Israel Medical Association Journal

Background: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic.

Objectives: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19).

Methods: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel.

Results: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02.

Conclusions: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.

Background: Emergency department (ED) overcrowding is associated with worse patient outcomes.

Objectives: To determine whether physician assistants (PAs), fairly recently integrated into the Israeli healthcare system, improve patient outcomes and ED timings.

Methods: We compared patients seen by physicians with patients seen by PAs and then by physicians between January and December 2018 using propensity matching. Patients were matched for age, gender, triage level, and decision to hospitalize. Primary endpoints included patient mortality, re-admittance. and leaving on own accord rates. Secondary endpoints were ED timing landmarks.

Results: Patients first seen by PAs were less likely to leave on their own accord (MD1 1.5%, PA 1.0%, P = 0.015), had lower rates of readmission within 48 hours (MD1 2.1%, PA 1.5%, P= 0.028), and were quicker to be seen, to have medications prescribed, and to undergo imaging without differences in timings until decisions were made or total length of stay. Patients seen by a physician with the assistance of a PA were attended to quicker (MD2 47.79 minutes, range 27.70–78.82 vs. MD + PA 30.59 minutes, range 15.77–54.85; P < 0.001) without statistically significant differences in primary outcomes. Mortality rates were similar for all comparisons.

Conclusions: Patients first seen by PAs had lower rates of re-admittance or leaving on their own accord and enjoyed shorter waiting times. Pending proper integration into healthcare teams, PAs can further improve outcomes in EDs and patient satisfaction.

Background: Transanal minimally invasive surgery (TAMIS) is a single port access platform used for full thickness local excision of rectal lesions. It is an appealing alternative to a radical resection of rectum that often can cause a significant bowel dysfunction described as low anterior resection syndrome (LARS). LARS is evaluated using a validated score. Functional outcomes of patients undergoing TAMIS has not yet been evaluated using the LARS score.

Objectives: To evaluate long-term bowel function in patients who underwent TAMIS.

Methods: In this case series, all patients who underwent TAMIS in a single tertiary institute between 2011 and 2017 were retrospectively reviewed. We evaluated bowel function using the LARS score questionnaire through telephone interviews.

Results: The study consisted of 23 patients, average age of 67 ± 6.98 year; 72% were male. The median follow-up from the time of surgery was 5 years. Six patients (26.08%) had malignant type lesions. The average height of the lesion from the anal verge was 7.4 cm. The average size of the specimen was 4 cm. The total LARS score revealed that 17 patients (73.91%) had no definitive LAR syndrome following the surgery. Four patients (17.39%) fit the description of minor LARS and only two (8.69%) presented with major LARS.

Conclusions: TAMIS provides relatively good long-term functional outcomes in terms of bowel function. Further randomized studies with larger cohorts are still needed to better evaluate the outcomes.

Background: Stress hyperglycemia (SH) is a common finding in patients in pediatric emergency departments (PED) and has been related to increased morbidity and mortality.

Objectives: To assess the incidence of SH among children visiting the PED. To identify which diseases predispose patients to SH and whether they indicate a worse outcome.

Methods: Data were collected retrospectively from the medical records of all children aged 0–18 years who visited the PED during the years 2010–2014 and who had a glucose level of ≥ 150 mg/dl. Data collected included age, gender, weight, blood glucose level, presence or absence of a pre-existing or a new diagnosis of diabetes mellitus, and previous treatment with medications affecting blood glucose levels or with intravenous fluids containing dextrose. Data were collected regarding hospitalization, duration of hospitalization, discharge diagnosis, and survival status.

Results: The study population included 1245 children with SH, which comprised 2.6% of all patients whose blood glucose level was measured in the PED during the study period. The mean age of children with SH was 49 months; 709 (56.9%) were male. The mean blood glucose level was 184 mg/dl. The rate of hospitalization was 57.8%. The mean duration of hospital stay was 5.6 days and mortality rate was 0.96%. The majority were diagnosed with a respiratory illness.

Conclusions: SH is a common phenomenon among children evaluated in the PED and is associated with a high incidence of hospitalization. It may serve as an additional clinical indicator of disease severity.

Background: Although indwelling catheters are increasingly used in modern medicine, they can be a source of microbial contamination and hard-to-treat biofilms, which jeopardize patient lives. At times 70% ethanol is used as a catheter-lock solution due to its bactericidal properties. However, high concentrations of ethanol can result in adverse effects and in malfunction of the catheters.

Objective: To determine whether low concentrations of ethanol can prevent and treat biofilms of Pseudomonas aeruginosa.

Methods: Ethanol was tested at a concentration range of 0.625–80% against laboratory and clinical isolates of P. aeruginosa for various time periods (2–48 hours). The following parameters were evaluated following ethanol exposure: prevention of biofilm formation, reduction of biofilm metabolic activity, and inhibition of biofilm regrowth.

Results: Exposing P. aeruginosa to twofold ethanol gradients demonstrated a significant biofilm inhibition at concentrations as low as 2.5%. Treating pre-formed biofilms of P. aeruginosa with 20% ethanol for 4 hours caused a sharp decay in the metabolic activity of both the laboratory and clinical P. aeruginosa isolates. In addition, treating mature biofilms with 20% ethanol prevented the regrowth of bacteria encased within it.

Conclusions: Low ethanol concentrations (2.5%) can prevent in vitro biofilm formation of P. aeruginosa. Treatment of previously formed biofilms can be achieved using 20% ethanol, thereby keeping the catheters intact and avoiding complications that can result from high ethanol concentrations.

Background: Transurethral prostatectomy is the gold standard surgical treatment of bladder outlet obstruction due to benign enlargement of the prostate, with more than 30,000 procedures performed annually in the United States alone. The success rate of this minimally invasive procedure is high and the results are durable. The development of urethral stricture is a long-term complication of the procedure and is noted in about 2% of patients. The stricture narrows the urethral lumen, leading to re-appearance of obstructive urinary symptoms. Traditionally, the evaluation of the stricture was performed by retrograde urethrography. Advancements in the fields of flexible endoscopy allowed rapid inspection of the urethra and immediate dilatation of the stricture in selected cases.

Objectives: To compare the efficacy of urethrography versus cystoscopy in the evaluation of urethral strictures following transurethral prostatectomy.

Methods: A retrospective review was conducted of a series of 32 consecutive patients treated due to post-transurethral resection of prostate (TURP) urethral stricture.

Results: Twenty patients underwent both tests. In 16 there was concordance between the two tests. Four patients had no pathological findings in urethrography but had strictures in cystoscopy. All strictures were short (up to 10 mm) and were easily treated during cystoscopy, with no complaints or re-surgery needed in 24 months follow-up.

Conclusions: Cystoscopy was superior to urethrography in the evaluation of post-TURP strictures. Strictures where often short and treated during the same procedure. We recommend that cystoscopy be the procedure of choice in evaluating obstructive urinary symptoms after TURP, and retrograde urethrography be preserved for selected cases.

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: 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: 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: Untreated dental caries or even dental manipulations, such as a tooth extraction, might cause direct spread of an odontogenic infection and consequently the development of life-threatening conditions such as deep neck infections (DNI). The most common source of DNI is of odontogenic origin (38.8–49%). Abscess formation or cellulitis can lead to life-threatening complications, despite new diagnostic imaging technology and widespread availability of antibiotics. 

Objectives: To demonstrate the dangers of DNI, which can create life-threatening situations.

Methods: Five cases of DNI of odontogenic origin, which were referred to the oral and maxillofacial surgery unit, are presented. 

Results: Clinical manifestations included trismus, dysphagia, dysphonia, dyspnea, and infection symptoms. In all cases, computed tomography confirmed diagnosis and extent of abscess. Complications included mediastinitis, respiratory distress, osteomyelitis of the jaws, and in rare cases the mandibular condyle. Treatment included securing the airway, immediate surgical drainage, removal of the infection source, and antibiotic therapy. All patients were discharged in stable and improved condition.

Conclusions: DNI treatment on an emergency basis requires proper diagnosis and effective management. To confirm diagnosis and prevent serious complications, it is essential for physicians to recognize the spaces of the head and neck that are likely to be affected by DNI.