Israel Medical Association Journal

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

Pediatrics stands at the forefront of medical innovation, from neonatal care to the management of complex acute and chronic conditions. The field continues to evolve, driven by pioneering research. Advances in genetics, technology, and personalized medicine are transforming pediatric care, addressing the diverse needs of children globally, and offering new opportunities to enhance health outcomes and quality of life.

Anorexia nervosa (AN) is a common psychiatric disorder primarily affecting adolescents and young adults. It is characterized by extreme restriction of food intake, distorted body image, and weight-gain anxiety. We report a case with rapid progression and severe metabolic changes in a young restrictive-type AN patient, highlighting unique aspects of this presentation and discussing pathophysiology.

An 11-year-old girl presented with a significant 29% weight loss over 4 months, leading to a body mass index (BMI) of 11.7 (< 1st BMI percentile for her sex and age). She presented with severe bradycardia and metabolic abnormalities including hypoglycemia, hypercholesterolemia, and hypothyroidism. Following diagnosis with restrictive type AN based on the DSM-5 [1] criteria and stabilization at our department, she was transferred to a specialized unit. The hypercholesterolemia our patient presented with is more typical of binge-eating/purging subtype AN, yet it was markedly elevated in this restrictive-type case.

It is indisputable that internal medicine is the cornerstone of medical activities, including medical education, in hospital clinical activities, and clinical and basic medical research.

The medical landscape in Israel is exceptionally demanding, far exceeding the norms of the countries that are members of the Organisation for Economic Co-operation and Development (OECD). We have fewer hospital beds per capita, a greater workload for each physician, and in the future, we will face the challenge of teaching more medical students across our current clinical fields.

The Israeli Society of Internal Medicine has made it its mission to advance internal medicine across all dimensions of the healthcare system in Israel. As such, for the third consecutive year, we are honored to present an issue of the Israel Medical Association Journal (IMAJ) dedicated to research in the different fields of internal medicine that are conducted by physicians from various departments across the country.

This year, we emphasize even more strongly that research is an integral part of our clinical practice. At a time when the basic sciences phase of residency is under threat, it is crucial to underscore its importance. In this issue of IMAJ, we have chosen to publish various studies that were conducted during the basic sciences phase of the residency in internal medicine, highlighting how this training period can be optimally utilized to advance research while simultaneously progressing and maturing through clinical training.

Background: Several studies have shown an association between increased red blood cell distribution width (RDW) and adverse outcomes in various acute diseases. Small studies have suggested that RDW is a useful predictor of acute pancreatitis severity.

Objectives: To determine the association between RDW at admission and early mortality in acute pancreatitis. To assess whether RDW adds to the predictive ability of the Glasgow Imrie Score.

Methods: In this observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Patients were divided into two groups according to RDW: normal RDW (RDW ≤ 14.5%) and elevated RDW (RDW > 14.5%).

Results: Within 30 days of admission, 29/438 patients (6.6%) with increased RDW and 20/1250 patients (1.6%) with normal RDW had died: univariate analysis (odds ratio 4.6, 95% confidence interval 2.45–7.9, P < 0.001), fully adjusted model (odds ratio 3.29, 95% confidence interval 1.75–6.26, P < 0.001). We calculated receiver operating characteristic curve (ROC) for RDW alone, Glasgow Imrie Score alone, and a combination of Glasgow Imrie Score with RDW. We assessed their ability to predict 30-day mortality. Area under the ROC curve (AUC) of RDW alone was 0.671 and Glasgow Imrie Score AUC was 0.682; Glasgow Imrie Score plus RDW had an AUC of 0.769.

Conclusions: In patients with acute pancreatitis, elevated RDW at admission was independently associated with increased 30-day mortality. The addition of RDW to a pancreatitis prognostic tool such as the Glasgow Imrie Score improves its predictive ability.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.

Diabetes mellitus (DM) is a serious and growing global health challenge. The number of people diagnosed with diabetes continues to rise, and it is projected that by 2035 more than 592 million individuals worldwide will have diabetes [1]. DM can impact the heart through various mechanisms. Vascular complications are associated with diabetes and include both epicardial coronary artery and small vessel disease. Cardiomyopathy and heart failure may also occur. Insulin resistance causes cardiomyocytes to have a reduced capacity for glucose utilization, leading to increased uptake of free fatty acids. This, in turn, results in triglyceride storage and lipotoxicity, which contribute to impaired cardiac contractility [2].

Diabetes may lead to the production of advanced glycation end (AGE) products, resulting in an accumulation of reactive oxygen species. This accumulation triggers inflammation that can cause myocyte apoptosis and mitochondrial dysfunction. AGE can also contribute to cardiac fibrosis, which increases myocardial stiffness and results in heart failure with preserved ejection fraction (HFpEF) [2].

The Dina Recanati School of Medicine at Reichman University offers a unique approach to preclinical medical education, combining strong scientific foundations with practical, clinical applications. This 4-year program includes two preclinical years focused on core medical knowledge and two clinical years of rotations. The curriculum emphasizes small-group learning, early clinical exposure, and a system-based block structure. Starting from the first week of the preclinical years, students will participate in biweekly clinical days, using simulations, virtual reality, and patient interactions to develop practical clinical skills. The community clinic mentorship offers real-world experience that complements the clinical program taught in class during the same week. Research is central, with students conducting supervised projects aimed at a medical doctor thesis publication. The teaching model ensures relevance by integrating clinical cases into all courses, guided by practicing physicians. Daily quizzes and block-style assessments replace traditional examination periods, promoting consistent learning. The innovative program balances clinical practice with scientific knowledge, preparing students for the challenges of modern medicine.

Background: Hospital-at-Home (HaH) programs offer medical services in the patient's home as an alternative to hospitalization across various medical fields. Previous studies have demonstrated that HaH provides several benefits for patients and the healthcare system. Rambam Health Care Center was the pioneer hospital in introducing HaH in Israel. Since April 2021, in collaboration with Maccabi Healthcare Services, the center has been providing home hospitalization services for patients with acute internal medicine illnesses based on an innovative model.

Objectives: To describe demographic data, background diseases, indications for HaH admissions, length of stay (LOS), 1-month and 1-week readmission rates, home mortality, and 1-month mortality.

Results: The study included 262 patients (135 men, 127 women), mean age 69.7 years (range 24–98, median 73). Patients had significant co-morbidities, with a Charlson Comorbidity Index score of 6.7. Among the patients, 170 were independent, 61 were incapacitated, and the remainder had various functional limitations. Most admissions were from internal medicine departments, 39 originating from the emergency department and the rest from other acute care wards. The primary indications for HaH admission included pneumonia, urinary tract infections, and cellulitis. The average hospital LOS was 48.9 hours, while the HaH LOS was 3.43 days. Readmission rates for the same initial conditions were 10% within 1 week and 14% within 1 month. Twenty-one patients died within 1 month of discharge from HaH, including one death during the HaH period.

Conclusions: This study highlighted the feasibility of home hospitalization as a viable alternative to traditional inpatient care in internal medicine.

Rehabilitation plays a crucial role in improving clinical outcomes for cardiac patients. The accessibility of traditional cardiac rehabilitation programs is often hindered by factors such as cost and geographical distance. In recent years, wearable monitor-based remote rehabilitation has emerged as a potential solution to improve accessibility. In this systematic review, we assessed the recent literature on remote cardiac rehabilitation utilizing wearable monitors. We conducted a comprehensive literature review using the MEDLINE database, focusing on all studies published in English until June 2023. The search utilized the keywords cardiac rehabilitation and remote monitoring to identify relevant studies on clinical outcomes, wellbeing, and adherence. Filters were applied to include human subjects only. Reviews, meta-analyses, and systematic reviews were used to expand the search, but excluded from the primary selection process. A total of 14 relevant papers were included following the selection process: nine randomized controlled trials and five cohort studies. The synthesis of articles found that remote cardiac rehabilitation monitored by wearable devices is as safe and effective as conventional rehabilitation and more effective than medical observation only. In addition, it enhances the availability of cardiac rehabilitation in cases of limited accessibility. Several limitations require further research including expanding the demographic diversity of the participants and improving the ease of use of the technology. While remote cardiac rehabilitation monitored by wearable devices shows promise, further research is needed to expand the participant pool and refine the wearable monitor technology's usability.

Background: Little is known about audiovestibular function in psoriasis, a chronic systemic inflammatory disease that affects 2% of the world’s population.

Objective: To investigate audiovestibular function in patients with psoriasis.

Methods: In this prospective case-control trial, we enrolled 33 patients with psoriasis and 30 healthy controls. Audiologic testing included audiometry, tympanometry, and otoacoustic emissions recording. The vestibular investigation consisted of a dizziness handicap inventory questionnaire, a complete clinical vestibular examination, and video head impulse testing.

Results: The psoriasis group showed significantly higher average hearing thresholds in both ears at all frequencies. Otoacoustic measurements differed significantly at 3000 Hz in the right (P = 0.026) and left ear (P = 0.034). The average dizziness handicap score was considerably higher in the psoriasis group, with a mean difference of 7.70 (P = 0.025). The number of patients with abnormal right anterior semicircular canal gain values was significantly higher in the psoriasis group (P = 0.047). Saccade analysis in the psoriasis group showed significantly higher number of patients with covert corrective saccades of the left posterior canal (P = 0.037) and significantly higher number of patients with abnormal interaural difference of corrective saccades in the plane of the right anterior-left posterior canals (P = 0.035).

Conclusions: The study demonstrates an association between psoriasis and audiovestibular impairment, which can affect quality of life. These results suggest that patients with psoriasis may be evaluated with audiometry for possible hearing loss. Vestibular testing may be pursued as clinically indicated.

Background: One-third of patients with acute decompensated heart failure (ADHF) develop worsening kidney function, known as type I cardiorenal syndrome (CRS). CRS is linked to higher mortality rates, prolonged hospital stays, and increased readmissions.

Objectives: To explore the impact of real-time monitoring of urinary output (UO) trends on personalized pharmacologic management, fluid balance, and clinical outcomes of patients with ADHF admitted to a cardiac intensive care unit.

Methods: Our study comprised 35 patients who were hospitalized with ADHF and continuously monitored for UO (UO_elec). Standard diuretic and fluid protocols were implemented after 2 hours of oliguria, and patient outcomes were compared to a historical matched control (HMC) group. Patients were assessed for daily and cumulative fluid balance (over 72 hours) as well as for the occurrence of acute kidney injury (AKI).

Results: Significantly more patients in the UO_elec group demonstrated negative fluid balance daily and cumulatively over time in the intensive care unit compared to the HMC group: 91% vs. 20%, respectively (P < 0.0001 for 72-hour cumulative fluid balance). The incidence of AKI was significantly lower in the UO_elec monitoring cohort compared to the HMC: 23% vs. 57%, respectively (P = 0.003). Moreover, higher AKI resolution, and lower peak serum creatinine levels were demonstrated in the UO_elec group vs. the HMC group.

Conclusions: Implementing real-time monitoring of UO in ADHF patients allowed for early response to oliguria and goal-directed adjustment to treatment. This finding ultimately led to reduced congestion and contributed to early resolution of AKI.

Nasopharyngeal angiofibromas represent a rare occurrence. They are characterized by vascular fibrous proliferation within the nasopharynx. While histologically benign, they exhibit a local aggressiveness, predominantly afflicting adolescent males. Despite their typically nasopharyngeal location, the exact etiology remains elusive.

Microscopically, angiofibromas manifest as a combination of vascular elements, featuring slit-like capillaries or dilated branched vessels, in addition to a stromal component comprising collagenous matrix and fibroblasts.

To the best of our knowledege, we presented the first documented example of an extra-nasopharyngeal angiofibroma in an adult male, which presented with a distinctive histologic pattern of epithelioid fibrous papule. Clinical manifestations included left-side aural fullness and gradual hearing loss over the course of 5 years. Examination revealed a mass within the left external auditory canal tethered to the posterior wall by a stalk. The audiometric assessment revealed a moderate to severe conductive hearing impairment in the left ear. Surgical excision of the mass was performed, with subsequent histopathological and immunohistochemical analysis unveiling this unforeseen diagnosis.

In this case report, we underscored the potential for angiofibromas to occur in atypical anatomical sites and highlighted the importance of recognizing their benign nature to prevent misdiagnosis as malignant tumors.

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.