Attitudes of Patients with Advanced Chronic Illnesses Toward Palliative Extubation in a Country Where It Is Illegal.

Background: Palliative extubation (PE) is the cessation of mechanical ventilation (MV) during terminal illness. Although PE is widely practiced in many countries, it remains illegal in others. Attitudes toward PE of patients at the highest risk for MV were scarcely explored before. Objective: To assess the attitudes of patients with advanced chronic illnesses (ACI) toward PE and other end-of-life decisions in a country where PE is illegal. Design: A prospective observational study using questionnaire-based interviews. Setting/Subjects: Patients with ACI hospitalized between 2021 and 2022 in a large tertiary center. Attitudes toward PE and mechanical ventilation were evaluated. Predictors for favoring/opposing PE were analyzed using multivariate logistical regression models. Results: A total of 152 (40% female, 75 ± 11 years) patients were included. The most common ACIs were advanced heart failure (32%), metastatic malignancy (32%), and chronic obstructive pulmonary disease (22%). Around 132 patients (87%) supported the legalization of PE, and their main reason was to avoid pain and suffering (87%). Legalization of PE would change the decision to avoid mechanical intubation in 34% of the cases. Most patients thought that the decision to perform PE should be made by the patient's physician and primary caregiver collaboratively (64%). Religious observance was an independent predictor for opposing PE (adjusted odds ratio 0.18; 95% confidence interval 0.06-0.59; p < 0.01), whereas the type of ACI was not. Conclusion: Most admitted patients with ACIs support the legalization of PE. Such policy change could have major impact on patients' end-of-life preferences. At-risk patients should be the focus of future studies in this area.

Rate and predictors of blood culture positivity after antibiotic administration: a prospective single-center study.

PURPOSE: Blood culture obtainment prior to antibiotic administration, in patients with suspected infection, is considered the best practice in international guidelines. However, there is little data regarding the effect of a single dose of antibiotics on blood culture sterilization. METHODS: We conducted a prospective study, enrolling consecutive patients with suspected infection, hospitalized in an internal medicine ward between December 2019 and January 2023. Included patients had a positive blood culture prior to antibiotic administration and a set of blood cultures taken within 24 h after a single dose of antibiotics. The rate of patients with pathogen isolation after antibiotic administration was assessed. Logistic regression was performed to examine factors associated with blood culture positivity. RESULTS: A total of 155 patients were recruited for the study of which 131 (50.8% female 77.5 ± 13.4 years) met the inclusion criteria. The overall rate of patients with a positive blood culture after a single dose of antibiotics was 42.0% (55/131 patients). Increasing time between antibiotic administration and post-antibiotic culture was an independent predictor for blood culture sterilization (odds ratio 0.89 [95% confidence interval, 0.83-0.97; p = 0.006] for every 60 min). Blood culture volume was an independent predictor for blood culture positivity in a sensitivity analysis which included 82 patients (OR = 1.26 [95% CI 1.03-1.57] for every 1 ml increase; p = 0.024). CONCLUSION: Blood culture positivity is reduced by antimicrobial therapy but remains high after a single dose of antibiotics. If cultures are not obtained prior to antibiotic administration, they should be obtained as soon as possible afterwards.

An old diagnostic tool for new indications: inpatient Holter ECG for conditions other than syncope or stroke.

Holter electrocardiography (ECG) assists in the diagnosis of arrhythmias. Its use in the inpatient setting has been described solely for the evaluation of stroke and syncope. Our aim was to assess its diagnostic value for other conditions in the internal medicine department. We included all hospitalized patients between 2018 and 2021 in a tertiary referral center. The primary outcome was a diagnostic Holter recording a new arrhythmia that led to a change in treatment. Overall, 289 patients completed a 24-h inpatient Holter ECG for conditions other than syncope or stroke, with 39 (13%) diagnostic findings. The highest diagnostic value was found in patients admitted for pre-syncope (19%), palpitations (18%), and unexplained heart failure exacerbation/dyspnea (17%). A low diagnostic yield was found for the evaluation of chest pain (5%). Heart failure with preserved ejection fraction (adjusted OR 2.3, 95% CI 1.1-5.4, p = 0.04), and baseline ECG with either a bundle branch block (AOR 4.2, 95% CI 1.9-9.2, p < 0.01) or atrioventricular block (first or second degree, AOR 5, 95% CI 2.04-12.3, p < 0.01) were among the independent predictors for a diagnostic test. Inpatient Holter ECG monitoring may have value as a diagnostic tool for selected patients with conditions other than syncope or stroke.

Serial Measurements of Neutrophil Gelatinase-Associated Lipocalin levels for Assessment of Contrast Induced Nephropathy among Chronic Kidney Disease Patients Who Underwent Elective Coronary Angiography.

BACKGROUND: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI). OBJECTIVES: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI. METHODS: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI. RESULTS: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34-17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23-12.81, P = 0.06). CONCLUSIONS: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Diagnostic delays among COVID-19 patients with a second concurrent diagnosis.

BACKGROUND: Little is known about the effect of a new pandemic on diagnostic errors. OBJECTIVE: We aimed to identify delayed second diagnoses among patients presenting to the emergency department (ED) with COVID-19. DESIGNS: An observational cohort Study. SETTINGS AND PARTICIPANTS: Consecutive hospitalized adult patients presenting to the ED of a tertiary referral center with COVID-19 during the Delta and Omicron variant surges. Included patients had evidence of a second diagnosis during their ED stay. MAIN OUTCOME AND MEASURES: The primary outcome was delayed diagnosis (without documentation or treatment in the ED). Contributing factors were assessed using two logistic regression models. RESULTS: Among 1249 hospitalized COVID-19 patients, 216 (17%) had evidence of a second diagnosis in the ED. The second diagnosis of 73 patients (34%) was delayed, with a mean (SD) delay of 1.5 (0.8) days. Medical treatment was deferred in 63 patients (86%) and interventional therapy in 26 (36%). The probability of an ED diagnosis was the lowest for Infection-related diagnoses (56%) and highest for surgical-related diagnoses (89%). Evidence for the second diagnosis by physical examination (adjusted odds ratios [AOR] 2.35, 95% confidence interval [CI] 1.20-4.68) or by imaging (AOR 2.10, 95% CI 1.16-3.79) were predictors for ED diagnosis. Low oxygen saturation (AOR 0.38, 95% CI 0.18-0.79) and cough or dyspnea (AOR 0.48, 95% CI 0.25-0.94) in the ED were predictors of a delayed second diagnosis.

Effect of patient COVID-19 vaccine hesitancy on hospital care team perceptions.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic posed new challenges in patient care worldwide. Vaccinations, which have proven efficacious in lowering the COVID-19 hospital burden, are still avoided by large populations. We, therefore, hypothesized that hospital care teams would have worse perceptions regarding the characteristics and care of patients with vaccine hesitancy. AIM: To evaluate whether patient vaccine hesitancy affected the hospital care team (HCT) perceptions. METHODS: We performed a prospective clinical study using structured questionnaires. We approached physicians and nurses with previous experience caring for COVID-19 patients from 11 medical centers across Israel during the fourth COVID-19 surge (September and October 2021). The participants completed a questionnaire with the following parts: (1) Sociodemographic characteristics; (2) Assessment of anger (STAXI instrument) and chronic workplace stress (Shirom-Melamed burnout measure); and (3) Three tools to assess the effect of patient vaccine hesitancy on the HCT perceptions (the difficult doctor-patient relation questionnaire, the medical staff perception of patient's responsibility questionnaire and the characterological derogation questionnaire). Results were evaluated according to each part of the questionnaire and the questionnaire as a whole. Associations between HCT perceptions and their baseline characteristics, anger or chronic workplace stress were assessed. RESULTS: The HCT experienced their relationship with unvaccinated patients as more difficult (P < 0.001, Cohen's d = 0.85), perceived unvaccinated patients as responsible for their medical condition (P < 0.001, d = 1.39) and perceived vaccinated patients as having a higher character value (P < 0.001, d = 1.03). Unvaccinated patients were considered selfish (P < 0.001), less mature (P < 0.001) and less satisfying to care for (P < 0.001). The relationship with unvaccinated patients was more difficult among HCT with higher burnout (r = 0.37, n = 66, P = 0.002). No correlations with baseline characteristics were found. All three study tools showed high internal consistency (α between 0.72 and 0.845). CONCLUSION: Our results should raise awareness of the possible effects of vaccine hesitancy on HCT perceptions regarding unvaccinated patients. In order to minimize the potential negative impact on patient care, designated departments should promote specific patient-centered preparations. Further investigations should assess whether vaccine hesitancy directly affects patient quality of care.

Safety and outcomes of an early discharge strategy with oxygen home therapy in stable severe COVID-19 patients.

BACKGROUND: COVID-19 disease leads to prolonged hospitalisations and adverse outcomes. We describe our strategy for routine early discharge of severe COVID-19 patients with home oxygen during the Delta variant surge. METHODS: Our strategy included COVID-19 patients requiring oxygen support via nasal cannula, with stabilised but not yet improved respiration (intervention group), that followed strict criteria. Severe COVID-19 patients discharged after improved respiration were considered the control group for comparison. Outcomes included readmissions from active COVID-19 and 30-day mortality. RESULTS: The intervention group included 129 patients, and the control 150. The groups' baseline characteristics were similar, although the control group had more advanced COVID-19 severity. Among the intervention group, 23 (17.8%) had readmissions secondary to active COVID-19, compared to none in the control group. The 30-day mortality rate was similar between the groups (5% vs. 7%). The intervention led to a shorter hospital stay [median 3 days (IQR 2-4) vs. 6 days (IQR 4-9), p < .01], while a very short hospitalisation was associated with readmissions (2.8 vs. 3.5 days, p = .02). A subsequent critical disease or death after the intervention occurred in old (81 years), multimorbid (3.4 ± 1.4) patients with a high percentage of acute kidney injury during their first hospitalisation (50%). CONCLUSIONS: Our discharge strategy led to a short hospital stay, a high readmission rate, and similar long-term outcomes. Considering the difference in disease severity before discharge, this intervention cannot be considered safe for our study population. Correct patient selection is crucial to ensure patient safety when considering early discharge.

Holter ECG monitoring for the evaluation of stroke in the internal medicine department.

BACKGROUND: Holter electrocardiogram (ECG) monitoring is commonly used to reveal an underling arrhythmia in stroke patients and can influence treatment and prognosis. While many patients with stroke are admitted to the internal medicine department, evidence for the role of Holter ECG in this setting is scarce. OBJECTIVE: determine the diagnostic value of Holter ECG monitoring for evaluation of stroke in internal medicine department. METHODS: We included consecutive patients admitted to one of nine internal medicine departments in a tertiary center between 2018 and 2021, who completed a 24-hour Holter ECG as part of the evaluation of stroke. The primary outcome was a diagnostic Holter monitoring with recording of a new atrial fibrillation or flutter, not evident in previous ECG. RESULTS: 271 patients completed a Holter monitoring for the evaluation of stroke. Four patients (1.5%) met the primary outcome, and anticoagulation treatment was initiated for all of them. Accordingly, the number needed to change decision was 67. Two additional patients (0.7%) had a non-diagnostic Holter finding which effected treatment plan. Mean time from hospital admission to Holter was 3.01 ±3.44 days, and longer time to Holter initiation correlated with a longer hospital stay duration (r (270) =0.692, p<0.001). CONCLUSION: Conducting a routine Holter ECG monitorig for hospitalized patients with stroke in the internal medicine department carry a negligible yield, and may result in an extended hospitalization with possible harm.

Holter ECG for Syncope Evaluation in the Internal Medicine Department-Choosing the Right Patients.

Physicians use Holter electrocardiography (ECG) monitoring to evaluate some patients with syncope in the internal medicine department. We questioned whether Holter ECG should be used in the presented setting. Included were all consecutive patients admitted with syncope to one of our nine internal medicine departments who had completed a 24 h Holter ECG between 2018 and 2021. A diagnostic Holter was defined as one which altered the patient's treatment and met ESC/ACC/AHA diagnostic criteria. A total of 478 Holter tests were performed for syncope evaluation during admission to an internal medicine department in the study period. Of them, 25 patients (5.2%) had a diagnostic Holter finding. Sinus node dysfunction was the most frequent diagnostic recording (13 patients, 52%). In multivariant analysis, predictors for diagnostic Holter were older age (OR 1.35, 95% CI 1.08−1.68), heart failure with preserved ejection fraction (OR 4.1, 95% CI 1.43−11.72), and shorter duration to Holter initiation (OR 0.73, 95% CI 0.56−0.96). There was a positive correlation between time from admission to Holter and hospital stay, r(479) = 0.342, p < 0.001. Our results suggest that completing a 24 h Holter monitoring during admission to the internal medicine department should be restricted to patients with a high pre-test probability to avoid overuse and possible harm.

Associations of vaccine status with characteristics and outcomes of hospitalized severe COVID-19 patients in the booster era.

BACKGROUND: The resurgence of COVID-19 cases since June 2021, referred to as the fourth COVID-19 wave, has led to the approval and administration of booster vaccines. Our study aims to identify any associations between vaccine status with the characteristics and outcomes of patients hospitalized with severe COVID-19 disease. METHODS: We retrospectively reviewed all COVID-19 patients admitted to a large tertiary center between July 25 and October 25, 2021 (fourth wave in Israel). Univariant and multivariant analyses of variables associated with vaccine status were performed. FINDINGS: Overall, 349 patients with severe or critical disease were included. Patients were either not vaccinated (58%), had the first two vaccine doses (35%) or had the booster vaccine (7%). Vaccinated patients were significantly older, male predominant, and with a higher number of comorbidities including diabetes, hyperlipidemia, ischemic heart disease, heart failure, immunodeficient state, kidney disease and cognitive decline. Time from the first symptom to hospital admission was longer among non-vaccinated patients (7.2 ± 4.4 days, p = 0.002). Critical disease (p<0.05), admissions to the intensive care unit (p = 0.01) and advanced oxygen support (p = 0.004) were inversely proportional to the number of vaccines given, lowest among the booster vaccine group. Death (20%, p = 0.83) and hospital stay duration (8.05± 8.47, p = 0.19) were similar between the groups. CONCLUSION: Hospitalized vaccinated patients with severe COVID-19 had significantly higher rates of most known risk factors for COVID-19 adverse outcomes. Still, all disease outcomes were similar or better compared with the non-vaccinated patients.

Concurrent myopathy and inflammatory cardiac disease in COVID-19 patients: a case series and literature review.

Adult COVID-19 patients can present with acute muscle and/or cardiac involvement. Our study aims to describe the incidence and characteristics of patients with the co-occurrence of COVID-19 myopathy and inflammatory cardiac disease. We retrospectively reviewed all COVID-19 patients admitted to a large tertiary center to assess the co-occurrence of myopathy and inflammatory cardiac disease. We conducted a literature review of prior relevant case reports. There were three COVID-19 patients with concurrent involvement from our center and five cases in the published literature. Overall, mean age was 57.7 ± 16, four were females (50%) and only two patients (25%) had major relevant comorbidities. Muscle involvement included rhabdomyolysis or myositis and cardiac involvement included myocarditis or pericarditis. Most patients (75%) had no respiratory COVID-19 symptoms. Troponin and creatine phosphokinase levels were higher than twofold of the upper limit of normal for all patients. Steroids were used in the treatment of most patients (75%). All patients had a resolution or improvement of their extra-pulmonary involvement while two (25%) deteriorated due to COVID-19 pneumonia. The incidence for this co-occurrence is 0.07% among hospitalized COVID-19 patients. Patients with these rare COVID-19 simultaneous manifestations have distinct features. They are generally younger, present with extra-pulmonary symptoms and do not have severe respiratory compromise. An underdiagnosis causing treatment delay is possible. Further study is needed.

Clinical and prognostic significance of elevated ferritin levels in hospitalised adults.

PURPOSE OF THE STUDY: Elevated ferritin levels are associated with a variety of infectious, malignant and inflammatory diseases. We aimed to investigate the prognostic value of markedly elevated ferritin levels in hospitalised patients with various medical conditions. STUDY DESIGN: Retrospective analysis of patients with a ferritin level higher than 2000 ng/mL hospitalised in Sheba Medical Center between 1 January 2007 and 31 December 2015. Medical conditions of these patients were recorded. In-hospital, 30-day and 1-year mortality rates were evaluated according to ferritin ranges and clinical categories. RESULTS: The study included 722 patients (63.4% men) with a mean age of 63.9±16.7 years. The most common clinical conditions associated with markedly elevated ferritin were infectious diseases and malignancies. The highest mean ferritin levels were associated with rheumatological/inflammatory conditions (16 241.3 ng/dL), particularly in patients with macrophage activation syndrome (MAS) (96 615.5 ng/dL). In-hospital, 30-day and 1-year mortality rates were 32.3%, 46.7% and 70.8%, respectively. The highest in-hospital, 30-day and 1-year mortality rates were observed among patients with solid malignancies (40.1%, 64.7% and 90.3%, respectively), whereas the lowest rates were found among patients with rheumatological/inflammatory conditions, including MAS (21.4%, 38.1% and 45.2%, respectively). Ferritin levels were not associated with mortality. CONCLUSIONS: In hospitalised patients, ferritin levels higher than 2000 ng/mL are mainly associated with infectious and malignant diseases but do not predict mortality.

Relation of Baseline Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Contrast-Induced Nephropathy following Percutaneous Coronary Intervention among Chronic Kidney Disease Patients.

BACKGROUND: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). METHODS: Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. RESULTS: Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96-40.3; p = 0.01). CONCLUSION: Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.

Potential role for furosemide in the treatment of acute respiratory distress syndrome (ARDS) and an unusual presentation of pulmonary embolism in a complex patient.

An 81-year-old woman was admitted to our hospital after experiencing syncope. She was diagnosed with a large pulmonary embolism and was hemodynamically unstable therefore requiring endotracheal intubation and norepinephrine support. She presented with an upper gastrointestinal bleed which prevented her from receiving tissue plasminogen activator. She was treated with enoxaparin and ceftriaxone. Her blood, sputum and urine cultures were negative. When transferred to our ward, her antibiotic treatment was changed to piperacillin-tazobactam. A lumbar puncture was not suggestive of a central nervous system infection. Chest X-rays demonstrated rapid advancement of diffuse bilateral infiltrates which were not present at first and were interpreted by radiology consultation as suggestive of acute respiratory distress syndrome. An echocardiography showed right ventricle dilatation without left-sided heart failure. Diuretics were added and with this treatment, a quick respiratory improvement was noted as she regained consciousness and extubated shortly after.

Incidence and risk factors of pneumothorax following pre-procedural ultrasound-guided thoracentesis.

BACKGROUND: Data regarding the incidence and risk factors of pneumothorax following pre-procedural ultrasound (US)-guided thoracentesis is scarce. We aimed to evaluate the incidence and risk factors of pneumothorax following pre-procedural US-guided thoracentesis in a tertiary medical center. METHODS: Retrospective analysis of patients who underwent pre-procedural US-guided thoracentesis in Sheba Medical Center between January 2016 and December 2018. Data collected included incidence of pneumothorax following thoracentesis, baseline clinical and demographic characteristics, and thoracentesis-associated factors. Outcomes evaluated included length of hospital stay, mortality, chest tube insertion and intensive care unit admission. RESULTS: A total of 550 patients with pleural effusions underwent pre-procedural US-guided thoracentesis. Sixty-six (12%) of them developed pneumothorax. Compared to patients who did not develop pneumothorax, those who developed pneumothorax had a higher rate of congestive heart failure (32.2% vs. 47%, P=0.026), a smaller depth of pleural fluid marking (3.4 vs. 3.2 cm, P=0.024), a larger amount of pleural fluid drained (1,093 vs. 903.5 mL, P=0.01), and were more likely to undergo bilateral procedures (7.6% vs. 2.3%, P=0.044). In the multivariate regression analysis, volume of pleural fluid drained was significantly associated with the development of pneumothorax (OR, 1.001, 95% CI, 1-1.001; P=0.042). CONCLUSIONS: The incidence of pneumothorax following pre-procedural US-guided thoracentesis was relatively high in the present study. The amount of pleural fluid drained was the main factor associated with the risk of developing pneumothorax in these cases.

Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review.

Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatologic diseases. Data regarding the clinical course, management and outcome of adults with MAS is limited. Therefore, we aimed to describe the clinical features, treatment and outcome of adult patients with MAS, and review the literature for previous cohorts. We retrospectively reviewed patients with MAS complicating rheumatologic diseases between the years 2007 and 2017. Through Pubmed, Medline and Scopus literature search we identified previous cases of adult patients with MAS. We identified 7 patients with MAS complicating rheumatologic diseases (5 females and 2 males). The median age of diagnosis was 32 (range 26-57) years. The median follow-up was 30 months (range 6.95-36.5) months. The underlying rheumatologic disease was adult onset Still's disease (AOSD) in 3 patients, systemic juvenile idiopathic arthritis (sJIA) in 2 patients, systemic lupus erythematosus (SLE) in 1 patient, and systemic vasculitis in 1 patient. Four patients developed MAS concurrently with the clinical development of the rheumatologic disease. All the patients were treated with systemic corticosteroids. Five patients were treated with cyclosporine A, one of which received combination therapy with anakinra, and one received tocilizumab. Two patients deceased during the hospitalization. We identified 92 patients from literature cohorts, 73 (79%) of them with AOSD. MAS developed concurrently with the underlying rheumatologic disease in 25 (27%) patients, and 30 (33%) patients deceased. Our cohort and previous cohorts demostrate that MAS often presents concurrently with the underlying rheumatologic disease and is associated with a high mortality rate. Further larger prospective studies are needed to determine the optimal management of MAS.

Cytokine expression in temporal arteries: comparative analysis between patients with biopsy-positive giant cell arteritis, biopsy-negative giant cell arteritis and biopsy-negative without arteritis.

OBJECTIVES: To investigate whether expression of pro-inflammatory cytokines in the temporal artery may aid in differentiating biopsy-negative giant cell arteritis (GCA) patients from those with a negative biopsy without arteritis. METHODS: We investigated cytokine expression in temporal artery biopsy (TAB) of 54 consecutive patients: 17 with biopsy-positive GCA, 17 with biopsy-negative GCA, and 20 biopsy-negative without arteritis. We compared the expression rate of the following cytokines among these 3 groups of patients: interleukin-6 (IL-6), osteopontin (OPN), COX-2, and TNF-α. RESULTS: IL-6 was expressed in 13 (76%) patients with biopsy-positive GCA, 0 patients in biopsy-negative GCA, and 1(5%) patient with biopsy-negative without arteritis (p<0.05). OPN was expressed in 17 (100%) patients with biopsy-positive GCA, 2 (12%) patients with biopsy-negative GCA, and 0 patients with biopsy-negative without arteritis (p<0.05). Cox-2 was expressed in 16 (94%) patients with biopsy-positive GCA, 0 patients with biopsy-negative GCA, and 3 (15%) patients with biopsy-negative without arteritis (p<0.05). TNF- α was expressed in 17 (100%) patients with biopsy-positive GCA, 14 (82%) patients with biopsy-negative GCA, and 8 (40%) patients with biopsy-negative without arteritis (p<0.05). CONCLUSIONS: IL-6, COX-2 and OPN are significantly more expressed in the presence of a positive TAB compared to a negative TAB. TNF-α is significantly more expressed in GCA patients compared to non-GCA patients. Thus, TNF-α expression may suggest a diagnosis of GCA despite a negative TAB. Further larger studies are needed to confirm these findings.

Clinical significance of positive anti-neutrophil cytoplasmic antibodies without evidence of anti-neutrophil cytoplasmic antibodies-associated vasculitis.

AIM: Anti-neutrophil cytoplasmic antibodies (ANCA) have a role in the diagnostic workup of ANCA-associated vasculitis. However, the clinical significance of positive ANCA in the absence of vasculitis is yet to be determined. Therefore, we sought to investigate the clinical spectrum and rate of patients with a positive ANCA without evidence of vasculitis. METHODS: Retrospective analysis of patients positive for cytoplasmic ANCA (C-ANCA) and proteinase 3 (PR3) or P-ANCA and myeloperoxidase (MPO) between 2007 and 2016 in the Chaim Sheba Medical Center, Israel. The proportion of patients who had no evidence of vasculitis among all patients with a positive C-ANCA/PR3 or P-ANCA/MPO was calculated according to tertiles of enzyme-linked immunosorbent assay (ELISA) antibody levels. RESULTS: Among 113 patients who tested positive for C-ANCA/PR3 or P-ANCA/MPO, 68 (60.1%) had no evidence of vasculitis. ELISA antibody titers were significantly higher among patients with vasculitis than those without (6.2 vs 3.2, for C-ANCA/PR3 and 5.4 vs 2.6 for P-ANCA/MPO, P < 0.05). The proportion of patients without vasculitis among all patients with a positive C-ANCA/PR3 and among all patients with a positive P-ANCA/MPO declined in parallel to the increases in ELISA antibody level tertiles (96%, 57% and 22% in the 1st, 2nd and highest tertiles, respectively, for patients with C-ANCA/PR3 patients and 100%, 66% and 20% in the 1st, 2nd and highest tertiles, respectively, for patients with P-ANCA/MPO). CONCLUSION: A significant proportion of patients with a positive C-ANCA/PR3 or P-ANCA/MPO do not have evidence of vasculitis, particularly those with low-medium ELISA antibody titers. Using a higher threshold of ANCA titers may be required to improve specificity.

Hematological malignancies mimicking rheumatic syndromes: case series and review of the literature.

It is well established that some rheumatic syndromes (RS) are associated with several hematological malignancies. We aimed to describe the clinical course of patients with hematological malignancies mimicking RS. We studied a series of four patients presenting with apparent RS who were eventually diagnosed with hematological malignancies, and reviewed the relevant literature. Our series consisted of 4 patients, with a mean age of 62.8 ± 20.3 years, who presented to our rheumatology unit between December 2012 and March 2018. Two patients were initially diagnosed with polyarthritis. One of these patients was eventually diagnosed with multiple myeloma and amyloidosis and the other was diagnosed with angioimmunoblastic T-cell lymphoma. The third patient was initially diagnosed with migratory arthritis and was eventually diagnosed with acute myeloid leukemia. The fourth patient was initially diagnosed with giant cell arteritis and eventually diagnosed with anaplastic large T-cell lymphoma. All the patients displayed a very good response to corticosteroid treatment. Vigilance for occult malignancy is essential in the diagnostic workup of RS. A good response to corticosteroids may constitute a major diagnostic pitfall in patients with hematological malignancies presenting with an apparent RS. In these cases, subtle clinical and laboratory features should elicit the clinician to seek for an occult malignancy.

Negative temporal artery biopsy: predictive factors for giant cell arteritis diagnosis and alternate diagnoses of patients without arteritis.

To investigate whether among patients with a negative temporal artery biopsy (TAB) there are clinical features that may differentiate between patients with an eventual diagnosis of giant cell arteritis (GCA) and those without arteritis, and to assess the eventual diagnoses of patients without arteritis. Retrospective analysis of patients with a negative TAB performed between 1/1/2000 and 31/12/2015. Information collected included baseline clinical and laboratory data. Patients' final diagnoses were obtained from medical records. Patients eventually diagnosed with GCA were compared with those without arteritis, and predictive features for GCA diagnosis were assessed. A total of 154 patients with a negative TAB were included in the study. Among them, 31 (20%) were eventually diagnosed with GCA. The leading alternative diagnoses of patients without arteritis were self-limited disease (23%), isolated polymyalgia rheumatica (PMR) (18%), and neurological conditions (17%). In the multivariate analysis, predictors for diagnosis of GCA among patients with a negative TAB included PMR (OR = 2.86, 95% CI 1.06-7.69), platelet count (OR = 1.28, 95% CI 1.07-1.53), and ACR score > 2 (OR = 13.4, 95% CI 4.27-42.03). Among patients with a negative TAB, the best predictors for diagnosis of GCA are fulfillment of the ACR criteria, a clinical diagnosis of PMR, and high platelet levels. These features may aid in the diagnostic work-up of patients with a negative TAB.