Israel Medical Association Journal

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: Oral anticoagulants (OAC) reduce the risk for stroke and death from all causes in patients with non-valvular atrial fibrillation (NVAF)

Objective: To explore adherence rates of OAC among patients with NVAF in long-term use in a real-world setting and to examine patient characteristics associated with good adherence.

Methods: We conducted a population-based cohort study with members of Clalit Health Services, Israel. All patients aged ≥ 30 years with a diagnosis of NVAF before 2016 who were treated with OAC were included. We included patients who filled at least one prescription per year in the three consecutive years 2016–2018. We analyzed all prescriptions that were filled for the medications from 1 January 2017 to 31 December 2017. We considered purchasing of at least nine monthly prescriptions during 2017 as good medication adherence.

Results: We identified 26,029 patients with NVAF who were treated with OAC; 10,284 (39.5%) were treated with apixaban, 6321 (24.3%) with warfarin, 6290 (24.1%) with rivaroxaban, and 3134 (12.0%) with dabigatran. Rates of good medication adherence were 88.9% for rivaroxaban, 84.9% for apixaban, 83.6% for dabigatran, and 55.8% for warfarin (P < 0.0001). Advanced age was associated with higher adherence rates (P < 0.001). Socioeconomic status was not associated with medication adherence. Good adherence with OAC was associated with lower low density lipoprotein (LDL) cholesterol and glucose levels.

Conclusions: Adherence rates to OAC in chronic use among patients with chronic NAVF are high. Investing in OAC adherence may have a wider health impact than expected.

Background: Adherence to treatment by adolescents and adults with cystic fibrosis (CF) is often poor.

Objectives: To assess the impact of a focused clinical intervention on adherence in individual patients, including help in problem-solving key barriers to adherence. To implement a patient-centered problem-solving intervention using CF My Way tools. To identify and overcome a selected barrier to adherence.

Methods: Medication possession ratios (MPRs), number of airway clearance sessions, forced expiratory volume (FEV₁), body mass index (BMI), and health-related quality of life (HRQoL) were measured before and after the intervention.

Results: Sixteen patients with CF, aged 23.4 ± 6.7 years, participated. MPR increased for colistimethate sodium and tobramycin inhalations from a median of 21 (range 0–100) to 56 (range 0–100), P = 0.04 and 20 (range 0–100) to 33.3 (range 25–100), P = 0.03, respectively. BMI standard deviation score rose from -0.37 to -0.21, P = 0.05. No significant improvements were found in FEV₁, airway clearance, or HRQoL scores.

Conclusions: The CF My Way problem-solving intervention increased adherence to medical treatments by removing barriers directly related to the needs and goals of young adults with CF

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: 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: Surgery for hip fractures within 48 hours of admission is considered standard. During the lockdown period due to the coronavirus disease-2019 (COVID-19) epidemic, our medical staff was reduced.

Objectives: To compare the demographics, treatment pathways, and outcomes of patients with hip fractures during the COVID-19 epidemic and lockdown with the standard at routine times.

Methods: A retrospective study was conducted of all patients who were treated surgically for hip fracture in a tertiary center during the COVID-19 lockdown period between 01 March and 01 June 2020 and the equivalent period in 2019. Demographic characteristics, time to surgery, surgery type, hospitalization time, discharge destination, postoperative complications, and 30- and 90-day mortality rates were collected for all patients.

Results: During the COVID-19 period, 105 patients were operated due to hip fractures compared to 136 in the equivalent period with no statistical difference in demographics. The rate of surgeries within 48 hours of admission was significantly higher in the COVID-19 period (92% vs. 76%, respectively; P = 0.0006). Mean hospitalization time was significantly shorter (10 vs. 12 days, P = 0.037) with diversion of patient discharge destinations from institutional to home rehabilitation (P < 0.001). There was a significant correlation between the COVID-19 period and lower 90-day mortality rates (P = 0.034). No statistically significant differences in postoperative complications or 30-day mortality rates were noted.

Conclusions: During the COVID-19 epidemic, despite the limited staff and the lack of therapeutic sequence, there was no impairment in the quality of treatment and a decrease in 90-day mortality was noted.