The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.

Role of C-Reactive Protein in Discrimination between Transudative and Exudative Pleural Effusions.

BACKGROUND: There is still no wide agreement regarding the efficacy of the serum levels of C-reactive protein (CRPs), pleural fluid levels of CRP (CRPpf), and their ratio (CRPr) in the discrimination between transudative (Tr) and exudative (Ex) pleural effusions (PEs). Most of the previous studies were conducted on small cohorts, and the role of CRPs in the CRPpf gradient (CRPg) in this discrimination has not been previously reported. The present study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPg, and CRPr in the discrimination between TrPE and ExPE in a relatively large cohort of patients with PE. METHODS: The study population included 492 patients with PE, 210 of them with TrPE and 282 with ExPE. The levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. RESULTS: The mean levels of CRPs, CRPpf, CRPg, and CRPr of the TrPEs were 11.3 ± 5.7 mg/L, 4.6 ± 2.8 mg/L, 6.7 ± 3.9 mg/L, and 0.40 ± 0.14, respectively, and for the ExPEs, they were 140.5 ± 112.8 mg/L, 52.8 ± 53.2 mg/L, 87.2 ± 72.4 mg/L, and 0.37 ± 0.15, respectively. The levels of CRPs, CRPpf, and CRPg were significantly higher in the ExPEs than in the TrPEs (p < 0.0001). No significant difference was found between the two groups for the levels of CRPr (p = 0.15). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating TrPE from ExPE was for CRPs, 20.5 mg/L with area under the curve (AUC) = 97% and p < 0.0001; for CRPpf, 9.9 mg/L with AUC = 95% and p < 0.0001; and for CRPg, 13.6 mg/L with AUC = 96% and p < 0.0001. CONCLUSION: CRPs, CRPpf, and CRPg are strong markers for discrimination between TrPE and ExPE, while CRPr has no role in this discrimination.

Early Detection and Intervention for Patients with Delirium Admitted to the Department of Internal Medicine: Lessons from a Pilot Initiative.

INTRODUCTION: Older patients who arrive to the emergency room with delirium have a worse prognosis than others. Early detection and treatment of this problem has been shown to improve outcome. We have launched a project at our hospital to improve the care of patients who arrive delirious to the medical emergency room. The present article describes lessons that can be learned from this pilot initiative. METHODS: All patients older than 70 years admitted to the department of internal medicine were screened for delirium in the emergency room using the 4AT screening tool. Data of patients with a 4AT score ≥5 (or with incomplete score) were transferred to the geriatric unit of the hospital. On the ward, the presence of delirium was confirmed by a geriatric nurse that validated that the patient could walk with support and ordered mobilization and physiotherapy (M&P). RESULTS: Over the 2 and a half years (10 quarters) allocated for the pilot project, 1,078 medical patients with delirium were included in this survey. In 59.3%, the diagnosis of delirium could be confirmed only after admission. Due to budgetary constraints, only 54.7% received the allocated specific intervention - early M&P. Since it was decided that randomization was not appropriate for our initiative, we found that patients who received M&P had lower (better) 4AT scores on admission, and lower mortality. No significant difference was found between the patients who received M&P and the others in length of hospitalization and discharge to nursing homes. Retrospective comparison of the two groups did not enable to determine whether M&P was given to the patients for whom it was most effective. CONCLUSIONS: It is often not possible to verify in the emergency room that the cognitive decline is indeed new, that is, is due to delirium, and measures must be taken to verify this point as soon as possible after admission. Due to numerous constraints, the availability of early M&P is often insufficient. Whenever resources are scarce and randomization is avoided, adequate criteria should be found for allocating existing dedicated staff to patients for whom early mobilization is likely to be most beneficial.

Diagnostic Value of C-Reactive Protein in Discrimination between Uncomplicated and Complicated Parapneumonic Effusion.

OBJECTIVES: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. METHODS: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. RESULTS: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. CONCLUSIONS: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.

[SPINAL SYNDESMOPHYTE SCORE DOES NOT CORRELATE WITH SERUM TESTOSTERONE LEVEL IN MALE PATIENTS WITH ANKYLOSING SPONDYLITIS].

AIMS: To examine statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS. BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory rheumatic disease primarily involving sacroiliac joints and spine. Structural damage, caused by AS, manifests with development of vertebral syndesmophytes and can be calculated as units of modified Spinal Ankylosing Spondylitis Syndesmophyte Score (mSASSS). The rate of growth of spinal syndesmophytes differs among individual AS patients, while male patients develop significantly more structural damage compared to females in general. METHODS: Twenty males with AS known for at least 5 years (average disease duration 12.8 years) and aged between 25 to 40 years donated 5 ml of peripheral blood for serum testosterone assay, and underwent X-ray films of cervical and lumbar spine. The mSASSS was calculated and correlation with serum testosterone levels was examined using Pearson correlation test. RESULTS: The mSASSS values of patients included in the final analysis ranged from 0-14 units and testosterone levels ranged from 8.4-25.5 nmol/L. No significant correlation was found between mSASSS values and testosterone levels in this cohort. CONCLUSIONS: This study did not find statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS.

Delirium induced by levofloxacin.

Delirium is the most frequent complication of hospitalization for elders and a potentially devastating problem. It is accompanied by high morbidity and mortality rate, and despite sensitive methods for its detection, delirium often is unrecognized and is missed by clinicians in up to 70% of delirious patients. Medications are considered one of the most common causes of delirium with sedatives, narcotics, dihydroperidines, antihistamines, and anticholinergics are most often implicated in its causation. Antibiotic-induced delirium has been infrequently reported where cephalosporins and macrolides are implicated in the majority of cases published. Delirium associated with fluoroquinolones has rarely been reported, and to the best of our knowledge only eight cases of levofloxacin-induced delirium have been described until yet in the medical literature, two of which from our medical ward. We describe another case of delirium associated with levofloxacin treatment in an elderly patient who was hospitalized in our medical ward for acute bronchitis. Description of three cases of levofloxacin-induced delirium from one medical ward (ours) and the other six from the rest of the world reflects the extreme under-recognition and under-diagnosis of drug-induced delirium generally, and levofloxacin-induced delirium specifically by physicians world-wide. It also seems likely that this severe and potentially fetal adverse effect of levofloxacin is much more common than previously reported. The present case and the other previously reported emphasize the urgent need of much more awareness by physicians to the occurrence of this serious but preventable and potentially reversible CNS complication of levofloxacin.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Acute Delirium Associated With Levofloxacin.

Delirium is considered as the most common complication afflicting hospitalized elderly patients, accompanied by high morbidity and mortality rate; and despite its high prevalence, it often remains unrecognized. Drug-induced delirium is a well-known entity with sedatives, narcotics and anticholinergics most often implicated in its causation. Delirium attributed to antibiotics, mainly cephalosporins and macrolids, has been infrequently reported, and until yet only seven cases of levofloxacin-induced delirium have been described in the medical literature. We describe another case of delirium associated with levofloxacin in an elderly patient who was hospitalized in our medical ward for pneumonia. The present case and the other cases previously reported should raise the awareness of physicians to this serious, underestimated, and underdiagnosed adverse effect of a commonly used antibiotic, levofloxacin.

[SUSTAINABILITY OF RITUXIMAB IN CONCOMMITANT TREATMENT WITH METHOTREXATE OR LEFLUNOMIDE IN PATIENTS WITH RHEUMATOID ARTHRITIS].

INTRODUCTION: Rituximab is a biologic agent approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate (MTX) or leflunomide (LEF). However, limited data in the literature suggests that rituximab may have the same efficacy profile whether used in combination with MTX or as monotherapy. The aim of our study is to compare the sustainability of rituximab as monotherapy to combined therapy with MTX or LEF in Israeli patients with RA. METHODS: A total of 35 RA patients treated with rituximab combined with MTX or LEF were compared with 26 RA patients treated with rituximab monotherapy regarding sustainability of rituximab treatment and its relationship to some patient and disease-related factors. RESULTS: There was no difference in patient-related and disease-related parameters between patients treated with rituximab as monotherapy or combined with MTX/LEF. The survival of rituximab was similar in both groups (88.5% in the monotherapy group and 82.6% in the combined therapy group, p=NS), with similar percentages of patients discontinuing this biologic agent, whether due to inefficacy or side effects. CONCLUSIONS: Rituximab may be considered as a biologic monotherapy in RA patients. Further prospective studies, evaluating sustainability of rituximab as a monotherapy in patients with RA are warranted.

Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy.

Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Tumor necrosis factor-alpha (TNF-α) plays a pivotal role in the defense against infection with this Gram-negative coccobacillus. Theoretically, patients who are treated with anti-TNF-α medications are at risk for developing chronic Q fever. We present two patients who developed Q fever while being treated with anti-TNF-α agents and discuss the significance of timely diagnosis of C. burnetii infection in these patients.

Acute sacroiliitis.

The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy.

Rapid progression to cardiac tamponade in Erdheim-Chester disease despite treatment with interferon alpha.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis with heterogeneous clinical manifestations. The most common presentation is bone pains typically involving the long bones. Approximately 75% of the patients develop extraskeletal involvement. Cardiac involvement is seen in up to 45% of the patients, and although, pericardial involvement is the most common cardiac pathology of this rare disease, cardiac tamponade due to ECD has been very rarely reported. We describe a case of a patient found to have ECD with multi-organ involvement and small pericardial effusion, which progressed to cardiac tamponade despite treatment with interferon alpha.

[KIDNEY DISEASES IN NORTH ISRAEL ACCORDING TO KIDNEY BIOPSIES - BNAI-ZION MEDICAL CENTER 14 YEARS' EXPERIENCE].

INTRODUCTION: Little is known about the prevalence of kidney diseases according to renal biopsy in Israel. Since updated literature worldwide emphasizes changing etiologies of chronic kidney disease, it is crucial to research and define the epidemiology and pathology of kidney disease in Israel. Hereby, we introduce an original review of the prevalence of kidney diseases in our study population, which we believe reflects the prevalence of kidney diseases in the population of Israel. AIMS: To investigate the prevalence of kidney diseases diagnosed by renal biopsy, according to age, gender, race and clinical symptoms. METHODS: A total of 155 kidney biopsies were conducted in the years 2000-2014 in Bnai-Zion Medical Center in Haifa, according to formal accepted indications. Most of the biopsies (65%) were needle aspirations in a retroperitoneal approach, in which 90% were ultrasound guided and the rest computed tomography guided, while the other 35% of biopsies involved laparoscopic approaches. RESULTS: The most common indications for kidney biopsy were nephrotic syndrome, nephritic syndrome and proteinuria (37.4%, 25.8% and 24.5%, respectively). Average glomeruli number per biopsy was 17.5 vs. 82.2 for needle aspiration and laparoscopic approach, respectively (statistically significant). The most common diagnosis was focal segmental glomerulosclerosis (FSGS), followed by chronic glomerulonephritis, IgA nephropathy, lupus nephritis, minimal change disease (MCD), membranous nephropathy and tubulointerstitial disease (20%, 11.5%, 11.5%, 10.1%, 9.5%, 8.1% and 6.1%, respectively). CONCLUSIONS: FSGS was the most common diagnosis in patients presented with nephrotic syndrome or proteinuria, men, and patients above 60 years of age. Patients below 30 years of age were mainly diagnosed with IgA nephropathy. DISCUSSION: In recent years, FSGS is becoming more prevalent compared with other chronic kidney disease especially in the older population. IgA nephropathy is still the most common diagnosis in young patients and in patients presented with hematuria. To the best of our knowledge, no data exists on the prevalence of kidney diseases in Israel, and our study is an important contribution to the epidemiological and clinical knowledge on the subject.

Increased aortic wall thickness for the diagnosis of aortitis: a computed tomography-based study.

AIMS: To evaluate the usefulness of computed tomography (CT)-measured aortic wall thickness (AWT) as a sole imaging finding for the confirmation of clinically suspected aortitis. METHODS: CT scans of 20 patients with the diagnosis of aortitis, endorsed by the abnormally thickened aortic wall, as a single imaging finding, and 250 patients without known aortitis were reviewed and AWT manually measured at the levels of thoracic descending aorta, upper abdominal aorta and infrarenal aorta, as well as the level of maximal AWT in patients with diagnosed aortitis. Patients' charts were analyzed and demographic data and data on co-morbidities extracted. Correlations of measured AWT with patients' demographic data and co-morbidities were calculated for the control patients. Age-dependent upper 97.5 percentile points for AWT were calculated for different age groups as a reference. AWT of patients, diagnosed with aortitis, was compared with these reference values. RESULTS: AWT had significant positive correlation with patient age (P < 0.001), gender (P < 0.03) and presence of aortic wall calcifications (P < 0.001). In nine of 20 patients, with diagnosed aortitis confirmed by the increased CT-measured AWT, the revised values of AWT were lower than the calculated upper 97.5 percentile points for the relevant age group. In four of these patients, the values of the measured AWT were in the range of mean + SD for AWT for the same age. CONCLUSIONS: The confirmation of suspected aortitis by the increased CT-measured AWT only may be equivocal and necessitate more specific imaging, particularly in elderly patients.

Entheseal involvement in systemic disorders.

The objective of this study is to review the data on entheseal involvement in systemic disorders. A Pubmed search utilizing the indexing terms "enthesis" and "enthesitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. A number of cadaver-based studies, as well as studies using ultrasonography and magnetic resonance imaging, have detailed new distinct aspects of enthesis physiology and pathology in a variety of rheumatic and non-rheumatic systemic disorders. Major progress has been done in characterization of separate components of the enthesis organ, imaging of entheses, elaboration of the role and features of entheseal disease in spondyloarthropathies, juvenile idiopathic arthritis, osteoarthritis, familial Mediterranean fever, hyperuricemia, and other systemic conditions. The knowledge acquired and summarized herein shows that entheses can be affected in various ways in variety of medical disorders with different pathogenesis. Better understanding of the risk factors, mechanisms and natural history of enthesopathies is warranted. The current progress in the understanding of entheseal involvement in systemic disorders represents just the first step in resolving the entheses-related enigmas.

Craniocervical junction involvement in ankylosing spondylitis.

PURPOSE: Available studies of craniocervical junction (CCJ) involvement in ankylosing spondylitis (AS) are based on conventional radiography, which has limited ability in the definition of many elements of the CCJ. The goal of the present study was to describe the spectrum of computed tomography (CT) findings in the CCJ in a cohort of patients with AS. METHODS: CT scans of the cervical spine of 11 patients with AS and 33 control subjects were reviewed, and imaging findings related to the CCJ were assessed. The standard anatomic intervals describing the CCJ were measured and compared to accepted normal standards. Findings representing pathology were described, categorized by localization, and relation to joints or ligaments of the CCJ. RESULTS: All AS patients were males with median age of 48 years and median disease duration of 20 years. The calculated median-modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) for the cervical spine was 8.5 ranging from 0 to 27. Disease-related changes in one or more elements of the CCJ were detected in all patients. Atlanto-occipital joints were involved in 8 patients, while 3 patients had disease of the atlanto-dental articulation. Enthesopathy of the CCJ was observed in 7 patients. CONCLUSIONS: The CCJ is frequently involved in AS patients with advanced disease and may be independent on the mSASSS. Both articulations and ligaments of CCJ may be affected in AS patients.

[93 YEARS OF CLINICAL EMPATHY, STATE-OF-THE-ART MEDICINE AND RESEARCH EXCELLENCE].

This issue of Harefuah is devoted to articles and reviews written by the medical staff of Bnai Zion Medical Center in Haifa. Celebrating 93 years since its inception, Bnai Zion Medical Center is home to the oldest public hospital in Haifa, and a founding affiliate of the Technion's Faculty of Medicine. Known for its centers of excellence and the impactful clinical and basic research developed, the hospital has a reputation for state-of-the-art medicine, both conventional and complementary. Bnai Zion prides itself as an innovation leader in medical and nursing education, with its staff's empathetic and personalized approach to patient care, and the center's dedication to applying emotional intelligence to medicine.