Israel Medical Association Journal

Background: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting.

Objective: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer’s guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds

Methods: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement.

Results: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer’s guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds.

Conclusions: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Background: Older age is an independent predictor of worse outcome from traumatic brain injury (TBI). No clear guidelines exist for the management of TBI in elderly patients.

Objectives: To describe the outcomes of elderly patients presenting with TBI and intracranial bleeding (ICB), comparing a very elderly population (≥ 80 years of age) to a younger one (70–79).

Methods: Retrospective analysis of the outcomes of elderly patients presenting with TBI with ICB admitted to a level I trauma center.

Results: The authors analyzed 100 consecutive patients aged 70–79 and 100 patients aged 80 and older. In-hospital mortality rates were 9% and 21% for groups 70–79 and ≥ 80 years old, respectively (P = 0.017). Patients 70–79 years old showed a 12-month survival rate of 73% and a median survival of 47 months. In patients ≥ 80 years old, 12-month survival was 63% and median survival was 27 months (P = NS). In patients presenting with a Glasgow Coma Scale score of ≥ 8, the in-hospital mortality rates were 41% (n=5/12) and 100% (n=8/8). Among patients ≥ 80 years old undergoing emergent surgical decompression, in-hospital mortality was 66% (n=12/18). Survivors presented with a severe drop in their functional score. Survival was dismal in patients ≥ 80 years old who were treated conservatively despite recommended operative guidelines.

Conclusions: There is a lack of reliable means to evaluate the outcome in patients with poor functional status at baseline. The negative prognostic impact of severe TBI is profound, regardless of treatment choices.

Background: The use of graphic depictions (pictorials) to represent medical conditions is an accepted method that can complement standard methodology of comprehensive geriatric assessment.

Objectives: To use the clinical pathway method to develop a comprehensive geriatric genogram assessment tool (CGGAT), which could supplement the written summary letter and recommendations.

Methods: We used the critical paths method to develop a tool to facilitate implementation of the comprehensive geriatric assessment recommendations. A multidisciplinary group of clinicians used the critical pathways method to develop a CGGAT.

Results: We used the CGGAT to depict the physical and functional status of patients and to complement the textual historical information, family dynamics, and current patient issues. CGGAT is a simple instrument that provides a visual structure and it can facilitate the sharing of information among team members, encourage interdisciplinary dialogue, enhance understanding and adherence on the part of patients and professionals, and reduce the burden on the clinicians who conduct the initial comprehensive geriatric assessment.

Conclusions: We showed the benefits and obstacles related to the adaptation of this new tool and provide recommendations for further development. 

Background: Sonographic estimation of birth weight may differ among evaluators due to its operator-dependent nature.

Objectives: To compare the accuracy of estimation of fetal birth weight by sonography between ultrasound-certified physicians and registered diagnostic medical technicians.

Methods: The authors reviewed ultrasound examinations that had been performed by either technicians or ultrasound-certified obstetricians between 2010 and 2017, and within 2 days of delivery. Inclusion criteria were: singleton viable pregnancy, details of four ultrasound measurements (abdominal circumference, bi-parietal diameter, head circumference, and femur length), and known birth weight. The estimated fetal weight (EFW) was calculated according to the Hadlock formula, incorporating the four ultrasound measurements. The mean percentage error (MPE) was calculated by the formula: (EFW-birth weight) x100 / birth weight.

Results: Technicians performed 9741examinations and physicians performed 352 examinations. The proportion of macrosomic neonates was similar in both groups. Technicians were more accurate than physicians in terms of the MPE, absolute MPE, proportion of estimates that fell within ± 10% of birth weight, and Euclidean distance (P < 0.0001 for all comparisons). They were also more accurate in terms of sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve. Furthermore, for fetuses weighing more than 4000 grams the technicians had a lower total false prediction rate.

Conclusions: Medical technicians in our institute performed better than physicians in estimating fetal weight. Further studies are warranted to confirm our findings and better delineate the role of repeat physician’s examination after an initial estimation by an experienced technician.

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: Ocular trauma in the pediatric population may lead to cataract formation. Managing traumatic cataracts in a visually immature child is a major challenge and can result in poor visual outcome.

Objectives: To review our long-term surgical experience with childhood unilateral traumatic cataracts.

Methods: A retrospective observational study of children with unilateral traumatic cataracts with minimal follow-up of 5 years was conducted. Main outcomes included final visual acuity (VA) and occurrence of complications.

Results: Of the 18 children included in the study, 83% were male. Mean follow-up time was 12.5 years. Median age at injury was 7.5 years. Eleven patients (61%) presented with penetrating trauma injuries and 7 (39%) with blunt trauma. Sixteen patients (89%) had cataracts at presentation, while in two the cataracts developed during follow-up. Of the 18 total, cataract removal surgery was conducted in 16 (89%) with intraocular lens (IOL) implantation in 14 (87.5%), while 2 remained aphakic (12.5%). Two (11%) were treated conservatively. Long-term complications included IOL dislocation in 5 (36%), glaucoma in 8 (44%), and posterior capsular opacity in 10 (71%). No correlation was found between final visual acuity and the time interval between injury and IOL implantation nor between final VA and age at trauma. However, the final VA did correlate with time of follow-up.

Conclusions: Severe complications occurred in over 30% of the patients during a long follow-up (mean 12.5 years). This finding shows the importance of discussions between the operating physician and the parents regarding the prognosis and necessity of scheduled follow-up.

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.

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.

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.

Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.