Israel Medical Association Journal

Leonardo da Vinci, the artist and scientist, was an archetype figure of the Renaissance era. He was an autodidactic polymath in natural sciences, engineering, and physical sciences, imbued with universality, prodigious inventive imagination, and curiosity to know and understand the world around him. Among his myriad activities, anatomy, physiology, and biomechanics of the musculoskeletal system and the underlying systems fully engaged him. Leonardo dissected dozens of human and animal corpses to study. His anatomical illustrations were precise, combining art and science with an impeccable integration of both. Multiple drawings, diagrams, sketches, and designs are found in his notes. Leonardo’s style was intensely personal, unveiling his thoughts, passions, and emotions. We analyzed significant biographic aspects of Leonardo's life, remarking on his scientific and life conceptions and their manifestation in his anatomical designs. The contribution of preceding anatomists is reported as a source of his inspiration as well as motivation to successors. Leonardo da Vinci left no publications, but rather an extensive collection of personal notebooks. Leonardo's contribution to modern anatomy was enormous and he is considered by the scientific and medical community as the father of the modern anatomy

Background: Multiple myeloma (MM) affects the long bones in 25% of patients. The advent of positron-emission tomography/computed tomography (PET/CT) scanners offers the possibility of both metabolic and radiographic information and may help determine fracture risk. To the best of our knowledge, no published study correlates these two factors with long bone fractures.

Objective: To evaluate the impact of PET/CT on fracture risk assessment in multiple myeloma patients.

Methods: We identified all bone marrow biopsy proven multiple myeloma patients from 1 January 2010 to 31 January 2015 at a single institution. We prospectively followed patients with long bone lesions using PET/CT scan images.

Results: We identified 119 patients (59 males/60 females) with 256 long bone lesions. Mean age at diagnosis was 58 years. The majority of lesions were in the femur (n=150, 59%) and humerus (n=84, 33%); 13 lesions in 10 patients (8%) required surgery for impending (n=4) or actual fracture (n=9). Higher median SUVmax was measured for those with cortical involvement (8.05, range 0–50.8) vs. no involvement (5.0, range 2.1–18.1). SUVmax was found to be a predictor of cortical involvement (odds ratio = 1.17, P = 0.026). No significant correlation was found between SUVmax and pain or fracture (P = 0.43).

Conclusions: Improved medical treatment resulted improvement in 8% of patients with an actual or impending fracture. The orthopedic surgeons commonly use the Mirels classification for long bone fracture prediction. Adding PET/CT imaging to study in myeloma long bone lesions did not predict fracture risk directly but suggested it indirectly by cortical erosion.

Background: Acute extremity compartment syndrome is a surgical emergency for which timely diagnosis is essential.

Objectives: To assess whether the time from the initial insult to the fasciotomy of compartment syndrome of the upper extremity affects outcomes and to examine the differences between compartment syndrome secondary to fractures and that resulting from a non-fracture etiology with regard to the time from insult to fasciotomy and the long-term patient outcomes.

Methods: Patients presented with documented fasciotomy treatment following acute upper extremity compartment syndrome and a minimum of 6 months follow-up. Patient information included demographics, cause of compartment syndrome, method of diagnosis, and outcome on follow-up.

Results: Our study was comprised of 25 patients. Fasciotomies were performed for compartment syndrome caused by fracture in 11 patients (44%), and due to insults other than fractures in 14 patients (56%). The average time to fasciotomy in patients without a fracture was 10.21 hours and 16.55 hours with a fracture. Fasciotomy performed more than 24 hours from the initial insult was not found to significantly affect long-term sequelae compared to fasciotomy performed earlier than 24 hours from the initial insult. The non-fracture group had more long-term sequelae than the fracture group (13/15 patients and 5/11 patients, respectively).

Conclusions: Most injuries treated for fasciotomy of compartment syndrome were non-fracture related, with more complications found in patients with non-fracture related injuries. Time interval from insult to fasciotomy did not affect outcome and was longer in the fracture group, suggesting longer monitoring in this group and supporting fasciotomy even with late presentation.

Background: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time.

Objectives: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients.

Methods: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0–3). The total inflammatory score was the sum of the scores.

Results: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P  = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01).

Conclusions: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset

Background: Syncope is a common reason for emergency department (ED) visits; however, the decision to admit or discharge patients after a syncopal episode remains challenging for emergency physicians. Decision rules such as the Boston Syncope Criteria have been developed in an attempt to aid clinicians in identifying high-risk patients as well as those who can be safely discharged, but applying these rules to different populations remains unclear.

Objectives: To determine whether the Boston Syncope Criteria are valid for emergency department patients in Israel.

Methods: This retrospective cohort convenience sample included patients who visited a tertiary care hospital in Jerusalem from August 2018 to July 2019 with a primary diagnosis of syncope. Thirty-day follow-up was performed using a national health system database. The Boston Syncope Criteria were retrospectively applied to each patient to determine whether they were at high risk for an adverse outcome or critical intervention, versus low risk and could be discharged.

Results: A total of 198 patients fulfilled the inclusion criteria and completed follow-up. Of these, 21 patients had either an adverse outcome or critical intervention. The rule detected 20/21 with a sensitivity of 95%, a specificity of 66%, and a negative predictive value of 99%.

Conclusions: The Boston Syncope Criteria may be useful for physicians in other locations throughout the world to discharge low-risk syncope patients as well as identify those at risk of complications

Background: Screening for asymptomatic urinary retention (AUR) in older adult men at hospital admission to the internal medicine department has never been studied.

Objectives: To assess the incidence of AUR in older adult men at hospital admission, its risk factors, and its outcome.

Methods: The study comprised 111 older adult men aged ≥ 75 years who were admitted to three internal medicine departments. All men underwent post-void residual (PVR) urine volume measurement on the morning following admission by using a portable ultrasound bladder scan. AUR was defined as a PVR urine volume of ≥ 200 ml without symptoms. Men with AUR had a follow-up phone call concerning symptoms and urinary catheter status30 days following hospitalization.

Results: Seven (6.3%) men had AUR. Relative to the 104 men without AUR, they had significantly higher prevalence of severe dependency (6/7 vs. 33/104, 85.7% vs. 31.7%, (P = 0.007), cognitive impairment (5/7 vs. 19/104, 71.4% vs. 18.3%, P = 0.005), and use of anticholinergic agents (4/7 vs. 19/104, 57.1% vs. 18.3%, P = 0.033). A urinary catheter was inserted in one man (14.3%), but it was removed later during hospitalization. No symptoms were reported and no urinary catheter was inserted following hospitalization in men with AUR.

Conclusions: AUR in older adult men at hospital admission is uncommon and has a favorable outcome. Hence, screening for AUR in all older adult men at admission is not recommended, but it may be considered in severely dependent older adult men with cognitive impairment who use anticholinergic agents

Background: Pregnant women with Marfan syndrome (MS) have a high risk of aortic dissection around delivery and their optimal management requires a multi-disciplinary approach, including proper cardio-obstetric care and adequate pain management during labor, which may be difficult due to the high prevalence of dural ectasia (DE) in these patients.

Objectives: To evaluate the multidisciplinary management of MS patients during labor.

Methods: Nineteen pregnant women (31 pregnancies) with MS were followed by a multi-disciplinary team (cardiologist, obstetrician, anesthesiologist) prior to delivery.

Results:^. Two patients had kyphoscoliosis; none had previous spine surgery nor complaints compatible with DE. In eight pregnancies (7 patients), aortic root diameter (ARd) before pregnancy was 40 to 46 mm. In this high-risk group, one patient underwent elective termination, two underwent an urgent cesarean section (CS) under general anesthesia, and five had elective CS; two under general anesthesia (GA), and three under spinal anesthesia. In 23 pregnancies (12 patients), ARd was < 40 mm. In this non-high-risk group three pregnancies (1 patient) were electively terminated. Of the remaining 20 deliveries (11 patients), 14 were vaginal deliveries, 9 with epidural analgesia and 5 without. Six patients had a CS; four under GA and two2 under spinal anesthesia. There were no epidural placement failures and no failed responses. There were 2 cases of aortic dissection, unrelated to the anesthetic management.

Conclusions: The optimal anesthetic strategy during labor in MS patients should be decided by a multi-disciplinary team. Anesthetic complications due to DE were not encountered during neuraxial block

Background: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound.

Objectives: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals.

Methods: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment.

Results: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1.

Conclusions: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings

Background: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair.

Objectives: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects.

Methods: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture.

Results: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group.

Conclusions: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.