Israel Medical Association Journal

Artificial intelligence in ophthalmology is used for automatic diagnosis, data analysis, and predicting responses to possible treatments. The potential challenges in the application and assimilation of artificial intelligence include technical challenges of the algorithms, the ability to explain the algorithm, and the ability to diagnose and manage the medical course of patients. Despite these challenges, artificial intelligence is expected to revolutionize the way ophthalmology will be practiced. In this review, we compiled recent reports on the use and application of deep learning in various fields of ophthalmology, potential challenges in clinical deployment, and future directions.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Background: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF.

Objectives: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine.

Methods: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF.

Results: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them.

Conclusions: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.

Background: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking.

Objectives: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents.

Methods: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses.

Results: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability.

Conclusions: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

Myelodysplastic syndrome (MDS) is frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory responses of the immune system. The biological linkage between MDS clones and the occurrence of autoimmune manifestations is mirrored by the response of the latter to MDS modifying therapeutic approaches [1]. We encountered a rare case of MDS coexisting with antiphospholipid syndrome (APS), which was effectively treated with a hypomethylating agent followed by allogenic bone marrow transplantation.

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 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.

Background: Spinal epidural abscess (SEA) is a rare disease with a potentially devastating outcome, and a reported incidence traditionally estimated at 0.2–2 cases/10,000 hospital admissions. Since the implementation in October 2007 of a program to increase medical personnel’s awareness of SEA, we have documented a sharp increase in the incidence of SEA at our medical center

Objectives: To investigate the cause of the increased incidence of SEA.

Methods: All cases diagnosed with SEA during the period 1998–2010 were retrospectively reviewed. Cases diagnosed before 2007 were compared with those diagnosed thereafter.

Results: From January 1998 to October 2007 SEA was diagnosed in 22 patients (group A), giving an annual incidence of 0.14–0.6 cases per 10,000 admissions. During the period November 2007 to April 2010, 26 additional patients were diagnosed (group B), yielding an incidence of 0.81–1.7 cases per 10,000 admissions (P < 0.01). The two groups did not differ significantly in epidemiological, clinical or laboratory characteristics, or in the causative bacteria isolated.

Conclusions: The threefold rise in the incidence of SEA observed at a tertiary medical center in Tel Aviv since November 2007 was not explained by different host characteristics or by more virulent bacterial isolates. We suggest that heightened awareness of the clinical presentation and timely utilization of MR imaging has resulted in more cases being identified. 

Objectives: To characterize the demographic and clinical features of malaria acquired in Kenya, and to assess the adequacy of preventive measures.

Methods: Data were collected from investigation forms at the Ministry of Health. All persons who acquired malaria in Kenya during the years 1999–2001 were contacted by phone and questioned about use of chemoprophylaxis, attitudes towards malaria prevention, and disease course. Further information was extracted from hospital records.

Results: Kenya accounted for 30 of 169 (18%) cases of malaria imported to Israel, and was the leading source of malaria in the study period. Of 30 malaria cases imported from Kenya, 29 occurred after short (1–2 weeks) travel to holiday resorts in Mombassa. Average patient age was 43 ± 12 years, which is older than average for travelers to tropical countries. Only 10% of the patients were fully compliant with malaria chemoprophylaxis. The most common reason for non-compliance was the belief that short travel to a holiday resort carries a negligible risk of malaria. Only 3 of 13 patients (23%) who consulted their primary physician about post-travel fever were correctly diagnosed with malaria. Twenty percent of cases were severe enough to warrant admission to an intensive care unit; one case was fatal.

Conclusions: Measures aimed at preventing malaria and its severe sequelae among travelers should concentrate on increasing awareness of risks and compliance with malaria chemoprophylaxis.

Objective: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family.

Family Description: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia.

Conclusion: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.