Israel Medical Association Journal

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

Background: Accuracy of the number and location of pathological lymph nodes (LNs) in the pathology report of a neck dissection (ND) is of vital importance.

Objectives: To quantify the error rate in reporting the location and number of pathologic LNs in ND specimens.

Methods: All patients who had undergone a formal ND that included at least neck level 1 for a clinical N1 disease between January 2010 and December 2017 were included in the study. The error rate of the pathology reports was determined by various means: comparing preoperative imaging and pathological report, reporting a disproportionate LN distribution between the different neck levels, and determining an erroneous location of the submandibular gland (SMG) in the pathology report. Since the SMG must be anatomically located in neck level 1, any mistake in reporting it was considered a categorical error.

Results: A total of 227 NDs met the inclusion criteria and were included in the study. The study included 128 patients who had undergone a dissection at levels 1–3, 68 at levels 1–4, and 31 at levels 1–5. The best Kappa score for correlation between preoperative imaging and final pathology was 0.50. There were nine cases (3.9%) of a disproportionate LN distribution in the various levels. The SMG was inaccurately reported outside neck level 1 in 17 cases (7.5%).

Conclusions: At least 7.5% of ND reports were inaccurate in this investigation. The treating physician should be alert to red flags in the pathological report

Background: The coronavirus disease-2019 (COVID-19) pandemic had enormous impact on many aspects of our society, including huge medical, social, and economic challenges.

Objective: To evaluate the impact of the first wave of the COVID-19 pandemic and the related movement restrictions on the incidence of hip fractures in different age groups.

Methods: This single center retrospective observational study included all patients over 60 years old admitted to our hospital with the diagnosis of hip fracture during March and April 2020. Exclusion criteria were periprosthetic or pathologic fractures and multitrauma. We collected the same data on all patients with hip fractures admitted during March and April of 2018 and 2019.

Results: Mean patient age increased from 81.7 to 85.0 years. Only two of 49 patients tested positive for COVID-19. The data show a decrease of 38% in fracture load, but a striking decrease of 85% and 59% among sexagenarians and septuagenarian, respectively. There was no decrease among nonagenarians. Early mortality, both at 30 days and 90 days, was twice as common during the pandemic. However, stratification by age group demonstrated that the risks of early mortality were the same as previous years. Mean waiting time for surgery decreased from 27.5 to 18.9 hours. Patient discharge to home over a rehabilitation facility increased from 9% to 17%.

Conclusions: The COVID-19 pandemic affected the epidemiology of hip fractures in the elderly. The incidence of fractures and age distribution were significantly different from other years. Discharge destinations were also affected. The management of hip fracture patients was not compromised.

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Background: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative.

Objectives: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold).

Methods: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant.

Results: The authors’ novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days.

Conclusions: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Background: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities.

Objectives: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19.

Methods: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March–April 2020 (during the COVID-19 outbreak) with March–April of the preceding year, 2019.

Results: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods.

Conclusions: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients

Background: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring.

Objectives: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB.

Methods: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB.

Results: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB.

Conclusions: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

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: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth.

Objectives: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism.

Methods: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms.

Results: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects.

Conclusions: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

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.

Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. 

Objectives: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not.

Methods: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods.

Results: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. 

Conclusions: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment. 

 

Background: Most spine tumors are resistant to radiation and chemotherapy. Complete surgical removal provides the best chance for long-term control of the tumor. Total en bloc spondylectomy (TES) is a radical new technique that entails total removal of the tumor and affected vertebras with clean margins.

Objectives: To review our initial experience with TES, focusing on feasibility, surgical challenges and the short-term outcome.

Methods: We retrospectively reviewed the hospitalization charts and follow-up data of all patients treated with TES for spine tumors in the spine unit at Tel Aviv Medical Center.

Results: TES was performed in 12 patients aged 13–78 years. Nine patients had primary spinal tumors and three had metastasis. Total en bloc removal was achieved in all cases with spondylectomy of one to three affected vertebras. There was no perioperative mortality and only one major intraoperative complication of injury to a major blood vessel. Late complications were mainly related to hardware failure.

Conclusions: Total en bloc spondylectomy is feasible and effective for the management of selected patients with extradural spinal tumors. Since the surgical procedure is demanding and carries significant risk, careful preoperative evaluation and collaboration with colleagues from other specialties are crucial.