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Background: Endoscopic middle meatal antrostomy (EMMA) is considered the standard approach for surgical management of antrochoanal polyps (ACPs). Recently, an endoscopic inferior meatal antrostomy (EIMA) approach for clearing lesions in the maxillary sinus was described. In this study, we compared the long-term outcome of patients with ACP following surgical treatment using one of these 2 approaches (EIMA or EMMA). Methods: The medical charts of all patients treated for ACPs in our institution between January 1, 2009, and July 1, 2020, were reviewed retrospectively. Patients were invited to complete a long-term follow-up assessment. Results: Thirty-eight patients were included in the study: EIMA was the only procedure performed in 25 patients (66%) and EMMA was the only procedure performed in 7 patients (18%). Both procedures were performed in 6 patients (16%): 2 patients (5%) underwent simultaneous EMMA and EIMA for better access and visualization and 4 patients (10.5%) underwent surgical revision consisting of EIMA secondary to failed EMMA at other institutions. Median follow-up was 44 months (range, 6 months–11 years). No evidence of recurrent ACPs, recirculation, synechiae, nasolacrimal duct injury, or bleeding was observed in any of our patients. Small nonobstructing cysts were observed in 2 patients (8%) following EIMA. Conclusions: EIMA prevents violation of the ostiomeatal complex. It provides access to the anteroinferior aspect of the maxillary sinus and should be considered as an alternative to EMMA in patients with ACPs.

Cow's milk allergy (CMA) is a common food allergy among infants. Information regarding the best timing for first exposure to cow's milk formula (CMF) is controversial and more evidence is required. Few randomized control trials have tried to accurately assess the timing and preventive effect of exposure to CMF on small cohorts.This study assessed the association between early, continuing exposure to CMF on the basis of the parents' preferences and the development of immunoglobulin E (IgE)-mediated CMA in a large birth cohort.Newborns were prospectively recruited shortly before birth and divided into 2 groups according to parental feeding preference for the first 2 months of life: (1) exclusive breastfeeding (EBF); or (2) at least 1 meal of CMF (with or without breastfeeding) daily. Infants were followed up monthly until the age of 12 months.Among 1992 infants participating in the study, 1073 (53.86%) were in the EBF group until 2 months of age. IgE-mediated CMA was confirmed in 0.85% (n = 17); all were in the EBF group. Within this group, the prevalence of IgE-mediated CMA was 1.58% compared with 0 in the other groups (relative risk, 29.98; P.001). Post hoc analysis revealed IgE-mediated CMA prevalence of 0.7% in the per-protocol EBF group vs 3.27% among breastfed infants who were exposed to a small amount of CMF during the first 2 months of life. A family atopic background did not affect the results.Early, continuing exposure to CMF from birth has the potential to prevent the development of IgE-mediated CMA and should be encouraged. However, the exposure needs to be consistent because occasional exposure increases the risk of developing IgE-mediated CMA and should be avoided.

Background: The effects of high-risk environment on young adults with mild asthma were never fully tested in practice, as most high-risk occupations do not welcome them. This study examines the effect of combat training on asthma worsening in the Israeli Defense Forces. Methods: Persons with asthma in remission and mild intermittent asthma who underwent combat training between 2014 and 2017 were compared in terms of disease worsening to their counterparts performing clerical duties during a follow-up of 8 months. Among combat trainees, exposure to known triggers for asthma exacerbation and health status on enlistment were assessed as risk factors for asthma exacerbation. Results: Asthma worsening among persons with asthma in remission was twice as common among those who are undergoing training compared to persons performing clerical duties. This difference was smaller among mild intermittent asthmatics. For both asthma severities, rates of asthma exacerbation requiring emergency room treatment were several times higher among the training group. Among individuals undergoing training, mild intermittent asthma was a significant risk factor for asthma worsening compared to asthma in remission (OR 1.99 [1.44–2.75]) while age (OR 0.67 [0.53–0.85]) and immigration to Israel (OR 0.55 [0.31–0.95]) were significant protective factors. Interpretation: Young adults with mild asthma are at significant risk for severe exacerbations when exposed to high-risk environment even among individuals who have long been symptom free. No single risk factor was found to have an independent effect suggesting a synergistic mechanism that is harder to mitigate.

Organophosphates (OPs) are widely used as pesticides and have been employed as warfare agents. OPs inhibit acetylcholinesterase, leading to over-stimulation of cholinergic synapses and can cause status epilepticus (SE). OPs poisoning can result in irreversible brain damage and death. Despite termination of SE, recurrent seizures and abnormal brain activity remain common sequelae often associated with long-term neural damage and cognitive dysfunction. Therefore, early treatment for prevention of seizures is of high interest. Using a rat model of paraoxon poisoning, we tested the efficacy of different neuroprotective and anti-epileptic drugs (AEDs) in suppressing early seizures and preventing brain damage. Electrocorticographic recordings were performed prior, during and after injection of 4.5 LD50 paraoxon, followed by injections of atropine and toxogonin (obidoxime) to prevent death. Thirty minutes later, rats were injected with midazolam alone or in combination with different AEDs (lorazepam, valproic acid, phenytoin) or neuroprotective drugs (losartan, isoflurane). Outcome measures included SE duration, early seizures frequency and epileptiform activity duration in the first 24 -hs after poisoning. To assess delayed brain damage, we performed T2-weighted magnetic resonance imaging one month after poisoning. SE duration and the number of recurrent seizures were not affected by the addition of any of the drugs tested. Delayed brain injury was most prominent in the septum, striatum, amygdala and piriform network. Only isoflurane anesthesia significantly reduced brain damage. We show that acute treatment with isoflurane, but not AEDs, reduces brain damage following SE. This may offer a new therapeutic approach for exposed individuals.

Nivolumab, an immune checkpoint inhibitor is used to treat advanced metastatic malignancies. Data showed that nivolumab can cause exacerbated response of T-Helper 2 cells and lead to airway inflammation.To present the upper airway findings of a 69-year-old woman after treatment with nivolumab.Case report.A 69-year old woman with no history of chronic rhinosinusitis developed complaints of nasal congestion, rhinorrhea, sneezing, and anosmia. These symptoms started after one year of treatment with nivolumab. Pale polyps were observed on fiberoptic endoscopy examination. A gradual increase in eosinophil blood counts was noted. On histopathology, heavy infiltrates of eosinophils were seen in the tissue.Nivolumab is used to treat various advanced metastatic malignancies, with a good safety profile. Nevertheless, physicians must be alert to the possibility of evolving type II inflammation in patients, as appropriate therapy can be provided to improve their quality of life.

Background Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods This retrospective study followed children up to 18 years old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018, and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments, and outcomes were extracted from electronic medical records. Results Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, and 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25 ± 15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2%, and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population, increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.

Objective: To determine whether application of a gum-elastic bougie (GEB), a visual stylet used to improve success rates of difficult intubations, reduces the time, and number of attempts to achieve successful intubation while wearing personal protective equipment (PPE). Design: A randomized cross-over study comparing orotracheal intubations performed on an AirMan ® Mannequin, using either a semirigid stylet or a GEB, while wearing an active hood with a charcoal impregnated suit and butyl rubber gloves. Setting: Simulation training field of the Israel Defense Force Medical Corps. Participants: 27 military physicians and 23 paramedics (PMs). Interventions: Comparing intubation with and without using the GEB while wearing PPE. Main outcome measure(s): Airway (AW) control was considered successful if the “lungs” of the mannequin expanded during bag ventilation. Three unsuccessful attempts or a procedure exceeding 60 seconds were regarded as a failure. Correlations between parameters of self-assessment of skills and successful intubation were also determined. Results: With the GEB, success rate was lower (82 percent versus 100 percent, p = 0.002), more attempts were needed (1.4 ± 0.7 versus 1.0 ± 0.2, p = 0.005) and time-to-achieve AW control was longer (43.6 ± 14.6 seconds versus 23.1 ± 10.5 seconds, P < 0.001) than without it. Participants with high self-assessment of GEB-assisted AW management skills needed less attempts to perform successful intubation with GEB than participants with low self-assessment (1.0 ± 0.0 versus 1.4 ± 0.8, p = 0.001), but not less time to achieve it. Conclusions: While donning PPE, the use of GEB (versus semirigid stylets) did not reduce the time or the number of attempts necessary to achieve successful intubation.

Introduction: Venom immunotherapy (VIT) is considered to be the gold-standard treatment for patients with Hymenoptera venom allergy. Data regarding VIT in bee venom (BV) allergic patients are scarce. Aim: The aim of this study was to evaluate the outcome of VIT in patients with exclusive BV allergy and to try to define risk factors for VIT-induced systemic reactions (VIT-ISR) and VIT failure. Methods: This is a retrospective study including data from all BV allergic patients that were treated by VIT in the Allergy Unit at the Meir Medical Center in the years 1995–2018. Results: Two hundred and forty-seven patients with exclusive BV allergy were included; 206 (83.4%) preferred to undergo rush buildup. Sixty-nine patients (27.9%) had at least 1 reaction during buildup, with the c-kit mutation being the only significant risk factor (100 vs. 28.9%, p = 0.02). Female gender (25.4 vs. 13.3%, p = 0.04), conventional buildup schedule (26.8 vs. 14.1%, p = 0.04), and c-kit mutation (100 vs. 16.8%, p < 0.01) but not tryptase level were found to be significantly more frequent in recurrent reactors. Females (20.3 vs. 9%, p = 0.03), patients with severe systemic reaction to the index sting (24.3 vs. 9.5%, p = 0.004), and c-kit mutation (66 vs. 12%, p = 0.05) but not tryptase level were found to be risk factors for severe systemic reactions. Conclusion: Despite the considerably high rate of VIT-ISR in patients with exclusive BV allergy, VIT can be performed safely and efficiently. C-kit mutation, and not basal serum tryptase level, seems to be a preferable biomarker for VIT-ISR in these patients.

Thrombin is a coagulation factor implicated in various pathological and physiological processes in the brain, exerting beneficial and deleterious effects in a concentration-dependent manner. Measurement of thrombin activity levels in pathological animal models is needed and in some cases, because of technical considerations, only frozen samples are available. In the current study, we used a quantitative method to evaluate thrombin activity in fresh and frozen brain sections of 43 male and female adult healthy mice. We stratified data per brain section, brain hemisphere, and mouse sex. We found lower thrombin activity in frozen sections compared with fresh sections, falling within levels considered central nervous system protective in previous studies. The results suggest that fresh section thrombin activity levels in healthy mice can be extrapolated from frozen brain sections. In addition, we found varying thrombin activity across the brain sections, with maximal activity in the olfactory system and hippocampus-containing sections. Thrombin activity did not vary between males and females, or between the right and the left hemispheres, in a statistically significantly manner.

Background Rush venom immunotherapy (VIT) is highly effective in Hymenoptera venom allergy. Still, specific data regarding its safety and efficiency in children are rather sparse. Objectives The objective of this study was to better evaluate the safety and efficiency of rush VIT in this specific age group. Methods Children younger than 16 years with systemic reaction to insect sting involving, at least, one body system other than skin and children aged 16-18 years with any kind of systemic reaction were offered conventional or rush VIT with a build-up phase that lasted 3 days. Results Eighty-four of 127 children together with their caregivers chose to receive rush VIT. Seventy of them were allergic to bee venom only. There was no difference between the children receiving rush or conventional VIT in the incidence of systemic reactions during the build-up phase (19% and 23.2%, respectively), nor was there any difference in regard to the severity of these reactions. Efficiency was improved with rush VIT, as reflected by a higher number of patients achieving the 100 mcg maintenance dose with the primary protocol (83 of 84 patients, 98.8%, and 39 of 43, 90.7%, for rush and conventional, respectively, P = .04). Conclusions Rush VIT in children is as safe as and more efficient than conventional VIT.

A biomarker that will enable the identification of patients at high-risk for developing post-injury epilepsy is critically required. Microvascular pathology and related blood-brain barrier dysfunction and neuroinflammation were shown to be associated with epileptogenesis after injury. Here we used prospective, longitudinal magnetic resonance imaging to quantitatively follow blood-brain barrier pathology in rats following status epilepticus, late electrocorticography to identify epileptic animals and post-mortem immunohistochemistry to confirm blood-brain barrier dysfunction and neuroinflammation. Finally, to test the pharmacodynamic relevance of the proposed biomarker, two anti-epileptogenic interventions were used; isoflurane anaesthesia and losartan. Our results show that early blood-brain barrier pathology in the piriform network is a sensitive and specific predictor (area under the curve of 0.96, P < 0.0001) for epilepsy, while diffused pathology is associated with a lower risk. Early treatments with either isoflurane anaesthesia or losartan prevented early microvascular damage and late epilepsy. We suggest quantitative assessment of blood-brain barrier pathology as a clinically relevant predictive, diagnostic and pharmaco!dynamics biomarker for acquired epilepsy.

Background: Venom immunotherapy (VIT) is considered to be the gold standard treatment for patients with hymenoptera venom allergy. This treatment induces systemic reactions (SR) in a significant number of patients. Objective: To evaluate the outcome of VIT in patients with known risk factors for VIT-induced SR and to compare rush VIT (RVIT) and conventional VIT (CVIT). Methods: All of the patients who received VIT and had at least one of the following risk factors were included: current cardiovascular disease, uncontrolled asthma, high basal serum tryptase, current treatment with β-blockers or angiotensin-converting enzyme inhibitors, and age >70 or Results: Sixty-four patients were included, and most of them (52; 81.5%) were allergic exclusively to bee venom. Thirty-five (54.7%) patients underwent RVIT and 29 CVIT. The incidence of patients who developed SR during the build-up phase was similar for RVIT and CVIT (25.7 and 27.5%, respectively; p = 1). However, the incidence of SR per injection was significantly higher in CVIT than in RVIT (5.6 and 2.75%, respectively; p = 0.01). Most reactions (79.1%) were mild, limited to the skin. Most of the patients (92.1%) reached the full maintenance dose of 100 μg. This dose was reached by a significantly larger number of patients receiving RVIT compared to CVIT (100 and 82.7%, respectively; p = 0.01). None of the patients experienced exacerbation of their concurrent chronic disease during VIT. Conclusion: VIT can be performed safely and efficiently in patients with risk factors for immunotherapy. In these patients RVIT appears to be safer and more efficient than CVIT.

Although chronic spontaneous urticaria (CSU) affects all age groups, data regarding CSU in adolescents is scarce.To characterize the epidemiology, demographics, and comorbidities associated with CSU in a large, cross-sectional nationwide population of adolescents.Medical records of 16-year-old candidate conscripts to the Israeli Defense Forces were reviewed. Data were collected on the prevalence and severity of CSU, as well as the demographics, medical comorbidities, medication use, and blood test results of affected individuals.Medical records of 1,108,833 consecutive 16-year-old adolescents were reviewed. A total of 6617 (0.6%) adolescents received CSU diagnoses. CSU was increased in female conscripts (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.07-1.19, P .001) and adolescents with higher socioeconomic scores (OR 1.92, 95% CI 1.56-2.32, P .001). Individuals with CSU were significantly more likely to have allergic diseases, including food allergy (OR 7.31, 95% CI 6.13-8.72), allergic rhinitis (OR 2.9, 95% CI 2.71-3.11), atopic dermatitis (OR 2.35, 95% CI 2.03-2.72), and asthma (OR 1.46, CI 1.35-1.57).Our work provides an account of CSU in a large cohort of adolescents. We found a strong link between CSU and atopic diseases. Further investigation is needed to decipher the mechanism underlying this observed association.

Background Unverified penicillin allergy label has negative health implications. To address this, several delabeling methods have been proposed. Objectives To appraise the long-term outcomes of the penicillin allergy evaluation in ambulatory patients, focusing on subsequent use of penicillins in individuals found not allergic. A secondary objective was to examine the consistency between the evaluation's recommendations and the allergy label. Methods A retrospective medical records review and phone survey were carried out in ambulatory patients who were evaluated for suspected penicillin allergy in our allergy unit. Patients with an uneventful oral challenge test (OCT) were interviewed regarding subsequent use of penicillins. Medical records were examined for antibiotic prescriptions and purchases. The records were also investigated for existing/erased penicillin allergy label and its consistency with the allergy evaluation. Results Six hundred thirty-nine patients with an uneventful OCT were available for the survey. During a 56-month follow-up, 70% (447 patients) had used penicillins at least once. One hundred ninety-two patients (30%) did not use penicillins. The main reason for not using penicillins was lack of a clinical indication. Three hundred thirty-five patients (51.22%) carried a penicillin allergy label in their electronic medical file in spite of an uneventful OCT. Conclusions Penicillin allergy annulling via OCT has proven to be effective. Most of the patients who previously avoided penicillins have reused penicillins safely.

Background: Immediate allergic reactions to β-lactam antibiotics are considered to be one of the most important drug hypersensitivities. A positive skin test (ST) with a combination of major and minor penicillin determinants is usually sufficient to recommend avoidance of the culprit drug, whereas a negative ST is usually followed by an oral challenge test (OCT). Recently, concern has been raised regarding the role of amoxicillin (AMX) ST in the diagnosis of AMX allergy. Objective: The aim of this study was to examine the additive value of AMX determinants in STs of patients with immediate hypersensitivity reactions to AMX or AMX-clavulanate (AMX-C). Methods: Patients with a history of immediate AMX or AMX-C allergy underwent an ST using a combination of penicilloyl-polylysine (PPL) and minor determinants as well as AMX. An ST with AMX-C was added when appropriate. Results: Thirty-one patients were evaluated. Eight patients, all of them with a history of AMX allergy, had positive reactions only to the AMX component. Two patients with AMX-C allergy had a positive ST reaction only to the AMX-C component. Moreover, only 14 patients (13 with AMX and 1 with AMX-C allergy) had a positive reaction to PPL, whereas most patients (54.8%) had positive reactions to other determinants. One patient, who was positive for AMX, developed several urticarial lesions after the test. Conclusions: Skin testing with AMX and AMX-C is mandatory in patients with immediate allergy to these drugs. Failure to perform it may result in a false-negative ST jeopardizing these patients with anaphylactic reactions during a hazardous OCT.

Heart failure is a major cause of death and disability and poses a significant public health concern. Approximately half of the patients admitted with heart failure, have preserved left ventricular ejection fraction. The association between systolic blood pressure (SBP) and long-term outcome in this group has not been well established.The aim of our study is to evaluate the association between admission SBP and short term and long-term mortality outcomes in patients with heart failure and preserved systolic function.1230 consecutive patients presenting with preserved left ventricular (LV) systolic function (defined as an LV ejection fraction ≥40%) were included in this survey. Patients were divided into quartiles according to admission SBP: low admission SBP (127mmHg), intermediate admission SBP (128-145mmHg), high admission SBP (146-170mmHg) and very-high admission SBP (170mmHg). Primary outcome included in hospital, one and four year mortality rates.Elevated admission SBP was found to be associated with improved short and long-term mortality (HR=0.25 95% CI - 0.09-0.7, p=0.007 and HR=0.7 95% CI - 0.56-0.88, p=0.002 for the highest versus low SBP group, respectively). This finding was most notable in patients with acute heart failure and patients with ejection fraction≥50%.Elevated admission SBP is associated with a favorable short and long-term outcome in patients with heart failure and preserved systolic function.Low admission SBP is an independent predictor for short and long-term mortality in patients with HF and PSF.

Introduction Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. Methods Sprague–Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 – no central antidotal treatment (n = 10); group 2 – treated with midazolam (MID) at 30 min after poisoning (n = 9), group 3 – treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n = 9) and controls (n = 6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel 1H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. Results All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID + SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3 h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24 h after poisoning. MID and MID + SCOP prevented much of the 3 h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4–0.75 (p Conclusions MR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties.

Background Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life. Although the condition can be controlled with phototherapy and/or a combination therapy of antihistamines and leukotriene antagonist in most patients, a subset of patients require additional therapy with omalizumab; however, efficacy data are sparse. Objective The objective of this study was to determine the efficacy and safety of omalizumab for treating SU. Methods A case series of 5 patients with SU refractory to antihistamine and leukotriene antagonist combination who were treated with omalizumab is described. In addition, a systematic review of studies evaluating patients with SU treated with omalizumab was conducted. The primary outcome was partial/complete clinical response. Secondary outcomes were 10-fold decreases in the baseline minimal urticarial dose and adverse events. Results Our case series included 5 patients with SU. Monthly omalizumab doses of 150 to 600 mg resulted in clinical improvement in all patients and complete remission in 4. No adverse effects were reported. The systematic review included 22 studies (48 patients). All patients failed to control disease with antihistamines before omalizumab treatment. Patients received omalizumab at monthly doses of 150 to 750 mg over a follow-up period of 4 to 200 weeks. Thirty-eight patients (79%) experienced clinical improvement. Four patients (11%) had mild adverse effects. Conclusions Omalizumab provided clinical benefits in approximately 80% of patients with SU. Patients failing to improve on standard omalizumab doses may benefit from higher monthly dosages.

Organophosphates (OP) are used extensively as pesticides and as chemical weapons. Cardiotoxicity is a major concern in survivors of the acute poisoning. To characterize the delayed cardiac effects of OP, rats were poisoned by intraperitoneal administration of dichlorvos. In group I, poisoning (0.25-, 0.75-, 1.4-LD50) was followed by application of atropine and obidoxime. In group II, poisoning (0.35-, 0.5-LD50) was done without antidotes. Cardiac evaluation included electrocardiography and echocardiography 2- and 6-week post-exposure, arrhythmia susceptibility following administration of Isoproterenol (150 mcg/kg), and histological evaluation. All poisoned animals displayed cholinergic symptoms. In group I, all animals exposed to 1.4-LD50 (n = 3) had profound convulsions and died despite antidote treatment. However, in the lower doses, all animals survived and no cardiac abnormalities were noted during follow-up. In group II, six animals had convulsions and died. Surviving animals had mild but significant prolongation of corrected QT at both 2 and 6 weeks, compared to shams. There were no notable echocardiographic, gravimetric, or histological differences between poisoned and sham animals. Our data indicate that dichlorvos poisoning is associated with QT prolongation without anatomical or histopathological abnormalities. This new model can be used to elaborate the molecular mechanism\s of QT prolongation following OP poisoning.

Objective Exertional leg pain is a characteristic musculoskeletal manifestation of familial Mediterranean fever (FMF). We aimed to define the frequency and characteristics of exertional leg pain in a large cohort of FMF patients and to evaluate for additional signs and symptoms of spondyloarthritis (SpA) in this patient population. Methods FMF patients were allocated into study or control groups based on the presence or absence of exertional leg pain. Randomly selected patients underwent magnetic resonance imaging (MRI) of the ankle as well as plain radiography of the sacroiliac joints. Results The prevalence of exertional leg pain among the 170 FMF patients included in the study was 58.2%. Patients with exertional leg pain had significantly more joint attacks (74.7% versus 40.8%; P < 0.0001), fever attacks (35.4% versus 15.5%; P = 0.004), and pleuritis attacks (48.5% versus 29.6%; P = 0.013) as well as more attacks per year. Elevations of inflammation markers were significantly more frequent among the study group (for the erythrocyte sedimentation rate, 44.4% of patients versus 21.1% of patients; P = 0.016) (for the C-reactive protein level, 48.4% of patients versus 31.8% of patients; P = 0.013), and M694V homozygosity was more prevalent among the study group (45.5% versus 21.1%; P = 0.001). Signs compatible with enthesopathy on MRI were observed in 73.5% of patients in the study group and in 33.3% of patients in the control group (P = 0.046). Definite SpA was diagnosed in 41.2% of the patients in the study group compared to none of the controls (P = 0.07) (odds ratio 1.7 [95% confidence interval 1.2–2.3]). Conclusion Exertional leg pain is a common manifestation of FMF and is a marker of a more severe disease phenotype. Additionally, exertional leg pain is frequently associated with sacroiliitis and an underlying ankle enthesopathy and should therefore be considered a new feature of SpA.

We aimed to evaluate the performance of medical personnel in using the IB1 topical protective lotion on their hands and wrists together with standard disposable medical gloves, compared to standard-issued medical chemical protective gloves. This randomized cross-over study included 144 medical personnel. Primary endpoints were time-to-completion of autoinjection; success rate, number of attempts, and time-to-achieve successful endotracheal intubation; time-to-achieve satisfactory tube fixation; time-to-draw and inject the content of an ampoule; and the total time-to-perform all medical procedures. Secondary endpoints included the subjective assessment of convenience to perform these four procedures with each protective measure. Mean time was significantly shorter using IB1 compared to chemical protective gloves for tube fixation, ampoule drawing, and the total time-to-perform all procedures (58.6±22.7 seconds vs. 71.7±29.7; 31.5±21.8 vs. 38.2±19.4; 137.4±56.1 vs. 162.5±63.6, respectively; P.001 for all). For all medical procedures, the use of IB1 was reported as significantly more convenient than the use of chemical protective gloves (P.001 for all comparisons). IB1 with standard medical gloves significantly shorten the time-to-perform medical procedures requiring fine motor dexterities and is subjectively more convenient than chemical protective gloves. IB1 should be considered as an appropriate alternative for medical teams in a chemical event.

Organophosphates are highly toxic substances, which cause severe brain damage. The hallmark of the brain injury is major convulsions. The goal of this study was to assess the spatial and temporal MR changes in the brain of paraoxon intoxicated rats. T2-weighted MRI and ¹H-MR-spectroscopy were conducted before intoxication, 3 h, 24 h, and 8 days postintoxication. T2 prolongation mainly in the thalami and cortex was evident as early as 3 h after intoxication (4-6% increase in T2 values, P 20% decrease, P 15%, P < 0.05). Animals who succumbed had extensive cortical edema, significant higher lactate levels and a significant decrease in NAA/creatine and NAA/choline levels compared to animals which survived the experiment. Organophosphates-induced brain damage is obvious on MR data already 3 h postintoxication. In vivo spectroscopic changes are more sensitive for assessing long-term injury than T2-weighted MR imaging. Early spectroscopic findings might be used as biomarkers for the severity of the intoxication and might predict early survival.

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.

Familial Mediterranean fever (FMF) is classically manifested with painful, irregularly recurrent, short-lasting bouts of serosal inflammation (mainly peritonitis, synovitis or pleuritis), accompanied by fever, and resolving spontaneously [1]. A rise then fall of acute-phase reactants is typical, but some patients might suffer from continuous inflammation and its associated manifestations [2]. The disease onset is usually in childhood or adolescence, but, in some patients, the initial symptoms develop later in life, during the ages of 20–40 years and sometimes even later [3]. In general, late-onset FMF has a mild phenotype and its genotype lacks the homozygous M694V genotype [3]. The clinical manifestations may vary between patients, including members of the same family and even between identical twins [4, 5]. Clinical diversity may also be seen in the same individual, with different site of attacks in different episodes.

Early respiratory support and airway (AW) control with endotracheal intubation (ETI) are crucial in mass toxicology events and must be performed while wearing chemical personal protective equipment (C-PPE).The aim of this study is to evaluate the efficiency of AW control by using second-generation supraglottic AW devices (SADs) as compared with ETI and first-generation SAD while wearing C-PPE.This is a randomized crossover trial involving 117 medical practitioners. Four AW management devices were examined: endotracheal tube, the first-generation SAD, laryngeal mask AW unique and 2 second-generation SAD, the laryngeal tube suction disposable, and supreme laryngeal mask AW (SLMA). Primary end point measured were success or failure, number of attempts, and time needed to achieve successful device insertion. Secondary end point was a subjective appraisal of the AW devices by study population.More attempts were required to achieve AW control with endotracheal tube, with and without C-PPE (P.001). Time to achieve AW control with ETI was, on average, 88% longer than required with other devices and improved with practice. The mean times to achieve an AW were longer when operators were equipped with C-PPE as compared with standard clothing. Subjectively, difficulty levels were significantly higher for ETI than for all other devices (P.0001).When compared with ETI, the use of SADs significantly shortened the time for AW control while wearing C-PPE. Second-generation SAD were superior to laryngeal mask AW unique. These finding suggest that SADs may be used in a mass toxicology event as a bridge, until definite AW control is achieved.

Sulfur mustard (SM) is an alkylating chemical warfare agent with high military significance due to its high toxicity, resistance and availability. SM was widely used in military conflicts, the last being the Iran-Iraq war with more than 100,000 Iranians exposed, one-third of whom are still suffering from late effects. The intensity of the delayed complications correlates to the extent, the area and the route of exposure. The clinical manifestations most commonly involve respiratory, ocular and dermal effects. Respiratory complications include dyspnea, cough and expectorations and various obstructive and restrictive lung diseases. Dermal complications are itching, burning sensation, blisters, dry skin, dermatitis and pigmentary changes. Ocular complications include photophobia, red eye, tearing, corneal ulcers and blindness. Although the picture remains incomplete the major mechanisms responsible for the clinical and pathological effects of SM are: DNA alkylation and cross-linking, protein modification and membrane damage in addition to induction of inflammatory mediators in the target tissues causing extensive necrosis, apoptosis and loss of tissue structure. The current report reviews long-term complications of SM exposure, focusing on new treatments tested in clinical trials conducted on humans. Such treatments include: N-acetyl cysteine, bronchodilators, corticosteroids, Interferon-gamma, furosemide and morphine for the respiratory complications. Ocular complications may entail: Invasive procedures treating corneal complication, limbal ischemia and stem cell deficiency. Treatment for dermatological complications include: anti-depressants, pimercrolimus, Unna's boot, capsaicin, phenol and menthol, Aloe vera and olive oil, curcumin and Interferon-gamma.

Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning.

Exertional leg pain is a characteristic musculoskeletal manifestation of familial Mediterranean fever (FMF). We aimed to define the frequency and characteristics of exertional leg pain in a large cohort of FMF patients and to evaluate for additional signs and symptoms of spondyloarthritis (SpA) in this patient population.FMF patients were allocated into study or control groups based on the presence or absence of exertional leg pain. Randomly selected patients underwent magnetic resonance imaging (MRI) of the ankle as well as plain radiography of the sacroiliac joints.The prevalence of exertional leg pain among the 170 FMF patients included in the study was 58.2%. Patients with exertional leg pain had significantly more joint attacks (74.7% versus 40.8%; P0.0001), fever attacks (35.4% versus 15.5%; P = 0.004), and pleuritis attacks (48.5% versus 29.6%; P = 0.013) as well as more attacks per year. Elevations of inflammation markers were significantly more frequent among the study group (for the erythrocyte sedimentation rate, 44.4% of patients versus 21.1% of patients; P = 0.016) (for the C-reactive protein level, 48.4% of patients versus 31.8% of patients; P = 0.013), and M694V homozygosity was more prevalent among the study group (45.5% versus 21.1%; P = 0.001). Signs compatible with enthesopathy on MRI were observed in 73.5% of patients in the study group and in 33.3% of patients in the control group (P = 0.046). Definite SpA was diagnosed in 41.2% of the patients in the study group compared to none of the controls (P = 0.07) (odds ratio 1.7 [95% confidence interval 1.2-2.3]).Exertional leg pain is a common manifestation of FMF and is a marker of a more severe disease phenotype. Additionally, exertional leg pain is frequently associated with sacroiliitis and an underlying ankle enthesopathy and should therefore be considered a new feature of SpA.

Objectives The objective of this study is to characterize the common risk factors, clinical presentation, imaging findings, treatment and outcome of nocardial infection. Design and settings A retrospective cohort study. We reviewed the charts of all patients with nocardiosis in the Chaim Sheba Medical Center, a tertiary medical center in Israel, between the years 1996 and 2011. Results A total of 39 patients who had positive culture of Nocardia were analyzed. The majority of our patients were immunocompromised (74.5%), mostly due to corticosteroid therapy. None had HIV/AIDS. The clinical presentation was either acute or a chronic smoldering illness. The three major clinical syndromes were pleuropulmonary, neurological and skin/soft tissue infection about 20.5% each. Pathology in the lungs was seen in most of the patients by CT scan; discrete nodules and wedge shaped pleural based consolidations were the most frequent findings. Brain lesions consistent with abscesses were detected in 10 patients by brain imaging. Some cases had relapsing disease in spite of antimicrobial treatment. 25% of examined isolates were resistant to trimethoprim/sulfamethoxazole. The duration of intravenous antimicrobial treatment ranged from one month to over a year in the severe cases. One year mortality rate was 32%. Conclusion Nocardiosis requires a high clinical index of suspicion in order to diagnose and treat promptly. Disease extent and bacterial susceptibility have important implications for prognosis and treatment.

The most common ophthalmologic manifestation of hypertension is hypertensive retinopathy. Our study was designed to evaluate the factors that determine retinal vessel caliber in hypertensive subjects.During a 6-month period, retinal photographs were taken of participants during a routine yearly check-up. The photographs were evaluated by an ophthalmologist and the diameters of the individual retinal vessels were measured and summarized by a computer program. Data including patient's medical history, physical examination and laboratory evaluations were collected. The findings of the ophthalmologic examinations were analyzed with respect to the relevant systemic data.We evaluated 285 subjects (43 women) with an average age of 62 ± 9 years (range 33-87). Hypertension was reported in 204 (71.6%) subjects and diabetes mellitus in 60 subjects (21%). The arteriolar calibers were inversely related to age (R = - 017; p = 0.01). Retinal arteriolar and venular calibers were wider in smokers and in subjects with dyslipidemia. History of hypertension was not associated with any vascular changes. However, retinal arteriolar caliber was inversely related to blood pressure levels. Diuretic treatment was associated with narrow retinal venular caliber.The association between different cardiovascular risk factors and hypertensive retinopathy is complex. Effective blood pressure control has a beneficial effect on the vascular changes in the retina.

Organophosphates are highly toxic substances, which cause severe brain damage. The hallmark of the brain injury is major convulsions. The goal of this study was to assess the spatial and temporal MR changes in the brain of paraoxon intoxicated rats. T2-weighted MRI and ¹H-MR-spectroscopy were conducted before intoxication, 3 h, 24 h, and 8 days postintoxication. T2 prolongation mainly in the thalami and cortex was evident as early as 3 h after intoxication (4-6% increase in T2 values, P0.05). On spectroscopy, N-acetyl aspartate (NAA)/creatine and NAA/choline levels significantly decreased 3 h postintoxication (20% decrease, P0.005), and 3 h lactate peak was evident in all intoxicated animals. On the 8th day, although very little T2 changes were evident, NAA/creatine and choline/creatine were significantly decreased (15%, P0.05). Animals who succumbed had extensive cortical edema, significant higher lactate levels and a significant decrease in NAA/creatine and NAA/choline levels compared to animals which survived the experiment. Organophosphates-induced brain damage is obvious on MR data already 3 h postintoxication. In vivo spectroscopic changes are more sensitive for assessing long-term injury than T2-weighted MR imaging. Early spectroscopic findings might be used as biomarkers for the severity of the intoxication and might predict early survival.

The threat of using chemical compounds by terrorists as weapons of mass casualties has been a rising concern in recent years. Carbamates, a group of reversible acetylcholinesterase inhibitors, could be potentially involved in such toxic mass casualty events because they can cause cholinergic crisis that could lead to fatality, similar to that of organophosphate poisoning. The medical management of carbamate poisoning consists of supportive measures and specific antidotal treatment, that is, the anticholinergic compound atropine. The administration of oximes, acetylcholinesterase reactivators, in carbamate poisoning is controversial because of the potential toxicity of oximes in conjunction with carbamate especially in the case of the carbamate--"carbaryl" poisoning. However, recent data suggest that this concern may be unwarranted. In this article, we review the current data regarding the pros and cons of using oximes against carbamates poisoning in a mass casualties event scenario. We also propose a new decision-making algorithm for the medical first responders in a mass casualties event suspected to be caused by a cholinergic substance (organophosphate or carbamate). According to this algorithm, treatment should consist of atropine and oxime regardless of the exact toxic compound involved. We speculate that in a mass casualties event, the benefits of using oximes outweigh the low level of potential risk.