This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD positivity group included patients with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients' demographic data, risk factors for CAD, and childhood socioeconomic status were recorded. RESULTS The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD positivity (odds ratio 1.83, 95% confidence interval 1.06-3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95% CI 1.44-7.84, P = 0.005). No association was noted with CagA positivity. CONCLUSIONS In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors.

Mid-term follow-up after laparoscopic sleeve gastrectomy in obese adolescents.

Abstract: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is gaining credibility as a simple and efficient bariatric procedure with low surgical risk. Since surgical treatment for morbid obesity is relatively rare in adolescents, few results have bten accumulated so far. OBJECTIVES To prove the safety and efficacy of LSG turgery in an adolescent population METHODS Data were prospectively collected regarding adolescent patients undergoing LSG. All patients underwent pre- and postoperative medical and professional evaluation by a multidisciplinary team. RESULTS Between the years 2006 and 2011, 32 adolescents underwent LSG in our center (20 females and 12males). Mean age was 16.75 years (range 14-18 years), mean weight was 121.88 kg (83-178 kg), and mean body mass index 43.23 (35-54). Thirty-four comorbid conditions were identified. LSG was the primary bariatric procedure in all the patients. Mean operative time was 60 minutes (range 45-80 min). Tiere were two complications (6.25%): an early staple line leak and a late acute cholecystitis. There were no deaths. Mean percent excess weight loss at 1, 3, 6, 9,12, 24, 36, 48, and 60 months post-surgery was 27.9%, 41.1%, 62.6%, 79.2%, 81.7%, 71%, 75%, 102.9% and 101.6%, respectively. Comorbidities were completely resolved or ameliorated within 1 year folllowing surgery in 82.4% and 17.6%, respectively. CONCLUSIONS LSG is feasible and safe in morbidly obese adolescents, achieving efficient weight loss and impressive resolution of comorbidities. Further studies are required to evaluate the long-term results of this procedure as well as its place among other bariatric options.

Association between cardiac manifestations and antiphospholipid antibody type and level in a cohort of Serbian patients with primary and secondary antiphospholipid syndrome.

Abstract: Background Antiphospholipid syndrome (APS, also known as Hughes syndrome) may manifest itself as a primary or secondary disease, most commonly with systemic lupus erythemathosus (SLE) and various cardiac manifestations. Objectives To report the first results from the Serbian National Cohort study, which was started in January 2000. Methods Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), beta2-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected. Results There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations. Conclusions Patients with secondary APS had a higher prevalence ofvalvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

Ki67 as a biologic marker of basal cell carcinoma: a retrospective study

Abstract: Background Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biological markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histological variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation. Objectives To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables. Methods In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up. Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histological analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion. Results Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes. Conclusions The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histological subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

The Israel Survey of Mental Health among Adolescents: prevalence of attention-deficit/hyperactivity disorder, comorbidity, methylphenidate use, and help-seeking patterns.

Abstract: Background The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed. Objectives To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with sociodemographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population. Methods The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14-17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months. Results Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents. Conclusions Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

Medical clowns facilitate nitrous oxide sedation during intra-articular corticosteroid injection for juvenile idiopathic arthritis.

Abstract: BACKGROUND Intra-articular corticosteroid injection (IACI), a common procedure in juvenile idiopathic arthritis, is usually associated with anxiety and pain. In a previous study, we concluded that nitrous oxide (NO2) provides effective and safe sedation for such procedures. Following the introduction of medical clowns in our hospital, we added them as an integral part of the team performing IACI. OBJECTIVES To prospectively evaluate the effect of a medical clown on pain perception during intra-articular corticosteroid injection for juvenile idiopathic arthritis using NO2 conscious sedation. METHODS Patients scheduled for IACI first met and interacted with the medical clown. During the procedure, the rheumatologist and the medical clown worked in parallel to create distraction. NO2 was administered. The patient, parent, physician, medical clown and nurse completed a visual analog scale (0-10) for pain. Change in heart rate ≥ 15% was recorded to evaluate physiologic response to pain and stress. RESULTS A total of 46 procedures were performed in 32 children: 23 girls, 9 boys, with a mean age of 10.9 ± 3.6 years. The median visual analog scale pain score for the patients, parents, physicians, medical clown and nurses was 2, 2, 1, 1 and 1, respectively. Five patients had increased heart rate and experienced increased pain. CONCLUSIONS Active participation of a medical clown during IACI with nitrous oxide for juvenile idiopathic arthritis further decreases pain and stress and results in a positive patient experience.

Moving forward with combat casualty care: the IDF-MC strategic force buildup plan "My Brother's Keeper".

Abstract: t hroughout modern history, military medicine, especially combat casualty care, has undergone substantial improvement and development. Indeed, the recent conflicts in Iraq and Afghanistan saw a dramatic reduction in battlefield mortality, as measured by the case fatality rate. The CFR1, which is the number of deaths divided by the number injured, was less than 10% in these large-scale conflicts, an unprecedented achievement in the history of military medicine [1] especially considering the increased severity of injuries. This can be attributed to innovative treatment modalities, including effective measures for hemostasis at the point of injury and improved force protection [2]. Above all however, it was the result of a structured process that included concepts such as “eliminating preventable death” [3], recognizing the importance of forward surgical capabilities [4-6], conducting focused research and development, as well as engaging international collaboration. Although most of these concepts were recognized and developed during previous conflicts, it is their integration into a structured and goal-oriented casualty care system that led to the unprecedented survival rates. The Israel Defense Force Medical Corps emerged from Israel’s last major military conflicts – the Second Lebanon War (2006) and Operation Cast Lead (2009) – with the feeling that medical care could be better optimized and adapted

Does selective use of computed tomography scan reduce the rate of "white" (negative) appendectomy?

Abstract: Background Appendectomies are the most common operations performed on an emergency basis. The accepted rate of "white" appendectomies is around 20%. In recent years, computed tomography (CT) scanning has been recognized as a valuable tool with high sensitivity and specificity in the diagnosis of acute appendicitis. The use of CT scans in the management of patients with suspected acute appendicitis is increasing worldwide. Objectives To assess whether introducing more liberal use of CT in the management of patients presenting to the emergency room with right lower quadrant pain or suspected acute appendicitis would reduce the rate of "white" appendectomies. Methods We conducted a retrospective study of the pathology reports and CT scans of all patients who underwent appendectomy during a 3 year period. We examined the correlation between the rate of CT scans performed and the rate of "white" appendectomies. Results Overall, we performed 797 appendectomies during the study period. In 2004, we performed 272 appendectomies and CT in 34 patients (12.5%). In 2005, we performed 275 appendectomies and CT in 83 patients (30.2%). In 2006, we performed 250 appendectomies and CT in 88 patients (35.2%). The percentage of "white" appendectomies decreased from 29% in 2004 to 21.1% in 2005 and to 18.8% in 2006. Conclusions It appears that a more selective use of CT scans in the management of suspected appendicitis could reduce the rate of "white" appendectomies.