Israel Medical Association Journal

Enthesitis is a term that refers to inflammation at tendon, ligament, or joint capsule insertions. The entheses are increasinlgly considered to be the primary site of joint inflammation in the spondyloarthropathies including psoriatic arthritis (PsA). Great advances have occurred in the understanding of enthesopathy, which has resulted in a better understanding of the etiopathogenesis of PsA. Enthesitis is difficult to assess on both clinical examination and on imaging because of the overlap in features between mechanical, degenerative, and inflammatory pathologies. Ultrasonography frequently detects entheseal abnormalities in patients with psoriasis, despite the absence of clinical symptoms of arthropathy and the longitudinal value of such lesions for PsA prediction remains unknown. The role of magnetic resonance imaging (MRI) in the assessment and monitoring of enthesitis is not fully agreed on but it is clearly superior for the assessment of spinal polyenthesitis and for diffuse peri-enthseal osteitis that can occur anywhere in the skeleton. Nuclear medicine, including conventional positron-emission tomography (PET) and high-resolution PET scan (hrPET), is more of a research tool for enthesitis and can, for example, help distinguish between PsA and osteoarthritis. Entheseal abnormalities are common in osteoarthritis, which creates diagnostic difficulty from PsA. Entheseal changes, especially on imaging, may also occur in rheumatoid arthritis (RA) and likely reflect the extension of the inflammatory process from the adjacent synovium. The nail is anatomically anchored to the skeleton via a mini-enthesis network. An association between ultrasonography determined distal interphalageal joint (DIP) extensor tendon enthesopathy and clinical nail disease was found, which highlights the pivotal role of the enthesis in this PsA risk factor. This review summarizes the relevant insights and implication of imaging for enthesitis, primarily in PsA but also in other arthropathies.

Background: Preterm birth is the leading cause of morbidity and mortality among neonates in the United States. Early recognition of sepsis in this population is a challenging task since overt clinical signs can be difficult to determine. C-reactive protein (CRP), one of the most frequently non-specific used laboratory test, can indirectly aid the diagnosis of neonatal sepsis.

Objectives: To evaluate the relationship between histological findings in the placenta of preterm newborns born after prolonged rupture of membranes, CRP levels, and blood cultures.

Methods: Medical records were reviewed of all preterm newborns born after prolonged premature rupture of membranes at a medical center in Israel between 2011 and 2014.

Results: Of 128 newborns with prolonged rupture of membranes, 64 had evidence of histological chorioamnionitis (HCA). Gestational age, birth weight, and Apgar scores were significantly lower, while CRP levels (on admission and 10–12 hours post-delivery) were significantly higher in preterm newborns born to mothers with histological evidence of chorioamnionitis, but values were within normal ranges. Duration of the rupture of membranes and white blood cell counts did not differ between groups.

Conclusions: CRP levels taken on admission and 10–12 hours after delivery were higher when HCA was present, but since there was a substantial overlap between those with and without HCA and the values for most were within normal range, the differences were not enough to serve as a tool to diagnose placental histological chorioamnionitis in preterm infants born after prolonged premature rupture of membranes and exposed to intrapartum antibiotics.

Background: Computed tomography (CT) brain perfusion is a relatively new imaging method that can be used to differentiate patients following epileptic seizures in the setting of acute neurological deficits (e.g., hemiparesis, hemiplegia, hemianopsia, aphasia) who arrive at the emergency room with a suspected stroke.

Objectives: To evaluate brain perfusion changes in patients who had an epileptic seizure.

Methods: We retrospectively identified 721 patients who presented at our stroke center between 2012 and 2015 with a suspected acute stroke and underwent examination thorough a stroke protocol, including cerebral CT perfusion (CTP) and CT angiography (CTA) within 8 hours from the onset of symptoms. 

Results: Out of 721 patients, 25 presented with ictal electroencephalography (EEG) findings within 24–72 hours from symptom onset without evidence of vascular occlusion on CTA. While 15 patients had to be excluded from the study due to concomitant brain pathology, we found a specific reduction in cerebral blood volume and cerebral blood flow occurring at the ictal zone, which was identified by a post hoc EEG investigation. 

Conclusions: Our study shows that CTP is an easily accessible tool in emergency department setting for the detection of changes in blood flow dynamics among postictal patients. Thus, we propose the use of CTP in emergency settings to discriminate between postictal changes and acute vascular events. 

 

Background: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases.

Objectives: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype.

Methods: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. 

Results: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05).

Conclusions: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.

 

Background: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. 

Objectives: To analyze the interplay between TD and PF in a cohort of SSc women. 

Methods: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. 

Results: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). 

Conclusions: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

 

Background: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture’s disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture’s disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis.

Objectives: To assess the predictive value of positive anti-GBM antibodies in a clinical setting. 

Methods: Data from anti-GBM antibody tests performed at one medical center between 2006 and 2016 were systematically and retrospectively retrieved. We recruited 1914 patients for the study. Continuous variables were computed as mean ± standard deviation, while categorical variables were recorded as percentages where appropriate. Sensitivity and specificity of anti-GBM titers were calculated. Kaplan–Meyer analysis was performed, stratifying survival according to the anti-GBM antibody titers.

Results: Of the 1914 anti-GBM test results detected, 42 were positive, 23 were borderline, 142 were excluded, and 1707 results were negative. Male-to-female ratio was 1:1.2. Sensitivity of anti-GBM test was 41.2% while specificity was 85.4%. Concerning the Kaplan–Meyer analysis, overall survival was 1163.36 ± 180.32 days (median 1058 days). 

Conclusions: Our study highlights the lack of sensitivity of serological testing of anti-GBM titers. Comparing survival curves, the survival correlated with anti-GBM titer only in a borderline way. Because highly sensitive bioassays are not routinely used in clinics, renal biopsy is still pivotal for Goodpasture’s disease diagnosis.

 

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: Syncope prognosis varies widely: 1 year mortality may range from 0% in the case of vasovagal events up to 30% in the presence of heart disease. 

Objectives: To assess the outcomes and prognosis of patients with implantable cardiac defibrillator (ICD) and indication of primary prevention and compare patients presenting with or without prior syncope.

Methods: We reviewed the charts of 75 patients who underwent ICD implantation with the indication of primary prevention and history of syncope and compared them to a control group of 80 patients without prior syncope. We assessed the number of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP), and death in each group during the follow-up.

Results: Mean follow-up was 893 days (810–976, 95% confidence interval) (no difference between groups). Patients with prior syncope had a higher ejection fraction (EF) (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01) and also received more electric shocks (18.7% vs. 3.8%, P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in inappropriate shocks (6.7% vs. 5%, P = 0.74), in cardiovascular mortality (cumulative 5 year estimate 29.9% vs. 32.2% P = 0.97) and any death (cumulative 5 year estimate 38.1% vs. 48.9% P = 0.18) during the follow-up.

Conclusions: Syncopal patients before ICD implantation seem to have more episodes of VT/VF and shock or ATP. No mortality differences were observed

 

The identification and prompt diagnosis of Horner syndrome (HS) is essential for preventing permanent damage. HS may arise when a lesion presents anywhere along the three-neuron oculosympathetic pathway that begins at the posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We present four cases and review the literature to familiarize the reader with the identification, diagnosis and treatment of Horner syndrome. The four patients, three adults and one child, were followed for at least 6 months following the initial diagnosis (range 6–18 months). There was partial resolution in three of the four cases, while the fourth resolved completely. There are numerous causes of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both adults and children, HS is seen more often following surgical procedures. Prompt recognition of the syndrome and correction of the offending agent may prevent permanent damage to the neuronal pathway. It is therefore recommended that practitioners be aware of the risks for development of iatrogenic HS and the signs for early detection.

Background: The prevalence and etiology of nephrolithiasis vary, depending on geography, gender and ethnicity. 

Objectives: To analyze the demographic data of return nephrolithiasis patients in a tertiary care center.

Methods: We retrospectively reviewed our prospective registry database of return patients seen at our outpatient clinic for nephrolithiasis. Data included gender, age at first visit, age at first stone event, body mass index (BMI), self-reported hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen at least twice and had undergone a metabolic workup. 

Results: A total of 260 return patients were seen during the period 2010–2015. The male:female ratio was 3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed since the first stone event to medical evaluation was 5 years (interquartile range 1–12 years). Hypertension was reported by 33.1% of the patients, DM by 23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of patients. The metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). We also found that 24.6% were obese (BMI ≥ 30 kg/m2) and showed higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and hyperuricosuria compared with non-obese patients. Significantly higher rates of obesity and LUV were detected in females compared with males. Patients over age 45 had lower rates of hyperuricemia compared with patients ≥ 45 years old (P = 0.038).

Conclusions: Factors related to nephrolithiasis can potentially differ among populations and countries. Our findings emphasize the significance of individualized national health programs to address local issues.

 

Background: Atrial fibrillation (AF) is a common complication of coronary artery bypass graft (CABG) surgery, occurring in 20%–40% of patients, mostly during the first week after surgery. It is associated with increased morbidity and mortality, but data are limited. 

Objectives: To assess the correlation between new-onset in-hospital AF following CABG and long-term AF, cerebrovascular accident (CVA), or death.

Methods: We conducted an analysis of 161 consecutive patients who underwent isolated CABG surgery in a tertiary center during the period 2002–2003. 

Results: Patients’ mean age was 72 years, and the majority were males (77%). Approximately half of the patients experienced prior myocardial infarction, and 14% had left ventricular ejection fraction < 40%. Postoperative AF (POAF) occurred in 27% of the patients. Patients were older and had larger left atrium diameter. POAF was strongly correlated with late AF (OR 4.34, 95%CI 1.44–13.1, P = 0.01) during a mean follow-up of 8.5 years. It was also correlated with long-term stroke but was not associated with long-term mortality. 

Conclusions: POAF is a common complication of CABG surgery, which is correlated with late AF and stroke. Patients with POAF should be closely monitored to facilitate early administration of anticoagulant therapy in a high risk population upon recurrence of AF.