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Daniella Vronsky,1 Amit Finkelstein,2 Shachaf Shiber,2,3 Moshe Heching,2,4 Noa Eliakim-Raz,1,2 Irit Ayalon-Dangur1 1Internal Medicine Department, Ward E, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel; 2Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Rheumatology, Rabin Medical Center, Petach Tikva, Israel; 4Department of Pulmonology, Rabin Medical Center, Petach Tikva, IsraelCorrespondence: Daniella Vronsky, Email vronskydaniella@gmail.comAbstract: Lofgren’s syndrome is a unique manifestation of sarcoidosis presenting with erythema nodosum, bilateral hilar lymphadenopathy and migratory polyarthritis. A concurrent vitamin B12 deficiency is not well described and may be related to a rare gastrointestinal manifestation of sarcoid and Lofgren’s syndrome. We describe a case of a 57-year-old male presented with migratory polyarthritis, erythemic nodules, edema of his legs and fever. His laboratory tests showed anemia with a profound vitamin B12 deficiency. Imaging demonstrated bilateral hilar adenopathy. Pathology revealed non-necrotizing granulomas consistent with sarcoidosis. The patient was started on prednisone and vitamin B12 supplements with improvement of his complaints and vitamin B12 levels. Sarcoidosis can manifest in many extrapulmonary organs, including the gastrointestinal tract, resulting in nutritional deficiencies, such as vitamin B12 deficiency. Treatment of these nutritional deficiencies includes treatment with steroids, as well as vitamin supplementation. We suggest this case to be a rare manifestation of gastrointestinal involvement in Lofgren syndrome; however, a biopsy from the GI tract was not performed to confirm the diagnosis. An informed consent was obtained from the patient. An institutional approval was not required for the publication of this case.Keywords: vitamin B12, sarcoidosis, Lofgren’s syndrome, gastrointestinal tract

Safwat Saleem,1 Roman Sonkin,2 Iftach Sagy,3,4 Refael Strugo,2 Eli Jaffe,2 Michael Drescher,1,5 Shachaf Shiber1,5 1Emergency Department, Rabin Medical Center – Beilinson Hospital, Petach-Tikva, Israel; 2Magen David Adom (Israel National Emergency Medical Service), Ramat Gan, Israel; 3Rheumatology Unit, Soroka Hospital, Be’er Sheva, Beer Sheva, Israel; 4Faculty of Medicine, University of the Negev, Be’er Sheva, Israel; 5Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Shachaf Shiber, Department of Emergency Medicine, Rabin Medical Center – Beilinson Hospital, 39 Jabotinski St, Petach Tikva, 4941492, Israel, Tel +972-54-4699750, Email sofereret@gmail.comObjective: Survival after out-of-hospital cardiac arrest (OHCA) depends on multiple factors, mostly quality of chest compressions. Studies comparing manual compression with a mechanical active compression-depression device (ACD) have yielded controversial results in terms of outcomes and injury. The aim of the present study was to determine whether out-of-hospital ACD cardiopulmonary resuscitation (CPR) use is associated with more skeletal fractures and/or internal injuries than manual compression, with similar duration of cardiopulmonary resuscitation (CPR) between the groups.Methods: The cohort included all patients diagnosed with out-of-hospital cardiac arrest (OHCA) at a tertiary medical center between January 2018 and June 2019 who achieved return of spontaneous circulation (ROSC). The primary outcome measure was the incidence of skeletal fractures and/or internal injuries in the two groups. Secondary outcome measures were clinical factors contributing to skeletal fracture/internal injuries and to achievement of ROSC during CPR.Results: Of 107 patients enrolled, 45 (42%) were resuscitated with manual chest compression and 62 (58%) with a piston-based ACD device (LUCAS). The duration of chest compression was 46.0 minutes vs. 48.5 minutes, respectively (p=0.82). There were no differences in rates of ROSC (53.2% vs.50.8%, p=0.84), cardiac etiology of OHCA (48.9% vs.43.5%, p=0.3), major complications (ribs/sternum fracture, pneumothorax, hemothorax, lung parenchymal damage, major bleeding), or any complication (20.5% vs.12.1%, p=0.28). On multivariate logistic regression analysis, factors with the highest predictive value for ROSC were cardiac etiology (OR 1.94;CI 2.00– 12.94) and female sex (OR 1.94;CI 2.00– 12.94). Type of arrhythmia had no significant effect. Use of the LUCAS was not associated with ROSC (OR 0.73;CI 0.34– 2.1).Conclusion: This is the first study to compare mechanical and manual out-of-hospital chest compression of similar duration to ROSC. The LUCAS did not show added benefit in terms of ROSC rate, and its use did not lead to a higher risk of traumatic injury. ACD devices may be more useful in cases of delayed ambulance response times, or events in remote locations.Keywords: cardiopulmonary resuscitation, CPR, fractures, active compression-decompression device, ACD

Resumo Introdução: A crioglobulinemia é uma vasculite de pequenos vasos mediada por imunocomplexos que normalmente envolvem a pele, os rins e os nervos periféricos. A síndrome antifosfolipídica (SAF) é um transtorno da hipercoagulabilidade autoimune que provoca trombose dos vasos sanguíneos. Pode se manifestar como um distúrbio microtrombótico que afeta múltiplos órgãos, denominado SAF catastrófica. Objetivo: Esta série de casos objetiva descrever os desafios de diagnóstico e tratamento que surgem quando esses dois graves transtornos estão presentes simultaneamente no mesmo paciente. Métodos: Foram descritos quatro pacientes internados em nosso hospital em decorrência de danos graves a múltiplos órgãos mediados pela vasculite crioglobulinêmica com SAF concomitante. Resultados: As manifestações clínicas incluíram úlceras de perna, livedo reticular, insuficiência renal e neuropatia periférica. As etiologias sugeridas para a combinação de síndromes foram a hepatite C, o lúpus eritematoso sistêmico e a doença mieloproliferativa retal associada a linfoma de zona marginal tipo células B. Todos os pacientes foram tratados com anticoagulantes, altas doses de corticosteroides, rituximabe, gamaglobulinas intravenosas e troca de plasma. Conclusão: A rara associação entre a SAF grave ou catastrófica e a crioglobulinemia deve ser considerada por médicos que atendem pacientes com isquemia ou necrose de múltiplos órgãos.

Objectives: To assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI)., Methods: Prospective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed., Results: Of 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4-100), specificity 88.4% (160/181; 83.7-93.1) and negative predictive value 98.8% (160/162; 97.1-100)., Discussion: BV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Atrial fibrillation (AF) is prevalent in individuals with essential hypertension (HTN). Masked hypertension occurs in up to 15% of the general population and is associated with adverse clinical outcome. The aim of the current study was to evaluate the prevalence of masked hypertension in apparently normotensive individuals with lone AF. A cross sectional analytical study performed at the Rabin Medical Center included all patients > 18 years who visited the emergency department (ED) in the years 2018-2021 with idiopathic AF, had normal blood pressure (BP) values during their ED visit and did not have a history of hypertension or current use of anti-hypertensives. Ambulatory blood pressure monitoring (ABPM) was performed in all eligible patients within 30 days from ED visit. Data collected included information from the ED visit and data extracted from the monitoring device. A total of 1258 patients were screened for eligibility, of which 40 were included in the analysis. The average age was 53.4 ± 16 years, 28 patients (70%) were males. Overall, 18 individuals (46%) had abnormal BP values according to the 2017 ACC/AHA guidelines for the diagnosis of hypertension. Of these, 12 had abnormal 24-h BP average (≥ 125/75 mmHg), one had isolated daytime abnormal average (≥ 130/80 mmHg) and 11 had isolated night time abnormal average (≥ 110/65 mmHg). Masked hypertension is prevalent in patients with lone AF without a diagnosis of HTN and performing ABPM in such individuals should be strongly considered., (© 2023. The Author(s).)

Introduction: The success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance., Methods: We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls., Results: In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients., Discussion: These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Safra, Tamari, Polak, Shiber, Matan, Karameh, Helviz, Levy-Barda, Yahalom, Peretz, Ben-Chetrit, Brenner, Tuller, Gal-Tanamy and Yaari.)

The diagnosis of adult-onset Still disease (AOSD) is challenging with ambiguous clinical presentation and no specific serological markers. We aim to evaluate the diagnostic utility of clinical, laboratory and serum ferritin features in established AOSD patients. We included all patients >18 years who were admitted to 2 tertiary medical centers (2003-2019) with serum ferritin above 1000 ng/mL. AOSD patients and non-AOSD controls were matched in 1:4 ratio for age and sex. The primary outcomes were sensitivity, specificity, positive/negative likelihood ratio and area under the curve (AUC) using clinical and laboratory characteristics based on the Yamaguchi classification criteria, in addition to serum ferritin. We identified 2658 patients with serum ferritin above 1000 ng/m, of whom 36 diagnosed with AOSD and 144 non-AOSD matched controls. Presence of arthralgia/arthritis showed the highest sensitivity (0.74), specificity (0.93), positive likelihood ratio (10.69), negative likelihood ratio (0.27) and AUC (0.83, 95% confidence interval 0.74-0.92) to the diagnosis of AOSD. On the other hand, serum ferritin showed variation and poorer results, depends on the chosen ferritin cutoff. Joint involvement showed the best diagnostic utility to establish the diagnosis of AOSD. Although clinicians use often elevated ferritin levels as an anchor to AOSD, the final diagnosis should be based on thorough clinical evaluation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The HEART Pathway is a diagnostic protocol designed to identify low-risk patients with chest pain who can be safely discharged from the emergency department (ED) without hospitalization. Studies have reported a negative bias in identifying myocardial ischemia in females versus males and a different clinical pattern of cardiac ischemia across genders. This study sought to determine if the HEART Pathway recommendations are affected by negative bias in females. Materials and Methods: A retrospective cohort study was conducted in the ED of an academic tertiary medical center. Admission/discharge decisions made by physicians in male and female patients presenting with chest pain in 4/2014-7/2019 were compared with HEART Pathway protocol predictions. Probabilities were estimated with logistic regression analysis, and odds ratios and 95% confidence intervals were calculated. Results: The cohort included 772 patients, 485 male (63%) and 287 female (37%), of median age 54 years. On the basis of their presenting symptoms, 278 patients (36%) were admitted by the ED physician and 494 (64%) were discharged. Using the HEART Pathway protocol, 227 patients (29.4%) would be expected to be admitted and 545 (70.6%) discharged. The real-life admission rate was higher than possible with the HEART Protocol ( p  = 0.001). In a regression model, male sex was a significant factor favoring admission among the patients for whom the HEART Pathway predicted admission ( p  = 0.007). Conclusions: As the HEART Pathway is a validated risk-stratification tool, there is a high likelihood that serious coronary artery disease may be overlooked in women, even those who seek timely medical assistance.

Goal: The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge., Background: Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden., Methods: Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days., Results: The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P<0.001) and surgical interventions (13.3% vs. 0.8%, P<0.001) within the same hospital admission, compared with the standard-care group. In the intervention group, 24 patients were discharged from the ED, of whom 17 patients visited the IBD clinic (median 5 d postdischarge) and the majority were referred to ambulatory IBD-MDT services (dietitian: 46.7%, psychologist: 6.7%, advanced endoscopist: 8.9%, and proctology services: 6.7%). The intervention group had significantly fewer ED revisits than the standard-care group (30 d: 4.4% vs. 19.8%, P=0.013; 90 d: 4.4% vs. 35.9%, P<0.001; 180 d: 6.7% vs. 43%, P<0.001)., Conclusion: Proactive specialized ED assessments and IBD-MDT interventions after a hospital discharge were preferable; they significantly reduced the ED revisit rate for at least 6 months., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Necrotizing soft tissue infection (NSTI) is a life-threatening infection associated with high morbidity and mortality. Treatment consists of surgery and antibiotics. Many studies have addressed NSTI and its subtypes, but few have reviewed the clinical, radiological, and pathological differences between the polymicrobial and monomicrobial diseases. The objective of our study was to evaluate the clinical, radiological, and pathological features of patients with polymicrobial (NSTI I) and monomicrobial (NSTI II) infections and their association with outcome., Methods: The cohort consisted of patients hospitalized with NSTI at a tertiary medical center in 2002-2019. The medical charts were reviewed for clinical, radiological, and pathological features. Findings were compared between patients in whom blood/tissue bacterial cultures yielded one or more than one pathological isolate. The primary clinical outcome measure of the study was all-cause mortality at 90 days. Secondary outcomes were duration of hospitalization, intensive care unit (ICU) admission, score on the LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), and need for vasopressor treatment., Results: A total of 81 patients met the inclusion criteria: 54 (66.6%) with monomicrobial NSTI and 27 (33.3%) with polymicrobial NSTI. There were no significant between-group differences in in-hospital and 90-day mortality. On multivariate analysis, the monomicrobial disease group had a significantly higher 90-day mortality rate in addition to higher rates of in-hospital mortality, ICU admission, and vasopressor use than the polymicrobial disease group., Conclusion: Our study is the first to compare the clinical, radiological, and pathological differences between the two most common types of NSTI. The results demonstrate better prognosis for polymicrobial NSTI, with minimal ICU stay, lower mortality, and lower use of vasopressors., Level of Evidence: Prognostic and epidemiological, level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Given rising antibiotic resistance and increasing use of delayed prescription for uncomplicated lower urinary tract infections (UTI), patients at risk for treatment failure should be identified early. We assessed risk factors for clinical and microbiological failure in women with lower UTI. This case-control study nested within a randomized clinical trial included all women in the per-protocol population (PPP), those in the PPP with microbiologically confirmed UTI, and those in the PPP with UTI due to Escherichia coli. Cases were women who experienced clinical and/or microbiologic failure; controls were those who did not. Risk factors for failure were assessed using multivariate logistic regression. In the PPP, there were 152 clinical cases for 307 controls. Among 340 women with microbiologically confirmed UTI, 126 and 102 cases with clinical and microbiological failure were considered with, respectively, 214 and 220 controls. Age ≥52 years was independently associated with clinical (adjusted OR 3.01; 95%CI 1.84-4.98) and microbiologic failure (aOR 2.55; 95%CI 1.54-4.25); treatment with fosfomycin was associated with clinical failure (aOR 2.35; 95%CI 1.47-3.80). The association with age persisted among all women, and women with E. coli-related UTI. Diabetes was not an independent risk factor, nor were other comorbidities. Postmenopausal age emerged as an independent risk factor for both clinical and microbiological treatment failure in women with lower UTI and should be considered to define women at-risk for non-spontaneous remission, and thus for delayed antibiotic therapy; diabetes mellitus was not associated with failure., Competing Interests: The authors have declared that no competing interests exist.

Background: Few studies have addressed external validity of randomized controlled trials in infectious diseases. We aimed to assess the external validity of an investigator-initiated trial on treatment for uncomplicated urinary tract infection., Methods: In the original study, women ( n  = 513) with urinary tract infection were randomized to nitrofurantoin or fosfomycin treatment in three countries between 2013 and 2017. In the present study we compared women who were screened for enrolment but excluded to women who participated in the trial, both groups in Israel. The primary outcome was the rate of emergency department index visits resulting in hospitalization within 28 days., Results: We compared 127 included to 110 excluded patients. The most common reasons for exclusion were logistic difficulties in recruitment and antibiotic use in the preceding month. Included patients tended to be older [39 (IQR 29-59) vs. 35.5 (IQR 24-56.25 years)], more likely to have history of recurrent infection and had more urinary symptoms. Among excluded patients, 13.6% (15/110) had initial visits resulting in hospitalization compared to 3.1% (4/127) of included participants ( p  = .003). The rate of emergency department visits within 28 days was similar in both groups. Clinical and microbiological failures were significantly more common in included patients [26% (33/127) vs. 1.8% (2/110), p  < .001; 7.9% (10/127) vs. 0% (0/110), p  = .003; respectively]., Conclusions: While differences were observed between included and excluded patients, the excluded group did not represent a more 'complicated' population. The present study shows the importance of collecting data on patients excluded from randomized controlled trials.

Background and Aims: Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome., Methods: Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30., Results: Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4 ± 330.3 pg/ml vs. 432.5 ± 196.4 pg/ml vs. 230.1 ± 85.5 pg/ml, respectively; P < 0.001) and positively correlated with the number of stenosed/occluded coronary arteries on angiography ( P < 0.001). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54, P = 0.01) as well as with recurrent ACS ( P = 0.04) and stroke ( P = 0.02) at 6 months., Conclusions: Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome., Competing Interests: All authors declare they have no conflicts of interest., (Copyright © 2021 Shachaf Shiber et al.)

Background: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs., Objectives: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type., Methods: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration., Results: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route., Conclusions: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

Background: Achieving a high degree of diagnostic accuracy of infections in the emergency department (ED) is crucial since a delay in diagnosis can lead to increased mortality, whereas overdiagnosis can lead to antibiotic overprescription. Limited data are available as to ED diagnostic accuracy of infections. The aim of this study was to demonstrate the degree of discordance of an ED diagnosis of pneumonia in relation to an internal medicine ward's discharge diagnosis of hospitalized adults., Methods: We reviewed the records of all adults hospitalized in internal wards from November 2017-January 2018 diagnosed with an acute infection by an ED physician. The primary outcome was the discordance degree of an ED pneumonia diagnosis compared to the internal ward discharge diagnosis. The influence comorbidities and clinical characteristics on the diagnostic discordance were also evaluated., Results: The study included 875 adults; 434 were admitted with an ED diagnosis of a specific infection. Pneumonia was the most frequent ED diagnosis (n = 195, 45%), of them, 56 (29%) were discordant diagnosis in the internal ward., Conclusion: Interpretation of chest X-rays with the assistance of a radiologist might help in reducing overdiagnosis and minimize antibiotic overprescription, thus improving the ED diagnostic accuracy of pneumonia., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pain is a widespread problem, affecting both men and women; studies have found that women in the emergency department receive analgesic medication and opioids less often compared with men., Aims: The aim of this study was to examine the administration and management of analgesics by the medical/paramedical staff in relation to the patients' gender, and thereby to examine the extent of gender discrimination in treating pain., Design: This is a single-center retrospective cohort study that included 824 patients., Settings: Emergency department of tertiary hospital in Israel., Participants/subjects: The patients stratified by gender to compare pain treatments and waiting times between men and women in renal colic complaint., Methods: As an acute pain model, we used renal colic with a nephrolithiasis diagnosis confirmed by imaging. We recorded pain level by Visual Analog Scale (VAS) scores and number of VAS examinations. Time intervals were calculated between admissions to different stations in the emergency department. We recorded the number of analgesic drugs administered, type of drugs prescribed, and drug class (opioids or others)., Results: A total of 824 patients (414 women and 410 men) participated. There were no significant differences in age, ethnicity, and laboratory findings. VAS assessments were higher in men than in women (6.43 versus 5.90, p = .001, respectively). More men than women received analgesics (68.8% versus 62.1%, p = .04, respectively) and opioids were prescribed more often for men than for women (48.3 versus 35.7%, p = .001). The number of drugs prescribed per patient was also higher in men compared with women (1.06 versus 0.93, p = .03). A significant difference was found in waiting time length from admission to medical examination between non-Jewish women and Jewish women., Conclusions: We found differences in pain management between genders, which could be interpreted as gender discrimination. Yet these differences could also be attributed to other factors not based on gender discrimination but rather on gender differences., (Copyright © 2019 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Background The association between bacteriuria and adverse pregnancy outcomes has been extensively described. The current practice of screening all pregnant women for bacteriuria is challenged by recent studies. We aimed to evaluate pregnancy outcomes among women with a positive urine culture, to assess the significance of positive urinary nitrites in this setting. Methods This was a retrospective cohort study at the emergency department (ED) of the Helen Schneider Hospital for Women, Israel, during 2014-2018. This included all gravida women >18 years old within the 20th week of pregnancy or above, admitted to the ED with diverse complains, who had urinalysis collected and subsequently had a positive urine culture. Clinical and obstetric characteristics were stratified by positive vs. negative nitrites in urinalysis. The primary outcome was premature delivery, and the secondary outcomes were a composite outcome of all recorded pregnancy complications and the significance of urinalysis in predicting urinary tract infection (UTI). Results Overall, 874 pregnant women with a positive urine culture were included. Of them, 721 (79%) patients had a negative nitrite in their urine exam (NNU-group) and 153 (21%) had a positive nitrite in their urine exam (PNU-group). Escherichia coli was the most common pathogen, with significantly higher rates of growth in the PNU-group vs. NNU-group [129 (84.3%) vs. 227 (38.4%), P < 0.001]. Premature delivery was recorded with no association of symptomaticity or nitrite status. Among symptomatic women with classic symptoms of UTI, PNU was significantly associated with decreased risk for major peripartum complications [odds ratio (OR) with 95% confidence interval (CI) of 0.22 (0.05-0.94)]. Conclusion Our findings support that PNU among symptomatic pregnant women with UTI-related symptoms was associated with lower risk of developing major adverse obstetrical outcomes.

There are several methods to treat vitamin B12 deficiency (VB12d): intramuscular (IM), oral, sublingual (SL), and intranasal vitamin B12 (VB12) preparations. Large studies comparing the efficacy of SL vs. IM supplements are lacking. The aim of the present study was to compare the efficacy of SL versus the standard IM administration of VB12 in restoring B12 levels. This was a retrospective analysis of data from the computerized pharmacy records of Maccabi Health Service (MHS). Data were recorded for all patients older than 18 years of age who were prescribed VB12 during January 2014-December 2017. The main outcome was the change in levels of serum vitamin B12 (sVB12) after treatment. Overall, there were 4281 patients treated with VB12 supplements. Of them, 830 (19.3%) patients were treated with VB12 IM injections and 3451 (80.7%) with SL tablets. The mean ± SD difference between sVB12 levels before and after administration of VB12 supplements was significantly higher in the SL group vs. IM injection group (252 ± 223 vs. 218 ± 184 ng/L, p < 0.001). SL VB12 significantly increased the odds ratio (OR) for an increase of sVB12 levels, compared to the IM group, OR 1.85, CI 95% 1.5-2.3, p < 0.001. This is the largest study that documents therapy with SL preparations of VB12 sufficient and even superior to the IM route. The SL overcomes the challenges of IM injections and should be the first line option for patients with VB12d.

Antiphospholipid syndrome (APS) is a multisystem autoimmune disease most commonly associated with recurrent arterial and venous thromboembolism and recurrent fetal loss. Other possible antiphospholipid antibody (aPL)-related clinical manifestations include cardiac involvement. The heart can be involved through immune mediated and /or thrombotic mechanisms. Mortality due to cardiovascular problems is elevated in APS. However, the cardiovascular risk in patients with primary APS (PAPS) compared with lupus-related APS is yet to be established. Cardiac symptoms of APS include valve abnormalities (thickening and vegetations), coronary artery disease (CAD), myocardial dysfunction, pulmonary hypertension, and intracardiac thrombi. Heart valve lesions are the most common cardiac manifestation, observed in approximately one third of PAPS patients and usually do not cause hemodynamic significance. Deposits of immunoglobulins including anticardiolipin (aCL), and of complement components, are commonly observed in affected heart valves from these patients. This suggests that an inflammatory process is initiated by aPL deposition, eventually resulting in the formation of valvular lesion. aPL may have a direct role in the atherosclerotic process via induction of endothelial activation. Multiple traditional and autoimmune-inflammatory risk factors are involved in triggering an expedited atherosclerotic arterial disease evident in APS. It is imperative to increase the efforts in early diagnosis, control of risk factors and close follow-up, in the attempt to minimize cardiovascular risk in APS. Clinicians should bear in mind that a multidisciplinary therapeutic approach is of paramount importance in these patients. This article reviews the cardiac detriments of APS, including treatment recommendations for each cardiac complication.

Background: Early assessment of urine residual volume (URV) at admission is essential in elderly men with urinary tract infection (UTI). Large URV might predispose these patients to subsequent complications; nevertheless, only scarce data are available concerning the impact of URV on the outcomes of elderly men with UTI., Objectives: To determine the impact of URV on the outcomes of elderly men hospitalized with UTI, including:  bacteremia rates, length of hospital stay, short and long-term mortality., Methods: Eligible subjects were hospitalized men aged ≥ 65 years with a discharge diagnosis of UTI whose URV was assessed at presentation. The clinical parameters and outcomes of patients with urinary retention (≥400ml) and ones without (URV ≤ 400ml) were compared., Results: Eighty out of 184 patients (43.5%) had urinary retention while 104 (56.5%) did not. The two groups didn't differ in their demographic and clinical parameters. Large URV at admission was significantly associated with increased 30-day mortality [OR=4 (95% CI 1.15-14), p=0.03] without significant impact on bacteremia rates and length of hospitalization., Conclusions: Large URV at admission in elderly men with UTI is associated with increased 30-day mortality. Further prospective studies with different URV cutoffs are needed to explore this association and its pathophysiology.

Background: Previous studies have shown that, in a variety of health care settings, patients often do not understand what health care professionals tell them about their diagnoses and care plans; this is particularly true among male patients. Emergency department (ED) settings present unique challenges to communication with patients due to the rapid pace of activity, substantial changes in personnel over the course of the day and the week, and the need for fast decision-making processes. The aim of our study was to investigate the extent to which patients in an Israeli ED comprehended their plan of care and whether there were gender differences in this regard., Methods: We conducted a questionnaire-based prospective study, in which patients admitted to the ED at Rabin Medical Center were evaluated during the years 2014-2016. The primary outcome was patients' comprehension of their plan of care, stratified by gender of patients. Plan of care included information related to diagnosis, treatment and discharge instructions. The secondary outcome was patients' satisfaction with the instruction process., Results: One hundred seventy seven ED patients met study criteria and were asked to participate in the study; 85% of them agreed to do so. Overall, 150 ED patients aged 18-80 were recruited [75 men (50%) and 75 women (50%)]. 80% of the respondents reported a satisfactory understanding of their plan of care. Overall, no gender-related differences were found. Differences between men and women concerning satisfaction with the instructions provided by nurses were found among non-Hebrew speakers, but not among Hebrew speakers., Conclusion: Contrary to most earlier studies, patients at our ED demonstrated a high degree of self-reported adequate comprehension concerning their plan of care, and overall no gender-related differences were found. These finding may be due in part to improved training of the medical staff to better communicate with the patients and to answer their questions. In addition, patients may feel more comfortable than in the past about asking the medical staff questions regarding their plan of care and diagnosis. The main implication of this study is that physician education programs should continue to emphasize patient-physician communications skills and improving methods for providing patients with information.

Background: Medical treatment of hunger-strike patients, especially those in incarceration facilities, may pose clinical and treatment challenges for the treating physicians., Objective: The aim of our study is to describe the epidemiology and clinical and laboratory characteristics of hunger-strike prisoners presenting to the emergency department (ED) and to describe etiologies of hospitalization and complications among this group., Method: We retrospectively examined clinical and laboratory manifestations of 50 hunger-strike prisoners who were referred for evaluation to the ED after a longstanding fast., Results: After a mean of 38 (28-44) days of a hunger strike, the most common complaints were chest pain and abdominal pain (14/60 [23.3%], 13/60 [21.6%], respectively). Mean weight loss percentage was 18.5%, and most patients were bradycardic (25/40 [62.5%]), and some hypothermic (16/50, [32%]). We describe several laboratory disturbances observed in these patients; leukopenia was the most common hematologic manifestation (31/50 [62%]), and a prolonged international normalized ratio was observed in 12/29 (41.3%) patients. We hospitalized 12% of the patients; the most common hospitalization cause was bradycardia (3/6 [50%])., Conclusions: Our study found that the most common clinical symptom was chest pain, which has not been previously reported among hunger strikers. We observed a substantial number of laboratory disturbances due to muscle wasting and protein loss and due to presumed vitamin and micronutrient deficiencies. We suggest monitoring electrocardiograms for heart rate, blood count, chemistry, coagulation tests, and vitamin levels., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: During the Ramadan fast Muslims celebrate a month of prayer, dawn-to-dusk fasting, and nightly feasts. We aimed to assess whether acute pancreatitis (AP) is more common during the Ramadan fast in individuals who celebrate it., Patients and Methods: The study was carried out at the emergency department of Rabin Medical Center, Israel. We compared the occurrence of AP in a fasting population and a nonfasting population during the Ramadan versus the rest of the year., Results: Over the 10-year study period, 1167 patients were admitted to the emergency department with AP. Of these, 1069 (91.6%) were nonfasting and 98 (8.4%) were fasting. Of these, 17/98 (17.3%) fasting patients and 95/1069 (8.8%) nonfasting patients were admitted with AP during the Ramadan [relative risk: 1.12; 95% confidence interval (CI): 1.004-1.2; odds ratio (OR): 2.15; 95% CI: 1.23-3.8; P=0.01]. During the Ramadan, the rate of AP out of referrals was 0.1% (17/15 068) in fasting patients versus 0.004% (95/213 913) in nonfasting individuals (OR: 2.54; 95% CI: 1.5-4.25). During the other months of the year, the rate of AP out of referrals was 0.009% (81/86 072) in fasting patients versus 0.008% (974/1 202 405) in nonfasting individuals (OR: 1.16; 95% CI: 0.92-1.45; P<0.001)., Conclusion: We found a high rate of AP in the fasting population during the Ramadan. Physicians should be aware of this link and suspect it for fasting patients presenting with epigastric pain during the Ramadan fast.

Importance: The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI)., Objective: To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis., Design, Setting, and Participants: Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel., Interventions: Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection., Main Outcomes and Measures: The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events., Results: Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively)., Conclusions and Relevance: Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion., Trial Registration: ClinicalTrials.gov Identifier: NCT01966653.

Lower extremity deep vein thrombosis (DVT) is a frequent cause of admission to the emergency departments (ED). Although the gold standard for diagnosis is the Duplex ultrasound examination, the current study used for diagnosis of DVT in the ED by emergency physicians is the point-of-care compression ultrasound (POCUS). To compare the sensitivity and specificity of the two-point and three-point compression ultrasound (2PCUS and 3PCUS respectively) for diagnosis of lower extremity DVT in an ED management. We prospectively recruited outpatients who were admitted to the ED with suspected lower extremity DVT. Each patient underwent 2PCUS and 3PCUS performed by a trained ED physician. The ED physician recorded the results and then referred the patient to the vascular clinic for the Duplex ultrasound examination. 195 patients recruited to this study between July 2015 and June 2016 in the ED of Rabin Medical Center-Beillinson Hospital, Israel. DVT was diagnosed by Duplex examination in 48 of 195 patients (24.6%). There were significant correlations among the findings regarding the deep veins on both the 2PCUS and 3PCUS tests and on the Duplex examination (p < 0.001). DVT at any vein was correctly diagnosed with the 2PCUS in 38 of48 patients with positive findings on Duplex examination and incorrectly diagnosed (false positive) in 2 of 133 patients without DVT (sensitivity 82.76%, specificity 98.52%). DVT was correctly diagnosed with the 3PCUS in 43 of 48 DVT and incorrectly diagnosed (false positive) in 2 of133 patients without DVT (sensitivity 90.57%, specificity 98.52%). The sensitivity of the 3PCUS was significantly higher than the 2PCUS (p < 0.001), while the specificity was similar. A short training is satisfactory for achieving a good clinical capability to identify DVT by ED physicians. The 3PCUS examination preformed in the ED, is a noninvasive, accurate and quick diagnostic test for evaluation of patients presenting with signs and symptoms suggestive of a DVT. By Using 3PCUS, the ED physicians may decrease time to diagnosis, definitive care and length of stay in the ED.

There is a limited literature discussing the long-term outcome of patients admitted to the emergency department with elevated blood pressure. The aim of the present study was to evaluate outcomes of patients with hypertension who attended an emergency department. All patients with hypertension who attended an emergency department without target organ damage were evaluated. A composite end point at 18 months, which included all-cause mortality, acute coronary syndrome, cerebrovascular accident, or hospitalization for heart failure, were compared between patients with hypertension and those with normotension. Overall, 410 patients were included in the study. Baseline characteristics were similar between patients with hypertension and those with normotension, except chronic renal failure being more prevalent in patients with hypertension. The composite primary end point occurred similarly in both groups; however, hospitalization for heart failure was significantly more common in patients with hypertension. Elevated blood pressure during an emergency department visit is associated with an increased risk for hospitalization for heart failure during an 18-month follow-up period compared with normotension., (©2018 Wiley Periodicals, Inc.)

Introduction: There are no obvious guidelines for therapy of elevated blood pressure (BP) in the emergency department (ED). Diastolic BP is probably more difficult to control compared with systolic BP., Aim: To characterize patients who respond with a significant decrease in diastolic BP in the ED, whether treated or not., Methods: In this retrospective cohort study, all patients attending a tertiary care ED with elevated BP were evaluated. Clinical characteristics of patients in whom diastolic BP decreased ≥20% were compared with those in whom diastolic BP decreased <20%., Results: Overall, 391 patients were included in the final analysis (64% females), of which diastolic BP of 106 (27%) patients decreased ≥20%. Patients in whom diastolic BP decreased ≥20% were older (70.1 ± 13 years vs. 65.9 ± 16.7 years, P = 0.011) and had a history of ischemic heart disease (IHD) and cerebrovascular disease (CVA) prior to the ED visit [30 patients (28.3%) vs. 45 patients (15.8%) for a history of IHD, P = 0.005 and 16 patients (15.1%) vs. 21 patients (7.4%) for CVA, P = 0.02]., Conclusions: A history of IHD is associated with a higher decrease in diastolic BP irrespective of the use of medical treatment during the ED visit whereas a history of TIA/CVA was associated with a higher decrease in diastolic BP only in patients who were treated in the ED.

Antiphospholipid syndrome (APS) is classified as the association of a thrombotic event and/or obstetric morbidity in patients persistently positive for antiphospholipid antibodies and/or lupus anticoagulant. To evaluate the incidence of subsequent thrombosis among women diagnosed with purely obstetric APS. We retrospectively reviewed and collected demographic and clinical data from the computerized charts of all patients with obstetric APS, from 1992 to 2017. Eligibility criteria included all women diagnosed with APS, according to the 2006 revised criteria, for whom the clinical manifestations were purely obstetric. The primary endpoint was the occurrence of subsequent thromboembolic events, following diagnosis of obstetric APS. The study included 115 women diagnosed with obstetric APS. During the study's follow up period, 12 (10.4%) women developed thrombosis. Of the 12 women who developed thrombosis, 9 (75%) of the thrombotic events were arterial. The site of arterial thrombosis was cerebral in all cases. Venous thrombosis occurred in 3 (25%) women, including one in each of the following sites-pulmonary embolism, ovarian vein thrombosis and proximal leg deep vein thrombosis. Our data suggests that women with obstetric APS are at risk for subsequent long-term thrombosis, especially arterial cerebral events. We did not identify any clinical or laboratory unique features among women with obstetric APS who will eventually develop thrombosis.

Background: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission., Objectives: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors., Methods: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit., Results: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95% CI 1.27-1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95% CI 0.393-2.5)., Conclusions: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow-up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Background: Cryoglobulinemia is an immune-complex-mediated small vessel vasculitis that classically involves the skin, kidneys and peripheral nerves. Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder which causes blood vessel thrombosis. It can present as a multi-organ microthrombotic disorder which is called catastrophic APS., Objective: In this case series we aim to describe the diagnostic and management challenges that arise when these two severe disorders simultaneously present in the same patient., Methods: We describe four patients who were admitted to our hospital due to multi-organ life threatening damage mediated by cryoglobulinemic vasculitis with concurrent APS., Results: Clinical manifestations included leg ulcers, livedo reticularis, renal failure, and peripheral neuropathy. Suggested etiologies for the combined syndromes were hepatitis C, systemic lupus erythematosus and myeloproliferative disease rectal maltoma. All of our patients were treated with anticoagulation, high-dose corticosteroids, rituximab, intravenous gammaglobulins and plasma exchange., Conclusion: The rare association of severe or catastrophic APS with cryoglobulinemia in patients should be considered by physicians who treat patients with multi-organ ischemia or necrosis., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Objectives: To assess serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in disease-modifying antirheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA), to investigate the association of sTREM-1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti-cyclic citrullinated peptide (CCP) antibody and to determine the predictive value of sTREM-1 with respect to clinical response to DMARD therapy., Methods: Twenty-two consecutive patients with DMARD-naïve ERA were prospectively evaluated for serum sTREM-1 by means of ELISA at diagnosis and at the following clinic visit after prednisone and/or DMARD has been administered, and related to DAS28 and serum level of anti-CCP antibody. We compared the sTREM-1 level to that of 31 patients with established RA as well as to 24 controls., Results: Serum sTREM-1 level was significantly higher in the DMARD-naïve ERA group (212.9 ± 388.9 ρg/mL) compared to established RA group (1478.0 ± 280.0 ρg/mL, P = 0.001) and normal control (34.4 ± 7.4 ρg/mL, P < 0.001). In the ERA group, elevated basal sTREM-1 level correlated with higher DAS28-CRP score (P = 0.001, HR 3.23, 95% CI 1.4-8.12), DAS28-ESR (P = 0.04, HR 2.34 95% CI 0.1-8.12), as well as predicted higher DAS28 score at the following encounter after DMARD treatment was administered (P = 0.001, HR 3.2 95% CI 1.1-7.2). Higher serum level of sTREM-1 correlated with higher titres of anti-CCP antibody (P < 0.001)., Conclusions: Our results suggest that serum sTREM-1 may provide a novel biomarker for DMARD-naïve ERA as well as for seropositivity for anti-CCP antibody and RA activity., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Antiphospholipid syndrome (APLS) is an autoimmune hypercoagulable syndrome characterized by thrombotic and obstetric manifestations. We sought to determine the rate of APLS feature in patients tested positive for antiphospholipid antibodies (APLA) regardless of the serum level of anticardiolipin (ACL) and/or anti-β2-glycoprotein I (β2GPI) antibodies. An inception cohort of individuals who were tested positive for ACL and/or β2GPI IgG/IgM antibody, and/or lupus anticoagulant (LAC) on two occasions of at least 12 weeks apart. A total of 243 patients were included; their mean age was 40.1 ± 15.9 years. Thrombotic vascular events occurred in 118 patients (48.5%) of the entire cohort, of which 62 patients (25.5%) suffered from an arterial event and 56 patients (23%) from thrombotic venous events. Obstetrical morbidity occurred in 106 female patients (43.6%). In our cohort, we found no difference in the frequency of thrombotic or obstetric manifestations of APLS between patients with ACL IgG/IgM of low serum antibody level (<40 U) and medium-to-high level (≥40 U) and/or anti-β2GPI IgG, IgM higher than the 99th percentile vs. lower (>20 U). We suggest that in 'real life' the diagnosis of APLS should not be excluded because of low titer of APLA.

Background: Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant., Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing any BL/BLI versus any carbapenem for the treatment of sepsis. The primary outcome was all-cause mortality. A broad search was conducted with no restrictions on language, publication status or date. Two reviewers independently applied the inclusion criteria and extracted the data. Assessment of risk of bias was performed using the domain-based approach. Subgroup analyses were used to investigate heterogeneity and focus on patient groups more likely to harbour ESBL-positive bacteria. Risk ratios (RRs) with 95% CIs were calculated and pooled., Results: Thirty-one RCTs were included. There was no difference between BL/BLIs and carbapenems in terms of mortality (RR 0.98, 95% CI 0.79-1.20), without heterogeneity. No differences were observed with regard to clinical or microbiological failure and bacterial superinfections. The results were not affected by risk of bias. No differences were detected in the subgroups of patients with nosocomial infections, Gram-negative infections and neutropenic fever. Adverse events requiring discontinuation were more common with BL/BLIs, on account of an increased incidence of diarrhoea. However, Clostridium difficile-associated diarrhoea (RR 0.29, 95% CI 0.10-0.87) was more frequent with carbapenems and seizures were more frequent with imipenem (RR 0.21, 95% CI 0.05-0.93)., Conclusions: No differences in efficacy between BL/BLIs and carbapenems exist in RCTs including patient populations with a certain, albeit unknown, rate of ESBL-positive bacteria causing infections., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study is to determine the effect of comorbidity assessed by the Charlson comorbidity index (CCI) at the time of diagnosis on the outcome of antineutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV).This is a longitudinal observational study of 30 consecutive patients with AAV who were diagnosed and followed from January 1996 to December 2011. The degree of comorbidity at diagnosis and last visit was scored according to the age-adjusted Charlson comorbidity index (CCI (a)). The post hoc analysis of increment in CCI during the study period and its predictive value for patient and renal survival were analyzed.Thirty patients with AAV were included in this study. A higher CCI (a) at diagnosis was positively correlated with higher activity score of AAV (P = 0.016), a CCI (a) >5, and with an increased risk for mortality (odds ratio 12; confidence interval 1.8-79.68, P = 0.014). The mean increment (Δ) of CCI (a) during the study period was 1.26 ± 2.03 (6-5). Correlation was found between lower Δ CCI (a) and chronic kidney disease (P = 0.036) and mortality (P = 0.002).Comorbidity at the time of diagnosis of AAV is associated with reduced patient and renal survival. We suggest including the CCI score in the assessment of patients with AAV at diagnosis and at disease relapse.

Background: Glucocorticoid (GC) therapy has been shown to prevent Graves' ophthalmopathy (GO) progression following radioactive iodine (RAI) treatment. However, the optimal regimen is controversial, with studies from recent years suggesting the use of lower doses and shorter GC treatment courses., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective controlled trials comparing GC regimens versus placebo, no treatment, or other GC regimens., Results: Eight trials evaluating 850 patients fulfilled inclusion criteria. In patients with preexisting GO, standard dose prednisone (0.4-0.5 mg/kg tapered over 3 months) was very effective for prevention of GO progression (OR 0.14 [CI 0.06-0.35], p<0.01) in patients with mild to moderate GO. Two studies evaluated low-dose prednisone (0.2-0.3 mg/kg for 4-6 weeks) in patients with mild GO or risk factors, but were limited by not including patients with preexisting GO in the control groups. Therefore, the two low-dose groups were evaluated using indirect comparisons with control groups matched for age and clinical activity score, showing excellent efficacy versus no treatment or placebo (OR 0.20 [CI 0.07-0.60], p=0.004) and no significant difference compared with standard dose (OR 1.7 [CI 0.52-5.52], p=0.47). In patients without preexisting GO, steroid prophylaxis had no beneficial effect (OR 1.87 [CI 0.81-4.3]), though there were insufficient data regarding patients with risk factors for GO development. GC prophylaxis had no impact on hyperthyroidism resolution (OR 1.05 [CI 0.69-1.58]), and GC side effects were common but mild., Conclusions: Current evidence supports a three-tier approach for prevention of GO progression following RAI. Standard dose prednisone is the best validated regimen and should be used in patients with mild to moderate GO who have high risk of progression, while low dose prednisone can be used in patients with mild GO, and in patients without preexisting GO who have risk factors and are selected for GC prophylaxis. Patients without preexisting GO and without risk factors should not be treated with GC prophylaxis.

We review the concept of informed consent in clinical medicine and in research. Informed consent is a complex practice designed to protect the legal rights of the patient, to maintain ethics in support of the patient's autonomy to arrive at his own decisions related to medical interventions, to ensure appropriate quality of care, and to build trust between the physician and the patient regarding medical procedures, medication or clinical research. It must be borne in mind that the patient's signature on a document of informed consent does not automatically imply comprehension. Physicians need to provide the information about the patient's condition, and in the case of research, they need to provide an exhaustive explanation related to benefits and the risks of the research project for the patient and to society. Physicians need to be available to readily answer patients' questions. Signing an informed consent form should not become a mere bureaucratic procedure of "going through the motions". Without emphasis on delivering understandable and relevant information, tailored to the recipient and clarifying that explanations have been properly understood, informed consent becomes but a bureaucratic burden. There is an urgent need to complete the process of conveying information by a structured mechanism aimed to ensure adequate comprehension. Only then will the process of obtaining informed consent become meaningful.

Objective: This study aimed to determine the value of hypocomplementemia in predicting the renal and patient survival of patients with antineutrophil cytoplasmatic antibody-associated vasculitis (AAV)., Methods: A retrospective analysis of 30 consecutive patients who were diagnosed with AAV and followed at our hospital from 1996 to 2011 was performed. Renal outcome was determined by the Modification of Diet in Renal Disease equation. Disease outcome measures included patient survival and accrual of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) from the date of diagnosis. Logistic regression analysis was used to identify predictors of survival., Results: At presentation, 6 (20%) patients had a low C3 level, which was significantly associated with older age (p = 0.009), higher C-reactive protein (p = 0.02), a lower eGFR (p = 0.03), and anti-MPO antibody positivity (p = 0.03). A low C3 level at presentation was significantly associated with a reduced eGFR at the last study visit (p = 0.015, OR = 11; 95% CI 1.27-95.15). During a mean follow-up of 9.0 ± 6.2 years, 8 (26.6%) patients had accrued CKD that was significantly associated with low C3 levels at presentation (p = 0.002, OR = 22; 95% CI 2.36-204.7). Mortality was significantly associated with low serum C3 levels at presentation (p = 0.02)., Conclusion: We found that a low serum C3 level at the time of diagnosis was significantly associated with reduced renal and patient survival in patients with anti-MPO AAV. Our results suggest a role for complement activation in the pathogenesis of AAV., (© 2014 S. Karger AG, Basel.)

Background: Tight control of disease activity is the recommended target of therapy for rheumatoid arthritis (RA)., Objectives: To determine the outcome of RA with respect to disease activity and the rate of remission, as measured by the DAS-28, in a real-world inception cohort., Methods: We conducted an observational cross-sectional study of a single-center real-world inception cohort of 101 consecutive patients being treated for RA in 2009-2010 in a rheumatology outpatient clinic. Patients were managed at the discretion of the attending rheumatologist with the goal of achieving remission. DAS-28 scores were calculated and analyzed by clinical and treatment variables derived from the medical files., Results: Mean patient age was 58.6 +/- 13.4 years and mean duration of disease 10.7 +/- 7.9years. Disease remission (DAS-28 < 2.6) was achieved in 26.7% of patients and low disease activity (> 2 .6 DAS-28 < 3.2) in 17%. Monotherapy with a conventional disease-modifying anti-rheumatic drug (C-DMARD, 21% of patients at last follow-up) was associated with a significantly lower mean DAS-28 score and C-reactive protein level than combined C-DMARD treatment (79% of patients), and with shorter disease duration than combined treatment with C-DMARDs or C-DMARD(s)+biological DMARD (40% of patients). Rheumatoid factor and anti-cyclic citrullinated peptide positivity had no effect on DAS-28 scores. Time from diagnosis was inversely correlated with DAS-28 scores., Conclusions: The achievement of low disease activity and remission in a significant portion of our inception cohort of patients with RA suggests that the treat-to-target strategy is feasible and effective in routine clinical practice.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease with clinical manifestations of arterial and venous thrombosis, obstetric manifestations, and the presence of antiphospholipid antibodies or lupus anticoagulant. Catastrophic APS is a rare variant of APS, defined as acute failure of at least three tissues, organs or systems caused predominantly by small vessel thrombosis confirmed by histopathologic evidence. Catastrophic APS develops rapidly and leads to death in 30% of cases., Methods: We evaluated 11 patients with catastrophic APS -8 of them with a probable diagnosis of catastrophic APS and 3 with a definite diagnosis--admitted to Beilinson hospital during the period 2003-2011., Results: Overall venous events numbered 18 and overall arterial events 10. The event duration per patient was 2.6 +/- 1.2 weeks (mean +/- SD). Deep vein thrombosis of the legs was quite common (7 events), as was venous intraabdominal thrombosis (10 events). Eight patients had microangiopathic anemia with schizocytes seen in the blood smear. The mean +/- SD hemoglobin level was 10.3 +/- 3.6 g/dl and the mean +/- SD creatinine level 0.98 +/- 0.78 mg/dl. All our patients had high acute-phase reactant and all had lupus anticoagulant positivity, The most common positive antibodies were immunoglobulin G anticardiolipin (8 patients) and IgG beta2-glycoprotein (7 patients). During the events warfarin was stopped and the patients were given intravenous heparin. All the patients received steroids in variable doses. Five patients underwent plasma exchange, two patients received rituximab and two patients intravenous immunoglobulin., Conclusions: Catastrophic APS, a rare syndrome, is important because of its major morbidity and mortality among young patients.

A case is presented of Capnocytophaga bacteraemia, in a juvenile chronic arthritis (JCA) patient receiving steroids, methotrexate and rituximab. This Gram-negative bacillus commonly found in dog saliva has been described to cause illness in immune compromised hosts such as oncology patients, those receiving cytotoxic or biological drugs, alcoholics or postsplenectomy. To the best of our knowledge, this is the first report of Capnocytophaga bacteraemia following rituximab treatment.