Israel Medical Association Journal

Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease.

Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged.

Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls.

Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups.

Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies

Background: Iron deficiency anemia is a widespread problem. Although oral and intravenous therapy are available, iron malabsorption is a distinct possibility.

Objectives: To evaluate the applicability of the oral iron absorption test (OIAT) as a simple and effective means of determining the degree of oral iron absorption.

Methods: The study comprised 81 patients diagnosed with iron deficiency anemia who were referred to a hematology outpatient clinic. Participants were given two ferrous sulphate tablets. Iron levels in the blood were evaluated at intervals from 30 to 180 minutes after iron administration.

Results: We divided patients into three distinct groups. The first group consisted of patients with little iron absorption with a maximum iron increment (Cmax) in the blood of 0–49 ug/dl. The second group had a moderate maximum absorption of 50–100 ug/dl, while a third group had considerable absorption of with maximum iron increase of over 100 ug/dl.

Conclusions: The oral iron absorption test, although not clearly standardized, is easy to conduct in any outpatient clinic. This test can readily and clearly determine absorption or nonabsorption of iron. This test can have major implications on the need of oral or intravenous iron therapy and can also determine the need for further gastrointestinal evaluation of the small intestine, where iron absorption takes place and the success of therapy on subsequent iron absorption

An arginine-rich apolipoprotein was discovered 50 years ago and became known as apolipoprotein E (ApoE) 10 years later. ApoE is associated with triglyceride-rich lipoproteins and mediates the clearance of these lipoproteins from the plasma. The ApoE-deficient hypercholesterolemic mice are an excellent platform for experimental atherosclerosis because they are similar to human pathology with regard to an atherogenic diet. ApoE is mainly produced in the liver and central nervous system cells. Three alleles determine six ApoE phenotypes with different metabolic effects and plasma cholesterol levels. Type III dysbetalipoproteinemia is associated with wide-spread atherogenesis with a defective ApoE2 resulting in delayed clearance of triglyceride-rich lipoproteins. ApoE4 substantially increases the risk including age of onset, progression, and prognosis of Alzheimer’s disease. Therefore, much effort has been directed to the elucidation of the pathogenic role of ApoE related to amyloid β (Aβ) acquisition in the brain. The ApoE trail passing from an enigmatic protein to a major player in cardiovascular and neurodegenerative disorders is reviewed

Leonardo da Vinci, the artist and scientist, was an archetype figure of the Renaissance era. He was an autodidactic polymath in natural sciences, engineering, and physical sciences, imbued with universality, prodigious inventive imagination, and curiosity to know and understand the world around him. Among his myriad activities, anatomy, physiology, and biomechanics of the musculoskeletal system and the underlying systems fully engaged him. Leonardo dissected dozens of human and animal corpses to study. His anatomical illustrations were precise, combining art and science with an impeccable integration of both. Multiple drawings, diagrams, sketches, and designs are found in his notes. Leonardo’s style was intensely personal, unveiling his thoughts, passions, and emotions. We analyzed significant biographic aspects of Leonardo's life, remarking on his scientific and life conceptions and their manifestation in his anatomical designs. The contribution of preceding anatomists is reported as a source of his inspiration as well as motivation to successors. Leonardo da Vinci left no publications, but rather an extensive collection of personal notebooks. Leonardo's contribution to modern anatomy was enormous and he is considered by the scientific and medical community as the father of the modern anatomy

Background: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction.

Objectives: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS).

Methods: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4.

Results: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54–88). ULD scan radiation exposure was comparable on average to 3.6–4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04–-0.08 vs. 0.08–0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization.

Conclusions: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.

Background: Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time.

Objectives: To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies.

Methods: The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013–2014 to the years 2015–2019.

Results: We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients’ relatives were satisfied with EOL care.

Conclusions: Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.

Background: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies.

Objectives: To describe the design and patient population of the first pediatric aerodigestive center in Israel.

Methods: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children’s Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020.

Results: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3–216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1–5 (5 = highest satisfaction) was 4.5.

Conclusions: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

Background: Fibromyalgia is characterized by diffuse musculoskeletal pain at the time of diagnosis, but many patients report their initial symptoms as being focal or local. 

Objectives: To evaluate, prospectively, the initial location of body pain in recently diagnosed patients with fibromyalgia.

Methods: Non-selected patients from the rheumatology clinic who were recently diagnosed with fibromyalgia (≤ 2 years) with symptoms of ≤ 4 years participated in our study. Demographic and clinical parameters were documented, as was the initial location of pain they had experienced. Sub-analysis of data according to gender and ethnicity was conducted using chi-squire test.

Results: The study comprised 155 patients. Mean age was 39.8 ± 11.7 years; 85% were female. Mean duration of symptoms was 2.11 years and of diagnosis was 0.78 years. Six patients (3.9%) reported initial symptoms of pain as being diffuse from the start, 10 (6.5%) could not remember the location of their initial symptoms, and 139 (90%) reported initial focal pain. Hands were reported as the initial area of pain for 25.2% of the patients, 19.4% reported the back, and 11% reported both trapezial areas as the initial area of pain. In 90% of the patients (excluding patients with back, abdominal, or chest pain) the initial symptoms were bilateral and symmetrical. No significant difference in initial presentation was found among different gender or ethnic groups. 

Conclusions: Pain in fibromyalgia patients usually presents as focal and symmetrical. Bilateral hand pain, followed by back pain, was the most common reported area of initial pain among fibromyalgia patients.

Background: Among dialysis patients, occlusive mesenteric vascular disease has rarely been reported.

Objectives: To report on the experience of one center with regard to diagnosing and treating this complication.

Methods: The retrospective case-series involved six patients (3 females, 3 males; age 52–88 years; 5/6 were smokers) on chronic hemodialysis at a single center. All patients with symptoms suggestive of occlusive mesenteric disease and a subsequent angiographic intervention were included. Demographic, clinical, and laboratory data were collected from patient charts for the period before and after angioplasty and stenting of the mesenteric vessels. A Wilcoxon signed-rank test was used to compare the relevant data before and after the intervention.

Results: All participants had variable co-morbidities and postprandial abdominal pain, food aversion, and weight loss. CT angiography was limited due to heavy vascular calcifications. All underwent angioplasty with stenting of the superior mesenteric artery (4 patients) or the celiac artery (2 patients). All procedures were successful in resolving abdominal pain, malnutrition, and inflammation. Weight loss before was 15 ± 2 kg and weight gain after was 6 ± 2 kg. C-reactive protein decreased from 13.4 ± 5.2 mg/dl to 2.2 ± 0.4 mg/dl (P < 0.05). Serum albumin increased from 3.0 ± 0.2 g/dl to 3.9 ± 0.1 g/dl (P < 0.05). Two patients underwent a repeat procedure (4 years, 5 months, respectively). Follow-up ranged from 0.5–7 years.

Conclusions: Occlusive mesenteric ischemia occurs among dialysis patients. The diagnosis requires a high degree of suspicion, and it is manageable by angiography and stenting of the most involved mesenteric artery.

Background: Limited data exist regarding the safety of ultrasound-guided femoral nerve blockade (US-FNB) in patients with hip fractures treated with anti-Xa direct oral anticoagulants (DOAC).

Objectives: To compare the safety outcomes of US-FNB to conventional analgesia in patients with hip fractures treated with anti-Xa DOAC.

Methods: This observational exploratory prospective study included 69 patients who presented to our emergency department (ED) in 3 years with hip fracture and who were treated with apixaban or rivaroxaban. Patients received either a US-FNB (n=19) or conventional analgesics (n=50) based on their preference and, and the presence of a trained ED physician qualified in performing US-FNB. Patients were observed for major bleeding events during and 30 days after hospitalization. The degree of preoperative pain and opioid use were also observed.

Results: We found no significant difference in the number of major bleeding events between groups (47.4% vs. 54.0%, P = 0.84). Degree of pain measured 3 and 12 hours after presentation was found to be lower in the US-FNB group (median visual analog scale of pain improvement from baseline of -5 vs. -3 (P = 0.002) and -5 vs.-4 (P = 0.023), respectively. Opioid administration pre-surgery was found to be more than three times more common in the conventional analgesia group (26.3% vs.80%, P < 0.0001).

Conclusions: Regarding patients treated with Anti-Xa DOAC, US-FNB was not associated with an increase in major bleeding events compared to conventional analgesia, although it was an effective means of pain alleviation. Larger scale randomized controlled trials are required to determine long-term safety and efficacy.

Background: Hip fractures in elderly patients are a major cause of morbidity and mortality. Variability in length of hospital stay (LOS) was evident in this population. The coronavirus disease-2019 (COVID-19) pandemic led to prompt discharge of effected patients in order to reduce contagion risk. LOS and discharge destination in COVID-19 negative patients has not been studied.

Objectives: To evaluate the LOS and discharge destination during the COVID-19 outbreak and compare it with a similar cohort in preceding years.

Methods: A retrospective study was conducted comparing a total of 182 consecutive fragility hip fracture patients operated on during the first COVID-19 outbreak to patients operated on in 2 preceding years. Data regarding demographic, co-morbidities, surgical management, hospitalization, as well as surgical and medical complications were retrieved from electronic charts.

Results: During the pandemic 67 fragility hip fracture patients were admitted (COVID group); 55 and 60 patients were admitted during the same time periods in 2017 and 2018, respectively (control groups). All groups were of similar age and gender. Patients in the COVID group had significantly shorter LOS (7.2 ± 3.3 vs. 8.9 ± 4.9 days, P = 0.008) and waiting time for a rehabilitation facility (7.2 ± 3.1 vs. 9.3 ± 4.9 days, P = 0.003), but greater prevalence of delirium (17.9% vs. 7% of patients, P = 0.028). In hospital mortality did not differ among groups.

Conclusions: LOS and time to rehabilitation were significantly shorter in the COVID group. Delirium was more common in this group, possibly due to negative effects of social distancing.

Background: Osteoporosis is a common medical condition in older ages. A devastating result of osteoporosis may be a hip fracture with up to 30% mortality rate in one year. The compliance rate of osteoporotic medication following a hip fracture is 20% in the western world.

Objectives: To evaluate the impact of the fracture liaison service (FLS) model in the orthopedic department on patient compliance following hip fracture

Methods: We performed a retrospective review of all patients with hip fracture who were involved with FLS. We collected data regarding kidney function, calcium levels, parathyroid hormone levels, and vitamin D levels at admission. We educated the patient and family, started vitamin D and calcium supplementation and recommended osteoporotic medical treatment. We phoned the patient 6–12 weeks following the fracture to ensure treatment initiation.

Results: From June 2018 to June 2019 we identified 166 patients with hip fracture who completed at least one year of follow-up. Over 75% of the patients had low vitamin D levels and 22% had low calcium levels at admission. Nine patients (5%) died at median of 109 days. Following our intervention, 161 patients (96%) were discharged with a specific osteoporotic treatment recommendation; 121 (73%) received medication for osteoporosis on average of < 3 months after surgery. We recommended on injectable medications; however, 51 (42%) were treated with oral biphsophonate.

Conclusions: FLS improved the compliance rate of osteoporotic medical treatment and should be a clinical routine in every medical center

Background: Proximal femoral fractures (PFF) are among the most common injuries in the elderly population treated by orthopedic surgeons. Postoperative complications, especially infections, are of great importance due to their effect on patient mortality and morbidity and healthcare costs.

Objectives: To assess the main causes for postoperative infection among PFF patients.

Methods: We conducted a retrospective analysis of PFF patients in our medical center between 2015 and 2017. Patients were divided into two groups based on whether there was postoperative infection during immediate hospitalization and 30 days after surgery. Factors such as time from admission to surgery, duration of surgery, and length of stay were analyzed. Groups were analyzed and compared using a t-test, chi-squared and Fisher’s exact tests.

Results: Of 1276 patients, 859 (67%) underwent closed reduction internal fixation, 67 (5%) underwent total hip arthroplasty, and 350 (28%) underwent hemiarthroplasty. Of the total, 38 patients (3%) were diagnosed with postoperative infection. The demographics and co-morbidities were similar between the two study groups. The incident of infection was the highest among patients undergoing hemiarthroplasty (6%, P < 0.0001). Length of hospitalization (15 vs. 8 days, P = 0.0001) and operative time (117 vs. 77 minutes, P = 0.0001) were found to be the most significant risk factors for postoperative infection.

Conclusions: Predisposition to postoperative infections in PPF patients was associated with prolonged length of surgery and longer hospitalization. We recommend optimizing fast discharge, selecting the appropriate type of surgery, and improving surgical planning to reduce intraoperative delays and length of surgery.