Israel Medical Association Journal

In non-ambulatory patients with cerebral palsy, the presence of scoliosis has a major impact on health and quality of life. The aim of this review is to raise awareness of caregivers from various professions to the extent of the problem, to explain the natural history of neuromuscular scoliosis and its pathophysiology, and to describe up-to-date optional conservative and surgical treatments.

Background: Recently, Israel established the first national-level adult cardiac surgery database, which was linked to the Society of Thoracic Surgeons (STS).

Objectives: To validate and compare the STS predicted risk of mortality (PROM) to logistic EuroSCORE I (LESI) and EuroSCORE II (ESII) in Israeli patients undergoing cardiac surgery.

Methods: We retrospectively studied 1279 consecutive patients who underwent cardiac surgeries with a calculable PROM. Data were prospectively entered into our database and used to calculate PROM, LESI, and ESII. Scores were normalized and correlated using linear regression and Pearson's test. To examine model calibration, we plotted the total observed versus expected mortality for each score and across five risk-score subgroups. Model discrimination was assessed by measuring the area under the receiver operating curves.

Results: The observed 30-day operative mortality was 1.95%. The median (IQ1; IQ3) PROM, LESI, and the ESII scores were 1.45% (0.69; 3.22), 4.54% (2.28; 9.27), and 1.88% (1.18; 3.54), respectively, with observed over expected ratios of 0.63 (95% confidence interval [95%CI] 0.42–0.93), 0.59 (95%CI 0.40–0.87), and 0.24 (95%CI 0.17–0.36), respectively, (STS vs. ESII P = 0.36, STS vs. LESI P = 0.0001). There was good correlation among all scores. All models overestimated mortality. Model discrimination was high and similar for all three scores. Model calibration of the STS, PROM, and ESII were more accurate than the LESI, particularly in higher risk subgroups.

Conclusions: All scores overestimated mortality. In Israeli patients, the STS, PROM, and ESII risk-scores were more reliable metrics than LESI, particularly in higher risk patients.

Background: C-reactive protein (CRP) blood level is associated with clinical outcomes of several diseases. However, the independent predictive role of CRP in the heterogeneous population of patients admitted to internal medicine wards is not known. 

Objectives: To determine whether single CRP levels at admission independently predicts clinical outcome and flow of patients in general medicine wards.

Methods: This study comprised 275 patients (50.5% female) with a mean age of 68.25 ± 17.0 years, hospitalized with acute disease in a general internal medicine ward. The association between admission CRP levels and clinical outcomes including mortality, the need for mechanical ventilation, duration of hospitalization, and re-admission within 6 months was determined.

Results: A significant association was found between CRP increments of 80 mg/L and risk for the major clinical outcomes measured. The mortality odds ratio (OR) was 1.89 (95% confidence interval (95%CI, 1.37–2.61, P < 0.001), mechanical ventilation OR 1.67 (95%CI, 1.10–2.34, P = 0.006), re-admission within 6 months OR 2.29 (95%CI, 1.66–3.15 P < 0.001), and prolonged hospitalization >7 days OR 2.09 (95%CI, 1.59–2.74, P < 0.001). Lower increments of10 mg/L in CRP levels were associated with these outcomes although with lower ORs. Using a stepwise regression model for admission CRP levels resulted in area under the receiver operating characteristics curves between 0.70 and 0.76 for these outcomes.

Conclusions: A single admission CRP blood level is independently associated with major parameters of clinical outcomes in acute care patients hospitalized in internal medicine wards.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience.

Objectives: To describe the establishment of a national CTEPH–PEA center in Israel and present results of surgery.

Methods: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH–PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center.

Results: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity.

Conclusions: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.

Spinal manipulation therapy (SMT) is commonly used as an effective therapeutic modality for a range of cervical symptoms. However, in rare cases, cervical manipulation may be associated with complications. In this review we present a series of cases with cervical spine injury and myelopathy following therapeutic manipulation of the neck, and examine their clinical course and neurological outcome. We conducted a search for patients who developed neurological symptoms due to cervical spinal cord injury following neck SMT in the database of a spinal unit in a tertiary hospital between the years 2008 and 2018. Patients were assessed for the clinical course and deterioration, type of manipulation used and subsequent management. A total of four patients were identified, two men and two women, aged 32–66 years. In three patients neurological deterioration appeared after chiropractic adjustment and in one patient after tuina therapy. Three patients were managed with anterior cervical discectomy and fusion while one patient declined surgical treatment. Assessment for subjective and objective evidence of cervical myelopathy should be performed prior to cervical manipulation, and suspected myelopathic patients should be sent for further workup by a specialist familiar with cervical myelopathy (such as a neurologist, a neurosurgeon or orthopedic surgeon who specializes in spinal surgery). Nevertheless, manipulation therapy remains an important and generally safe treatment modality for a variety of cervical complaints. This review does not intend to discard the role of SMT as a significant part in the management of patients with neck related symptoms, rather it is meant to draw attention to the need for careful clinical and imaging investigation before treatment.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.

Background: Fibromyalgia is a syndrome of unknown etiology that is characterized by widespread pain, which severely impairs quality of life. Several forms of occupational and alternative therapy have demonstrated beneficial effects in fibromyalgia patients.

Objective: To assess the effects of participation in a floral design course on physical and psychiatric symptoms in a cohort of fibromyalgia patients.

Methods: This study was conducted as an observational study. Women diagnosed with fibromyalgia over the age of 18 were recruited to participate in one of two 12-week flower design (floristry) courses. Demographic details, disease activity indices, and anxiety and depression scores were calculated for all participants at baseline, week 12, and study completion. Physical and mental health of the two groups were compared throughout the study time-points.

Results: The study was completed by 61 female fibromyalgia patients who were included in the final analyses; 31 patients participated in the first floristry course and 30 in the second. Significant improvements in the 36-Item Short Form Survey physical and mental health components, visual analog scale, Fibromyalgia Impact Questionnaire, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale scores for the entire study population and for each group separately could be seen following participation in each floristry course.

Conclusions: Participation in a floristry course may lead to a significant improvement in pain and psychiatric symptoms in fibromyalgia patients. These findings highlight the potential benefit of utilizing occupational therapy programs, such as a floristry course, for improving quality of life in fibromyalgia.

Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.

Rheumatic diseases commonly affect women of childbearing age, when women may be contemplating pregnancy or they discover an unplanned pregnancy. Therefore, specific issues about pregnancy planning and management are commonly encountered in patients during these times. Knowledge of the effect of pregnancy on disease activity is important for counseling. This review summarizes recent data on the course of different rheumatic diseases during pregnancy and the postpartum period. Rheumatoid arthritis and systemic lupus erythematosus are the most commonly investigated diseases. Data are increasing about spondyloarthritis. Sparse data are available for other rheumatic diseases. Despite the differences in these diseases and the various courses these disease take during pregnancy, a common feature is that active maternal disease in the months prior to conception increases the risk of flares during pregnancy, which in turn can lead to adverse pregnancy outcomes. Therefore, maternal and fetal health can be optimized if conception is planned when disease is inactive so that a treatment regimen can be maintained throughout pregnancy.

Microvascular damage, clinically expressed by Raynaud’s phenomenon, is generally the first symptom of the disease and the injured vascular cells, both endothelial and perivascular, may transdifferentiate to myofibroblasts, thus leading to collagen deposition in the tissue and consequent fibrosis. Systemic sclerosis (SSc, scleroderma) is complex disease characterized by autoimmunity, vasculopathy, and fibrosis. It has been shown that microvascular damage may be the first symptom of SSc. Injured endothelial cells and pericytes may transdifferentiate into myofibroblasts, the cells responsible for fibrosis and collagen deposition in the tissue. Based on these factors, the process of myofibroblast generation may link two pivotal events of SSc: microvascular damage and fibrosis. Understanding the development, differentiation, and function of myofibroblasts is therefore crucial to individuate early pathogenetic events and develop new therapeutic target for SSc, a condition in which no disease-modifying agents are available. The aim of this review was to discuss the possible origins of myofibroblasts in SSc, highlighting the process of endothelial mesenchymal transition and pericytes to myofibroblast transition and to show how these events may contribute to pathogenesis of the disease.