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: Autologous hematological stem cell transplantation (HSCT) is a novel therapy for systemic sclerosis (SSc) that has been validated in three randomized controlled trials.

Objectives: To report the first Israeli experience with HSCT for progressive SSc and review the current literature.

Methods: Five SSc patients who were evaluated in our department and were treated by HSCT were included. Medical records were evaluated retrospectively. Demographic, clinical, and laboratory data were recorded. Continuous data are presented as the mean ± standard deviation. Categorical variables are presented as frequencies and percentages.

Results: Five SSc patients were treated with HSCT. Four patients were adults (mean age 53 ± 12 years) and one was a 12-year-old pediatric patient. All patients were female. HSCT was initiated 1.4 ± 0.8 years after diagnosis. Two patients were RNA POLIII positive, two were anti-topoisomerase 1 positive, and one only antinuclear antibodies positive. All patients had skin and lung involvement. The mean modified Rodnan Skin Score was 29 ± 4.7 before HSCT, which improved to 10.4 ± 9.6 after HSCT. The forced vital capacity improved from 68 ± 13% to 90 ± 28%. Diffusing capacity of the lungs for carbon monoxide increased by 6%. Among severe adverse events were cyclophosphamide-related congestive heart failure, antithymocyte globulin-related capillary leak syndrome, and scleroderma renal crisis. All symptoms completely resolved with treatment without sequela. No treatment related mortality was recorded.

Conclusions: HSCT is an important step in the treatment of progressive SSc in Israel. Careful patient selection reduces treatment related morbidity and mortality.

Background: Heart failure centers with specialized nurse-supervised management programs have been proposed to improve prognosis. The Heart Failure Center in Beit Shemesh, Israel, is located within a large primary care facility. The specialist team supervised the managememt of patients both within the frame of the center and while they were hospitalized.

Objectives: To evaluate the health services utilization by heart failure patients treated at a heart failure center and their clinical outcome.

Methods: In this retrospective study, we compared the clinical outcome of patients treated at a heart failure center to patients who received the standard care in 2013–2014. The clinical outcome included primary care visits, emergency room visits, hospitalizations, and death.

Results: The study comprised 430 heart failure patients; 82 were treated at the heart failure center and 348 under standard care. At baseline, no significant differences were seen in clinical parameters between the groups. Healthcare utilization was higher among the study group. No significant changes in healthcare utilization were found. During follow-up, patients treated in a heart failure center were more likely to get recommended heart failure medications. Mortality was significantly lower in patients treated in the heart failure center compared with those receiving standard care 3.6% vs. 24%, respectively (P = 0.001), hazard ratio 0.19, 95% confidence interval 0.06–0.62, P = 0.005.

Conclusions: Joint management of heart failure by primary clinics and a specialized community heart failure center reduced mortality. There was no decrease in healthcare utilizations among heart failure center patients, despite the reduction in mortality.

Background: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited.

Objectives: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC.

Methods: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist.

Results: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7–7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1–12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1–5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9–26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2–not reached).

Conclusions: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC. 

Background: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency.

Objectives: To identify a unique heterogeneity pattern that is associated with true MMR loss.

Methods: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing.

Results: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases.

Conclusions: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.

Background: There is a need for standardized and objective methods to measure postural instability (PI) and gait dysfunction in Parkinson's disease (PD) patients. Recent technological advances in wearable devices, including standard smartphones, may provide such measurements.

Objectives: To test the feasibility of smartphones to detect PI during the Timed Up and Go (TUG) test.

Methods: Ambulatory PD patients, divided by item 30 (postural stability) of the motor Unified Parkinson's Disease Rating Scale (UPDRS) to those with a normal (score = 0, PD-NPT) and an abnormal (score ≥ 1, PD-APT) test and a group of healthy controls (HC) performed a 10-meter TUG while motion sensor data was recorded from a smartphone attached to their sternum using the EncephaLog application.

Results: In this observational study, 44 PD patients (21 PD-NPT and 23 PD-APT) and 22 HC similar in age and gender distribution were assessed. PD-APT differed significantly in all gait parameters when compared to PD-NPT and HC. Significant difference between PD-NPT and HC included only turning time (P < 0.006) and step-to-step correlation (P < 0.05).

Conclusions: While high correlations were found between EncephaLog gait parameters and axial UPDRS items, the pull test was least correlated with EncephaLog measures. Motion sensor data from a smartphone can detect differences in gait and balance measures between PD with and without PI and HC.

Background: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited.

Objectives: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function.

Methods: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250–500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids.

Results: Polyp tissue viability was retained for 2–3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production.

Conclusions: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

Background: Falls are a common complication in persons with stroke (PwS). Reliable assessment of balance responses to unexpected loss of balance has the potential to identify risk for falls. 

Objectives: To examine inter-observer reliability of balance responses to unannounced surface perturbations in PwS and to explore the concurrent validity of a balance recovery assessment protocol.

Methods: Two observers evaluated balance recovery strategies and fall threshold (a fall into a harness system) in 15 PwS and 15 healthy adults who were exposed to forward, backward, right, and left unannounced surface translations in six increasing intensities while standing. 

Results: Observer agreement was 100% for the fall threshold. Kappa coefficients for step strategies were 0.960–0.988 in PwS and 0.886–0.938 in healthy adults, 0.905–0.988 for arm reactions in PwS and 0.754–0.926 in healthy adults. Significant correlations were found between fall threshold and Berg Balance Scale (r = 0.691), 6-minute walk test (r = 0.599), and fall efficacy scale-international (r= -0.581). 

Conclusions: A trained examiner can reliably classify reactive balance responses to surface perturbations. The high frequency of falls observed in PwS highlights the importance of assessing reactive balance responses to different directions and intensities of surface translations.

Background: Asthma is a common respiratory disease, which is linked to air pollution. However, little is known about the effect of specific air pollution sources on asthma occurrence.

Objective: To assess individual asthma risk in three urban areas in Israel characterized by different primary sources of air pollution: predominantly traffic-related air pollution (Tel Aviv) or predominantly industrial air pollution (Haifa bay area and Hadera). 

Methods: The medical records of 13,875, 16- 19-year-old males, who lived in the affected urban areas prior to their army recruitment and who underwent standard pre-military health examinations during 2012–2014, were examined. Nonparametric tests were applied to compare asthma prevalence, and binary logistic regressions were used to assess the asthma risk attributed to the residential locations of the subjects, controlling for confounders, such as socio-demographic status, body mass index, cognitive abilities, and education.

Results: The asthma rate among young males residing in Tel Aviv was 8.76%, compared to 6.96% in the Haifa bay area and 6.09% in Hadera. However, no statistically significant differences in asthma risk among the three urban areas was found in controlled logistic regressions (P > 0.20). This finding indicates that exposure to both industrial- and traffic-related air pollution is associated with asthma prevalence.

Conclusions: Both industrial- and traffic-related air pollution have a negative effect on asthma risk in young males. Studies evaluating the association between asthma risk and specific air pollutants (e.g., sulfur dioxide, particulate matter, and nitrogen dioxide) are needed to ascertain the effects of individual air pollutants on asthma occurrence. 

 

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.